27E Internistendagen Abstractboek

27 e Internistendagen

• 22-24 2015 april • MECC • Maastricht • Abstractboek 27 Internistendagen Abstractboek (Abstracts submitted to the Anual Meeting of the Netherlands Association of Internal Medicine, 22-24 April 2015, Maastricht, the Netherlands)

22-24 april 2015 MECC Maastricht INHOUD

27e Internistendagen Abstractboek

22-24 april 2015 MECC, MAASTRICHT

Voorwoord ?

I Presentations ‘Schop de Heilige Huisjes omver!’ II Oral Presentations III Acute Medicine IV Diabetes Mellitus V Endocrinology VI Gastroenterology VII General Internal Medicine VIII Geriatric Medicine IX Haematology X Immunology/Allergology XI Infectious Diseases XII Intensive Care XIII Nephrology XIV Oncology XV Rheumatology XVI Vascular Medicine XVII Other

1 Voorbereidingscommissie

An Reyners - voorzitter Paul van Daele Kees Hovingh Harry Koene Robin Peeters Hilde Royen Patricia Stassen Roderick Tummers-de Lind van Wijngaarden (JNIV) Joost Wiersinga

Deelnemende verenigingen

Nederlandse Internisten Vereniging (NIV) Internistisch Vasculair Genootschap Juniorafdeling Nederlandse Internisten Vereniging Nederlandse Federatie voor Nefrologie Nederlandse Vereniging voor Allergologie Nederlandse Vereniging voor Endocrinologie Nederlandse Vereniging voor Gastro-Enterologie Nederlandse Vereniging voor Haematologie Nederlandse Vereniging voor Immunologie Nederlandse Vereniging voor Klinische Farmacologie en Biofarmacie Nederlandse Vereniging voor Medicale Oncologie Nederlandse Vereniging voor Medical Onderwijs NIV Sectie Acute Interne Geneeskunde NIV Sectie Intensive Care NIV Sectie Ouderengeneeskunde Vereniging voor Infectieziekten

Organiserende vereniging

Nederlandse Internisten Vereniging (Medicinae Internae B.V.) Postbus 20066 3502 LB Utrecht Tel: 030-282 32 29 Fax: 030-282 32 25

Congressecretariaat

Congress Company Postbus 2428 5202 CK ’s-Hertogenbosch Tel. 073-700 35 00 Fax 073-700 35 05 E-mail: [email protected]

Uitgever

Van Zuiden Communications B.V. Postbus 2122 2400 CC Alphen aan den Rijn Tel.: 0172-47 61 91 Fax: 0172-47 18 82 E-mail: [email protected] Internet: www.vanzuidencommunications.nl

2 VOORWOORD/INTRODUCTION

Met genoegen presenteren wij u het Abstractboek van de 27e Internistendagen, gehouden van 22-24 april in het MECC te Maastricht. De abstracts betreffen zowel case reports als wetenschappelijk onderzoek. Uit heel Nederland zijn in groten getale abstracts ingestuurd. Een uitdaging dit jaar was het beperken van het aantal woorden tot een maximum van 250. Er zijn 298 abstracts ingediend die zijn opgenomen in dit Abstractboek. Uit deze abstracts zijn er 30 geselecteerd voor een presentatie tijdens de Internistendagen. Deze abstracts worden eerst vermeld, gevolgd door de overige abstracts welke per vakgebied zijn terug te vinden. De selectie van de abstracts heeft plaatsgevonden op basis van (wetenschappelijke) inhoud, originaliteit en presentatie. De abstracts zijn anoniem door drie leden van de commissie beoordeeld. De abstracts met de hoogste score zijn geselecteerd voor presentatie. Tijdens de Internistendagen zullen de presentaties zo veel mogelijk per onderwerp gebundeld gepresenteerd worden.

Het grote aantal abstracts dat elk jaar wordt ingezonden, onderschrijft dat dit een belangrijk onderdeel is van de Internistendagen. De arts-assistenten krijgen een podium aangeboden om resultaten van hun onderzoek of van bijzondere observaties in de kliniek te presenteren. De toehoorders krijgen op deze manier een kijkje in de keuken van waar we in Nederland allemaal mee bezig zijn en komen zelf wellicht op ideeën voor onderzoek.

Evenals voorgaande jaren zal er per sessie een winnaar worden aangewezen die een prijs van 250 euro zal krijgen. Het allerbeste abstract van een wetenschappelijk onderzoek, een case report en Heilig Huisje zal na afloop via de NIV-site bekend worden gemaakt. Deze winnaars krijgen een publicatie in The Netherlands Jourmal of Medicine aangeboden.

In dit Abstractboek treft u ook de ingezonden abstracts aan van de Heilige Huisjes. Tijdens de plenaire sessie op vrijdag- ochtend 24 april zullen de auteurs proberen hun Heilige Huisje om te laten vallen.

Wij wensen u veel plezier toe met het lezen van de abstracts, maar nodigen u vooral uit te komen luisteren en discussiëren met de arts-assistenten naar aanleiding van hun onderzoeksresultaten en leerzame patiëntencasuïstiek uit heel Nederland.

Commissie Internistendagen,

An Reyners, voorzitter Paul van Daele Kees Hovingh Harry Koene Robin Peeters Hilde Royen Patricia Stassen Roderick Tummers-de Lind van Wijngaarden Joost Wiersinga

3 I PRESENTATIONS ‘Schop de Heilige Huisjes’ II ORAL PRESENTATIONS omver!’ O01 Mucositis in a patient from the mediterrranean; More than just Behçet’s disease [Presentaties Heilige huisjes volgen z.s.m.] S.M.W. Koop ZGT, Department of Internal Medicine, Almelo, the Netherlands

A 59 year old Turkish man presented himself with complaints of severe painful mucositis since 3 months. A trial treatment with prednisone had had some effect, however after treatment was discontinued symptoms worsened again. The patient had also recently developed skin lesions complained of a painful red eye. Physical examination showed severe ulcerations on lips, tong and palate. Chest, abdomen, hand palms and glans penis showed multiple erythematous and vesiculous lesions with a diameter up to 5mm. His eyes showed signs of conjunctivitis. The combination of oral and genital ulcers and eye symptoms made us suspect Behçet’s disorder as a possible explanation. However the criteria for Behçet require the absence of other systemic disorders. Infectious diseases like Lues and HIV were excluded. Systemic inflammatory disorders like SLE and Crohn’s disease were deemed less likely due to the absence of gastro-intestinal disorders and arthritis. Auto-immune markers like ANA and ANCA were negative. A skin biopsy was taken for further analysis of the skin lesions. This showed evidence of pemphigus vulgaris, with a preference for paraneoplastic pemphigus. Imaging of thorax and abdomen was obtained showing multiple masses around thoracal and abdominal aorta, around the spleen and in the retroperitoneum. Biopsy of the retroperitoneal lesion showed a low grade B-cellymphoma stage III, most likely marginal zone lymphoma. Treatment with R-CVP has been initiated. Oral ulceration in patient from the Mediterranean can point to more diseases than just Behcet’s disease and excluding these disorders is a viable part in the diagnostic process.

O02 Management of rectal cancer in octogenarians in a teaching hospital in the southern part of the the Netherlands between 2008-2011

A.S.J. van Vuuren, F. van den Bermortel Atrium-Orbis Medical Centre, Department of Oncology, Heerlen, the Netherlands

Background: Rectal Cancer (RC) treatment is multidisciplinary, decreasing recurrence rates at cost of toxicity. Evidence from guidelines is based on studies in young fit patients, however most patients are elder and little

4 evidence is available to guide treatment. Risks of complica- Kaplan Meier analysis and a Cox proportional hazards tions are increased. The aim of our study is to evaluate the model. diagnostic process, treatment, adverse events and outcome Results: 109 patients were identified at our hospital of octogenarians treated for RC. between 01.01.2001 and 01.06.2014, 22 patients in the Methods: Octogenarians with RC diagnosed between T-group and 87 in the TN-group. Death rate at the end of 2008-2011 were identified by hospital registry. Case follow up was 74.3%. Median follow up was 18.5 months records were studied according to a predefined list of in the T-group and 31.0 months in the TN-group. Median parameters. OS was 29 months in the T-group and 33 months in the Results: 61 octogenarians (mean age 82) with RC, mean TN-group. (p = 0.445) adjusted Charlson morbidity score 4,3 (range 3-8) were Conclusion: This study shows no overall survival difference identified. 13% of these patients were not discussed in patients with adjuvant trastuzumab treatment failure in multidisciplinary, an amount decreasing over the years relation to trastuzumab naïve patients. In order to rule out from 21% (2008) to 8% (2011). In 95% of patients staging a type II statistical error, a multicenter study is planned. was properly performed. 25% of patients were not treated according to multidisciplinary treatment plan. In the O04 An unusual cause of hypokalaemia trimodality group 31% of patients interrupted chemotherapy due to adverse events and hospitalization was C.Y. Bruggeman, M.J. Agterof, I.M.M.J. Wakelkamp almost doubled compared with the bi-modality treatment St. Antonius Hospital, Department of Internal Medicine, group ( 50 vs. 30%). Of 15 patients with survival data 47% Utrecht, the Netherlands died < 6 months, 77% died < 1 year of diagnosis. Conclusion: Most octogenarians were properly staged and Case: A 73-year old woman was referred to the Emergency discussed multidisciplinary with increasing numbers over Room because of hypokalaemia (2.5 mmol/L). She had years. However 25% of patients were not treated according complaints of fatigue, weight loss and she was thirsty. to treatment plan. Increased toxicity was documented Physical examination showed a blood pressure of with increasing treatment modalities and life expectancy 190/90 mmHg, a small buffalo hump and the liver was appeared short. Information regarding clinical condition enlarged. Laboratory investigations showed beside the and patient preference should be weighed multidisciplinary hypokalaemia, a metabolic alkalosis and increased liver for the best personalized treatment. function tests. Because of the combination: hypokalaemia, hypertension and buffalo hump we suspected O03 Survival of patients with Her2 positive metastatic Cushing syndrome and indeed measured increased cortisol breast cancer after failure of adjuvant treatment with (1833nmol/l) and ACTH (35.5 pmol/l) levels. Treatment with trastuzumab potassium was started. Ultrasound and computed tomography of chest and H.N. Rier1, M. Hooning2, A. Jager2, J.J.E.M. Kitzen1, abdomen showed liver, bone and lymph node metastasis S. Sleijfer2, M.D. Levin1 and a hypodensity of the uterus. Liver biopsy and a cervical 1Albert Schweitzer Hospital, Department of Internal Medicine, PAP smear showed small cell carcinoma. Chemotherapy Dordrecht, the Netherlands, 2Erasmus MC, Department of with carboplatin/etoposide was started. Cortisol levels Epidemiology, Rotterdam, the Netherlands dropped after chemotherapy commenced and hydrocortisone suppletion was started in a normal Addison Background: Survival of patients with Her2 positive suppletion dose of 10-5-5 mg/day. We could abolish metastatic breast cancer has improved dramatically since potassium treatment after the first chemotherapy cycle the availability of trastuzumab. Because most trials contain and the hypertension decreased rapidly. breast cancer patients, who have never been exposed to After three cycles of chemotherapy there was a good trastuzumab in adjuvant setting (TN-group), these trials response and the treatment was continued. might not be representative for the current population of Discussion: Cushing’s syndrome as first presentation of patients adjuvantly treated with trastuzumab (T-group). cervical small cell carcinoma due to ectopic adrenocortico- In this retrospective study we hypothesized that survival tropin hormone production is very rare. Only two percent of Her2 positive metastatic breast cancer patients in the of cervical cancers are small cell carcinoma, most of which T-group is worse than in the TN-group. are not neuroendocrine active. Because of its rarity, no Methods: All patients with Her2 positive metastatic breast clinical trials have been performed. Treatment is based cancer receiving palliative trastuzumab were identified and on experience with small cell lung cancer. The prognosis divided into a group that received adjuvant trastuzumab for metastatic disease is very poor. Lastly, management of treatment (T-group) and a trastuzumab-naïve group cortisol levels should be part of treatment. (TN-group). Overall survival (OS) was estimated using

5 O05 Stevens-Johnson syndrome as a complication of He was suffering from a melanoma with metastasis gemcitabine monotherapy to the lymph nodes, liver and lung for which he was treated with ipilimumab, an immunotherapeutic agent. S. Jainandunsing, R.S. Boersma, K.E.S. Duthoi, Physical examination revealed a hemodynamically stable J.W.J. van Esser man with normal results of heart, lungs and abdomen. Amphia Hospital, Department of Internal Medicine, Breda, Neurological examination revealed no abnormalities either. the Netherlands Laboratory findings demonstrated slight leucocytosis of 14.9x109/L with eosinophils 0.9x109/L and CRP 12mg/L. Introduction: As gemcitabine is increasingly used as ESR, hemoglobin, platelets, renal and hepatic function anti-neoplastic therapy, one should be aware of its toxic were normal. Initially, cerebral metastasis was considered effects. Cutaneous adverse reactions like Stevens-Johnson to be the cause of his complaints. An MRI was performed syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), two days later, showing pituitary enlargement. Extensive have been reported following gemcitabine in combination laboratory investigations revealed severe hypopituitarism with radiotherapy. Both TEN and SJS cause high mortality. with low levels of TSH, FT4, testosterone and gonado- Case report: A 62-year old female known with FIGO stage tropins and normal ACTH with low cortisol, caused by IIIB ovarian cancer received carboplatin/paclitaxel because hypophysitis, one of the immune-related adverse events of relapse. Secondary to unresponsive disease and the of ipilimumab. Immediate treatment with high-dose occurrence of paraneoplastic CREST syndrome, therapy corticosteroids and hormone replacement was started and was switched to gemcitabine. Patient was admitted ten days the patient’s symptoms resolved rapidly. Subsequently he following her first gemcitabine infusion with fever and developed two other autoimmune-related toxicities, i.e. painful erythematous Nikolsky negative maculae located diarrhoea caused by colitis for which he needed infliximab on her torso and upper extremities, and mucosal lesions. and peroneus neuropathy. Eventually these events were Skin biopsy was compatible with SJS. Her predicted SJS/ well controlled. Even though response evaluation showed TEN-associated mortality risk was calculated as 12.1%. progressive disease, the patient is still alive today. This case Analgesics, antibiotics and high-dose prednison were report illustrates that patients treated with ipilimumab started with complete resolution of skin abnormalities. can present with various symptoms that may be based Discussion: We present a patient with SJS as a compli- on serious, potentially life-threatening immune-related cation of gemcitabine monotherapy. To date SJS has only adverse events that can occur in virtually all organs and been reported when gemcitabine is combined with radio- require urgent treatment. Vigilance is therefore warranted therapy. The Algorithm for Drug Causality for Epidermal when patients taking ipilimumab report complaints. Necrolysis pointed towards gemcitabine as a causative agent. The exact mechanism of gemcitabine-induced O07 Chemotherapy-induced peripheral neuropathy skin toxicity remains unknown. Distinction between in multiple myeloma patients. Results from the SJS and TEN is mandatory and is based on the extent of PROFILES registry detached skin, with mortality for SJS, SJS/TEN-overlap and TEN, 9%, 29% and 48%, respectively. Rapid institution A.J.M. Beijers1, S. Oerlemans2,3, F. Mols2,3, M.C. Minnema4, of immunomodulatory therapy is reported to prevent L.V. van de Poll-Franse2,3, G. Vreugdenhil1 progression of SJS towards TEN. However, consensus is 1Máxima Medical Centre, Department of Internal Medicine, lacking. Veldhoven & Eindhoven, the Netherlands, 2Tilburg University, Conclusion: SJS may also occur following gemcitabine CoRPS – Medical and Clinical Psychology, Tilburg, the monotherapy. Early identification and management of Netherlands, 3The Netherlands Comprehensive Cancer gemcitabine-associated SJS is highly important to prevent Organisation (IKNL), Location Eindhoven, Eindhoven,the TEN. Netherlands, 4UMC Utrecht Cancer Centre, Department of Haematology, Utrecht, the Netherlands O06 A patient suffering from various immune-related adverse events following treatment with ipilimumab Background: Multiple myeloma (MM) patients often experience chemotherapy-induced peripheral neuropathy J. Rutgers, D. Piersma (CIPN). We aimed to examine the prevalence and severity Medisch Spectrum Twente, Department of Internal Medicine, of CIPN and the influence on health-related quality of life Enschede, the Netherlands (HRQOL) in a population-based sample of MM patients. Methods: All MM patients diagnosed between 2000 and A 55-year-old man was referred to the emergency 2014 as identified by the the Netherlands Cancer Registry, department with complaints of severe headache, nausea location Eindhoven, and alive at registration, were eligible. and vertigo since five days and a short episode of diplopia. With a response rate of 74%, 130 patients completed the

6 EORTC QLQ-CIPN20, EORTC QLQ-C30 and EORTC with the platelet P2Y12 receptor inhibitor clopidogrel or QLQ-MY20 mean 3.5 years since diagnosis. placebo. Results: Patients received treatment with one (49%) or Results: Thrombocytopenic mice (platelet counts < 1% of more (42%) neurotoxic agents (total 92%), including uninfected controls) showed a reduced survival during thalidomide (50%), bortezomib (48%), lenalidomide pneumococcal pneumonia (27% vs 75% amongst controls; (39%) and/or vincristine (7%). Neuropathy symptoms p = 0.003), which was associated with higher bacterial that bothered patients most during the past week were loads in lungs, spleen, and blood. Thrombocytopenic trouble getting an erection (46% of men), tingling toes/ mice showed enhanced coagulation activation (thrombin- feet (30%), numbness in toes/feet (20%), tingling fingers/ antithrombin complexes) in plasma. Proinflammatory hands (19%) and trouble opening jars/bottles (19%). cytokine levels were higher in plasma but not in lungs of There were no differences in neuropathy subscale scores thrombocytopenic mice. Although clopidogrel treatment between patients who received treatment with only one strongly prolonged the bleeding time, it did not impact on vs. a combination of more neurotoxic agents. Patients bacterial loads during pneumococcal pneumonia. who received treatment with neurotoxic agents within the Conclusion: Platelets play a protective role during pneumo- last 3 months reported significant worse sensory subscale coccal pneumonia independent of their aggregation. scores than patients who received their last treatment more than 12 months before (21 vs. 12; p = 0.01). Patients with O09 Coombs positive haemolytic anaemia and thrombo- many sensory symptoms reported significant and clinically cytopenia, not always Evans syndrome? relevant worse HRQOL scores on all EORTC QLQ-C30 and QLQ-MY20 subscales. E.M. van Leeuwen-Segarceanu, A. Huisman, Conclusion: CIPN is a common side-effect reported in 54% K.M.K. de Vooght, R.E.G. Schutgens, R.A.P. Raymakers of MM patients. Especially many sensory symptoms have a UMC Utrecht, Department of Haematology, Utrecht, the negative influence on HRQOL. Future studies should focus Netherlands on the prevention and treatment of CIPN. Introduction: Evans syndrome (ES) is defined by the O08 Thrombocytopenia impairs host defense during combination of autoimmune haemolytic anaemia (AIHA) murine Streptococcus pneumoniae pneumonia and immune thrombocytopenia (ITP). We present a case in which ES masked the presence of a different (lethal) F.E. van den Boogaard1, M. Schouten2, S.F. de Stoppelaar3, disorder. J.J.T.H. Roelofs4, X. Brands4, M.J. Schultz4, C. van ‘t Veer4, Case report: A 70-year old patient, with chronic hepatitis T. van der Poll4 B, presented for routine follow-up at his gastroenterologist. 1Tergooi, Department of Internal Medicine, Hilversum, the The patient was still working and was asymptomatic Netherlands, 2VUmc, Department of Nephrology, Amsterdam, besides some fatigue. His laboratory examination showed the Netherlands, 3Flevo Hospital, Department of Internal the following results: haemoglobin 5.5 mmol/L, reticulo- Medicine, Almere, the Netherlands, 4AMC, Department of cytes 191x109/L, thrombocytes 12x109/L, LDH 668U/L, Pathology, Amsterdam, the Netherlands haptoglobin < 0.1g/L, positive Coombs (anti-IgG 4+), eGFR 57ml/min/1,73m2 (stable since years). The patient Background: Streptococcus pneumoniae is the most common was diagnosed with ES and started on prednisone 1mg/ causative pathogen in community-acquired pneumonia. kg, three days after presentation. The same night his In patients, thrombocytopenia is correlated with an condition deteriorated, he became agitated, vomited and adverse outcome of pneumonia. Platelets can modulate became unconscious. In the morning, he was transported the host response to infection in several ways, i.e. by to the Emergency department where he developed a cardio- facilitating clot formation, production of antimicrobial respiratory arrest and died. Autopsy and post-mortal CT proteins and interaction with neutrophils. We studied the scanning of the brain did not reveal a clear cause of death. effect of thrombocytopenia during murine pneumococcal Previously retrieved blood was retrospectively showed an pneumonia. ADAMTS-13 activity < 1%. Furthermore, anti-ADAMTS13 Methods: Pneumonia was induced in mice by intranasal antibodies were positive, consistent with the diagnosis of inoculation of S. pneumoniae. Platelets were depleted thrombotic thrombocytopenic purpura (TTP). Schistocytes by anti-mouse thrombocyte serum; controls received were not analyzed at diagnosis and could not be retrospec- non-immunogenic serum. Mice were observed in a tively investigated. survival study or sacrificed after 24 or 48 hours for Conclusion: ES was diagnosed because of a strong harvesting of bronchoalveolar lavage fluid (BALF), lungs, Cooms-positive haemolytic anemia and thrombocyto- spleen and plasma. In separate studies mice were treated penia. There was no suspicion of TTP, in the absence of neurological signs, kidney dysfunction and fever. In

7 retrospect this patient suffered from AIHA and TTP, a A.M. Aalbers1, M.F. Aarts2, Y. Kusumanto1, S.D. Krol3, very rare combination, which has only been reported in C.A.M. Marijnen3, E.F.M. Posthuma1 three patients before. We conclude that schistocytes and 1Reinier de Graaf Gasthuis, Department of Internal Medicine, ADAMTS13 should be measured in case of AIHA and Delft, the Netherlands, 2The Netherlands Cancer Registry, thrombocytopenia. Comprehensive Cancer Centre South, Eindhoven, the Netherlands, 3Leiden University Medical Centre, Department O10 Post-Transfusion Purpura – a case report with fatal of Clinical Oncology, Leiden, the Netherlands end Background: Chronic lymphocytic leukaemia (CLL) is I.E. de Kruijff1, J.W.J. van Esser1, A. van Gammeren2 a common hematologic malignancy that mainly occurs 1Amphia Hospital, Department of Internal Medicine, Breda, in the elderly population. The standard chemoimmuno- the Netherlands, 2Amphia Hospital, Department of Clinical therapy for young and fit symptomatic patients consists Chemistry, Breda, the Netherlands of fludarabine, cyclophosphamide, and rituximab, while for the less fit it consists of chlorambucil monotherapy or Introduction: Post-transfusion purpura (PTP) is a rare in combination with rituximab. In addition, drugs directly immunological disorder that causes severe thrombocyto- targeting the B-cell receptor signaling pathway are about penia 5-10 days after platelet- or erythrocyte transfusion. It to be added to the therapeutic armamentarium. All therapy occurs predominantly in women, sensitized by pregnancy options are palliative. Elderly CLL patients frequently have or previous transfusion. Due to sensitisation, alloanti- comorbidities, and sometimes even mild chemoimmuno- bodies are made, in most cases against Human Platelet therapy is not an option for palliation. Splenic irradiation Antigen (HPA)-1a. These antibodies not only destroy (SI) was historically used as primary treatment of CLL. transfused platelets, but also patient’s own platelets. As Cases: We report the incidence of comorbidities in a consequence (severe) bleeding may occur. The precise CLL patients as present in the cancer registry of the mechanism is unknown. Therapy consists of; avoidance Comprehensive Cancer Centre South (IKZ). We next of transfusion, but when needed transfusion wit HPA-1a- present four elderly patients with symptomatic advanced negative blood products should be given. Most cases are stage CLL with multiple comorbidities who were unfit self-limiting, but in rare cases intravenous immuno- to undergo systemic chemoimmunotherapy. Instead, globulin (IVIG) can help. palliative SI was given consisting of 12 fractions of 0.5 Gy. Case: A 57-year old, HPA-1a-negative, woman, mother of All patients obtained good partial or complete hematologic two children, was admitted to the hospital for chemothera- response, with a dramatic reduction in leukocyte counts peutic treatment of acute myeloid leukaemia. Secondary to and normalisation of hemoglobin and thrombocyte levels. chemotherapy induced pancytopenia, she received multiple Treatment was well tolerated. Response duration was 17 platelet- and erythrocyte transfusions. Because of poor and 20 months in two patients, after which a second course increments on platelet transfusions, antibodies were tested, of SI was initiated with similar beneficial effect. Two other but found negative. By way of precaution, washed platelets patients were well at last follow-up 6 and 10 months after were transfused, without improvement of her increment. start of radiotherapy. Subsequently, keeping her HPA-1a negative status in our Conclusion: Our results show that, although an old tool, SI mind, she was transfused with platelets of a HPA-1a- should not be forgotten as a potentially effective palliative negative donor, unfortunately without an increment. At treatment option in frail patients with symptomatic CLL. that point additional antibody testing showed anti-HPA-1a and anti Human Lymphocyte Antigen (HLA) antibodies. O12 The role of PET-CT-scan in patients with elevated IVIG was added, but without result. Two days after the inflammatory markers without fever? first IVIG, patient developed an intracerebral bleeding and subsequently died. S.M. Popma, E. Bons, M. Vincken, A.S.M. Dofferhoff Conclusion: PTP is a rare and intriguing compli- Canisius Wilhelmina Hospital Nijmegen, Department of cation of transfusion that can manifest in all patient Internal Medicine, Nijmegen, the Netherlands categories. If a patient develops thrombocytopenia 5-10 days after transfusion, PTP should always be taken into Background: A PET-CT-scan is often used in the diagnostic consideration. work-up in fever of unknown origin. Less is known about patients with elevated inflammatory markers without fever. O11 The beneficial effect of splenic irradiation in frail The aim of this study is to determine the role of PET-CT- patients with chronic lymphocytic leukaemia scanning in the diagnostic process of patients with elevated inflammatory markers without fever.

8 Methods: We retrospectively analysed the data of with Dubin Johnson syndrome(DJS). However, genetic patients with elevated CRP and/or ESR who underwent a analysis of the ABCC2 gene, the culprit in DJS, revealed PET-CT-scan between 01-01-2011 and 31-12-2012. Exclusion no mutations. A novel heterozygous mutation in the criterion was fever. ABCB11-gene (c.1308+1 G>A) was found, consistent with Results: 49 patients were included in the study (26 male, a structural abnormality in the bile salt export pump, as 23 female). Age ranged from 31-86 (mean: 64,5) years. In seen in BRIC2. This particular mutation has never been 25 patients (51%) the PET-CT-scan showed a significant described before. The course of this disease is benign, the abnormality. 12 (24%) patients were diagnosed with a risk of recurrent cholestasis during oral contraceptive use non-infectious inflammatory disease (NIID) (vasculitis or pregnancy is high. (7), PMR (3) and rheumatoid arthritis (2)), all treated Conclusion: We present a patient with jaundice during use successfully with prednisone. 9 (18%) patients were of OC due to a first episode of BRIC2 caused by a novel diagnosed with a neoplasm, one benign tumor, 8 extensive mutation in the ABCB11-gene. malignancies not eligible for curative treatment. In 4 (8%) patients an infection was found, three were cured, O14 Adequate correction of substantial hyperglycaemia in one suffered from a fatal inoperable mycotic aneurysm. patients with insulin-treated diabetes using a novel In 16 patients (neoplasm (3), infection (2), NIID (11)) the algorithm diagnosis would not have been found without performing a PET-CT-scan, 12 had a curable disease. So in every 4 H.M. de Wit1, E.E. Engwerda2, B.E. de Galan2, C.J. Tack2 PET-CT-scans made, 1 patient has a treatable condition, 1Academisch Medical Centre, Department of Endocrinology, probably not to be found by other diagnostic tests. Amsterdam, the Netherlands, 2Radboudumc, Department of Conclusion: In our study PET-CT-scanning in patients with Internal Medicine, Nijmegen, the Netherlands elevated inflammatory markers without fever has a high yield for detection of clinically relevant diagnoses (51%). Background: Correction of substantial hyperglycaemia We found a number needed to diagnose, to find a treatable in patients with diabetes is often difficult because of cause, of 4. hyperglycaemia-induced glucose toxicity leading to peripheral insulin resistance. Usually, standard sliding O13 First episode of benign recurrent intrahepatic scale regimens, barely adjusted to individual needs, are cholestasis type 2 after use of oral contraceptives applied both in the outpatient and in-patient setting. We tested a simple formula based on the insulin sensitivity G.P.M. Luiken, S.C.E. Schuit, D. Sprengers, J. Alsma factor to estimate the insulin dose needed to correct Erasmus MC, Department of Internal Medicine, Rotterdam, substantial hyperglycaemia in individual diabetic patients. the Netherlands Methods: This analysis was part of a randomized controlled cross-over trial conducted in insulin-treated patients with Introduction: Cholestasisis a frequently encountered diabetes, comparing the efficacy of two insulin pens problem. We present a case of cholestasis caused by a first for the administration of rapid-acting insulin to correct episode of benign recurrent intrahepatic cholestasis type 2 spontaneous hyperglycaemia (18-23 mmol/l). The dose (BRIC2) after use of oral contraceptives (OC). of rapid-acting insulin to be injected was calculated Case report: A 16-year-old female presented with jaundice, as follows: ([measured glucose-value in mmol/l - 6] ÷ itching and fatigue. She had been using ethinylestradiol / [100 ÷ total daily insulin dose]) - 1.5. Plasma glucose levels levonorgestrel for 3 months, and used desloratidin for hay were measured for 6 hours after insulin administration. fever. Family history was unremarkable. Results: 20 patients (10 type 1 diabetes, 10 type 2 diabetes, Apart from jaundice, physical examination was mean age 53.4 years, HbA1c 8.6%, TDID 96.1 U/day) unremarkable. Laboratory results showed elevated underwent 40 experiments. Glucose values dropped levels of bilirubin (157 mmol/L), conjugated bilirubin from 21.3 ± 0.4 to 7.3 ± 0.4 mmol/l after injection of (136 mmol/L), aspartate aminotransferase (80 U/L), alanine 21.7 ± 1.9 insulin units. After 196.2 ± 11.7 minutes, plasma aminotransferase (116 U/L) and bile acids (60 mmol/L). glucose levels dropped below 10 mmol/l. The formula Other liver function tests were normal. Antibodies against predicted well on 27 occasions (67.5%), slightly under- hepatitis viruses, cytomegalovirus and Ebstein-Barr predicted insulin needs on 6 (15%) occasions (glucose virus, and extensive immunologic testing were negative. nadir at 12.3 ± 0.5 mmol/l) and over-predicted on 7 (17.5%) Ultrasonography of the liver was normal. occasions (glucose < 5.0 mmol/l, requiring exogenous OC is a rare cause of cholestasis, and an underlying genetic glucose administration). disorder was suspected. Conclusion: We developed an easy-to-use formula to Urine coproporphyrines showed a ratio of coprophor- calculate individualized insulin correction doses. Using phyrin-1 to coprophorphyrin-3 of 60%: 40%, consistent

9 this formula substantial hyperglycaemia could be corrected A 26-year old woman, pregnant for 34+1weeks, known in ~3 hours in the majority of diabetic patients. with diabetes mellitus type 1 ( HbA1c 57) was seen at the obstetric emergency department with sickness and O15 In vivo evidence for chylomicrons as mediators of vomiting since one day. Her glucose during the day postprandial inflammation was 12-15 mmol/l. The first hours of admittance her glucose stayed between 12-17mmol/l. A few hours later M.A. de Vries1, B. Klop1, A. Alipour1, G.J.M. van de Geijn1, the internist was consulted. The patient revealed that she J.W. Janssen1, P. Valdivielso2, J.R. Villodres2, had not taken her insulin because of reduced intake due J. Ramírez Bollero2, M. Castro Cabezas1 to vomiting. The glucose was 23 mmol/l and there was a 1Sint Franciscus Gasthuis, Department of Internal Medicine, critical ketoacidosis (pH 7.12). Fetal monitoring showed Rotterdam, the Netherlands, 2Hospital Virgen de la Victoria, severe fetal distress, necessitating an urgent caesarian Department of Internal Medicine, Malaga, Spain section, while the mother’s glucoses were stabilized. After the caesarian section she was immediately transferred to Background: The postprandial situation is a pro-inflam- the intensive care unit. The neonate had severe acidemia, matory condition linked to the development of atheroscle- with a pH < 6.50 and was resuscitated for 11 minutes. The rosis. We evaluated the relationship between apolipoprotein neonate was transferred to a neonatal intensive care unit, (apo) B48 and postprandial leukocyte activation. but died of asphyxia several hours after birth. Diabetic Methods: Leukocyte activation markers were measured keto-acidosis is seen in type 1 as in type 2 diabetes (0.3-3 by flow cytometry in patients with and without coronary %). Because of the catabolic state in pregnancy it can artery disease (CAD). In 12 healthy subjects, leukocyte occur in normoglycaemia. Predisposing factors include activation markers, triglycerides and apo B48 were vomiting, the use of beta-mimetic drugs, infections, a determined after an oral fat load. history of insulin therapy omission, continuous subcu- Results: 94 patients were included. Fasting apo B48 taneous insulin infusion, the use of glucocorticoids (for was significantly higher in patients with CAD (n=56, fetal lung maturation) and diabetic gastroparesis. Doctors 7.9 ± 4.9 mg/L) than in subjects without CAD (n = 38, of all kind should be aware of the different mechanism of 5.7 ± 3.7 mg/l, p = 0.019), and higher in males (n = 51, ketoacidosis in the pregnant diabetic patient, because of 8.0 ± 4.8 mg/l) than in females (n = 43, 5.8 ± 4.0 mg/l, the severe consequences. A diabetic pregnant patient who p = 0.025). Fasting apo B48 and triglycerides correlated presents with vomiting or fasting is ketoacidotic until the positively with fasting monocyte CD11b and granulocyte contrary is proven. CD66b expression. No correlations were found between these inflammatory markers and plasma total apo B or O17 The story of the lost proteins LDL-C. Plasma apo B48 increased after an oral fat load (n = 12), with the maximal increase after 2 hours, from 3.6 S.E. van der Wiel1, A.G.L. Bodelier2, J.W.J. van Esser2 ± 1.9 mg/l to 6.4 ± 3.1 mg/l (p < 0.001). Monocyte CD11b Amphia Hospital, Departments of 1Internal Medicine and expression also increased, with the maximal increase after 2Gastroenterology , Breda, the Netherlands 4 hours, from 14.8 ± 2.3 au to 16.5 ± 2.2 au (p = 0.043). The postprandial apo B48 response correlated positively Introduction: Protein-losing enteropathy (PLE) can be with postprandial monocyte CD11b (Spearman’s rho: a manifestation of several disorders, characterized by 0.615, p = 0.033), but no correlations were found between excessive loss of plasma proteins into the gastrointestinal postprandial triglycerides and postprandial leukocyte tract. Treatment of underlying disease will mostly solve the activation markers. protein loss, however not in our case. Conclusion: This study suggests that chylomicrons may be Case: A 69- year old male with no relevant medical directly responsible for postprandial leukocyte activation. history, was admitted to our hospital with complaints The postprandial chylomicron response may be a stronger of fatigue and bilateral peripheral oedema. Physical mediator of postprandial inflammation than postprandial examination was unremarkable, except tibial oedema. triglyceridemia. Laboratory testing revealed a decreased serum albumin (25 g/l), total protein (41 g/l) and elevated faecal Alpha O16 Ketoacodosis in pregnancy: normoglycemia does not 1-Antitrypsin (576 mg/100 gram). Extensive diagnostic rule out a ketoacodisis evaluation showed no abnormalities. Capsule endoscopy and double balloon enteroscopy was performed, which E.S. van der Valk, S.W. van Thiel, M.S. Lunshof showed a diffuse whitish appearance of the small bowel Amphia Hospital, Department of Internal Medicine, Breda, mucosa with extensive lymphangiectasia and macroscopic the Netherlands loss of milky fluids. Based on these findings PLE due to extensive small intestinal lymphangiectasia of unknown

10 cause was suspected. A medium chain triglycerides diet ApoB +4% and -7%); p < 0.001 for all differences between was started, later combined with Lanreotide. The oedema study periods. Thyroid hormone excess did not clinically resolved and serum albumin and total protein increased, significantly affect ASAT, ALAT, Gamma-GT, alkaline but did not return normal. 1.5 years after presentation phosphatase, total or conjugated bilirubin levels, in both our patient developed abdominal pain with a palpable studies. mass, histological examination showed a diffuse large Conclusion: Supra-physiological thyroid hormone levels B-cell Non Hodgkin Lymphoma. Treatment with chemo- were associated with reductions in TC, LDL-C and ApoB therapy and Rituximab was initiated, resulting in complete levels but not with increased liver parameters. This may remission. We suspected that the PLE was a paraneoplastic suggest that the effects of eprotirome on liver parameters phenomenon, however treatment did not completely resolve as previously reported were compound specific rather than symptoms. thyroid hormone-dependent. Conclusion: We described a patient with PLE most likely based on Non Hodgkin lymphoma. Despite complete O19 There’s no smoke without a fire remission, the PLE did not disappear, suggesting the possibility of irreversible damage to the lymphatic system S.L. Gerritse1, Y. Tan2 of the small intestine. 1Amphia Hospital, Depatment of Internal Medicine, Breda, the Netherlands, 2Sint Fransiscus Vlietland Group, O18 Effects of supra-physiological levothyroxine Department of Pulmonary Medicine, Rotterdam, the dosages on lipids, lipoproteins and liver parameters Netherlands in healthy volunteers: A randomized controlled crossover study Case: A 23 year old male, with an unremarkable medical history, presented to the Emergency department with a B. Sjouke1, L.P.B. Elbers2, B. van Zaane2, blurred vision, near syncope, headache, nausea and chest R.M. Stoekenbroek3, J.J.P. Kastelein3, G.K. Hovingh3, pain. He stated that he had taken neither medication nor V.E.A. Gerdes2 drugs. Physical and neurological examination showed no 1AMC/Tergooi, Departments of Vascular Medicine/ Internal abnormalities. Laboratory tests were unremarkable. ECG Medicine, Amsterdam/Hilversum, the Netherlands, 2 AMC/ showed no acute ischemia. His social history revealed Slotervaart Hospital, Departments of Vascular Medicine/ working in a shisha lounge (an establishment where people Internal Medicine, Amsterdam, the Netherlands, 3 AMC, share flavored tobacco by water pipe or hookah). He had to Department of Vascular Medicine, Amsterdam, the light up the water-pipes by inhaling through the hose. He Netherlands lighted up 20-30 water-pipes on an average work day. He complained having a headache almost every day after work, Background: We recently observed that treatment with the in the absence of the other present symptoms. Arterial liver specific thyroid hormone agonist eprotirome resulted blood gas analysis showed an FCOHb level of 23,2%. The in significant increases in liver parameters and a modest patient was administered high-dose oxygen (15 l/min) decrease in atherogenic lipids and lipoproteins in euthyroid via a non-rebreather mask. After four hours the patient’s patients with familial hypercholesterolemia. It is unknown FCOHb level was decreased to 2,1% and he was discharged whether the effects of eprotirome on liver parameters were from the hospital with no further manifestations. due to either a drug specific effect or induced ‘local hyper- Conclusion: Smoking the hookah is becoming increas- thyroidism’. We studied the effects of supra-physiological ingly popular among young adults. Due to the process of levothyroxine dosages on liver parameters, plasma lipids charcoal combustion a hookah smoker inhales 10 times and lipoproteins. more carbon monoxide than a cigarette smoker. Due Methods: We performed a post-hoc analysis of a single to its nonspecific symptoms carbon monoxide intoxi- blind, randomized controlled, cross-over trial, comprising cation is probably more common than generally realized. two studies. In both, healthy volunteers received levothy- Emergency admission staff should asked specifically roxine or no medication for 14 days. In Study A, 16 about water-pipe exposure in patients presenting with individuals received 0.3 mg/day. In Study B, 12 individuals nonspecific (neurologic) symptoms, followed by carboxy- received 0.45/0.60 mg/day (body weight dependent). hemoglobin measurement. Results: Reductions in total cholesterol (TC) (change after levothyroxine usage: -11% and -15% in study A and B, O20 Survival of elderly renal patients choosing either respectively), LDL-cholesterol (-13% and -17%) and ApoB conservative management or renal replacement levels (-8% and -16%) were observed, compared with the therapy control period (change after no medication: TC +6% and -4%, for study A and B respectively; LDL-C +6% and -5%; W.R. Verberne, W. Bos

11 St. Antonius Hospital, Department of Internal Medicine, no complaints. His sister deceased at 16 years of age Nieuwegein, the Netherlands due to unknown renal disease. Diagnostic kidney biopsy showed glomerular and vascular AA amyloidosis. Background: The number of elderly patients with end-stage Serum amyloid A level was elevated. Analysis for an renal disease (ESRD) increases. Informed decision-making underlying cause showed no abnormalities. Therapy with on renal replacement therapy (RRT) is an important part of ACE-inhibitor and Anakinra was initiated and for 1.5 year nephrologists’ care. Patients with a poor prognosis on RRT renal function remained stable but eventually deterio- may choose conservative management (CM). Adequate rated, and renal replacement therapy was started. Because survival data, specifically of elderly patients, are needed for of his sister’s history with unknown renal disease, we proper counselling. We compared survival of elderly renal referred the patient for genetic testing. Two mutations on patients treated either with CM or RRT. the mevalonate kinase (MVK) gene were found which is Methods: Retrospective single-centre cohort study known to cause HIDS. (2005-2014) of ESRD patients aged ≥ 70 years (at the Discussion: As far as we know, this is the first case report moment they opted for CM or RRT). which describes a patient without any clinical symptoms Results: 117 patients chose CM; 194 chose RRT. CM of HIDS, who presents with severe AA amyloidosis. Even patients were older (mean 82.0 vs. 75.9 years, p < 0.001). in patients with lots of inflammatory attacks this is a The Davies comorbidity scores did not differ significantly rare complication of HIDS. This case report shows us between both groups. The overall median survival of that we should be aware of an unusual presentation of elderly ESRD patients was longer on RRT when survival clinical diseases and that genetic testing can be helpful in was calculated from the date of treatment decision and unravelling clinical mysteries. from the time eGFR < 20 ml/min, < 15 ml/min and < 10 ml/min (all: p < 0.001). However, no significant O22 Development and evaluation of in vivo engineered survival advantage of RRT was observed in patients aged vascular grafts in a porcine model ≥ 80 years and in all patients aged ≥ 70 years with high Davies comorbidity scores (Davies score 3 or higher). There T.C. Rothuizen1,2, F. Damanik3, J.F. Hamming4, also was no survival advantage of RRT in patients aged M.J.T. Visser4, I.E. Hoefer5, L. Moroni3, T.J. Rabelink2,4, ≥80 years with mild Davies comorbidity scores (Davies J.I. Rotmans2,4 score 1-2). 1Rijnland Hospital, Department of Internal Medicine, Conclusion: In this second largest cohort study reported Leiderdorp, the Netherlands, 2Leiden University Medical so far, there is no survival advantage of RRT over CM Centre, Department of Nephrology and Einthoven Laboratory in patients aged ≥80 years and in patients aged ≥ 70 for Experimental Vascular Medicine, Leiden, The Netherlands, years with high comorbidity. This provides important 3University Twente, Department of Tissue Regeneration, information for better decision-making in elderly patients Enschede, the Netherlands, 4Leiden University Medical Centre, with ESRD. Department of Surgery, Leiden, the Netherlands, 5University Medical Centre Utrecht, Department of Experimental O21 A rare presentation of a rare complication of a rare Cardiology, Utrecht, the Netherlands disease Background: Vascular access remains the Achilles’ heel of S.G. Kuiper hemodialysis. Tissue engineered blood vessel (TEBV) may HagaZiekenhuis, Department of Internal Medicine, Den offer an alternative. Polymer rods were developed that upon Haag, the Netherlands implantation evoke an inflammatory response culminating in encapsulation by a fibrocellular capsule. We hypoth- Introduction: Hyperimmunoglobulin D syndrome (HIDS) esized that, after extrusion of the rod, the fibrocellular presents typically early in life with attacks of fever with capsule differentiates into an adequate vascular conduit, lymphadenopathy, gastro-intestinal discomfort, arthralgia, after grafting into the vasculature. skin lesions, and aphthous ulcers. Amyloidosis is an Methods: Per pig, 8 rods were implanted subcutaneously. infrequent but serious complication (2.9%). We describe After 4 weeks, rods with tissue capsules grown around a patient who presents with amyloidosis which finally it, were harvested. Per pig, 2 tissue capsules were grafted appeared to be HIDS, although he lacked any clinical bilaterally as carotid artery interposition. One and 4-week symptoms of HIDS. later, patency was evaluated by angiography whereupon Case report: A 49-year old man, without a relevant medical pigs were sacrificed and tissue capsule morphology was history, was referred with newly diagnosed nephrotic evaluated. syndrome and renal insufficiency (kreatinine 250 umol/l, Results: Rods were encapsulated by thick, well vascu- proteinuria 10 g/day). Besides edema, he experienced larized tissue capsules, mainly composed of circumfer-

12 entially aligned fibroblasts, collagen and few leukocytes, department of other hospitals without consulting treating with adequate mechanical strength. Patency was 100% physician AMZ. One of these patients was admitted with after 1week and 87,5% after 4weeks. Time to hemostasis a respiratory infection. after cannulation with a dialysis needle was < 3minutes. In conclusion, chemotherapy administration is safe and After vascular grafting, the graft composition changed complication rates as expected in a relatively young and substantially. Luminal area increased 3,25-fold (p < 0.0001) healthy breast cancer population. accompanied by an increase in wall thickness and an increased aSMA-positive area from 29,4 ± 3% before O24 Predicting mortality in acutely hospitalised older grafting to 61,2 ± 3% after grafting (p < 0.0001). While patients; the APOP study leukocytes were no longer present in the wall, the lumen was largely covered with endothelial cells. Interestingly, J. de Gelder1, J.A. Lucke1, N. Heim1, A.J.M. de Craen1, a substantial portion of (myo)fibroblasts present before A.J. Fogteloo1, G.J. Blauw1, S.P. Mooijaart2 grafting expressed smooth muscle cell markers. Burst 1Leiden University Medical Centre, Department of Geriatrics, pressure remained stable after grafting. Leiden, the Netherlands, 2IEMO, Department of Gerontology Conclusion: Autologous TEBVs were created with sufficient and Geriatrics, Leiden, the Netherlands mechanical strength enabling autologous vascular grafting with a 4week-patency of 87,5%. Future studies should Introduction: Acutely admitted older patients are at evaluate its potential as arteriovenous-graft. increased risk for mortality, but at the moment of presentation it is unknown which factors predict mortality. A O23 First experience with chemotherapy administration feasible approach to improve outcomes is needed, by in Alexander Monro Breast Cancer Hospital (AMZ): starting to identify the vulnerable patient. In the present is it safe? retrospective follow-up study we therefore aimed to develop a prediction model on 90-days mortality. E. Göker, S. Grosfeld, I. de Graaf, J.N.H. Timmer-Bonte Methods: A retrospective follow-up study among all Alexander Monro Breast Cancer Hospital, Department of patients aged 70 years and over who were admitted to Medical Oncology, Bilthoven, the Netherlands the Acute Medical Unit (AMU) of the Leiden University Medical Centre in 2012 was conducted. Potential early The Alexander Monro Breast Cancer Hospital is the predictors of 90-days mortality were assessed and included first (only) specialized breast cancer (BC) clinic in the vital signs, laboratory results, comorbidity and number of the Netherlands. All medical staff, all diagnostic and medications used at home. treatment facilities required in integrated breast cancer Results: In total 517 individual patients were admitted care are available with exception of an intensive care to the AMU in 2012. Ninety days after admission 94 unit. Specialisms occasionally needed in breast cancer patients (18.2%) had died. The final prediction model care (e.g. cardiologists, pulmonologists) are not in-house consisted of six significant (p < 0.025) predictors: oxygen services, but we collaborate with different caregivers in saturation, Charlson Comorbidity Index, thrombocytes, hospitals all over the the Netherlands. Since the start of urea, C-reactive protein and non-fasted glucose, with an AMZ we encounter professional scepticism and even c-statistic of 0.738 (95% CI: 0.678-0.798). Using as a overt disapproval whether it is safe to treat BC in a ‘private’ cut-off the level for the highest quintile of mortality risk (zelfstandig behandelcentrum) setting. (n = 106) resulted in an average 44% mortality risk within We present the first data of chemotherapy-treated patients 90-days. (pts). From opening in 5/2013 until 1/2015 168 pts (median Conclusion: With an internally validated prediction model age 54 yrs, range 26-75, no severe comorbidity) were we were able to predict 90-days mortality in acutely hospi- eligible for chemotherapy according to the current Dutch talised older patients, using routinely available clinical BC guidelines. Only 14 pts preferred chemotherapy- parameters. Such prediction models may serve at the first treatment in a hospital closer to home. 80 pts have step to target high risk patients and design tailored care completed chemo(immuno) therapy and 74 pts are on trajectories. At the moment a large prospective follow-up actual treatment still. The majority (98%) is treated with study is conducted to assess more determinants and curative intent: 67/154 (44%) in neoadjuvant setting, endpoints to enhance performance of the model. 58% received docetaxel-doxorubicin-cyclophosphamide (TAC) and 23% AC(-T)). No fatal complications were O25 BCG-vaccination enhances immunogenicity seen. Chemotherapy-related hospital admission rate was of subsequent influenza vaccination in healthy 8 pts (5%) with median duration 1 day (range 1-3): febrile volunteers: a randomized placebo-controlled double- neutropenia (2pts), severe mucositis (2pts) and miscella- blind pilot study neous (4pts). Only three patients presented on emergency

13 J. Leentjens1, M. Kox1, R. Stokman1, J. Gerretsen1, 2Pharmacovigilance Centre Lareb, ’s-Hertogenbosch, the D. Diavatopoulos1, R. van Crevel1, G. Rimmelzwaan2, Netherlands P. Pickkers1, M. Netea1 1Radboudumc, Department of Internal Medicine, Nijmegen, Background: Medication safety is an important topic in the Netherlands, 2Erasmus MC, Department of Viroscience, healthcare nowadays. Pharmacovigilance, the monitoring Rotterdam, the Netherlands of drug safety after approval for marketing, depends mainly on the quality and quantity of reported adverse Background: Mortality due to influenza infection drug reactions(ADR). To increase pharmacovigilance remains unacceptably high. Seasonal vaccination is the awareness among medical students, we developed and backbone of influenza management but often does not evaluated a Student-run Pharmacovigilance program, result in protective antibody titres. Non-specific effects of together with pharmacovigilance centre Lareb. BCG-vaccination in humans have been reported, mediated Method: A pilot study was performed in which teams of by trained immunity and heterologous adaptive immune (1st-4th year) medical students assessed real ADR-reports responses. As these effects increase the function of from patients/healthcare professionals reported to Lareb. myeloid immune cells with antigen-presenting immuno- After assessment on causality, students searched for a genicity, we hypothesized that BCG vaccination could also pharmacological explanation and wrote a feedback letter enhance immune responses to other vaccines, including to the reporter and a summary for the pharmacovigilance- influenza vaccine. databases of the European Medicines Agency and WHO. Methods: Healthy volunteers received BCG vaccine (n = 20) This student-assessment was then verified by Lareb staff, or placebo (n = 20) in a randomized double-blind fashion, who evaluated student-handling it in an e-questionnaire. followed by an intra-muscular injection of trivalent Results: From May to December 2014, 89 different influenza vaccine 14 days later. Hemaglutination inhibiting ADR-reports selected by Lareb staff were handled, with the (HI) antibodies and cellular immunity measured by top 3 reported ADRs being; palpitations, urinary retention cytokine production capacity were assessed 7, 14 and 28 and agitation. 35 students and 3 Lareb staff members days later. participated. Lareb staff rated the student-assessments Results: In BCG-vaccinated subjects, HI antibody (very)useful (> 92%), scientifically substantiated (> 88%), responses against the 2009 pandemic H1N1 vaccine complete (not lacking information) and without inaccu- strain were significantly enhanced compared with the racies (both > 92%). Altogether the student-assessments placebo group, and seroconversion occurred more rapidly were rated mean 8.3 (1-10; min-max). Compared to self- Statistical significant differences were not reached for the handling, Lareb staff indicated student-assessment cost response to A/H3N2 and B vaccine strains. In addition, less time in 33% assessments, neutral in 55%, and cost apart from more pronounced pro-inflammatory effects extra time in 11%. following BCG vaccination on ex-vivo leukocyte responses, Conclusion: The Student-run pharmacovigilance program nonspecific effects of influenza vaccination were also is a win-win venture. It offers students a valuable ‘pharma- observed, with modulation of cytokine responses against covigilance experience’, creates awareness in future doctors unrelated pathogens. with the potential to increase ADR-reporting, and didn’t Conclusion: BCG vaccination prior to influenza vaccination cost Lareb staff extra time overall. The learner effects need results in a more pronounced increase and accelerated to be investigated in future studies. induction of functional antibody responses against the 2009 pandemic H1N1 influenza vaccine strain. These O27 The missing link in Austrian syndrome results may have implications for the design of vaccination strategies and could lead to improvement of influenza M.H.E. Vossen, L. Dawson vaccination efficacy, which could have a major impact on Reinier de Graaf Gasthuis, Department of Internal Medicine, public health. Delft, the Netherlands

O26 The Student-run pharmacovigilance program, a Introduction: Streptococcus pneumoniae infection with win-win venture for medical education and pharma- pneumonia, meningitis and endocarditis is known as covigilance centre Lareb Osler’s triad or the Austrian syndrome. Case description: A 41-year old female, known with T. Schutte1, J. Tichelaar1, M.O. Reumerman1, R. van Eekeren2, insuline dependent diabetes mellitus and multiple L. Rolfes2, M.C. Richir1, E. van Puijenbroek2, M.A. Agtmael1 sclerosis, treated with insulin, Interferon B, losartan 1VUmc, Department of Internal Medicine, section and pravastatin, presented with flu-like symptoms and Pharmacotherapy, Amsterdam, the Netherlands, fever. On physical examination the airway was free, respiratory rate 50/min, saturation 90% with peripheral

14 cyanosis while breathing oxygen in a non-rebreather consenting critically ill patients in a mixed adult ICU/ mask. Pulmonary examination revealed audible rales MCU unit. Blinded CGM guided by intermittent glucose located in the right upper lobe. Blood pressure was measurements were compared with non-blinded CGM, 160/85 mmHg, pulse 130/min, temperature 40° Celsius. according to a novel nurse-driven protocol with a target- She was comatous (E2M4V1) with an ophisthotonus and range of 4.4-6.1 mmol/l. immediately intubated.On suspicion of pneumonia and Results: 22 intermittently guided and 29 CGM-guided meningitis blood cultures and lumbar puncture were patients were included. In both groups severe hypogly- performed and ceftriaxone was started. Both cultures cemia was no longer prevalent. In the CGM group the were positive for Streptococcus pneumoniae, therefore mean glucose level significant decreased (p = 0.005) along the antibiotic was switched to penicillin. However, fever with a significant increase of time in target glycemic range relapsed and a heart murmur was heard. A transesoph- (from 38% to 59%) and a decrease of CV. ageal echocardiography showed large mitral and pulmonal Conclusion: CGM enables safe IIT by reducing dysglycemia valve vegetations with a severe mitral valve insufficiency. and preventing hypoglycemia. More experience with CGM An urgent valve replacement was performed; the patient may be needed to reach a lower CV. recovered fully. Discussion: The incidence of Streptococcus pneumoniae O29 Determinants of mortality in the first 90 days after endocarditis has decreased from 10-15% to 1-3% over admission to the Emergency Department in older the last years. Therefore, the Austrian syndrome is patients: a retrospective follow-up study rarely seen. Risk factors are impaired systemic host responses such as diabetes or conditions affecting local J.A. Lucke, S.E. Hofman, J. de Gelder, A.J. Fogteloo, clearance mechanisms. The mortality of patients with C. Heringhaus, B. de Groot, A.J.M. de Craen, G.J. Blauw, Austrian syndrome when solely treated with antibiotics N. Heim, S.P. Mooijaart is 63-80%. Treatment with a combination of antibiotics Leiden University Medical Centre, Emurgency Unit, Leiden, and valve replacement has decreased mortality to 32%. the Netherlands We recommend in patients with a combination of Streptococcus pneumoniae pneumonia and meningitis Background: Older people attend the emergency screening for endocarditis. department (ED) at increasing rates and are at risk of poor outcome. Besides the higher vulnerability of older patients O28 Continuous intravenous glucose measurements in associated with poor outcome, little is known about the Intensive and Medium Care patients, treated with association of routinely collected clinical parameters at Intensive Insulin Therapy (IIT) presentation and risk of mortality in the period after ED presentation. J. van Dam- Kastelein, E.A. Vlot, H.S. Moeniralam Methods: We conducted a retrospective follow-up study St. Antonius Hospital, Department of Intensive Care, at the ED of the Leiden University Medical Centre in Nieuwegein, the Netherlands 2012. Patients aged 70 years or older were included. Determinants were age, gender, time of the ED visit, way Background: The majority of critically ill patients is of arrival, triage category, consulting medical specialty, hyperglycemic. Lower glucose levels in a very narrow performed blood tests and the number of clinical measure- range reduces mortality and morbidity. However, the ments taken. Outcome measurement was mortality within low frequency and manual blood glucose monitoring 90 days after the investigated ED visit. Cox regression limits the safety of intensive insulin therapy (IIT). The analyses were performed to analyse the association. higher incidence of hypoglycemia and strong fluctua- Results: 3921 patients were included. Ninety day mortality tions in glucose levels induced by IIT are also associated was 10.5%. Determinants associated with mortality were with a higher mortality. Undoubtedly, intensive glucose age (hazard ratio [HR] 1.06, 95% confidence interval monitoring is a prerequisite for safe IIT. [95%CI] 1.04-1.08), arrival at night (HR 1.41, 95%CI The aim of the Glucose Level at the Intensive Care (GLIC) 1.01-1.97), blood tests performed (HR 2.61, 95%CI study is to evaluate if continuous glucose monitoring 1.60-4.27) and being assigned to a non-surgical specialty (CGM) in critically ill patients treated with IIT is (HR: 0.68, 95%CI 0.50-0.93). Triage category showed the useful to reach and maintain the glucose target-range strongest association with 90 day mortality with increasing of 4.4-6.1 mmol/l, to prevent hypoglycemic events, to hazards for subsequent levels of urgency; HR for the decrease blood glucose coefficient of variation (CV), and to highest level of urgency was 13.82 (95%CI 8.43-22.67) reduce nurse staff workload. compared to the lowest levels of urgency. Methods: CGM with an intravenous glucose sensor Conclusion: Mortality in older persons is associated with (GlucoClear, Edwards Lifesciences) was performed on parameters routinely collected in the ED. These associa-

15 tions could help develop models that predict poor outcome, Introduction: Intentional or accidental intoxications are which is a first step towards prevention strategies. common in the Emergency Department (ED), but they are not always sufficiently recognized. When intoxications are O30 CYP2D6 metabolism in frail elderly compared to suspected, the causative agent, or combination of agents non-frail elderly often remain unclear, making these patients a diagnostic challenge. F.L. Opdam1, A.S. Modak2, S.P. Mooijaart1, M.W.M. de Waal1, Case: A 45-year-old woman was presented to the ED M. Louwerens1, H. Gelderblom1, H.J. Guchelaar1 because of an altered consciousness. Medical history 1Leiden University Medical Centre, Department of Medical revealed hypertension, depression and alcohol abuse. The Oncology, Leiden, the Netherlands, 2Cambridge Isotope Lab patient’s partner found her behaving abnormally. No signs Inc, Department of Research and Development, Andover, of intentional intoxication were found. United States of America At physical examination the patient was disoriented and she spoke with slurred speech. Besides, she was suspect Background: Frailty is a clinical phenotype that is for having visual hallucinations. She had dilated pupils, associated with adverse health outcomes. Since frail a dry tongue, red skin, and urinary retention of more patients might be prone for adverse drugs events and about than 1 liter. Except for a Glasgow Coma Score of E4M6V3, 15-20% of commonly prescribed drugs are metabolized by neurological examination was unremarkable. Additional CYP2D6, it was hypothesized that CYP2D6 metabolism testing, including routine laboratory analysis, an electro- is altered in frail patients compared to healthy subjects. cardiogram and a CT-scan of the cerebrum showed no Methods: The 13C-dextromethorphan breath test abnormalities. The clinical presentation fitted the anticho- (13C-DM-BT) was used to determine CYP2D6 phenotype linergic toxidrome and an intoxication with venlafaxine using 13C-dextromethorphan (13C-DM) as a probe. Eleven (her known prescribed medication) was suspected. Plasma frail and twenty-two non-frail (according to the Fried venlafaxine concentrations, however, were very low. The criteria) subjects aged 70-85 years were phenotyped for patient was admitted for observation and treated with CYP2D6. intravenous fluids. Results: Frailty score and individual parameters of frailty, After 24 hours she recovered completely. She denied Karnofsky score, HADS score and ADL score were not taking any drugs. However, further testing using LC-MS whereas length, weight and BMI were significantly (liquid chromatography-mass spectrometry) revealed high correlated to CYP2D6 phenotype. There was no difference concentrations of promethazine, confirming our suspected in CYP2D6 phenotype between frail (AUCDOB2h 319 ± diagnosis. We informed the patient’s general practitioner, 169”min) and non-frail subjects (AUCDOB2h 298 ± 159”min, who referred her for psychiatric treatment. p = 0.728), even when corrected for BMI. We observed This case illustrates the importance of knowledge of higher CYP2D6 metabolism in women (AUC DOB2h toxidromes and good collaboration with the hospital 362 ± 162 “min) compared to men (AUC DOB2h 252 ± 142 pharmacist. Because of thorough testing the patient could “min, p = 0.036), independent of frailty in the selected age receive proper treatment. group. Conclusion: Frail and non-frail subjects did not differ in C002 Metabolic acidosis: a rare complication of chronic CYP2D6 phenotype. Our study does not suggest a role alcoholism for CYP2D6 in explaining why frail subjects are more sensitive to adverse drug reactions. I.E.A. Wijting, G. Buunk Amphia Hospital, Department of Internal Medicine, Breda, the Netherlands III ACUTE MEDICINE Case: A 49-year old patient, known with chronic alcoholism, presented on the emergency departement C001 ‘Mad as a hatter, red as a beet, hot as hades, dry as a with vomiting. Since vomiting started, there was no bone’ and so on… intake of alcohol anymore. At physical examination, A case report there were signs of dehydration, tachypnea and an oral aceton foetor. Laboratory investigation showed a metabolic N.A.F. Verheijden, J. Alsma, Z. Brkic, B.C.P. Koch, acidosis with a high anion gap and a high osmol gap. S.C.E. Klein Nagelvoort – Schuit Urine dipstick showed the presence of ketone bodies. Erasmus MC, Department of Internal Medicine, Rotterdam, Evaluating this acidosis we found a high acetoacetate and the Netherlands a high beta-hydroxybutyrate level in the blood. The beta- hydroxybutyrate/acetoacetate-ratio was high in accordance

16 to the diagnosis alcoholic ketoacidosis. Treatment consisted (n = 1655, median 2:34, range: 0:08-11:04). In VUmc, a of suppletion of 250 mg thiamine followed bij infusion larger percentage ESI 1, 2 and 3 patients didn’t achieve of glucose 5%. Patient had a full recovery during this the 4 hour target (14%, 20% and 19%) compared to ESI 4 treatment. and 5 patients (2.7% and 0%), p < 0.001. In St. Antonius Clinical background: Alcoholic ketoacidosis (AKA) is a rare Hospital, a greater percentage of Orange and Yellow complication of alcohol-abuse in malnourished patients. categorized patients exceeded 4 hours (32% and 28%) Epidemiological data are absent in the the Netherlands. In compared to Red (8%) and Green/Blue (13%), p < 0.001. patients with a recent history of alchohol abuse, presenting There was a significant dependency between exceeding with a high-anion gap, high-osmol gap metabolic acidosis, 4 hours and consultations (p < 0.001), the amount of AKA should be considered. Three main mechanisms are radiology tests (p < 0.001), and age > 65 years. causing a state of keto-acidosis: a low insulin/glucagon- Conclusion: Factors leading to ED stagnation were similar ratio with increased lipolysis, the redox shift of the NAD+/ in both hospitals namely old age, involvement of more NADH-ratio to NADH due to the degradation of alchohol specialists and radiological tests. to acetaldehyde and a decrease in the renal clearance of ketone bodies in consequence of the dehydration. Lipolysis C004 The survival of patients admitted because of health- and metabolites of alcohol are essential in formation of care-related adverse events is similar to that after ketone bodies. The presence of high concentrations of admission for other reasons beta-hydroxybutyrate and acetoacetate and a elevated beta-hydroxybutyrate/acetoacetate-ratio are obligate in the F.J.H. Magdelijns, L. Schepers, E. Pijpers, C.D.A. Stehouwer, diagnosis of AKA. An elevated serum beta-hydroxybutyrate P.M. Stassen is the golden standard. Treatment consists of thiamine, Maastricht UMC+, Department of Internal Medicine, followed by glucose intravenously. Maastricht, the Netherlands

C003 What are we waiting for? Factors influencing Background: Health-care-related adverse events (AEs) often completion times in an academic and peripheral lead to hospitalization, can have grave consequences, and emergency department may even lead to death. To improve the quality of care, awareness of the magnitude of the relationship between I.L. Vegting1, N. Alam2, K. Ghanes3, O. Jouini2, F. Mulder2, AEs and death is important. The aim of our study was M. Vreeburg2, T. Biesheuvel2, J. van Bokhorst2, P. Go4, to investigate differences in mortality between patients G. Koole2, P. Nanayakkara2 admitted because of an AE and those admitted because of 1Sint Lucas Andreas Hospital, Department of Internal other reasons. Medicine, Amsterdam, the Netherlands, 2VUmc, Department Methods: We conducted a retrospective cohort study in one of Internal Medicine, Amsterdam, the Netherlands, 3Ecole university hospital in the the Netherlands. We reviewed Centrale Paris, Mathematics, Chatenay-Malabry, France, charts of patients admitted through the ED by internists 4St. Antonius Hospital, Department of Surgery, Nieuwegein, in the period May-October 2010. Patients were included if the Netherlands they were admitted because of an AE. The control group consisted of a random selection of patients admitted Background: A long completion time in the Emergency during the same period for other reasons. We investigated Department (ED) is associated with higher in hospital mortality at 28 days, one and two years after admission. morbidity and mortality. Completion time > 4 hours is a Results: In total, 573 admissions were included: 363 frequently used cut-off point. This study examined which because of an AE and 210 because of other reasons. The factors contribute to a completion time > 4 hours on the 28 day mortality was 8.7% (8.3% in AE group and 9.5% in ED’s of the VUmc and the St. AntoniusHospital. the controls, p = 0.57), which increased to 33.9% after two Methods: Time steps in the process of diagnosis and years. We found no significant differences in mortality treatment of ED-patients were measured during 4 weeks. after 28 days, one and two years between the AE group and Patients triaged as Emergency Severity Index (ESI) category the controls. A higher Charlson Comorbidity Index and age 2/3 or Manchester Triage System orange/yellow were were associated with mortality. followed prospectively for detailed information between Conclusion: This study demonstrates that AEs leading 12:00-23:00. to admission are not associated with a higher 28 days, Results: In VUmc, 89% of patients had a completion time one and two years mortality risk compared with other < 4 hours. The average completion time (n = 2262) was admission reasons. However, high overall mortality after 2:10 hours, (median 1:51, range: 0:05-12:08). In the St. acute admission was found in the entire study population. Antoniushospital, 77% had a completion time < 4 hours (n = 1656). The average completion time was 2:49 hours

17 C005 Gentamicin is frequently underdosed in patients levels and hypoxemia. Despite advanced life support and with sepsis in the emergency department maximal supportive care, there was a further derangement of her metabolic acidosis, worsening of the hyperkalemia M. Cobussen1, V. Hira1, J.M.L. de Kort2, D. Posthouwer1, and difficulties ventilating the patient. She died due to P.M. Stassen1, M.B. Haeseker1 severe complications after ingestion of sodiumazide. Since 1Maastricht UMC+, Department of Medical Microbiology & suicide was suspected, we informed the municipal coroner. Infectious Diseases, Maastricht, the Netherlands, 2Dr. Horacio Background: Sodiumazide is a biocide, used in labora- E. Oduber Hospital, Department of Internal Medicine, tories as a sterilizer. It inhibits the cytochrome-c-oxidase; Oranjestad, Aruba an enzyme which is involved in the respiratory electron transport chain of mitochondria. In this process oxygen Background: Gentamicin is frequently used for empirical is reduced to water and protons are translocated across treatment of sepsis in the emergency department (ED). the membrane, establishing a transmembrane difference In our hospital, the dose of gentamicin is 5 mg/kg given of proton electrochemical potential, that is then used once. In this study, we investigated the adequacy of by the ATP synthase tot synthesize ATP. Inhibiting dosing of gentamicin in patients with sepsis in the ED the cytochrome-c-oxidase will lead to inhibition of ATP and differences in outcome between underdosed and synthesis, whereafter cell metabolism is stopped. Clinical adequately dosed patients. symptoms of a sodiumazide intoxication, which may be Methods: Body weight, length, dose of gentamicin, and nearly immediate, are hypotension, bradycardia, central clinical characteristics of patients who visited our ED from nerve system depression, respiratory depression and April 2011 until April 2012 and who received gentamicin pulmonary edema. There is no antidote and sodiumazide at the ED were retrospectively retrieved from electronic can not be filtered during dialysis. patient files. Underdosing of gentamicin was defined as Conclusion: Intoxication with sodiumazide is a rare, but a dose <4.5 mg/kg and was based on actual body weight. almost always lethal emergency. For obese patients (BMI > 30), adjusted body weight was calculated. C007 Risk stratification by AbbMEDS and CURB-65 in Results: We included 173 patients with sepsis who received relation to treatment and disposition of the septic gentamicin. Thirty four (19.6%) patients were underdosed. patient at the emergency department The mean gentamicin dose was 3.8 ± 0.5 mg/kg in the underdosed group. Mortality within 28 days showed a A.A. Roest, J. Tegtmeier, J.J. Heyligers, J. Duijst, A. Peeters, trend in underdosed patients, compared to adequately H.F. Borggreve, A.M.L. Oude Lashof, C.D.A. Stehouwer, dosed patients (20.6% vs. 11.5%, p = 0.17). Underdosed P.M. Stassen patients were more often admitted to the intensive care Maastricht UMC+, Department of Internal Medicine, unit (ICU) directly from the ED (20.6% vs. 7.2%, p < 0.05). Maastricht, the Netherlands Conclusion: Gentamicin is underdosed in 19.6% of the patients with sepsis in our ED. Adequate dosing of Background: Sepsis leads to high mortality. The abbMEDS gentamicin might decrease mortality and improve clinical (abbreviated Mortality Emergency Department Sepsis) outcome of infection. Standardized weighing and strategies score assesses sepsis severity and predicts mortality. aimed at correct dosing might decrease underdosing of In community-acquired pneumonia, the CURB-65 gentamicin. (Confusion, Urea, Respiration, Blood pressure, Age) also provides guidance with regard to antibiotic treatment and C006 Suicidal intoxication with sodiumazide disposition. We investigated the predictive value and feasibility of the S.M. Platvoet-Sijtsma, C. Franca, A. Thijs abbMEDS and CURB-65 in sepsis patients at the ED and VUmc, Department of Internal Medicine, Amsterdam, the the relationship between the three risk categories of both Netherlands scores and antibiotic treatment and disposition. Methods: In this retrospective cohort study, we included Case: A 27-year-old woman died on our emergency ward 725 sepsis patients at the ED. We investigated the value in due to metabolic failure after ingestion of an unknown predicting 28-day mortality and feasibility of abbMEDS amount of sodiumazide. She was found in respiratory and CURB-65. We assessed the relationship between the distress, together with a friend who had also taken three risk categories per score and antibiotic treatment (e.g. sodiumazide (and also died). After on site intubation she narrow or broad-spectrum) and disposition (i.e. admission was transported to our hospital. Upon arrival she had a and type of ward). circulatory arrest, massive pulmonary edema and a severe Results: Both abbMEDS and CURB-65 were good metabolic acidosis with hyperkalemia, elevated lactate predictors of 28-day mortality (AUC 0.77 [95%CI

18 0.72-0.83] and 0.72 [95%CI 0.67-0.77], respectively) and feasible (complete score 92.7 and 93.9%, respectively). In S. Popal, B.W. Verbaan, G.C.M. Vreeburg, B.P. Ramakers the high risk category of the abbMEDS, all patients were Bernhoven Hospital, Department of Intensive Care, Uden, admitted and treated with broad-spectrum antibiotics. the Netherlands In the high risk category of the CURB-65, 2.5% were not admitted and 4.4% received no antibiotics. Introduction: Antithyroid drug-induced-neutropenia is Conclusion: Both abbMEDS and CURB-65 are good a rare and potentially life-threatening complication. We predictors of 28-day mortality and are feasible in septic describe a patient with septic shock due to necrotizing ED patients. In addition, the abbMEDS matches current laryngitis and epiglottitis as a result of Methimazole- clinical management concerning antibiotic treatment and induced agranulocytosis. disposition, while this is less so for the CURB-65. In the Case presentation: A 57-year-old female, was referred to future, use of the abbMEDS at the ED may improve sepsis the emergency department with a stridor after a five-day care by providing clinical guidance. history of arthralgia and progressive sore throat. Her clinical condition was progressing fast toward a septic C008 A man with a sudden paralysis due to a triiodothy- shock and an upper airway obstruction for which she ronine intoxication was intubated and transported to the ICU. A nasopha- ryngoscopy showed necrotizing laryngitis and epiglot- H. Grootjans titis. Her medical history revealed a recently diagnosed UMC Groningen/Medisch Spectrum Twente, Department of hyperthyroidism for which she started treatment with Internal Medicine, Enschede, the Netherlands Methimazole. Laboratory findings demonstrated decreased white blood cell count with complete agranulocytosis, Medication is easily ordered on the internet. Here we increased inflammatory parameters, acute kidney injury report a case of a Caucasian male with a thyrotoxic periodic and acute liver failure. A sputum smear demonstrated paralysis (TPP) due to an autointoxication with triiodothy- Staphylococcus aureus and Streptococcus pneumonia. ronine (T3). This active thyroid hormone was purchased by Treatment consisted of antibiotics adjacent to granulocyte the patient online to lose weight. TPP is a rare but potential colony-stimulating factor (G-CSF) for 5 days until reconsti- life-threatening emergency, which makes fast recognition tution of neutrophils. Although regular inspection of the and treatment essential. larynx and epiglottis showed improvement of the necrotic A 34-year old previous healthy man was brought to the tissue and epiglottitis, continuous swelling of the larynx emergency department because of a fast progressive was observed. On day 11, (Leucocytes 21.4x109 cells/l) a paralysis of both arms and legs. Since weeks he was CT-scan was performed, demonstrating bilateral abscesses experiencing palpitations, excessive sweating and anorexia. in the sternocleidomastoid muscle and ultrasound-guided The patient was hemodynamic stabile with a heart rate of percutaneous and surgical drainage was performed. On 105/bpm. Laboratory results demonstrated a decreased day twenty-four, 7 days after abscess drainage, she was potassium of 2.0 mmol/l and a thyrotoxicosis based on extubated and 4 days later she was discharged from the an elevated T3 level of 3.7 nmol/l with suppressed TSH hospital. and FT4 levels (< 0,01 mU/l and 4 pmol/l, respectively). A Conclusion: Although ATD-induced agranulocytosis sinustachycardia (130/bpm) and a prolonged QT-interval on remains a rare complication, patient education remains a 12-lead ECG, typical for TPP were both observed. Because essential. When severe agranulocytosis is accompanied of possible fatal arrhythmias associated with a long by severe infectious complications, treatment with G-CSF QT-syndrome, the patient was admitted to the intensive has been associated with shorter recovery time and less care unit. Intravenous potassium chloride was admin- antibiotics use. istered which restored the potassium level and muscle strength within a day. After recovery the patient reported C010 Intoxication with hydroxychloroquine he had been taking T3 in a dose of 100 mg daily for 6 weeks until a few weeks before admission, in combination with P.E.B. Verwer, G. Buunk amphetamines a few days before. Amphetamines are Amphia Hospital Breda, Department of Internal Medicine, known to aggravate TPP because of its sympathomimetic Breda, the Netherlands effect. This case shows the possible serious health risk of free Patient L, 19 years old, presented on the Emergency availability of prescription drugs on the internet. Department several hours after he had intoxicated himself with an uncertain amount of tablets of hydroxychloroquine C009 Necrotizing laryngitis and epiglottitis in a patient (Plaquenil) of his girlfriend. The exact amount was not with Methimazole-induced agranulocytosis known but probably 20-30 tablets of 200 mg. In the first

19 two hours patient started vomiting. At presentation, vital dropped to 6,81 and there was a lactate of 12,6 mmol/l. functions and physical examination were unremarkable. Pupils were non-responsive and wide. The echocardiogram Electrocardiography showed an increased ventricular showed a dying heart. Laboratory tests did not reveal traces conduction time of 140 ms. Laboratory tests showed of alcohol or drugs. Because of elapsed time, the poor hypokaliemia of 3.2 mmol/l. The potassium decreased neurological status and the refractory suicidality for more finally till 2.8 mmol/l. ABG analysis showed a respiratory than 7 years, treatment was terminated after 45 minutes. alkalosis without compensation. Patient received oral High serum levels of Baccatin-III (1.05 mg/l), Paclitaxel charcoal and laxatives but vomited several times. He was (0.45 mg/l) and cephalomannine (0.26 mg/l) confirmed admitted to the ICU and treated with a 2 mg/kg bolus yew poisoning. and continuous infusion of diazepam. He was sedated Conclusion: We present a biochemical confirmed case of and intubated and ammonium chloride was administered yew poisoning. The fact that the needles were crushed orally, in order to increase renal elimination. The next before ingestion, might have accelerated the fatal course. day the EKG normalised and diazepam was stopped. Patient woke up without neurologic sequelae. Patient C012 Patient with gasflow leaving the veins was discharged after an assessment by the psychiatrist. The plasma level of hydroychloroquine was 2821 mcg/l ( B. de Klerk, H.J. Pluim, I.A. Boven, R. Fijnheer > 2500 mcg/l is toxic). Meander Medical Centre, Department of Internal Medicine, Intoxications with hydroxychloroquine are rare but can Amersfoort, the Netherlands be serious and lethal. Treatment recommendations are charcoal for gastrointestinal decontamination, however A 63-year old female enters the Emergency Department this is only effective within 1 hour after the intoxi- with fever and abdominal pain. She had no relevant cation. Furthermore early intubation and sedation and medical history. This was the worst pain she had ever correction of the potassium levels are recommended. had, spread over her entire abdomen. It started the same Diazepam intraveneously is used for sedation and it may evening, with only a little diarrhea as present complaint. also have a beneficial effect in case of hemodynamic In physical examination her temperature was 40.2 degrees, deterioration, though the evidence for treatment with high her pulse 114 beats per minute and her bloodpressure dose diazepam is limited. 140/90 mmHg with a saturation of 96%. There was no abdominal distention and no other clue in the physical C011 Taxus baccata (Yew) smoothie: a lethal drink examination. Because of her severe pain she immediately went for an ultrasound examination of her abdomen. L.M. van der Burg, S.H.A. Diepeveen The ultrasound was not conclusive for any diagnosis. Isala, Department of Internal Medicine, Zwolle, the Five minutes after return, the patient became respiratory Netherlands insufficient and her blood pressure dropped. We tried to resuscitate her, but she died 90 minutes after entering the Introduction: Yew contains toxic alkaloids which block ED. When the co-workers of the mortuary prepared the cardiac calcium channels and increase intracellular patient for transfer, blood was bubbling out of her mouth calcium concentrations leading to cardiac rhythm distur- and while removing the infusion needles, gas was flowing bances. Baccatin-III, paclitaxel and cephalomannine are for as long as ten seconds from the veins. Blood tests could yew poisoning markers. Crushed needles seem to enhance not be performed due to extreme hemolysis. The next day, alkaloid absorption, leading to more rapid signs of yew autopsy showed all organs in a very flaccid condition. A intoxication. Since there is no antidote known, treatment Clostridium Perfringens was detected in blood cultures, an is strictly supportive. anaerobic gram-positive bacterium that rarely causes gas Case: A young female took approximately 20 grams of gangrene and massive intravascular hemolysis. This is an yew needles during the day, but no medical emergency extreme case leading to death in a female that was for our occurred. Overnight she crushed needles in a blender concern healthy without any known risk factors. and drank the smoothie. Two hours later she was found pulseless. She regained rhythm and spontaneous breathing C013 Metformin intoxication: a case of a combination of on basic life support. However, soon after arrival in the severe hypoglycaemia and lactic acidosis (LA) emergency department a second cardiac arrest occurred. At first a shockable rhythm (wide complex tachycardia and D.E. Agterhuis1, H. Freling2, M. Henstra2, T.h.F. Veneman2 ventricular fibrillation) was present. Three electric shocks ZGT, Depaertments of 1Internal Medicine and 2Intensive Care, were administered and then asystole emerged. 10 mg Almelo, the Netherlands adrenaline, 4,5 mmol calcium gluconate and 100 ml 8,4% sodium bicarbonate were administered without effect. pH

20 Case: A 40-year-old patient, who was seen in good health results in management difficulties and potentially impedes sixteen hours earlier, was presented to our Emergency patient care. Department after being found unconscious (E1M1V1). His Objective: To compare the characteristics and outcomes medical history consisted of DM2 and schizophrenia. between elderly NSC-patients and Specific Complaint At the Emergency Department respiration was normal, (SC)-patients. Primary outcomes are ED-return-visits and blood-pressure 78/50 mmHg, pulse 100 bpm, extremities 30-day mortality. were cold and pupils symmetrical but non-responsive to Methods: A retrospective cohort study was conducted light. Rectal temperature was 29.9 Celsius. amongst elderly patients (≥ 65years) visiting the ED for Laboratory-examination showed a plasma glucoseconcen- internal medicine at Máxima Medical Centre between tration <0.1 mmol/L, leukocytecount 32.0x10^9, metabolic 01-09-2010 and 31-08-2011. NSC describes indefinable acidosis (pH 6.92, pCO2 6.7 Kpa, bicarbonate 10 mmol/l), complaints without providing a pre-differential diagnosis aniongap 34, plasma lactateconcentration 18.8 mmol/L and to initiate standardized patient evaluation. ethanol < 0.1 g/l. Liver-enzymes and kidneyfunction were Results: In total, 1784 patients were enrolled, 244 (13.7%) normal. Urine toxicologyscreen was negative. At his home presented with NSC. Comorbidity was higher in the all boxes of previously prescribed medication were found, NSC-group (CCI 3.0 versus 2.4, p < 0.001). No discrepancy accept for the metformin packages. in level of triage was observed between the groups The differential-diagnosis included acute metformin (p = 0.300). ED-length of stay was higher in the NSC-group intoxication with severe LA and hypoglycaemia. Treatment (182 versus 170 minutes, p = 0.004). Hospitalization was started with volume- and glucose-infusion, and (84.0% vs, 71.1%, p < 0.001) and length of hospital stay (9 hemodialysis for removal of metformin and lactate. versus 6 days, p < 0.001) were higher in the NSC-group. Noradrenaline was needed for hemodynamic support. The Returning home after discharge was similar in both patient developed acute renal failure and a severe aspiration groups (58% vs. 53%, p = 0.120). ED-return-visits were less pneumonia. frequent in the NSC-group (OR 0.67, 95%CI 0.46-0.96). The plasma-metforminconcentration was extremely The 30-day mortality was 20.1% compared with 11.0% in high: 72 mg/l (therapeutic range 1-2mg/l). After the SC-group (HR1.90, 95%CI 1.38-2.61). tempering sedative medication, the patient regained full Conclusion: The ED-return-visits were lower for the consciousness, was successfully extubated and discharged NSC-group. However, NSC-patients had more comor- in good condition after nine days with complete recovery bidities, and more adverse health outcomes, such as of kidney function. higher 30-day mortality. These results imply the need for a Discussion: The pathogenesis of LA in metformin overdose protocol and will be used in the development of a fast-track is complex and not completely understood. Many published pathway for elderly NSC-patients at the ED. cases do not mention metformin plasmaconcentrations. Furthermore, hypoglycaemia as severe as < 0.1 mmol/l C015 A case of ‘popper’ induced methaemoglobinaemia has not been described earlier in metformin users. The presence of hypotension, acidosis, elevated aniongap, A.J.W. Gulpen, G. Vreugdenhil hyperglycaemia and coma are associated with a severe Máxima Medical Centre, Department of Internal Medicine, outcome. Veldhoven, the Netherlands

C014 Elderly patients with non-specific complaints at the Case: A 51-year old man with no relevant medical history emergency department presented to the emergency department by ambulance, after a collapse in a sauna. He had head trauma and was J.J.H. Wachelder1, L.P.A.M. Hubens1, S.H.A. Brouns1, complaining of headache. He had a few seconds loss of H.R. Haak1, H.R. Haak2, H.R. Haak3 consciousness. He consumed 1L beer before the collapse. 1Máxima Medical Centre, Department of Internal Medicine, At presentation the patient had blue lips, his oxygen Eindhoven, the Netherlands, 2Maastricht University, saturation was 89% with an respiratory rate of 18/min, Department of Internal Medicine, Maastricht, the under 100% oxygen through a non-rebreather mask. His Netherlands, 3CAPHRI School for Public Health and Primary blood pressure was 95/60 mmHg with a pulse of 60/min. Care, Department of Health Services Research, Maastricht, His Glasgow coma scale was 15. He had a small laceration the Netherlands on his forehead. Laboratory measurements showed no abnormalities. Arterial blood gas showed a pH of 7.39, Background: ‘Feeling weak’ or ‘being tired’ typifies pCO2 38 mmHg, HCO3- 22 mmol/l and a methemo- Non-Specific Complaints (NSC), presented by an globin level of 22.5% (ref. 0.4-1.2%). When the patient was increasing amount of elderly patients at the emergency stable, his history was taken again. He admitted the use of department (ED). Limited knowledge about NSC-patients 60 mL poppers in the sauna. He was treated with 100%

21 oxygen and methylene blue 1-2 mg/kg. After 1 hour the C017 It is ALL in the chest: pericardial tamponade, central cyanosis disappeared and the methemoglobin level pneumothorax and pleural effusion as presenting decreased to 0.9%. manifestation of acute lymphoblastic leukemia. Discussion: This patient was diagnosed with methaemoglobinaemia. Methaemoglobinaemia can be caused by M.K. Szymanski, G.J. Braunstahl, E.J. Libourel, congenital disorders, but the most frequent cause is drugs A.J.B.W. Brouwers exposure, for example poppers. Alkyl nitrites (‘poppers’) Sint Franciscus Gasthuis, Department of Internal Medicine, have been used increasingly for the vasodilator effects and Rotterdam, the Netherlands smooth muscle relaxation leading to an pleasant feeling. Methemoglobin contains ferric iron (Fe3+) instead of Introduction: Acute lymphoblastic leukemia (ALL) is the ferrous iron (Fe2+) and is unable to bind oxygen. The ferric most common form of cancer in children. The survival form also interferes with the oxygen unloading, resulting rates have improved recently, but the final treatment results in a left shift of the oxygen dissociation curve. are dependent on quick diagnosis and introduction of treatment. Quick diagnosis might be difficult as there are C016 A subtle sign on the chest X-ray: always look both no specific symptoms of ALL. We present a case of ALL ways! that presented with pleural and pericardial effusion and pneumothorax. S.J. van Asselt, T.J. Olgers, J.C. ter Maaten Case: A 19-year old patient, with a history of recent UMC Groningen, Depatment of Internal Medicine, respiratory tract infection treated with antibiotics, Groningen, the Netherlands presented to the pulmonologist with acute respiratory distress. Chest X-ray showed left-sided pleural effusion and A 60-year old male presented to the emergency right-sided pneumothorax. Despite immediate placement department with a near collapse. He complained of of pleural tubes, he remained in respiratory distress and excessive watery diarrhea since one day without blood was admitted to the Intensive Care. Echocardiography or abdominal pain. He was diagnosed with diffuse large showed cardiac tamponade with right atrial collapse B-cell lymphoma 3 months earlier for which he received and acute pericardiocentesis was performed. CT R-CHOP. Two days earlier nasogastric tube feeding was thorax revealed a large mediastinal mass with airway started because of anorexia. Physical examination showed compression and pulmonary infiltrates. Laboratory results a tachypnea (26/min), tachycardia (138 beats/min), blood showed increased LDH (1030 U/l) and leukocytosis pressure of 105/55 mmHg and a temperature of 36.4 °C. (37.8x10^9/l) with 33% blasts in the peripheral bloodsmear. His abdomen was tender without signs of peritonitis. Blood Immunophenotypic analysis diagnosed a T-lineage ALL. results showed a worsened pancytopenia with leucocytes Patient was initially treated with steroids, combined with of 0.0 109/L (ref.4.0-10 109/l) and C-reactive protein intravenous fluid therapy and rasburicase to prevent tumor level of 320 mg/l (ref.0.0 to 5.0 mg/l). Arterial blood gas lysis syndrome. After stabilization, further treatment with showed a respiratory alkalosis with a high alveolar-arterial chemotherapy could be initiated a few days later. gradient. For exclusion of pneumonia a chest X-ray was Conclusion: This case shows a dramatic acute presentation performed showing a subtle and unusual pattern of ‘free’ of ALL with pericardial tamponade, pneumothorax and air under the left diaphragm. Abdominal CT demonstrated pleural effusion. Only a few case reports describe pleural pneumatosis intestinalis (PI) from the distal esophagus and pericardial involvement at the time of diagnosis. till the proximal jejunal wall without signs of neutropenic Our case highlights also how multidisciplinary approach enterocolitis (typhlitis) or obstruction. Blood culture (pulmonologist, cardiologist, intensivist and hematologist) yielded Streptococcus mitis so the PI might be caused by an can be crucial to quick diagnosis and introduction of infection and mucosal disruption due to the nasogastric treatment of ALL. tube. Broad-spectrum antibiotics were initiated at the ICU. Unfortunately, the next day the patient suddenly deterio- C018 Unconscious and homeless: caused by which rated and died. Permission for autopsy was not obtained. substance? Here, the diagnosis of PI was made early because of systematic interpretation of the chest X-ray. Abdominal CT E.M. van der Weijde, R.A. Carels might not have been made if chest X-ray was normal. This Ikazia Hospital, Department of Internal Medicine, case illustrates the importance of a systematic approach in Rotterdam, the Netherlands interpreting additional investigations. Case report: A homeless person was admitted to the Emergency Department after he was found unconscious outdoors. Medical history reported epilepsy and use of

22 carbamazepine and valproic acid. Physical examination was stabilized 45 minutes after induction, allowing for showed: respiration 8 times per minute, oxygen saturation completion of the operation. He was ventilated for two 90%, dilated pupils, alternating state of consciousness hours post-operatively and recovered uneventfully. One (Glasgow Coma Scale 6 -11) and hypothermia (34.5 °C). month later he was tested for allergies to all medication Laboratory results showed no abnormalities. Urine used peri-operatively. A positive reaction was found to drug screen was positive for tricyclic antidepressants propofol. Since its introduction in 1973, propofol has (TCA) and cannabis. Because of this result we initially become one of the most frequently used anaesthetic diagnosed intoxication due to these substances.The next drugs because of its outstanding safety profile. Allergic day, patient reported double vision and headache. He had reactions to propofol are seldom seen (< 1:10,000); anaphy- an upward gaze with a downbeat nystagmus and ataxic lactic shock is even more rare (< 1:100,000). With the gait. The carbamazepine serum level was elevated: 18 mg/l development of the Dutch guideline of procedural sedation (normal 4-12 mg/l). The level of etoxycarbamazepine, and/or analgesia outside the operation theatre we expect the active metabolite, was 23 mg/l (normal 0.5-4 mg/l), increased use of propofol and thus more cases of propofol which indicated a chronic overdose. Carbamazepine was induced anaphylaxis. Awareness is important for prompt temporarily stopped and activated carbon was shortly diagnosis and treatment, which includes epinephrine, the given. Our patient recovered fully. drug of choice to reverse anaphylactic shock and prevent Discussion: Patients with an altered mental status are a morbidity and mortality. diagnostic challenge. In this case urine drug screen was positive for TCA. Pharmacy data showed no history of TCA C020 Is rhythm observation necessary in patients with usage, but we suspected he used medication of another moderate hypercalcemia? person. Because of this suspicion, carbamazepine was not discontinued. Only after serum levels were known A.A.W. Mulder, C.G. ter Meulen, B.A.J. Veldman carbamazepine was stopped.Carbamazepine is a common CWZ, Department of Internal Medicine, Nijmegen, the cause of intoxication. Symptoms can vary from ataxia to Netherlands coma. Some reports show that in carbamazepine overdose, some drug screens provide false-positive results for TCA. Background: Hypercalcemia is a relatively common We conclude that knowledge of substances that cause false problem in the emergency department and the outpatient positive results in drug screens is important in preventing clinic. The Dutch guideline of acute medicine advices to mistakes. take into consideration rhythm observation in patients with moderate to severe hypercalcemia, especially if they have a C019 Anaphylactic reaction to propofol as a rare cause of shortened QT-interval. This advice has been based on data anaphylactic shock: a case report of case reports and small case series. Methods: In a retrospective study we investigated 82 C.W. Buiter, T. Rustemeyer, B.L. ten Tusscher consecutive patients with hypercalcemia (3.5mmol/l or VUmc, Department of Intensive Care, Amsterdam, the higher). Their treatment and outcome were assessed. Netherlands Terminally ill patients with known malignancies were excluded. ECGs were collected and the QTc was measured. A 41-year-old male presented with a submandibular Complications were registered, such as rhythm distur- phlegmonous abcess and increased respiratory effort. bances and causes of death. Haemodynamic parameters were unremarkable. Results: Forty-seven (57%) patients were admitted with Emergency tracheostomy was scheduled. He was already rhythm observation. Of the 68 available ECGs 20 (29%) on treatment with antibiotics. After awake fibreoptic had a shortened QTc. Ten rhythm disturbances were nasal intubation, he was anesthetised with remifentanyl, scored: ventricular fibrillation (1), atrial fibrillation (3 propofol and rocuronium. The abcess was incised and new, 3 known), bradycardy (1), brady-tachyarrhythmia (1), drained. Shortly hereafter he became haemodynami- bigemini (1). Two had a myocardial infarction (MI), one cally unstable (pulse 150/min, systolic blood pressure of which had ventriculair fibrillation, followed by asystole 50mmHg). Initially the deterioration was thought to and died. Nine died in the first 4 days: 7 malignancy, 1 MI be caused by endotoxin release. Despite treatment and 1 leukemia. The patients who died with malignancy, with fluid therapy and vasopressors shock persisted, treatment of hypercalcaemia was discontinued, as their ventilatory pressures increased and SaO2 dropped to 87%. prognosis was dismal. Within 5 days of treatment, all Re-examination of the patient revealed bronchospasm and patients had a plasma calcium below 3.5mmol/l, with diffuse urticaria. He was treated for suspected anaphylaxis exception of 3 in which treatment was discontinued with norepinephrine, clemastine, dexamethason and due to their poor prognosis and the patient with the MI ranitidine. No epinephrine was administered. The patient (4.08mmol/l).

23 Conclusion: No severe rhythm disturbances or death 1Isala, Diabetes Centre/Department of Internal Medicine, related to hypercalcemia were found in patients with Zwolle, the Netherlands, 2UMC Groningen, Department of moderate hypercalcemia. Rhythm observation seems not Internal Medicine, Groningen, the Netherlands, 3Linköping necessary in this group. University, Department of Endocrinology, Linköping, Sweden

Case: A 49-year old patient, known with chronic IV DIABETES MELLITUS alcoholism, presented on the emergency departement with vomiting. Since vomiting started, there was no intake of alcohol anymore. At physical examination, C021 Liragutide during Fasting is not associated with there were signs of dehydration, tachypnea and an oral Hypoglycemia aceton foetor. Laboratory investigation showed a metabolic acidosis with a high anion gap and a high osmol gap. A.W.A. Koot, H. de Boer Urine dipstick showed the presence of ketone bodies. Rijnstate, Depertment of Internal Medicine, Arnhem the Evaluating this acidosis we found a high acetoacetate and Netherlands a high beta-hydroxybutyrate level in the blood. The beta- hydroxybutyrate/acetoacetate-ratio was high in accordance Background: Subclinical hypothyroidism (SH), defined as to the diagnosis alcoholic ketoacidosis. Treatment consisted a raised serum thyroid stimulating hormone (TSH) with of suppletion of 250 mg thiamine followed bij infusion a normal free thyroxine (FT4), is occasionally observed of glucose 5%. Patient had a full recovery during this in morbidly obese patients. It is currently not known treatment. whether thyroid hormone treatment is indicated. The aim Clinical background: Alcoholic ketoacidosis (AKA) is a rare of the present study was to assess the changes in thyroid complication of alcohol-abuse in malnourished patients. hormone levels in thyroxin naïve patients with SH in Epidemiological data are absent in the the Netherlands. In response to weight loss induced by Roux-en-Y Gastric patients with a recent history of alchohol abuse, presenting Bypass (RYGB). with a high-anion gap, high-osmol gap metabolic acidosis, Methods: Serum levels of TSH and FT4 were measured at AKA should be considered. Three main mechanisms are baseline in 503 consecutive patients presenting for RYGB. causing a state of keto-acidosis: a low insulin/glucagon- In patients diagnosed with SH de novo, these measure- ratio with increased lipolysis, the redox shift of the NAD+/ ments were repeated 12 months after RYGB. NADH-ratio to NADH due to the degradation of alchohol Results: SH de novo was present in 61 out of 503 patients to acetaldehyde and a decrease in the renal clearance of (12.1%). Their preoperative mean serum TSH was ketone bodies in consequence of the dehydration. Lipolysis 5.8 ± 2.0 mU/l and FT4 15.2 ± 2.1 pmol/l. TSH levels and metabolites of alcohol are essential in formation of ranged from 4.04-13.80 mU/l, TSH levels > 10 mU/l were ketone bodies. The presence of high concentrations of observed in 3 (0.5%) patients. RYGB induced a decrease beta-hydroxybutyrate and acetoacetate and a elevated in BMI from 47 ± 8 kg/m2 to 33 ± 6 kg/m2 at 12-month beta-hydroxybutyrate/acetoacetate-ratio are obligate in the follow-up (p < 0.001), and this was associated with a diagnosis of AKA. An elevated serum beta-hydroxybutyrate decrease in TSH and FT4 to 2.8 ± 1.3 mU/l (p < 0.001) and is the golden standard. Treatment consists of thiamine, 13.9 ± 2.3 pmol/l (p < 0.001), respectively. SH completely followed by glucose intravenously. resolved in 53 (87%) of the de novo cases. Conclusion: After RYGB SH resolves in about 90% of C023 Plasma matrix metalloproteinases are associated patients. This suggests that follow-up alone is sufficient in with incident cardiovascular disease and all-cause the majority of patients, and that preoperative treatment mortality in patients with type 1 diabetes: a 12-yr with thyroid hormone is not indicated in antibody negative follow-up study SH. S.A. Peeters1, L. Engelen2, J. Buijs3, A. Jorsal4, C022 Different effects of intraperitoneal and subcu- H.H. Parving5, L. Tarnow4, P. Rossing4, C.G. Schalkwijk2, taneous insulin administration on the growth- C.D.A. Stehouwer1 hormone – insulin-like growth factor-1 axis in type 1 1Maastricht UMC+, Department of Internal Medicine, diabetes Maastricht, the Netherlands, 2Maastricht University, Department of Internal Medicine, Maastricht, the P.R. van Dijk1, S.J.J. Logtenberg2, S.I. Chisalita3, Netherlands, 3Atrium-Orbis Medical Centre, Department of C.A. Hedman3, K.H. Groenier2, R.O.B. Gans2, N. Kleefstra1, Internal Medicine, Heerlen,the Netherlands, 4Steno Diabetes H.J. Arnqvist3, H.J.G. Bilo1 Centre, Gentofte, Denmark, 5Rigshospitalet, Department of Medical Endocrinology, Copenhagen, Denmark

24 Methods: Study design: 2 year open label randomized Background: Correction of substantial hyperglycaemia controlled trial, comparing metformin versus control in patients with diabetes is often difficult because of group. hyperglycaemia-induced glucose toxicity leading to Study population: pregnant women with a high risk of peripheral insulin resistance. Usually, standard sliding GDM, between 18 and 40 years old in the first trimester scale regimens, barely adjusted to individual needs, are of pregnancy. applied both in the outpatient and in-patient setting. We Intervention: intervention starts at 14 weeks of pregnancy, tested a simple formula based on the insulin sensitivity the intervention group (n = 200) receives Metformin factor to estimate the insulin dose needed to correct twice daily 500 mg for the first week, after that twice daily substantial hyperglycaemia in individual diabetic patients. 1000 mg. The control group (n = 200) receives no inter- Methods: This analysis was part of a randomized controlled vention. All the subjects are instructed to follow a dietary cross-over trial conducted in insulin-treated patients with advice with a maximum of 2000 calories/day. diabetes, comparing the efficacy of two insulin pens Study procedures: subjects will visit our centre in the first for the administration of rapid-acting insulin to correct trimester, then blood samples will be collected. The oral spontaneous hyperglycaemia (18-23 mmol/l). The dose glucose tolerance test (OGTT) will be performed at 24 of rapid-acting insulin to be injected was calculated and 28 weeks of gestation. Women with a history of GDM as follows: ([measured glucose-value in mmol/l - 6] ÷ will do an OGTT at 16 weeks. If the OGTT is borderline [100÷total daily insulin dose]) - 1.5. Plasma glucose levels normal, it will repeated every 4 weeks, according to current were measured for 6 hours after insulin administration. Dutch guidelines. Subjects will visit their own gynae- Results: 20 patients (10 type 1 diabetes, 10 type 2 diabetes, cologist or obstetrician for regular pregnancy check-ups. mean age 53.4 years, HbA1c 8.6%, TDID 96.1 U/day) Conclusion: METC application approved, inclusion started underwent 40 experiments. Glucose values dropped October 2014. from 21.3 ± 0.4 to 7.3 ± 0.4 mmol/l after injection of 21.7 ± 1.9 insulin units. After 196.2 ± 11.7 minutes, plasma C025 Changes in glucose lowering drug use before and glucose levels dropped below 10 mmol/l. The formula after a cancer diagnosis among individuals with predicted well on 27 occasions (67.5%), slightly under- diabetes predicted insulin needs on 6 (15%) occasions (glucose nadir at 12.3 ± 0.5 mmol/l) and over-predicted on 7 (17.5%) M.M.J. Zanders1, H.R. Haak2, M.P.P. van Herk-Sukel3, occasions (glucose < 5.0 mmol/l, requiring exogenous R.M.C. Herings3, L.V. van de Poll-Franse1, J.A. Johnson4 glucose administration). 1IKNL, Research Department, Eindhoven, the Netherlands, Conclusion: We developed an easy-to-use formula to 2Máxima Medical Centre and Maastricht UMC+, Department calculate individualized insulin correction doses. Using of Internal Medicine, Eindhoven/Veldhoven/Maastricht, the this formula substantial hyperglycaemia could be corrected Netherlands, 3PHARMO Institiute, Research Department, 4 in ~3 hours in the majority of diabetic patients. Utrecht, the Netherlands, University of Alberta, School of Public Health, Edmonton, Canada C024 Metformin vs. Control to prevent gestational diabetes mellitus (GDM) in women with a high risk for Background: This study explores changes in glucose GDM, an open label randomized controlled trial lowering drug (GLD) use associated with cancer development and treatment among diabetic individuals. H.S. Brink, M. Alkemade, J. van der Linden Methods: New GLDs users (1998-2011) living in the Maasstad Hospital, Department of Internal Medicine, ECR-PHARMO catchment area were selected (n = 52,228). Rotterdam, the Netherlands Those with a primary cancer diagnosis were considered cases (n = 3,281) and matched with eligible controls Background: GDM is a frequent pregnancy complication without cancer during follow-up (n = 12,891). Conditional and associated with complications for mother and child. logistic regression analysis was used to assess changes in At present, the drug of choice for treatment of GDM is GLD use, i.e. treatment drop and initiating insulin, for Insulin. Metformin is an accepted alternative for insulin, cases compared to controls due to specific cancer types with comparable glycemic control and neonatal outcomes. in four time windows (3-6 and 0-3 months before cancer Aim/study parameters: the primary objective is to diagnosis; 0-3 and 3-6 months after cancer diagnosis). study the effect of Metformin on the incidence of GDM Results: In the 3-6 months before cancer diagnosis, gastro- in women with a high risk for GDM. The secondary intestinal and pancreas cancer were associated with higher objective is to study maternal and neonatal outcomes and odds of starting with insulin (OR 3.9;95%CI 1.3-12.1 and complications. OR 4.9;95%CI 1.3-18.1). Colorectal (OR 3.4; 95%CI 1.4-8.4) and gastrointestinal (OR 13.6;95%CI 5.0-36.9) cancers were

25 associated with increased odds of initiating insulin in the Conclusion: Among users of GLDs, HbA1c decreased 3 months after cancer diagnosis. After this period, these with 0.12%-0.18% (1-2 mmol/mol) per year before CRC odds were increased for breast (OR 4.6;95%CI 1.7-12.6) diagnosis. Only among CC patients, HbA1c increased and pulmonary (OR 3.3;95%CI 1.2-9.1) cancers. Within after diagnosis (0.12% per year; 1.3 mmol/mol). In (un) all time windows odds of treatment drops were higher for diagnosed cancer patients the HbA1c measure to visualise patients with gastrointestinal cancers, while for all other glycaemic control might be influenced by anti-anaemic cancers (except breast and prostate) odds were only higher preparations. after cancer diagnosis. Conclusion: Already 3 to 6 months before the diagnosis C027 A sodium-glucose co-transporter as replacement of gastrointestinal or pancreas cancer a higher odds of therapy for carbohydrate restriction in diabetes initiating insulin use was observed, suggesting reverse mellitus type 2 causation. Stopping GLDs was common after cancer diagnosis, while the diagnosis of most cancer types was M. Smits, P.F.M.J. Spooren, G.J. van Rooyen associated with the start of insulin. Elisabeth-TweeSteden Hospital, Department of Internal Medicine, Tilburg, the Netherlands C026 Impact of cancer diagnosis and treatment on glycaemic control among individuals with colorectal Introduction: Glycaemic control may be difficult to achieve cancer using glucose lowering drugs in type 2 diabetics, who are extremely sensitive for carbo- hydrates. In addition to medication, a low carbohydrate M.M.J. Zanders1, M.P.P. van Herk-Sukel2, R.M.C. Herings2, diet can improve glycaemic control dramatically. However, L.V. van de Poll-Franse1, H.R. Haak3 adherence to this diet is often hard. SGLT2 inhibitors, such 1IKNL, Research Department, Eindhoven, the Netherlands, as dapaglifloxin, cause glucosuria and may replace a strict 2PHARMO Institute, Research Department, Utrecht, the low carbohydrate diet. We demonstrate the success of this Netherlands, 3Máxima Medical Centre and Maastricht theory in two patients. UMC+, Department of Internal Medicine, Eindhoven/ Case reports: A 70-year old woman with longstanding Veldhoven/Maastricht, the Netherlands diabetes was treated with metformin and insulin. The last five years glycaemic control deteriorated despite increasing Background: This study aims to evaluate the impact doses of insulin. A low carbohydrate diet improved HbA1C of cancer and its treatment on HbA1c-values among levels, but adherence was difficult and HbA1c increased. individuals with colorectal cancer (CRC) using glucose Treatment with dapaglifloxin was introduced and improved lowering drugs (GLDs). immediately glycaemic control. Methods: Patients with primary CRC (1998-2011) were A 68-year diabetic since 2004 was treated unsuccesfully selected from the Eindhoven Cancer Registry and linked with metformin, glimeperid and sitagliptin. Insulin is to the PHARMO Database Network including out-patient raising doses was started and caused weight gain without pharmacy and clinical laboratory data. Patients with more a good glycaemic control . Despite better glycaemic control than two years of GLDs use prior to cancer diagnosis were after a low carbohydrate diet he could not continue this included. Linear mixed effects models were conducted diet. Eventually, dapaglifoxin was started, which led to an to evaluate changes in HbA1c for colon cancer (CC) and impressive decrease of HbA1C. rectal cancer (RC) patients in the four years around CRC Discussion: It has been proven that SGLT2 inhibitors can diagnosis. improve glycaemic control in type 2 diabetics. In these two Results: Of all CRC patients (n = 4,714), 294 (6%) GLDs carbohydrate sensitive diabetics, unable to achieve satifying users with CC and 144 (3%) with RC were selected. In control, using conventional treatment including insulin, the crude model, mean HbA1c at cancer diagnosis was we demonstrate a miraculous improvement of glycaemic 6.9% (51.6 mmol/mol) among CC patients and 7.1% control during treatment with a SGLT2 inhibitor. We (53.5 mmol/mol) among RC patients. Among CC patients, hypothesize that extremely carbohydrate sensitive diabetic

HbA1c decreased with 0.12% per year (p = 0.0002) before patiens may benefit more from SGLT2 inhibitors besides cancer diagnosis in the adjusted model and after diagnosis conventional treatment. Further research is necessary to it increased with 0.12% per year (p = 0.02). In subgroup prove this theory. analyses, effects on HbA1c were more pronounced in users of anti-anaemic preparations, these prepara- C028 ‘Cold-turkey’ withdrawal of insulin at the start of tions are suggested to interfere with HbA1c. Among RC liraglutide treatment in type 2 diabetes patients patients, HbA1c decreased before diagnosis with 0.18% per year (p = 0.0006), whereas after diagnosis it changed K.J. Bhansing, M.L. Duizer, A.H. Mudde, A.H. Mulder not-significantly.

26 Slingeland Hospital, Department of Internal Medicine, The measurement was repeated with different point of care Doetinchem, the Netherlands devices showing values of 11.6 mmol/l and 12.2 mmol/l. These measurements were compared with another venous Background: Several studies show a significant reduction sample revealing a value of 3.7 mmol/l. After cleaning the of HbA1c, weight and insulin dose when a incretin agonist hand carefully, fingerstick measurements showed values like liraglutide is added to insulin treatment in type 2 of 4.8 mmol/l and 5.1 mmol/l. Most likely the indentified diabetes patients. In the the Netherlands this ‘add on discrepancy was caused by spilled invisible glucose 5% treatment’ is not reimbursed by the health insurance solution. In search for an explanation, we found that the companies. Therefore, we analyzed the results of our glucose infusion was switched between arms earlier. The experience when switching from insulin to liraglutide solution which corresponds with 278 mmol/l of glucose, with regards to body weight and glycaemic control in type had spilled onto the fingers from which the samples were 2 diabetes patients. obtained. Methods: 41 consecutive obese (BMI ≥ 35 kg/m2) patients Conclusion: When detecting an unexplained high glucose suffering from type 2 diabetes and treated with insulin concentration, be aware of contamination by glucose were included. Insulin was replaced by liraglutide infusion solution as a possible explanation. In addition, combined with metformin and a sulfonurea derivate. Body always confirm unsuspected high glucose levels with a weight and HbA1c were collected at baseline and after 3, 6 venous glucose measurement. and 12 months. Results: Mean age was 60.5 years (SD 9.4), and mean BMI C030 Toe-Brachial Index by photoplethysmometry; an 39.8 kg/m2 (SD 6.0). The mean disease duration was 12.1 interesting tool to screen for confounding peripheral years (SD 6.8). Mean HbA1c was 69 mmol/mol (SD 14) arterial disease in diabetic patients with therapy and mean insulin dose was 96 IU (SD 41). Body weight resistant polyneuropathy significantly decreased at all time points (-6.9, -8.8 and -9.2 kg) (p < 0.01) compared to baseline. HbA1c showed a A.N.C. Gosselt, B.P.M. Imholz non-significant reduction compared to baseline (-1.3, -4.2, Elisabeth-TweeSteden Hospital, Department of Internal -1.6 mmol/mol). After one year 25 patients (61%) used Medicine, Tilburg, the Netherlands liraglutide without insulin therapy. Hyperglycaemia was the most common cause to restart insulin. Background: Patients with severe therapy resistant diabetic Conclusion: This study illustrates that a ‘cold turkey’ polyneuropathy retain a sedentary lifestyle. Consequently switch from insulin to liraglutide combined with oral claudicational complaints are underreported and therefore antidiabetics is possible in the majority (61%) of obese type co-existent peripheral arterial disease (PAD) can remain 2 diabetes patients. Clinical relevant weight loss without clinically silent. Screening is suggested using the ankle- loss of glycaemic control is achieved. brachial pressure index. In patients with diabetes, this index is often unreliable due to medial calcinosis. This C029 Hyper or Hypo: a story of discrepancy with an has lead to the development of toe-brachialis index (TBI). invisible cause Recently this elegant technique using photoplethysmometry (Systoe®) was validated. T. Boerstra, H.E. van der Wiel, W.M. Tielgroenestege Cut-off values for abnormal TBI remains subject of IJsselland Hospital, Department of Internal Medicine, Capelle discussion. We used TBI to estimate the prevalence of aan den IJssel, the Netherlands silent PAD in patients with therapy resistant painful diabetic polyneuropathy. Case report: An 81-year old man, suffering from type 2 Methods: Patients with documented severe diabetic diabetes and adrenocortical deficiency was admitted for peripheral neuropathy who denied typical complaints of colonoscopy. He received intravenous infusion with glucose claudication were screened for possible PAD by means of 5% and insulin to avoid glucose dysregulation. A glucose the commercially available Systoe® device. All measure- level of > 25 mmol/l was measured with fingerstick blood ments were performed by a single investigator after samples obtained from the hand opposite of infusion after 20 minutes supine rest in warm ambient conditions. We cleaning the finger with ethanol. Strangely an explanation assessed the prevalence of silent PAD bij calculating TBI for this dysregulation could not be identified. Surprisingly, with a strict (< 0.6) and liberal (< 0.7) cutt-off value. confirmation of the high value by venous glucose Results: We included 144 patients, mean age 65 years, 60% measurement revealed a glucose level of 3.4 mmol/l. male. Of these patients 49 (34%) had a TBI below the strict Treatment of this falsely found hyperglycemia is potentially cut-off value in one or both legs. Using the more liberal dangerous, especially in adrenocortical deficiency. cut-off this amounted to 72 (50%).

27 Conclusion: The high prevalence of silent PAD in patients Target postprandial levels are < 7,8 mM at 1-hour and/or with severe diabetic polyneuropathy as assessed by TBI < 6,7 mM at 2-hour. In daily practice we advocated insulin may be a contributing factor to the presumed neuropathic treatment if on diet treatment 1 postprandial value /week complaints. We propose further research to assess the was >9 mM or 2 values/ week > 8 mM, based on self blood possible effects of vascular treatment in these patients. glucose monitoring (SMBG), adjusted once or twice weekly. Methods: retrospective patient record file study of 252 C031 Two-year follow-up of GLP-1 analogues and insulin GDM pregnancies in 2012-2014. Descriptive and Chi in clinical practice square statistics. Results: 252 GDM women conceived 254 children; 2 E.F.S. van Velsen, R.J.M. van Leendert, R.M. Kiewiet-Kemper children died; 12% were native Dutch, the remainder Albert Schweitzer Hospital, Department of Internal Medicine, non-native: Turkish 18%; Moroccan 39%, other 31%. 71% Dordrecht, the Netherlands had BMI over 25 kg/m2; 49% had BMI over 30. Insulin treatment was necessary in 16%; 84% needed only diet. Background: Previous (clinical) studies showed a Large for gestational age (weight > p90) occurred in 16%, significant reduction in HbA1c, weight and total daily macrosomia (>4000 g) in 5%, small for gestational age insulin dose when a Glucagon-like-peptide-1 (GLP-1) ( weight < p10) in 5%, neonatal hypoglycaemia in 16%, analogue was added in type 2 diabetes patients already on hyperbilirubinaemia in 7%, shoulder dystocia in 3%. These insulin treatment (e.g. Van Velsen et al. Neth J Med. 2014 results are in line with the results of published randomized Dec;72(10):523-7). Therefore, in a clinical setting, we inves- trials. Diet treated had less overall complications than tigated the long-term effect of adding GLP-1 analogues in insulin-treated: 32 vs. 57 % (X2 p < 0.05). patients with type 2 diabetes using insulin. Conclusion: In GDM the prevalence of complications is Methods: From April 2010 until October 2012 we included highest in the group on insulin; methods for optimisation 158 patients suffering from type 2 diabetes, treated with of treatment in this group are required insulin and having a BMI ≥ 35 kg/m2, who started GLP-1 analogues (liraglutide/exenatide). HbA1c and body weight C033 First nationwide real-life results on the efficacy of were registered each six months during two-year follow-up. real-time continuous glucose monitoring in the Results: HbA1c decreased significantly in the first Netherlands: the bidon-tracing study 6 months (-5.0mmol/mol compared to baseline; p < 0.001). However, after 24 months a slight increase H.W. de Valk back to baseline was observed (-2.9mmol/mol compared to UMC Utrecht for the BIDON-TRACING study group, baseline; p = 0.06). After 24 months, 28% of the patients Department of Internal Medicine, Utrecht, the Netherlands had stopped using GLP-1 analogues due to insufficient glycaemic control. On the other hand, 34% of the patients Background and methods: Real time continuous glucose were able to stop using insulin therapy. A significant monitoring (rtCGM) was introduced as innovation in weight reduction was observed in the first 6 months glucose monitoring leading to improvement in glycaemic (-11.9kg compared to baseline; p < 0.001), which persisted control in type 1 diabetes. In the Netherlands, rtCGM was at 24 months (-14.7kg compared to baseline; p < 0.001). endorsed for use in type 1 diabetes in adults on insulin Conclusion: By adding a GLP-1 analogue in obese patients pump and HbA1c ≥ 64 mmol/mol, during pregnancy with type 2 diabetes already on insulin therapy, a reduction and in children. To evaluate the real-life use of rtCGM, of body weight and insulin use can be achieved. However, a multicenter registry was set up using the BIDON- in the long-term glycaemic control might become an issue structure (Basisstructuur Innovatief Diabetes Onderzoek despite an ongoing decrease of body weight. Nederland), a new hospital-based diabetes research consortium. C032 Gestational diabetes mellitus (GDM) in real life Results: Sixty of the potential of 90 hospitals participate practice: does insulin help? in this ongoing study and 784 adult patients are recruited: 86 (11.0%) ex-users, 473 (60.3%) current users, 225 (28.7%) M. Brok, M. Zuidema, B. Hermsen, B.J. Potter van Loon new users. We report on the latter group. rtCGM was given Sint Lucas Andreas Hospital, Department of Internal for poor control in 52.1%, pregnancy in 18.2% and other Medicine, Amsterdam, the Netherlands indications in 29.8%, mostly severe hypoglycemia, high glucose variability or pregnancy wish. Baseline: mean Background: Since the publication of the HAPO study age 39 years (range 18-69), 72.4% males, type 1 diabetes (Metzger, NEJM 2008) the adaptation of the guidelines 94,4%, insulin pump 90,7%, Hba1c 61.1 mmol/mol (range has resulted in more structural testing and an increase 36-116). In patients treated for poor glycemic control,HbA1c in the prevalence of gestational diabetes mellitus (GDM). fell in six months from 71.3 to 62.8 mmol/mol (p < 0.001).

28 Conclusion: This study results show that a flexible K. Yozgatli1, D.J. Mulder1, M.J. Noordzij1, P.H.N. Oomen2, nationwide research consortium in diabetes research is J. Jager3, M. Castro Cabezas4, T. Brouwer5, A.J. Smit1, possible and successful in the Netherlands, that a first J.D. Lefrandt1 observational study as proof of principle shows that rtCGM 1UMC Groningen, Department of Vascular Medicine, in poorly controlled type 1 diabetes in real-life setting Groningen, the Netherlands, 2MC Leeuwarden, Department has an efficacy comparable to landmark studies and that of Internal Medicine, Leeuwarden, the Netherlands, rtCGM is given for not formally endorsed indications, 3Diakonessenhuis, Department of Internal Medicine, Meppel, indicating relevant targets for research efforts. the Netherlands, 4Sint Franciscus Gasthuis, Department of Internal Medicine, Rotterdam, the Netherlands, 5Onze C034 Remission of diabetes 2 after bariatric surgery : Lieve Vrouwe Gasthuis, Department of Internal Medicine, population based data Amsterdam, the Netherlands

L.J.M. de Heide, M. Hettema, M. van Oijen, J.P. Yska, Background: The UKPDS study showed that glycemic N. Veeger, E. van Roon, J. Apers control (HbA1c) predicts vascular complications in type 2 MC Leeuwarden, Department of Internal Medicine, diabetes (T2DM). The DCCT study showed that accumu- Leeuwarden, the Netherlands lation of Advanced Glycation Endproducst (AGEs) from skin biopsies predicts vascular complications in type 1 Background: According to medical literature remission diabetes. Tissue AGEs can be measured non-invasively of diabetes after bariatric surgery is achieved in up to 90 with the AGE-reader™ using Skin AutoFluorescence (SAF). percent of patients. However remission has been variably The aim of this study was to compare the predictive value defined in these publications. A consensus statement of HbA1c and SAF for microvascular complications and recently defined complete (or partial) remission of diabetes major adverse cardiovascular events (MACE, defined as as an HbA1c < 42 (or 48) mmol/mol, a fasting plasma stroke, myocardial infarction or death) in patients with glucose < 5,6 ( 5,6-6,9) mmol/l in the absence of pharma- T2DM. cological treatment. Methods and results: A prospective cohort study of 514 Methods: In this retrospective analysis of 129 patients T2DM patients (mean age 64 ± 11 years, DM duration with diabetes 2 who underwent bariatric surgery in our 14 ± 9 years) from five Dutch hospitals was performed. centre data on HbA1c and medication prescriptions before After a median follow-up of 5.1 (IQR 4.3-5.9) years, 79 (15%) and after 12 and 36 months were retrieved from hospital patients died and 49 (9%) were lost to follow-up. 133 (26%) records, general practices and pharmacies. Fasting glucose developed a microvascular complication and 189 (37%) values were not available and therefore skipped from the MACE. Tertiles of HbA1c were significantly associated definition of remission. with development of microvascular complications (logrank Complete and partial remissions were calculated as well as p = 0.022), but not with MACE. Tertiles of SAF were reduction in medication use (DDD). significantly associated with MACE (logrank p = 0.003). Results: Use of oral antidiabetics was reduced from 100% Cox regression analysis showed SAF was associated with to 29% and insulin use from 33% to 9%. DDD of oral MACE: crude HR 1.53 (95%CI 1.24-1.89), p = 0.0007 antidiabetics decreased from 1.13 to 0.65 per patient after per unit increase, and after correction for UKPDS score: 12 months. HR 1.28 (1.03-1.60), p = 0.026. HbA1c was predictive for In 96 patients with complete data on medication use microvascular complications: crude HR 1.20 (1.06-1.36), and HbA1c at 12 months, complete and partial remission p = 0.004, and after correction for UKPDS score: HR 1.20 were achieved in 41% and 56%. After 36 months (n = 45) (1.06-1.36), p = 0.004. this was 47% and 58%, respectively. At baseline HbA1c, Conclusion: This study shows that accumulation of AGEs percentage of insulin users and DDD were not different is the best predictor for MACE, and HbA1c for microvas- in patients with available data compared to those without. cular complications in patients with T2DM after a 5-year Conclusion: Complete remission of type 2 diabetes, follow-up. defined by strict criteria can be achieved in 41% after bariatric surgery after 12 months and remains stable after C036 Screening for depression in people with diabetes 36 months. identifies only few patients with elevated depressive symptoms who are not currently treated for C035 Accumulation of advanced glycation endproducts is emotional difficulties Associated with Macrovascular Complications and Mortality, and Glycemic Control with Microvascular S.C.M. Vogels1, G. Nefs2, P.F.M.J. Spooren1, I. Ritmeijer1, Complications in Type 2 Diabetes Mellitus F. Pouwer2

29 1Elisabeth-TweeSteden Hospital, Department of Internal treatment of HCV can cure DM2. However an etiological Medicine, Tilburg, the Netherlands, 2Tilburg University, role has not been described for autoimmune hepatitis. Department of Medical and Clinical Psychology, Tilburg, the Case: A 69-year old Caucasian woman was diagnosed Netherlands with steatosis hepatitis in 2001, she had a body mass index (BMI) of 33.1, she drank about two glasses of alcohol Background: People with diabetes (PWD) are at increased a day. In 2008 she developed type 2 diabetes and she had risk for depression, especially when they are treated in to be treated with metformin and insulin. In 2009 she secondary care facilities. Comorbid depression results in was diagnosed with an autoimmune hepatitis, which was worse outcomes such as increased incidence of diabetic identified by a liver biopsy, positive autoantibodies, ANA complications. The Dutch Internal Medicine Association and AMA and marked elevation of IgG. Prednisone and Guidelines recommend to screen for depression in PWD, treatment was started and in 2010 azathioprine was added. but do not specify how or how often. We investigated She did not lose weight and she continued to be treated whether a questionnaire facilitates identifying patients with a low dose of prednisone. During the treatment with elevated depressive symptoms not receiving treatment course het HbA1C dropped to normal, an she no longer for emotional difficulties. needed insulin nor metformin. Methods: Consecutive PWD on routine visit at the internal Conclusion: Treatment of autoimmune hepatitis in this medicine outpatient clinic of the Elisabeth TweeSteden patient resulted in the cure of DM2 despite the use Hospital Tilburg were invited to complete Patient Health of prednisone and weight loss. Indicating a possible Questionnaire-9 (PHQ-9) and were asked permission to be mechanism is involved in both DM2 and autoimmune contacted for follow-up if scoring high. Also, self-reported hepatitis. current treatment for emotional difficulties was recorded. Using descriptive statistics, we investigated if patients with C038 Do HbA1c levels improve after referral to the elevated depressive symptoms were currently treated. endocrinologist and do levels remain stable after Results: 385 patients were included of whom 49 (13%) backreferral to the general practitioner? had a PHQ-9 score ≥ 12. Of those with elevated scores, 37 gave permission to be contacted. In total, 26(70%) of the M.M.E. Krekels1, D.M. de Leeuw2, B.J. Looij1, contacted patients did not currently receive treatment for H.W.M.P. Bergmans2, P.W. de Leeuw1 emotional difficulties, which is 7% of the 385 screened 1Atrium-Orbis Medical Centre, Department of Internal patients. Medicine, Sittard-Geleen, the Netherlands, 2MCC Omnes, Conclusion: The percentage of high PHQ-9 scores was Department of Family Medicine, Sittard-Geleen, the lower than the prevalence of depression amongst PWD Netherlands reported earlier. Because we used in-hospital as opposed to at home screening used by others, we may have left out Background: Due to increasing healthcare costs, both those with most severe symptoms. Only a small percentage health insurance companies and the Ministry of Health of the total amount of patients screened consisted of create incentives for less referrals to the hospital. It has untreated high-scoring patients. Hence the PHQ-9 seems not been established yet that referral results in better of limited additional value when consulting PWD. regulation and if so whether this effect is sustained over time. C037 Treatment of autoimmune hepatitis also cured Methods: We performed a retrospective pilot study of 144 diabetes mellitus type 2 patient records. Patients were eligible when they had been referred by the general practitioner with type 2 diabetes B.A.M. de Weijer, C.R.G.M. Daemen and insufficient regulation (HbA1c of > 7.3% or 56 mmol/ Tergooi, Department of Internal Medicine, Hilversum, the mol). Netherlands Results: So far, twenty-eight patients could be studied in detail: 18 males and 10 females. Their weight averaged Introduction: The prevalence of type 2 diabetes mellitus 95 kg and their HbA1c upon referral 75 mmol/mol. Due to (DM2) is increasing worldwide. The relationship between the intervention at the outpatient clinic HbA1c decreased DM2 and liver disease is well described. The liver plays to 55 mol/mol just before backreferral. After backreferral a pivotal role in glucose metabolism. Insulin enhances to the general practitioner HbA1c increased again slightly glycogen synthesis by the liver and decreases glucose to 63 mmol/mol after one year and to 65 mmol/mol after production. Studies suggest that the risk of chronic liver two years. disease in patients with diabetes is increased. Hepatitis Conclusion: Referral to the endocrinologist improved C (HCV) is well known to increase the risk of DM2 and HbA1c values. However, levels tended to rise again after 1 and 2 years. It is unclair wheter this is due to less strict

30 control in the setting of the general practitioner or to treatment normalized blood pressure, HbA1c and liver- natural causes. enzymes. Patient B (22-year old female) was referred for steroid-induced diabetes. At twelve years she was treated for aplastic anemia with polychemotherapy, total body V ENDOCRINOLOGY irradiation, and allogeneic stem cell transplantation. She was exposed to long term methotrexate and cyclosporin for graft-versus-host disease. Metformin was initiated but she C039 Spontaneous remission of acromegaly and Cushing’s required increasing insulin dosages. She was hypertensive Disease following pituitary apoplexy: two case with lipodystrophy of the extremities and buttocks; BMI reports was 22 kg/m2. Triglycerides, C-peptide and liver-enzymes were elevated, ultrasonography confirmed steatohepatitis. S.H.P.P. Roerink1, E.J. van Lindert2, A.C. van de Ven2 Due to myocardial ischemia, pioglitazone was not started. 1Radboudumc/Rijnstate, Department of Internal Medicine, Current treatment consists of metformin and 200IU of Nijmegen, the Netherlands, 2Radboudumc, Department of insulin/day. Neurosurgery, Nijmegen, the Netherlands Leptin levels were increased in both patients without evidence for auto-immunity or known pathogenic DNA Celiac disease (CD ) is an auto-immune disorder with mutations. chronic inflammation of the small intestine leading to Discussion: Lipodystrophy may be associated with villous atrophy and malabsorption. In this case report intensive cytostatic treatment in childhood, since the we highlight a patient with an extensive DVT continuing phenotype, characterized by loss of fat tissue of the into the iliac vein up to the inferior vena cava. She had no extremities and buttocks in the presence of elevated known thrombogenic risk factors besides the use of oral (instead of low) leptin levels, did not match previously contraceptives. Because of the presence of iron-deficiency reported types of lipodystrophy. As the number of patients anaemia in addition to the thrombosis we searched for that survive childhood cancer increases, this association an underlying condition. CD was diagnosed, which was might well become relevant. presumed to be the cause of the anaemia, and possibly had played a role in the occurrence of the DVT through a link C041 Subclinical hypothyroidism in obesity disappears with the antiphospholipid syndrome. Next to the classical after weight loss induced by Roux-en-Y Gastric clinical picture of CD, the extra-intestinal presentations are Bypass surgery emerging. Literature describing the association of CD with other autoimmune diseases, namely those with hyperco- W. Schijns, I.C.M. Janssen, J. Homan, K. Dogan, agulability, is growing. Therefore, it is important to create E.O. Aarts, B. Betzel, F.J. Berends, H. de Boer awareness of these associations. Rijnstate, Surgery Department, Arnhem, the Netherlands

C040 A novel clinical phenotype of acquired partial Background: Subclinical hypothyroidism (SH), defined as lipodystrophy associated with intensive childhood a raised serum thyroid stimulating hormone (TSH) with cytostatic treatment a normal free thyroxine (FT4), is occasionally observed in morbidly obese patients. It is currently not known M.F. Nijhoff, E.P.M. van der Kleij-Corssmit, I.M. Jazet, whether thyroid hormone treatment is indicated. The aim A.M. Pereira of the present study was to assess the changes in thyroid Leiden University Medical Centre, Department of Internal hormone levels in thyroxin naïve patients with SH in Medicine/Endocrinology, Leiden, the Netherlands response to weight loss induced by Roux-en-Y Gastric Bypass (RYGB). Lipodystrophy is characterized by subcutaneous fat loss, Methods: Serum levels of TSH and FT4 were measured at fat maldistribution, and metabolic syndrome. We present a baseline in 503 consecutive patients presenting for RYGB. novel phenotype of partial acquired lipodystrophy, possibly In patients diagnosed with SH de novo, these measure- associated with childhood chemotherapy. ments were repeated 12 months after RYGB. Patient A (42-year old female) was referred for diabetes. Results: SH de novo was present in 61 out of 503 patients At six years she was diagnosed with leukemia for which (12.1%). Their preoperative mean serum TSH was she received seven years of polychemotherapy. She 5.8 ± 2.0 mU/l and FT4 15.2 ± 2.1 pmol/l. TSH levels was hypertensive with lipodystrophy of the extremities ranged from 4.04-13.80 mU/l, TSH levels > 10 mU/l were and buttocks; BMI was 23 kg/m2. Liver-enzymes were observed in 3 (0.5%) patients. RYGB induced a decrease elevated, ultrasonography revealed steatohepatitis. HbA1c in BMI from 47 ± 8 kg/m2 to 33 ± 6 kg/m2 at 12-month worsened despite increasing insulin dosages. Pioglitazone follow-up (p < 0.001), and this was associated with a

31 decrease in TSH and FT4 to 2.8 ± 1.3 mU/l (p < 0.001) and 1Haga Hospital, Department of Internal Medicine, Den 13.9 ± 2.3 pmol/L (p < 0.001), respectively. SH completely Haag, the Netherlands, 2Leiden University Medical Centre, resolved in 53 (87%) of the de novo cases. Department of Internal Medicine, Leiden, the Netherlands Conclusion: After RYGB SH resolves in about 90% of patients. This suggests that follow-up alone is sufficient in A 17-year old patient from South Asian descent was the majority of patients, and that preoperative treatment referred by the orthopedist with bilateral stress fractures with thyroid hormone is not indicated in antibody negative of the tibia. At presentation he suffered from severe bone SH. and muscle pains in his arms and legs. His medical history was unremarkable. There were no symptoms of malab- C042 Low dose corticosteroid stress prophylaxis sorbtion, he was a strict vegetarian and led a sedentary indoor life. Physical examination was normal, besides a N. Holle, M.J. Blans, M.M.G.J. van Borren, J.M.M. de Boer BMI of 26.45 kg/m2 and severe pains when moving. At Rijnstate, Department of Endocrinology, Arnhem, the presentation laboratory tests showed a hypercalcemia of Netherlands 2.69 mmol/l, undetectable 25-OH vitamin D, phosphate of 0.51 mmol/L, an elevated PTH of 247 nmol/l, and normal Background: To date, many different corticosteroid stress renal function. Screening for celiac disease was negative. prophylaxis regimens to prevent adrenal crisis are being Bone markers were extremely elevated with an alkaline used without sufficient evidence for their need and efficacy. phosphatase (AP) of 4068 U/l, P1NP > 2400 ng/mL Methods: We prospectively studied 41 patients with and beta Crosslaps 3.900 ng/ml. X-rays of the verterbral primary AI (n = 13), secondary AI (n=9) or patients on collom showed codfish vertebrae. Since his osteoma- chronic AST (n = 19). All patients on AST used a dose lacia/rickets was thought to be caused by longstanding equivalent to ≥ 7,5 mg/day of prednisolone. Hydrocortisone vitamine D deficiency due to lifestyle and deficient diet, treatment started at 06.00h with one oral dose of 20 mg, he was started on vitamin D suppletion despite his severe followed by 100 mg/24h hydrocortisone intravenously. autonomous hyperparathyroidism. Already upon 5 weeks Hydrocortisone treatment was considered effective if of treatment his bone and muscle pains disappaered and plasma cortisol levels were within the normal range for bone markers improved drasticly, with AP lowering to 619 conditions of physical stress and if there was no evidence U/l and a decrease in PTH to 35 nmol/l. This was despite of unexplained hypotension or the combination of hypona- pathological bilateral femur fractures and left-sided collum tremia/hyperkalemia. To establish normal values for fracture, all inflicted by bed-chair mobilization. Since the plasma cortisol during physical stress, we obtained plasma deterious effect of the hyperparathyroidim on his fragile cortisol levels in 81 patients admitted to the ICU with skeleton will continu despite improvement of vitamin presumed normal adrenal function. D levels and a parathyroidectomy is unavoidable. This Results: Plasma cortisol levels of all patients were case shows that in 2014 it is possible to develop vitamin comparable to the cortisol levels observed in the 81 d-deficient rickets even in the the Netherlands. ICU controls (979 ± 51 nmol/l vs. 1232 ± 135 nmol/l, p = 0.08). Perioperative cortisol levels were > 500 nmol/l C044 Multiple paraganglioma’s with an odd location in all but one patient (cortisol 272 nmol/l). There was no difference in cortisol levels between patients with M. Cloos-van Balen, E.P.M. van der Kleij-Corssmit, H. Pijl AI and with AST (937 ± 50 nmol/l vs. 1030 ± 95 nmol/l, Leiden University Medical Centre, Department of Internal p = 0.36). Unexplained hypotension or a combination of Medicine, Leiden, the Netherlands hyponatriemia/hyperkalemia was not observed. Conclusion: A hydrocortisone stress regimen with an oral Catecholamine secreting tumours known as (sympathetic) loading dose of 20 mg followed by continuous hydrocor- paraganglioma or pheochromocytoma are rare, with an tisone at a rate of 100 mg/24 h appears to provide adequate incidence of 0.8 per 100.000 persons per year. They plasma cortisol levels and is without complications related originate from the chromaffin cells of the adrenal gland to cortisol deficiency. or the sympathetic ganglia. Most of the sympathetic paragangliomas arise in the adrenal gland, followed by C043 Severe rickets and autonomous hyperparathyroidism paraganglia in the abdominal, thoracic and pelvic region. due to longstanding vitamin D-deficiency In very rare cases they arise in a solid organ other than the adrenal gland. L.M. van der Pol1, M. Snel2, A.T.A. Mairuhu1, We present a case of a 30 year old previously healthy N.M. Appelman-Dijkstra2 female, who had 5 incidentalomas on a CT scan made in work-up for an appendicitis: 1 in the right adrenal gland, 2 in the left adrenal gland and 2 in the processus uncinatus

32 of the pancreas. 24 hour normetanefrine excretion was Results: We found one known mutation, one known very high. An MIBG scan revealed uptake only in the right deletion and four SNPs in the extracellular regions of adrenal gland lesion. Somatostatin receptor scintigrafy IGSF1. We will present the genotypic and phenotypic data was negative. Family history of paraganglioma was also of the patients with variants in IGSF1. negative. Differential diagnostic there were 2 options: Conclusion: Central hypothyroidism combined with multiple (dedifferentiated) primary and or metastatic growth hormone deficiency is explained by IGSF1 defects paragangliomas and/or multiple neuroendocrine tumours in a small minority of the patients. possibly in the face of a neuroendocrine syndrome. Both adrenal glands were removed and she underwent C046 Contraceptives and the dexamethasone suppression a Whipple procedure. Microscopic and immunohisto- test: Is one week discontinuation sufficient? chemic evaluation showed that all 5 lesions were paragangliomas with negative immunohistochemistry for SDHB, M. Kuindersma1, M.B. Vastbinder2, A.H. Mudde1, suggesting an SDH-related heritable paraganglioma- A.H. Mulder1 syndrome. The patient will be referred for genetic 1Slingeland Hospital, Department of Internal Medicine, counselling. Doetinchem, the Netherlands, 2Erasmus MC, Department of A pubmed search for paraganglioma and pancreas revealed Internal Medicine, Rotterdam, the Netherlands 24 cases of a paraganglioma in the pancreas. There was only one case that described a combination of a paragan- Background: In suspected hypercortisolism, the 1 mg glioma in the adrenal gland and in the pancreas. dexamethasone suppression test is the usual initial test. In fertile women false positive test results are commonly C045 Screening of IGSF1 in Dutch patients with Central due to the use of oral contraceptives. By elevating cortisol Hypothyroidism and GH deficiency, participating in binding globulin these contraceptives increase the total the HYPOPIT study serum cortisol concentration. Little is known about the duration of this effect. We tested whether one week M. Elizabeth, R.P. Peeters, T.J. Visser, A.C.S. Hokken-Koelega, cessation of oral contraceptives is sufficient to obtain L.C.G. de Graaff adequate test results. Erasmus MC, Department of Endocrinology, Rotterdam, the Methods: Ten healthy female volunteers without symptoms Netherlands or signs of overt hypercortisolism, aged 20-55 years, who used oral contraceptives underwent a 1-mg dexamethasone Introduction: The Dutch HYPOthalamic and PITuitary suppression test. Tests were repeated one and six weeks gene (HYPOPIT) study investigates the causes of Isolated after withdrawal of the contraceptives. In addition, 24-hour Growth Hormone Deficiency (IGHD) and Combined urinary cortisol excretion and a late-night salivary cortisol Pituitary Hormone Deficiency (CPHD). Former projects were measured. within the HYPOPIT study showed that only a small Results: Seven women (70%) had inadequate suppression minority of the Dutch IGHD and CPHD cases could be of cortisol by 1 mg dexamethasone while using oral explained by mutations in GH1, GHRHR, HMGA2 and contraceptives. One week after the contraceptives were CDK6 in IGHD patients and PROP1, HESX1, POU1F1, withdrawn, the number of false-positive results signifi- LHX3, LHX4, OTX2, SHH and HHIP in CPHD patients. cantly decreased to one patient (p = 0.02). Six weeks after Mutations in immunoglobulin superfamily gene 1 discontinuation all tests were normal. The 24-hour urinary (IGSF1, highly expressed in pituitary and testis) have cortisol excretion and late-night salivary cortisol results recently been associated with central hypothyroidism. were normal at all time points. Initially, IGSF1-related central hypothyroidism was only Conclusion: The results of the 1 mg dexamethasone described in combination with macro-orchidism. Later suppression test performed one week after cessation of oral on, IGSF1 mutations were also reported in patients with contraceptives are accurate in almost all subjects . In case central hypothyroidism without macro-orchidism, but of inadequate suppression , a second test may be performed with additional pituitary hormone deficiencies. Therefore, after six weeks. In this manner the contraceptives have to we chose to study IGSF1 as a new candidate gene for those be withdrawn for only one week in nearly all cases. CPHD patients who have central hypothyroidism combined with growth hormone deficiency. C047 Follow-up of patients with hyperglycemia in the Patients and methods: We screened 80 male and 14 female Emergency Department without a history of diabetes patients with the combination of central hypothyroidism mellitus and growth hormone deficiency for mutations in exons 10 to 17, encoding the extracellular region of IGSF1. K.M. van Veggel1, M.K. Kruithof2, E. Roelandse-Koop2, E.M.W. Eekhoff2, P.W.B. Nanayakkara2

33 1Alrijne Hospital, Department of Internal Medicine, insufficiency. Adrenal antibodies were negative. Computed Leiderdorp, the Netherlands, 2VUmc, Department of Tomography revealed bilateral adrenal myelolipomas Emergency Medicine, Amsterdam, the Netherlands (left: 8cm, right: 4cm). Upon recovery, strikingly, patient recalled he had been diagnosed with congenital adrenal Background: Hyperglycemia is a common finding in the hyperplasia (CAH) during childhood and had been treated Emergency Department (ED). Although hyperglycemia with dexamethasone till the age of 18. Since then he can be caused by stress, it may also indicate undiagnosed was lost to follow-up. He forgot to mention this earlier, diabetes mellitus 2 (DM2). DM2 is a major international assuming it was irrelevant. Patient recovered quickly and health problem, resulting in significant morbidity and was discharged on hydrocortisone and fludrocortisone. mortality. Early detection is important. However, hypergly- Discussion: We report a patient presenting with a first cemia in ED patients is often overlooked and unaddressed. adrenal crisis and large bilateral adrenal myelolipomas Methods: We conducted a retrospective cohort study after more than 30 years of untreated CAH. Adrenal of adult patients who were seen at the ED of an urban myelolipomas are rare benign tumors, comprising adipose academic hospital in the the Netherlands between the 1st of and hematopoietic tissue. Although hormonally inactive, January and the 29th of February 2008, who had an initial they are associated with adrenal disorders such as CAH. plasma glucose level ≥ 7.8 mmol/l. The medical records Ongoing ACTH stimulation may well have contributed to of these patients were retrieved to evaluate whether these development of these myelolipomas. Interestingly, it took patients were referred for follow-up for further diagnostic over 30 years to develop the first episode of adrenal crisis, testing and eventual treatment. triggered by gastro-enteritis. Additionally, the expanding Results: During the data collecting period 5317 patients adrenal myelolipomas may have affected the remaining were presented at the ED, 343 of these patients were adrenal tissue, which may have contributed to the adrenal identified with a plasma glucose ≥ 7.8 mmol/l. Using crisis as well. This case illustrates that patients with CAH exclusion criteria, eventually 154 patients were included in may benefit greatly from long-term follow-up. this study. The prevalence of incidentally found hyperglycemia in ED patients without a history of diabetes mellitus C049 Case Report: Malignant insulinoma manifesting in this period was 2.9%. early postpartum For 98.7% of the hyperglycemic patients no follow-up was arranged by the treating physician. E.C. Gertje1, A.M.E. Walenkamp1, W.J.M. Glaudemans1, Conclusion: A substantial percentage (2.9%) of our study A.J.C. Ijtsma1, K. Hoogenberg2, R.P.F. Dullaart1 population had a hyperglycemia and thus was at risk 1UMC Groningen, Department of Endocrinology, Groningen, for undiagnosed diabetes mellitus and prediabetes. To the Netherlands, 2Martini Hospital, Department of Internal date, recognition and follow-up of hyperglycemia in ED Medicine, Groningen, the Netherlands patients is poor. We presume that major health benefits may be achieved when the follow-up of hyperglycemia is Background: Insulinomas are insulin-producing neuroen- performed more frequently. docrine tumors. Insulinomas presenting during pregnancy and the early postpartum period are very rare. C048 Adrenal crisis and large bilateral adrenal myeloli- Methods: This study describes a 33-year old woman pomas in a patient with untreated congenital adrenal with hypoglycemia postpartum. Abdominal computed hyperplasia for over 30 years tomography and endoscopic ultrasound showed two lesions of the pancreas. A 11C-5-hydroxy-L-tryptophan F.H.F. Deelen, N.M.J. Hanssen, B. Havekes (11C-HTP) PET-CT scan demonstrated additional uptake Maastricht UMC+, Department of Endocrinology, Maastricht, in lymph nodes and in the liver, suggesting malignant the Netherlands insulinoma. Six months after pylorus-preserving pancrea- toduodenectomy and excision of liver and lymph node Case report: A 51-year-old male presented with acute-onset metastases, tumor progression was noted on repeated muscle cramps and dizziness, following an episode 11C-HTP PET-CT scans without recurrent hypoglycemia. of gastro-enteritis. Initially, medical history seemed The patient was enrolled in a clinical trial, and was unremarkable. His blood pressure was 66/35 mmHg, randomized for treatment with a dual pan-class I phosph- pulse rate 90/min, temperature 35.7 °C. Physical oinositide 3-kinase inhibitor and mammalian target examination was otherwise unremarkable. Laboratory of rapamycin inhibitor, on which there was no tumor results included natrium 121 mmol/l and potassium progression during 21 months follow-up. A systematic 7.72 mmol//l. Suspecting an adrenal crisis, fluid and research on PubMed and MEDLINE with the search steroid replacement was initiated and hyperkalemia was strategy ‘insulinoma AND pregnancy’ OR ‘insulinoma corrected. A serum cortisol of 75 nmol/l confirmed adrenal AND postpartum’ was performed on English, Dutch, and

34 German publications. All publications about (malignant) C051 Relapsing Paget Disease of Bone in remission with insulinoma during pregnancy and in the early postpartum single zoledronate infusion period (≤ three months postpartum) were reviewed in addition to the described case report. E.M. Winter, N.M. Appelman-Dijkstra, N.A.T. Hamdy Results: Insulinoma manifesting during pregnancy or Leiden University Medical Centre, Department of early after delivery has been described in thirty-one cases, Endocrinology, Leiden, the Netherlands including only three cases of malignant insulinoma. Management of malignant insulinoma requires an individ- Paget Disease of Bone (PD) is a benign focal disorder of ualized approach; optimal medical treatment is evolving. bone remodelling in which bone becomes structurally Conclusion: The usefulness of 11C-HTP PET-CT in the disorganized and less compact, resulting in increased diagnosis of malignant insulinoma was demonstrated in risk of deformity and fractures especially of weight- the present case. Hypoglycemia may particularly become bearing bones. The regional increases in bone turnover manifest in the postpartum period when insulin action are due to abnormal osteoclast morphology, number and increases consequently to decreased levels of placenta- function, believed to be due to a latent virus infection on a derived counter-regulatory hormones after delivery. background of genetic predisposition. Radiologic features are characteristic and associated with C050 A rare cause of hyponatremia of a pregnant woman increased serum Alkaline Phosphatase (AP) activity and after a high energetic trauma increased uptake on skeletal scintigraphy in affected sites. The role of bisphosphonates in the treatment of PD H. van der Valk, M.E.A. van Eersel, K. Bartelet, has long been established. The highly potent nitrogen- A.A.M. Franken containing bisphosphonate zoledronate administered as Isala, Department of Endocrinology, Zwolle, the Netherlands single infusion has been shown to be highly effective in achieving complete and long-lasting remission. The internist was consultated at the surgical ward because We present the 35 year follow-up of a patient with of decreasing sodium levels in a 25 year old woman. She polyostotic PD illustrating the incomplete and short-lived was admitted a few days before because of a high energetic response to various antiresorptive agents available for car accident. On arrival at the emergency department she treatment of PD in the course of his illness and demon- was in hypovolemic shock because of multiple injuries strating the clearly superior efficacy of a single zoledronate including an open book (pelvis) fracture, multiple liver infusion, achieving not only complete clinical and lacerations and a solutio placentae which led to intrauterin biochemical remission after his 10th exacerbation, but also foetal death at 35 weeks. A laparotomy was performed long-lasting remission for so far 6 years after treatment. followed by a sectio caesaria and placing of a fixature Treatment with single infusion of zoledronate is strongly extern. advocated as cornerstone treatment in the optimal At the moment of consultation she normotensive and management of patients with active PD. normovolemic. Laboratorium testing showed a serum sodium of 125 mmol/l and a urinary sodium of 111 mmol/l. C052 Periodic hypokalemic thyreotoxic paralysis Because of the extensive abdominal trauma an adrenal insufficiency was suspected. The very low morning cortisol E.E. Vink, C. Fokke, N. Vogtlander, B. Kleijnen (0.03 mmol/l) is in line with this. Adrenal insufficiency Gelre Hospitals, Department of Internal Medicine, Apeldoorn, also can be secondary or tertiary, so other hormones were the Netherlands tested: T3 0,6 nmol/l , FT4 5,2 pmol/l , TSH 0,77 mU/l and IGF-1 3.4 nmol/l. Matching an anterior pituitary insuf- A 17-year old Vietnamese man presented to the emergency ficiency. Treatment was started with levothyroxine and department with weakness of the limbs. He already hydrocortison. experienced these complaints twice, whereof he spontane- Given the massive blood loss during pregnancy this case ously recovered within a day. No other symptoms were shows a example of Sheehan’s Syndrome (SS). Hypertrophy reported, he was not on medication, herbs or drugs, and and hyperplasia of lactotrophs during pregnancy results his medical -and family history were unremarkable. in the enlargement of the anterior pituitary, without a Physical examination revealed normotension corresponding increase in blood supply. This makes the (132/80 mmHg) and tachycardia (105/min). Muscle anterior pituitary vulnerabel for ischemic injury during strength was diffusely reduced on the Medical Research hypotension. The spectrum of clinical presentation widely Council (MRC) scale: arms 4, legs 2-3, and the dorsal ranges from non-specific complaints to severe pituitary flexors of the left foot 1. Sensibility, reflexes and arm insufficiency that causes coma and even death. coordination were unaffected.

35 Laboratory analysis showed a hypokalemia of 2.0 mmol/L individual stability of cortisol over time and the effect of and the diagnosis of hypokalemic periodic paralysis lifestyle variables on cortisol levels. was suspected. The fractional potassium excretion was Results: Lifestyle factors did not show the same importance 2.49%, excluding renal potassium loss. Magnesium and nor direction of effect for every individual. Furthermore, arterial pH were normal (respectively 0.73 mmol/l and many time series displayed trends and very little stability 7.41). Further analysis showed a hyperthyroidism (TSH over time. < 0.01 mU/l; FT4 47 pmol/l) with positive auto-antibodies Conclusion: In conclusion, the two conditions necessary to to the TSH-receptor (14.4 IE/l). The ECG showed signs of be able to generalize group-based findings to the levels of hypokalemia. the individual and vice versa have not been met. Thus, It is Potassium was intravenously and orally supple- important for future studies to consider within-individual mented, which resulted in rapid normalization of processes when studying the HPA-axis. potassium concentrationand the paralysis disappeared. Hyperthyroidism was treated with thiamazole and C054 A surprising cause of hypokalemia tachycardia with propanolol. He is currently free of symptoms, levothyroxine has been added. A.W.M. Janssen, M.A.H. Berrevoets, J.W.A. Smit Hypokalemic periodic paralysis is very rare among Radboudumc, Department of Internal Medicine, Nijmegen, Caucasians, but is a frequent complication in thyreotoxic the Netherlands Asian men (2%). Potassium suppletion should be started carefully since the hypokalemia is the results of a shift. Introduction: Hypokalemia is a common problem in the The exact pathophysiology of this hypokalemia remains hospital. We present a case of hypokalemia with a rare unknown. cause. Case: A 66-year-old woman presented with rapid weight C053 Cortisol dynamics in healthy individuals loss, general weakness and hypertension. Her medical history included cardiovascular disease and nicotine S.L. van Ockenburg1, A.M. Beltz2, I.P. Kema3, E.H. Bos3, abuse. Biochemistry indicated nephrotic range proteinuria H. de Boer4, P. de Jonge3, R.O.B. Gans3, P.C.M. Molenaar2, (4.9g/24h) with preserved kidney function, metabolic J.G.M. Rosmalen3 alkalosis and hypokaliemia (2,4 mmol/l). Cushing 1Isala, Department of Internal Medicine, Zwolle, the syndrome was demonstrated by unsuppressed cortisol after Netherlands, 2Pennsylvania State University, Department 1 mg dexamethason overnight (0.68 mmol/L) and increased of Developmental Psychology, State College, United States 24h urinary cortisol excretion (823 nmol/24h). Cortisol of America, 3UMC Groningen, Department of Clinical levels showed no daily variation. Adrenocorticotropic Chemistry, Groningen,the Netherlands, 4MC Leeuwarden, hormone (ACTH) was 13,2 pmol/l (2,2-13,2 pmol/l). The Department of Internal Medicine, Leeuwarden, the aggressive medical history and absence of classical signs Netherlands and symptoms of Cushings disease were suggestive of an ectopic ACTH source. PET-CT showed periclavicular, Background: Studies investigating the hypothalamic- mediastinal and hilair lymphadenopathy, and masses pituitary-adrenal axis (HPA-axis) often focus on between- in both lungs suspect for malignancy. Bronchoscopy individual differences. Yet, for findings at the group confirmed the diagnosis metastatic small cell lung level to be generalizable to the level of the individual two carcinoma (SCLC), which was considered the obvious conditions have to be met. First, the population has to be source of ACTH. Nephrotic-range proteinuria was also homogeneous for the process under study (i.e. all subjects considered paraneoplastic. Clinical conditions did not allow need to obey the same statistical model). Second, the a kidney biopsy. Patient was treated with metyrapon. She process that is investigated needs to have stable statistical was discharged home with palliative care, because of her characteristics over time (e.g. should not contain trends). poor condition. These conditions can only be validly studied by obtaining Discussion: Ectopic ACTH secretion from aggressive and analyzing time series of individual subjects. tumors, such as SCLC, lacks the phenotypic manifestations Methods: In the current study 10 healthy adults collected of Cushing disease while it is dominated by hypertension, saliva samples thrice daily, and daily 24-h urine samples hypokaliemia, metabolic alkalosis, and weight loss. It also for 63 consecutive days. Cortisol in saliva and urine was can be found in other neuroendocrine tumors such as measured by means of liquid chromatography tandem carcinoid or pheocromocytoma. The nephrotic syndrome mass spectrometry. Furthermore, participants filled out is a malignancy-associated nephropathy, associated with an electronic diary twice a day to report about sleep and solid tumors. It usually resolves after treatment of the lifestyle factors. Time series were analyzed by means of malignancy. unified structural equation modeling to assess the within-

36 Conclusion: Small cell lung carcinoma with ectopic Case report: A 74-year old man was admitted because of ACTH-production is a rare cause of hypokalemia. pain and progressive weakness of the lower extremities. His medical history reported diabetes mellitus type 2 and C055 DICER1 germline mutation and familial thyroid Crohn’s disease in remission. He complained of pain of his carcinoma pelvis during movement since several years and reduced strength in his legs. Since 3 weeks he could barely walk. E.A. de Kort1, D. Koolen2, M.J. Jongmans2, There was no history of trauma. Because of pyrosis he M.S. Klein Hesselink3, T.h.P. Links3, M.J. Pouwels1 used chronic Antagel® and Gastilox® (daily dose Aldegraat 1Medisch Spectrum Twente, Department of Internal Medicine, 5100 mg, Magnesium 3000 mg). Enschede, the Netherlands, 2Radboudumc, Department Laboratory results showed a phosphate level of of Clinical Genetics, Nijmegen, the Netherlands, 3UMC < 0.2 mmol/l, alkaline phospfatase 552 mmol/l, calcium Groningen, Department of Endocrinology, Groningen, the 2.28 mmol/l, vitamin D 100 nmol/l, PTH 3.2 pmol/l. Liver Netherlands and kidney functions were normal. A CT thorax-abdomen showed old ribfractures of the left Context: Dicer, encoded by the DICER1 gene, plays a costa 2 and 7 and old bilateral inclavated collum fractures. central role in targeting messenger RNA for post-transcrip- A DEXA scan showed osteoporosis of the hip joint. A bone tional gene silencing. Germline mutations in DICER1 scintigrafy showed diffuse increased uptake of radiotracer. are associated with a rare cancer syndrome, the DICER1 Discussion: The severe hypophosphatemia was probably syndrome, involving childhood pleuropulmonaryblastoma caused by the extensive use of phosphate binding antacids. and rarely, differentiated thyroid carcinoma. Bilateral fractures without trauma due to osteoporosis are Here we report two siblings who developed thyroid rare. More likely, the fractures were caused by osteomalacia carcinoma during adolescence, and who were found to due to hypophosphatemia. Antacid induced osteomalacia carry a germline DICER1 mutation. has been described in several case-reports. Like in this Cases: Two siblings visited our endocrinology clinic for case, the patients presented with multiple bone fractures. follow up after thyroid cancer. The 18-year-old sister It appears that the extensive use of antacids is not without had been treated for a follicular thyroid carcinoma at 13 a risk of severe complications. years of age. The 20-year-old brother had been diagnosed The patient received phosphate suppletion. His muscle with papillary thyroid carcinoma at the age of 17. Both strength improved well and he regained his ability to patients had no particular medical history prior to their walk. The fractures were treated conservatively. He was diagnoses; their family history was non-contributory. transferred to a rehabilitation center for further recovery. They were included in the national study on pediatric thyroid carcinoma, and will be tested for associated somatic C057 Unexpected complication of a toxic multinodular mutations including microRNA expression. Prompted goitre by their early age at diagnosis and the strong familial association of the thyroid carcinoma, we decided to P.M.M. van Hauten, R. Ekhart, G.S. Bleumink investigate for possible inherited genetic alterations. Whole Rijnstate, Department of Internal Medicine, Arnhem, the exome sequencing was carried out and revealed a DICER1 Netherlands germline mutation c.1363del (p.(Val455fs)) in both patients. Discussion: Limited cases of differentiated thyroid Introduction: Multinodular goitre (MNG) is the most carcinoma in association with DICER1 syndrome have common thyroid gland disorder with a prevalence of been reported, all following early radiation exposure related 0.7 per 1000 patients in general practice. It can be to pleuropulmonaryblastoma. To our knowledge, this is accompanied by hyperthyroidism and mechanical the first family carrying a DICER1 mutation that presents complaints as tracheal compression or dysphagia. Here we with thyroid carcinomas as primary and solitary tumors, describe an uncommon, but potentially life-threatening hence without a diagnosis of the more common and more complication of a toxic MNG. characteristic features of the DICER1 syndrome. Case report: A 89-year-old woman without relevant medical history besides a recently diagnosed toxic MNG was C056 Over-the-counter drugs: A severe side effect of admitted to the hospital with nausea and diarrhea. Despite antacids treatment thyroxine level was still elevated. Physical examination revealed a painless swelling of the left L. de Kleijn, S. Shamelian arm with pitting oedema. Duplex ultrasound showed Jeroen Bosch Hospital, Department of Internal Medicine, thrombosis in the left jugular vein and subclavian vein. ’S-Hertogenbosch, the Netherlands Computed tomography showed a large retrosternal mass originating from the left thyroid lobe, located adjacent

37 to the brachiocephalic vein causing compression and Bleeding or necrosis in a pheochromocytoma is a rare alteration of blood flow. The patient started with anticoagu- but possibly catastrophic presenting symptom. Negative lation therapy. Thorough anamnesis, physical examination, diagnostics can be misleading shortly after the bleeding. chest X-ray and abdominal ultrasound revealed no signs of This case underlines the importance of clinical suspicion concomitant malignancy. and close follow-up in situations were the diagnosis is not Discussion: This case illustrates that benign MNG can be clear cut. associated with venous thrombosis of the upper extremity due to direct local compression. Reviewing literature, this C059 Pituitary mass causing symptomatic hyponatremia has only been described three times before. In addition, hyperthyroidism is known to cause a hypercoagulable H.K. Glas, S. Anten state and literature shows a higher incidence rate of venous Alrijne Hospital, Department of Internal Medicine, thromboembolism in patients with hyperthyroidism Leiderdorp, the Netherlands compared to the general population. Severe complications are pulmonary embolism and intracranial propagation of A 63-year-old woman with no remarkable medical history the thrombus. In conclusion, venous thrombosis of the presented with weakness, lethargy, headache and visual upper extremity can be a dangerous and even fatal compli- disturbances. At the emergency department (ED) a cation of a toxic MNG. decrease in blood pressure occurred, without other signs of shock, temperature of 35.1 degrees and no oedema. C058 A pheo is a pheo until proven otherwise : always Laboratory results revealed hyponatremia (112 mmol/l), trust your clinical suspicion! low-normal potassium, normal renal function and elevated CRP. Urine sodium was 97 mmol/l with an osmolality of R. Stienstra, F.L. Ubels, L.J.M. de Heide 471 mosmol/kg. Suspecting hyponatremia due to either MC Leeuwarden, Department of Internal Medicine, SIADH or adrenal insufficiency NaCl 3% and hydrocor- Leeuwarden, the Netherlands tisone were administered. The cortisol level at the ED was 153 nmol/l. TSH was low-normal, but free T4 and A 56-year old Caucasian woman, presented to our hospital T3 markedly decreased, suggesting secondary hypothy- with severe hypertension, headache and back pain followed roidism. Other pituitary axes function tests showed low shortly by cardiogenic shock with hypotension and levels of ACTH, LH, FSH and IGF-1, and a slightly respiratory failure. CAG showed spasm of the LAD and elevated prolactin. MRI yielded an intra-/suprasellar mass, RCA but no atherosclerosis. Aortic dissection and renal compatible with a Rathke’s cleft cyst. Ophthalmic analysis artery stenosis were ruled out by computed tomography, showed partial bitemporal hemianopsia. After initiating which showed an enlarged right adrenal gland. Serum hormonal replacement therapy the patient was referred for metanephrines were elevated on admission but normalized neurosurgical removal of the pituitary cyst. afterwards. Treatment with volume resuscitation, alpha- Symptomatic pituitary masses generally present with and betablockade was instituted which led to clinical headache, visual disturbance and hormonal dysfunction. recovery. No abnormalities were found on MIBG and Hyponatremia is a less known complication and is F-DOPA-PET-scans. On follow-up plasma metanephrines usually linked to primary adrenal insufficiency, typically remained normal and a CT-scan showed a decrease in the accompanied with hyperkalaemia due to mineralcorticoid volume of the adrenal gland. deficiency. Since ACTH-deficiency is known to directly We postulated that a bleeding in the adrenal gland may cause inappropriate elevation of the antidiuretic hormone have resulted in the release of catecholamines which (ADH) it can cause the syndrome of inappropriate ADH resulted in a cardiogenic shock, but a pheochromo- secretion (SIADH). In contrast to most causes of SIADH cytoma could not be ruled out. Because of the clinical however it does not react to water restriction but corrects improvement, biochemical normalisation and radiological after administration of glucocorticoids. regression, adrenalectomy was not performed but the Conclusion: hyponatremia as a result of low ACTH and patient remained in close follow-up. Three years after the hypopituitarism caused by a Rathke’s cleft cyst first presentation, patient suffered from palpitations and a headache. The serum metanephrines appeared slightly C060 Short-term effect of estrogen on human bone elevated and F-DOPA-PET-scanning showed increased marrow fat uptake of the right adrenal gland compatible with a pheochromocytoma. She underwent a successful laparo- A.G. Veldhuis-Vlug1, E.J. Limonard1, L. van Dussen1, scopic adrenalectomy with histological confirmation of J.H. Runge1, M.W. Tanck1, E. Endert1, A.C. Heijboer2, the diagnosis. E. Fliers1, C.E. Hollak1, E.M. Akkerman1, P.H. Bisschop1

38 1Academic Medical Centre, Department of Internal Medicine, 45 mmol/l and 525 mosmol/kg. TSH and cortisol were Amsterdam, the Netherlands, 2VU University Medical Centre, within the normal range. SIADH due to pneumonia was Department of Clinical Chemistry, Endocrine Laboratory, diagnosed and the patient was admitted to the ICU for Amsterdam, the Netherlands antibiotic treatment and hypertonic sodium infusion. Patient was discharged with sodium levels of 134 mmol/l Background: Bone marrow (BM) fat is functionally distinct with follow up at the outpatient clinic. from subcutaneous and visceral fat, increases with aging Within one-week after discharge, patient returned to and menopause and is inversely related to bone mass. the emergency department with similar symptoms. BM fat fraction can be measured by MRI using Dixon X-thorax showed no signs of pneumonia, however, Quantitative Chemical Shift Imaging (QCSI). Previously, sodium levels had again declined to 130mmol/l. Urine we observed pronounced variation in BM fat fraction in sodium and osmol were 182 mmol/l and 789 mosmol/kg. premenopausal women compared to postmenopausal Synacthen-test revealed an insufficient cortisol response women. We hypothesized that this variation is associated (0.31 mmol/l:t=30min and 0.36 mmol/l:t=60min). Though with variations in estrogen concentrations during the TSH was within the normal range, T4 was found to be menstrual cycle. significantly decreased(2.6pmol/l), indicating a pituitary Methods: We measured vertebral BM fat fraction (BM-ff) gland deficiency. Subsequent MRI showed an empty cella. with QCSI twice a week during one month in 10 healthy Specified anamnesis highlighted that patient had multiple regularly ovulating women. In addition, we measured blood transfusion because of a complicated labor 17-years BM-ff weekly for 6 consecutive weeks in 6 healthy ago. Since then, patient did not have menstruations and postmenopausal women before, during and after two lactation was absent. Patient was treated with hydrocor- weeks of oral 17-b estradiol treatment (2 mg/day) and tisone and levothyroxine. we determined serum concentrations of bone turnover Discussion: Sheehan’s syndrome, also known as markers C-terminal crosslinking telopeptides of collagen postpartum hypopituitarism, is caused by ischemic type I (CTx) and procollagen type I N propeptide (P1NP). necrosis of the pituitary gland due to hypovolemic shock Data were analyzed by a linear mixed model. during childbirth. Its diagnosis is often delayed due to Results: The vertebral BM-ff showed a consistent pattern of atypical clinical presentation. Recurrent hyponatremia variation during the menstrual cycle: an increase during may be the first indication for the diagnosis of Sheehan’s the follicular phase (p = 0.03), a peak around ovulation syndrome. and a decrease during the luteal phase (p = 0.09). The BM-ff decreased 5% during two weeks of 17-b estradiol administration (p < 0.001) and increased again after VI GASTROENTEROLOGY cessation. P1NP concentrations increased (p < 0.05) and CTx concentrations decreased (p < 0.001) during 17-b estradiol administration. C062 Limited value of the auscultation of bowel sounds to Conclusion: We demonstrated that the menstrual cycle assess intestinal motility and 17-b estradiol administration rapidly change vertebral bone marrow fat fraction, suggesting that 17-b estradiol S.H.W. van Bree1, W. Bemelman1, M. Hollmann1, influences bone marrow fat independent of bone mass. R. Bennink1, F.O. The2, G.E.E. Boeckxstaens3 1AMC, Department of Internal Medicine, Amsterdam, the C061 Recurrent hyponatremia as presentation of Netherlands, 2Onze Lieve Vrouwe Gasthuis, Department of Sheehan’s syndrome Gastroenterology, Amsterdam, the Netherlands, 3KU Leuven, Department of Gastroenterology, Leuven, Belgium J.W. Buikema Sint Lucas Andreas Hospital, Department of Internal Background: Auscultation for the presence of audible Medicine, Amsterdam, the Netherlands peristalsis in the abdomen as a sign of intestinal contraction is routinely used. However, whether this Case: A 52-year-old Columbian woman presented to actually correlates with effective intestinal transit remains the department of internal medicine with symptoms of unclear. We evaluated whether bowel sounds reflect coughing, fever and general discomfort. Anamnesis was postoperative recovery of intestinal motility by studying limited by language issues. the relationship between GI transit and clinical symptoms X-thorax showed a pneumonia of the right lung. after intestinal surgery. Laboratory investigations revealed elevated inflammatory Methods: 95 patients requiring segmental colectomy for parameters and sodium of 99 mmol/l with serum osmol malignant colorectal disease were enrolled. 24 hours after of 209 mosmol/kg. Urine sodium and osmol levels were surgery, patients ingested indium-111 labelled water to

39 assess GI transit on postoperative day two. Colonic transit growth and ischemic necrosis. Immunophenotype is was measured by calculating the geometrical center (GC) CD2 +, CD 56 +, epsilon chain of cytoplasmatic CD 3 +, of activity (segment 0=small intestine; 1 = proximal-; expression of TIA-1 and granzyme B. T cell receptors 2 = distal colon; 3 = toilet). are not expressed. There is a very high association with Results: Data on intestinal transit and clinical symptoms Epstein Barr Virus. on postoperative day 2 were available in 60 patients. Seven Conclusion: NKTCL is a rare disease which is difficult patients developed a major complication with paralytic to diagnose. When carcinoma is suspected, but cannot ileus requiring a nasogastric tube. In these patients be confirmed through histopathological evaluation, indium-111 had still not reached the colon at day 2. In immunophenotyping for T-cell lymphoma should be the remaining patients, recovery of colonic transit was considered. significantly correlated with clinical recovery (p < 0.001). In 100% of patients without complete recovery of colonic C064 Arteriobiliary fistula after percutaneous transhepatic transit bowel sounds were audible. Moreover, in 6 out biliary drainage for cholangitis of 7 patients with a paralytic ileus, demonstrating no significant intestinal propulsive activity, there was still N.A. Zwietering, E. Keulen, F. Peters presence of audible peristalsis. Atrium-Orbis Medical Centre, Department of Internal Conclusion: Our data indicate that the absence of audible Medicine, Sittard-Geleen, the Netherlands peristalsis poorly reflects postoperative dysmotility. Conversely, the tolerance of solid food and having had We present a case of a 69-year-old woman who developed defecation best indicate recovery of GI transit. Thus, bowel abdominal pain and abnormal cholestatic liverenzymes. sounds lend supporting information to other findings but Abdominal ultrasound showed dilated intra- and extra- are not pathognomonic for any particular process. hepatic bile ducts and cholecystolithiasis. A diagnostic ERCP (endoscopic retrograde cholangiopancreatography) C063 Search for a natural killer was scheduled for the next day and was not successful because of an untraceable papilla of Vater. Subsequently we L. Louter, A.J. van der Meer, R.F.J. Schop decided to admit our patient and scheduled a PTCD (percu- IJsselland Hospital, Department of Internal Medicine, Capelle taneous transhepatic cholangiodrainage). A left-sided aan den IJssel, the Netherlands PTCD was performed. It was a complex procedure, mainly due to patient’s pain and difficult access. A rendez-vous Case report: A 72-year old female with a history of Colitis ERCP showed no macrolithiasis and possible external Ulcerosa, presented with fatigue, severe weight loss and compression of the distal common bile duct (CBD). An an altered defecation pattern. At physical examination endoprosthesis was placed. Two months after the initial no lymphadenopathy or abdominal masses were present. PTCD patient developed jaundice, fever and melena. Laboratory results showed: ESR 29 mmol/l and lactate A renewed ERCP showed Mallory Weiss lesions at the dehydrogenase 290 IU/l. CT scan of chest and abdomen gastric cardia and clots in the CBD. The endoprosthesis revealed multiple intrapulmonary lesions and a circum- was changed for a wallstent, that seemed to be somewhat ferential thickening of the colon descendens, without compressed distally. Finally an abdominal CT with contrast lymphadenopathy. With the working diagnosis of colorectal showed an active arterial bleed from a false aneurysm in carcinoma with pulmonary metastases, colonoscopy was the left liverlobe (2.7 x 1.7 cm) and contrast in the CBD performed. Multiple ulcerative lesions were seen in the with the suspicion of fistula to the bile ducts. Additional colon transversum. Histopathological examination showed CT-angiography confirmed this suspicion and successful inflammation, but no malignant cells. In two weeks that coil embolisation was performed. the patient was admitted, her clinical condition deterio- Learning points [Moet dit niet zijn Lessons?] rated with progressive dyspnea and respiratory failure. CT • Hemobilia after PTCD is rare but might have serious scan was repeated, and showed massive progression of all consequences and therefore needs to be acknowledged intrapulmonary lesions. Despite extensive treatment our in time. patient died of respiratory failure. Autopsy was performed • Probability of pseudo-aneurysm or arteriobiliary fistula and immunophenotyping of the pulmonary lesions as the underlying cause of hemobilia is about 1%. revealed the diagnosis extra nodal Natural Killer T-cell • Angiography and collaboration with an interventional lymphoma, nasal type (NKTCL). Revision of the tissue radiologist is vital. from colon biopsy showed a similar immunophenotypic pattern. C065 Ten year follow up of a real-life HIV-HCV coinfected Discussion: NKTCL is a rare extra nodal Non Hodgkin patient cohort in Antwerp lymphoma. Microscopic pattern shows angiodestructive

40 A. Boerekamps1, S. Bourgeois2, A. de Weggheleire3, A 39-year old woman was seen at our Emergency P. Michielsen4, S. Francque4, L. Lynen3, E. Florence3, Department with acute onset of vomiting. Her medical T. Vanwolleghem4 history was unremarkable expect for alcohol abuses until 1Diakonessenhuis Utrecht, Department of Internal Medicine, a year before presentation. Physical exam showed an Utrecht, the Netherlands, 2ZNA campus Stuivenberg, obese woman, hemodynamicaly uncompromised. Except Departments of Gastroenterology and Hepatology, Antwerp, mild epigastric pain physical exam revealed no abnor- Belgium, 3Institute of Tropical Medicine, Department of malities. Laboratory investigations showed acute renal Clinical Science, Antwerp, Belgium, 4Antwerp University failure with electrolyte imbalances (creatinine 909 mmol/l, Medical Centre, Departments of Gastroenterology and potassium 2.4 mmol/l, sodium 126 mmol/l, magnesium Hepatology, Antwerp, Belgium 0.66 mmol/l, phosphate 5.79 mmol/l). Electrocardiography showed a prolonged corrected QT interval. For this reason, Background: Life expectancy of antiretroviral treated she was admitted to the IC for intravenous suppletion and HIV-patients is rising, resulting in more non-aids related fluid resuscitation. morbidity, like viral hepatitis induced liver disease. Abdominal ultrasound was performed which showed Succesfull HCV treatment is known to lower overall a mass in the region of the pancreas head of unknown mortality in chronic HCV mono-infected patients. We origin. After her renal function normalised additional aimed to identify, in a large real life HIV-HCV co-infected investigations (abdominal CT-scan, gastroduodenoscopy, cohort, factors associated with baseline severity of liver MRCP) showed an acute pancreatitis of the pancreas disease and its progression. head region with compression of the proximal duodenum Methods: Patients were selected over a retrospective and gastric content retention consequently. The etiology period of 10 years in 3 large Antwerp HIV-HCV reference of her pancreatitis was assigned to alcohol abuses, after hospitals, if they had detectable antibodies against HIV exclusion of other known risk factors. The fact that only and repetitive positive serum HCV RNA titers. Clinical the pancreatic head region was compromised remained outcome and fibrosis, identified on liver biopsy or by shear remarkable. wave elastography, were retrieved from patient files. Despite our patient had no complaints of vomiting or Results: 154 chronic HIV-HCV coinfected patients were decreased intake, she kept developing electrolyte distur- identified, of whom 82,5% were men. Infection occurred by bances when electrolyte suppletion was stopped. She men-who-have-sex-with men contact (57.1 %), intravenous was readmitted for this reason several times. Another drug use (24.0%), iatrogenic exposure (10.4%) or hetero- explanation for the electrolyte disturbances was not found. sexual contact (4.5%). Genotype 3a and 1a significantly Conclusion: Electrolyte disturbances are a known compli- correlated with IVDU (P < 0.001) and MSM contact cation of pancreatitis for which IC admission may be (p < 0.001) respectively. required. Electrolyte disturbances can exist both because At presentation 53.8% of patients had moderate to severe of gastric losses by vomiting or diarrhoea, intracellular liver fibrosis. The degree of baseline fibrosis correlated shifts, or by losses via sequestration in peripancreatic with age (p = 0.010) and alcohol use (p = 0.008). 68.2% of tissue during acute pancreatitis. patients received antiviral HCV treatment with an overall success rate of 43.2%. This was associated with lower C067 Hyperammonaemia as a late complication following liver fibrosis progression (p = 0.045), but not with a better bariatric surgery overall outcome, including hospitalization rate and overall mortality (p = 0.73). J. Sint Nicolaas, L.U. Biter, A.J.P. van Tilburg, T.C. Jansen, Conclusion: Treatment of chronic HCV in HIV-HCV A.J.W.B. Brouwers coinfected patients impacts on liver fibrosis progression, Sint Franciscus Gasthuis, Department of Internal Medicine, but does not reduce hospitalisation rate or overall mortality, Rotterdam, the Netherlands suggesting persisting HIV-associated disease outcomes in this real life cohort. A 54-year-old woman was admitted to the Intensive- Care-Unit (ICU) from the surgical ward with a low C066 Acute renal failure as a consequence of acute Glasgow Coma Scale (GCS: E1-M4-V5) requiring tracheal pancreatitis intubation. She had been in the hospital for analysis of malnourishment and weight loss (55 kg) after bariatric V. de Jonge, R.J.T.h. Ouwendijk, A. Dees surgery (mini-gastric-bypass [MBG]) in 2012. Clinical Ikazia Hospital, Department of Internal Medicine, examination showed neurologic deficits with nystagmus Rotterdam, the Netherlands ocular movements and hyperreflexia of her extremities. A CT-cerebrum showed no abnormalities. Laboratory findings yielded an ammonia level of 182 mmol/l (normal

41 < 45), explaining the low level of consciousness. Other Perforation of the gastric wall by a fish bone through the abnormal laboratory findings were low anti-thrombin- liver is rare. The incidence of foreign objects passing the level: 27% (normal range > 80%), mild elevation of gastrointestinal tract results in obstruction or perforation liver enzymes: ALAT: 37, ASAT: 34 U/l (normal: <31), in only 1%. This patient uses immunosuppressive drugs gamma-GT: 207 U/l, (normal < 35) , alkaline phosphatase: masking the symptoms . This patient is prone for serious 179 U/l (normal: < 120) and bilirubin 25 mmol/l (normal: complications; Gastritis or pancreatits have much higher < 17). Factor V levels were normal. Differential diagnosis prevalence but using immunosupressive drugs must make included medication/hepatitis induced acute liver us alert for possible exotic outcomes. failure (ALF), vena porta thrombosis, Budd Chiari or hyperammonaemia caused by urea-cycle disorders or C069 A malignant polyp: now what? bacterial overgrowth in the proximal MBG-lumen. ALF was rejected considering no hyperbilirubinemia and/or M. de Vries, A.H. Mulder, D.J. Bac ascites. Serology tests were negative for viral hepatitis. Gelderse Vallei Hospital, Department of Internal Medicine, CT-scanning showed steatosis but no portal thrombosis or Ede, the Netherlands signs for Budd-Chiari. Urea-cycle defects were not demonstrated. Treatment included lactulose enemas, rifaximin, Background: January 1st 2014 population screening hemodialysis, and enteral/parenteral feeding to lower for colorectal carcinoma has been implemented in the ammonia levels. After these interventions, she recovered Netherlands. We expect to detect early stage malignant with a persistent low ammonia level and normalisation polyps more frequently. It is difficult to predict which of antithrombin. We hypothesize the hyperammonaemia malignant polyps are at risk for lymph node or distant in this case was caused by liver dysfunction due to metastasis. The concept Guideline ‘Colorectal Carcinoma malnourishment as a complication of her bariatric surgery, 2013’ (guideline CRC) proposes to divide malignant although bacterial overgrowth might have played a role in polyps in a high and low risk group. Only follow-up is the pathogenesis. recommended in low risk polyps. In high risk polyps surgical resection should be considered. This study aimed C068 A prickly meal to determine whether it is safe to divide the malignant polyps in risk groups to facilitate decision-making for B.J.M. Benner, M.P.G.F. Anten, Y.C. Schrama surgical resection. Sint Franciscus Gasthuis, Department of Internal Medicine, Methods: We conducted a retrospective observational Rotterdam, the Netherlands cohort study. We studied histopathologic features from malignant polyps in a group of 45 patients from the A 57-year old woman presents with abdominal pain, pathology database from Ziekenhuis Gelderse Vallei Ede, since three days . It’s a progressive and continuous pain the the Netherlands. We checked whether malignant with fever and cold shivers. Medical history includes polyps with a poor outcome belonged to the high or low Systemic Lupus Erythematosus and auto-immune risk group. Hepatitis, for which prednisolon and mycofenolaatmofetil Results: In the resection group residual disease was found are used. During physical examination only the upper in three patients (17%). All malignant polyps were high right abdomen is very painful during palpation, but not risk because of small or unknown resection margin. In like perforation. the follow-up group disease recurrence was found in two Laboratory tests shows elevated inflammation markers patients (7%). The resection margin of the previously and elevated alkaline phosphatase. Therefore the differ- removed malignant polyp was <1mm or unknown, so they ential diagnosis consists of cholecystitis, pneumonia with were high risk polyps. upper abdominal pain or pancreatitis. By abdominal CT, Conclusion: Our findings contribute to the recommen- a perforation was diagnosed with a possible metal object dation given in the guideline CRC. Polypectomy alone ending in the liver, with two small abcesses at the end. seems to be sufficient in T1 colorectal carcinomas with a A gastroscopy shows a fish bone which has perforated the resection margin ≥ 1mm, a moderate or good tumor differ- gastric wall in the direction of the liver. With a forceps entiation and absence of lymfovascular invasion. the fish bone could be removed from the stomach. In retrospect the patient remembers to have eaten fish in a C070 Pericarditis as the first manifestation of Crohn’s restaurant two days before the abdominal pain begins. disease After removal and antibiotic treatment with cefuroxime and metronidazole right from the start a decrease in Y.C.L. Haan, M.N. Klaver, W.P.J. Jansen, H.V. Stel, abdominal pain and inflammation markers was seen I.M. Minderhoud, P.J. de Vries therefore patient could be discharged in good condition.

42 Tergooi, Department of Internal Medicine, Hilversum, the and has had secondary amenorrhea since. In addition, Netherlands several months before presentation, she develops pares- thesias of the legs, for which she eventually undergoes a We present a case involving a 21-year-old man with CT-scan of the cerebrum. This CT-scan shows a suprasellar chest pain. He mentioned no other complaints. Physical mass with a size of 25 x 15 x 19 mm, suggestive of a crani- examination showed an oral aphthous lesion and fever opharyngeoma, for which a neurosurgical operation is but was otherwise unremarkable. Laboratory examination planned. revealed an elevated CRP of 61 mg/l, elevated WBC of Her medical history reveals a stage IIB Hodgkin’s 26.3 x 109/l, elevated PR3-ANCA of 8.7 IU/ml and iron- lymphoma 22 years before presentation, for which she deficiency anemia of 6.2 mmol/l. Electrocardiography received chemotherapy and involved field radiation therapy. showed diffuse ST-segment elevation and PTa-segment After the navigational MRI is performed, the neuro- depression suggestive of pericarditis, which was surgery is cancelled as the MRI shows leptomeningeal confirmed by echocardiography with signs of pericardial enhancement suggestive of a central nervous system tamponade. Besides pericardial effusion, CT scanning lymphoma. Cerebral spinal fluid (CSF) shows 1225/3ml was unremarkable. No definitive cause for the pericar- leukocytes, of which 26/3ml are granulocytes, 385/3ml ditis was identified and the patient was discharged with erythrocytes, glucose 0.7 mmol/l and total protein 1.67 ibuprofen and pantoprazole. Because of concurrent g/l. Immunophenotyping of these lymphocytes reveal iron deficiency anemia, iron suppletion was prescribed. no monoclonal population, but Borrelia species serology Esophagogastroduodenoscopy two months after first and DNA in the CSF are positive. The patient is treated presentation demonstrated a severe aphthous gastritis with ceftriaxone 2000mg once daily during thirty days, with submucosal hemorrhages. Gastric biopsies showed and already after a few days she claims to be reborn. a Helicobacter negative patchy acute inflammation with Afterwards, the leptomeningeal enhancement on the MRI many eosinophils and histiocytes, without vasculitis or has disappeared and the suprasellar mass is unchanged. necrosis, suggestive of Crohn’s disease. A few days later the In addition, her menstrual cycle has recovered, suggesting patient presented with recurrent pericarditis with effusion, a role for neuroborreliosis in the pituitary insufficiency of confirmed by ultrasound. The recurrent pericarditis was this patient. Co-existence of these two rare diseases urges attributed to the active Crohn’s disease, and the patient a common etiology but could not be confirmed. was started on prednisolone 60mg once-daily with good effect on the symptoms and regression of the pericardial C072 An unusual cause of high anion gap metabolic effusion. acidosis: 5-oxoprolinemia following paracetamol and Pericarditis is a rare extraintestinal manifestation of flucloxacillin exposure inflammatory bowel disease. To our knowledge, only five cases of pericarditis preceding the diagnosis of Crohn’s M.J. Krol-van Straaten, M. Kallenberg disease, have been published. In our patient, the recurrent HagaZiekenhuis, Department of Internal Medicine, Den pericarditis was attributed to the previously undiagnosed Haag, the Netherlands Crohn’s disease. To prevent life-threatening complications of pericarditis, early recognition and treatment of the Case report: A 53-year old man was admitted with a underlying cause is required. Staphylococcus aureus septic artritis of the left hip with positive blood cultures. A femoral head ostectomy was performed and antibiotic treatment with flucloxacillin 12 VII GENERAL INTERNAL MEDICINE g/day was commenced. Paracetamol 1 g four times daily was added for pain control. Laboratorium studies revealed an unexplained high C071 A patient can have as many diseases as she damn aniongap metabolic acidosis (bicarbonate 13 mmol/l, well pleases aniongap 20). Lactate concentration was within normal range and no ketones were present. A.H.E. Roukens, P. van Balen, M.G.J. de Boer, Under suspicion for 5-oxoprolinemia, paracetamol A.M. Pereira Arias was stopped and the patient was treated with sodium Leiden University Medical Centre, Department of Infectious bicarbonate. The diagnosis was confirmed by an abnormal Diseases, Leiden, the Netherlands elevation of urine 5-oxoproline concentration. Discussion: 5-oxoproline (pyroglutamic acid) accumulation A 39-year old Dutch woman with has severe headaches and due to paracetamol induced depletion of glutathione stores, fatigue for a few years, for which she takes painkillers on a is increasingly being recognised as an important cause of daily basis. She has a 4 year old son by natural conception high anion gap metabolic acidosis. With the consequent

43 disruption of the gamma-glutamyl cycle, large amounts pulse 76 bpm, temperature 38.7 °C) with erysipelas of of gamma-glutamylcysteine are metabolized to produce the right leg. C-reactive protein (311 mg/l) and creatinine oxoproline. Moreover, flucloxacillin lowers 5-oxoprolinase- (234 mmol/l) were elevated and chest X-ray, abdominal dependent breakdown of pyroglutamic acid. As in our case, ultrasound, urinary sediment, and liquor punction were acquired 5-oxoprolinase deficiency (by penicillins) or the normal. Flucloxacillin was initiated, but hypotension presence of other risk factors of glutathion depletion such and lethargy were progressive, and he developed severe as malnutrition or sepsis seem necessary for symptom polyarthritis. As microbiologic tests remained negative development. and his condition worsened severely despite piperacillin/ Conclusion: This case highlights the importance of early tazobactam and inotropic support, high-dose prednisone detection of oxoprolinemia as a cause of high anion gap was initiated under suspicion of systemic autoimmune acidosis after exclusion of commoner causes such as lactic disease. From that moment he improved rapidly and acidosis and ketoacidosis. If oxoprolinemia is suspected, prednisone could be phased out within one week. As causative medications should be stopped immediately PET-CT, renal biopsy, bronchoalveolar lavage, and and urinary organic acids measured. Replenishment of immune and infection serology (all performed just before glutathione stores with N-acetylcysteine may be beneficial. initiation of steroids) were normal and joint puncture revealed crystals, our conclusion was erysipelas and gout C073 Fever and chestpain in a psychiatric patient, an with severe inflammatory response, without evidence unrecognized adverse effect of clozapine for autoimmune disease. However, shortly afterwards he was re-admitted with a urinary tract infection. M.J. Krol-van Straaten Despite broad-spectrum antibiotics, again hypotension HagaZiekenhuis, Department of Internal Medicine, Den occurred, requiring inotropic support. After re-initiation Haag, the Netherlands of prednisone, his condition again improved spectacu- larly. Therefore, we performed an ACTH stimulation Case report: A 21-year old patient was refered from a test which conformed the diagnosis of hypocortisolism. psychiatric facility because of 40 oC fever after recent Repeated history taking revealed that he had been using start of clozapine for psychosis. He complained about a preparation containing corticosteroids, prescribed a headache and sore throat . Differential diagnosis was by a foreign doctor because of (for us) unknown skin malignant neuroleptic syndrome or clozapine induced abnormalities. agranulocytosis. Both were excluded and after one day of Discussion: This patient suffered from hypocortisolism clinincal observation he returned the psychiatric facility due to long-term use of steroids. A minor infection resulted with a diagnosis of presumed viral infection.However, 3 in severe hemodynamic instability twice, illustrating the days later he returned because of chest pain and persisting importance of a thorough medical history and hence rapid fever. Physical examination was again unremarkable, recognition and treatment. no pericardial friction rub. Troponin- T was elevated (0.230, normal < 0.014 ) and on the EKG questionable C075 A systematic review and meta-analysis on the effects ST elevation. Cardiac MRI showed active pericarditis and of exercise training versus hypocaloric diet: distinct diminished right and left ventricular function. effects on body weight and visceral adipose tissue Discussion:Clozapine is a potent antipsychotic . Besides the well known adverse effects of agranulocytosis and R.J.H.M. Verheggen1, M.F.H. Maessen1, D.J. Green2, malignant neuroleptic syndrome it can cause an acute A.R.M.M. Hermus1, M.T.E. Hopman1, D.H.T. Thijssen1 myopericarditis. This rare but serious side effect occurs 1Radboudumc, Departments of Fysiology/Internal Medicine, typically within 4 weeks after start of clozapine therapy. Nijmegen, the Netherlands, 2School of Sport Science, Conclusion: fever and chest pain after recent start of University of Western Australia, Department of Exercise and clozapine can be due to drug induced myopericarditis. Health, Crawley, Australia

C074 Relapsing severe sepsis: the revelance of the medical Background: Exercise training (training) and hypocaloric history diet (diet) are frequently prescribed for weight loss in obesity. Whilst changes in body weight are commonly D.J.L. van Twist, H. Masquiller, A. Koster used to evaluate lifestyle interventions, visceral adiposity Viecuri Medical Centre, Department of Internal Medicine, (VAT) is a stronger predictor for morbidity and mortality. Venlo, the Netherlands Currently, it is not known whether training or diet has superior effects on VAT. The aim of this study is to Case: A 69-year old Japanese male was admitted because compare the impact of training versus diet on VAT in of fever. We saw a lethargic patient (BP 90/48 mmHg, overweight/obese humans.

44 Methods: Pubmed, Cochrane, Web of Science and Embase lymphoma and the patient was referred to the hematologist were systematically searched for studies that evaluated the for further treatment. effects of training or diet (duration >4 weeks) on radio- This case illustrates the importance of reviewing radiographic quantified VAT in overweight/obese humans. logical findings critically and correlating them to the Results: 117 Studies (n = 4,815) were included. Training clinical picture to choose the right steps in the diagnostic (effect size (SMD): -0.47; 95%CI -0.56/-0.39) and diet process. (SMD -0.63; 95%CI-0.71/-0.55) caused VAT loss (both p < 0.0001). When comparing diet versus training, C077 Don’t judge a book by its cover: skin rash in Stills diet caused a larger weight loss (SMD 0.308; 95%CI disease 0.02/0.596; p = 0.04). In contrast, a trend was observed towards a larger VAT decrease in training (SMD -0.59; J.M.J. Lemmers, E. Waizy 95%CI -1.248/0.071; p = 0.08). Changes in weight and Elisabeth-Tweesteden Hospital, Department of Internal VAT showed a strong correlation after diet (R2 = 0.737, Medicine, Tilburg, the Netherlands p < 0.001), and a modest correlation after training (R2 = 0.451, p < 0.001). In the absence of weight loss, Case report: A 23-year old previously healthy woman, training is related to 6.1% decrease in VAT, whilst diet was admitted to the hospital because of a skin rash. A showed virtually no change (1.1%). progressive itching, red maculopapular rash covering Conclusion: Both training and diet reduce VAT. Despite her body accompanied by fever, chills, throat ache and a larger effect of diet on weight loss, training tends to arthralgia of knees and wrists developed over the previous have superior effects in reducing VAT. Finally, weight loss two weeks. In the past she had a similar rash after using does not necessarily reflect changes in VAT. Therefore, amoxicillin. Her General Practitioner started prednisone examining weight loss may lead to spurious conclusions 30mg for 1 week before admission, with suspicion of when evaluating benefits of lifestyle-interventions. an allergy. On examination we found fever 39.7 °C, tachycardia and diffuse light red urticarial rash visible on C076 When you and the radiologist ‘see’ different things face, trunk, and extremities. Laboratory results showed: in the same picture CRP 89 mg/L, leukocytes 14.3 *10e9, ferritin 719 mg/l, GGT45U/l, ALAT 55U/l, urine sediment was negative. The B.P. Jallah presumptive diagnosis of auto-immune disease was made, Maastricht UMC, Department of Internal Medicine, prednisone was continued. During follow-up skin rash and Maastricht, the Netherlands fever turned out to be intermittent with appearance in the evening. Serology was negative for antinuclear antibody Internists frequently consult the radiologist in and Rheumatoid factor. Additional imaging eg. X-thorax the diagnostic process. The evolution of radiological and abdominal ultrasound showed no abnormalities. A techniques makes us rely more often on the opinion of the skin biopsy showed chronic peri-vascular inflammation. radiologist. Some barely look at the pictures themselves. Based on previous noted data, according to Yamaguchi That we also need to look and correlate radiological with criteria the diagnosis of Adult Onset Stills Disease was clinical findings is illustrated in the case below. made. Prednisone was continued for several weeks with A 63-year old woman was referred to the emergency good response. department with fever up to 40 °C and progressive pain Key-points: Adult onset stills disease is an uncommon for 5 days in the right upper abdomen. Her medical history inflammatory disorder, with unknown etiology. As it was unremarkable. Deep breathing aggravated the pain is a diagnosis of exclusion, the diagnostic evaluation is and there was shortness of breath. Physical examination extensive. In this case report the skin rash initially was revealed a slight tachycardia, temperature of 38.3 °C and a mistaken for an allergic reaction. In skin rash without tender abdomen in the right upper quadrant. obvious trigger Still is a diagnosis to consider. Laboratory results showed abnormal liver enzymes. Pulmonary embolism was ruled out with CT-angiography. C078 An unusual and fatal complication of chronic However, the CT- scan showed two hypodense liver regions periaortitis labeled as hemangiomas or cysts by the radiologist. This did not fit with our clinical picture and after we C.M. Gant, M. Vloedbeld, A.J. Ouwehand, A.J.J. Woittiez convinced the radiologist a MRI-liver was done. The ZGT, Department of Internal Medicine, Almelo, the hypodense regions were then characterized as hepatocel- Netherlands lular carcinoma. Again this was inconsistent with the clinical picture, moreover, Alpha-fetoprotein levels were A 55-year old male patient with a medical history of normal. Liver biopsy finally revealed a non-Hodgkin alcohol abuse and excessive smoking was referred to the

45 outpatient clinic with complaints of abdominal pain and urine tested negative for ketones. We suspected the weight loss. Physical examination was normal, except presence of unknown endogenous anion as the cause for tenderness in the lower abdomen. Laboratory results of the acidosis and because she received flucloxacilline revealed a normal renal function and an elevated CRP we made a presumptive diagnosis of a pyroglutamaat (66 mg/ml). CT abdomen showed elaborate atherosclerosis acidosis. Flucloxacilline was switched to cefazoline and of the abdominal aorta and a para-aortal mass, suspect urine was tested for pyroglutamic acid. Within days the for periaortitis. After exclusion of secondary causes such acidosis recovered completely. After several weeks urine as malignancy and infection, the patient was diagnosed tests became available and tested strongly positive for with idiopathic chronic periaortitis, and treated with pyroglutamic-acid. 60 mg oral prednisone per day. After an initial good Pyroglutamic acidosis has to be considered as a cause of a response, there was an increase in abdominal pain, and high-aniongap metabolic acidosis in patients treated with in CRP (to 27), after four weeks of therapy. Several weeks flucloxacilline. Pyroglutamic acidosis is a rare side-effect thereafter, CT abdomen was repeated. This now showed of flucloxacilline and is mediated through its effect on the aortal dilation, with a maximal diameter of 5.6 cm, highly enzyme 5-oxoproline acid in the g-glutamylcyclus. Through suspicious for mycotic aneurysm. Blood cultures were inhibition of this enzyme, pyroglutamic-acid levels in positive for Streptococcus pneumoniae. PET-CT showed a plasma increase resulting in high-anion gap metabolic nodule with infected necrosis in the right lung. The patient acidosis. was referred to a specialized centre for surgical intervention. The procedure was complicated by extensive bowel C080 A case of Paraquat intoxication ischemia. A total colectomy was performed, after which the patient deceased. This case report concerns a patient with I. Flierman, L. van Gils chronic periaortitis, which is complicated by an infective Rode Kruis Hospital, Department of Internal Medicine, aortitis with S. pneumoniae during immunosuppression. Beverwijk, the Netherlands Clinical deterioration during treatment of chronic periaortitis should prompt to rapid re-evaluation (with a MRI or A 60-year old Surinamese female came to our emergency CT-scan, and blood cultures) to diagnose rare complica- room with swallowing difficulties since two days. Initial tions such as infective aortitis. To our knowledge this is examination by the ENT specialist showed mucositis of the the first case described in the literature. oropharynx and hypopharynx suggestive for ingestion of a toxic agent. She denied autointoxication. Laboratory results C079 Pyroglutamic acidosis: a rare side effect of showed acute renal failure and liver test abnormalities. flucloxacilline Gastroscopy showed extensive ulceration of the esophagus. After a few hours our patient did admit autointoxication E.E. Vink, T. van Bemmel, j. Kuenen, M. Bosselaar, with Paraquat, a herbicide used in agriculture. She had G.W.D. Landman taken three sips (approximately 40 ml) of Paraquat three Gelre Hospitals, Department of Internal Medicine, Apeldoorn, days prior and she had vomited a few minutes afterwards. the Netherlands The Paraquat serum concentration on admission, three days after ingestion, was < 1mg/ml. Because of renal A 66-year old female with rheumatoid arthritis treated failure, dialysis was initiated and nasogastric tube feeding with prednisolone and adalimumab, was admitted with a was started because of swallowing difficulties. After one community acquired Staphylococcus aureus bacteriemia week renal function started to recover and also her liver complicated by spondylodiscitis and epidural abscesses function improved. After several weeks she was able to without evidence for central nervous system involvement. eat again. After five weeks of treatment with continuous dosed Paraquat intoxication has a high mortality rate (44%). flucloxacilline (8 grams/24-h) she became tachypnoeic. An There is a strong correlation between paraquat serum arterial bloodgas examination showed a metabolic acidosis levels and outcome; ingestion of more than 30ml is often with partial respiratory compensation (pH 7.30, pCO2 lethal. Paraquat can directly cause cell damage but also 1.7 kPa, HCO3 6 mmol/l, BE -18.7 mmol/l, O2 sat 0.98, triggers a pronounced secondary inflammatory response pO2 14.2Pa) with an increased aniongap (25, corrected for eventually leading to multi-organ failure. Since there is no decreased albumin (15 g/l))and a normal osmolgap. specific antidote, the treatment is supportive care. Like in Our differential diagnosis was renal acidosis, ketoaci- our patient, renal function can show spontaneous recovery dosis, lactate acidosis or a pyroglutamic acidosis due after a few weeks. to paracetamol. However, our patient had a eGFR of Paraquat intoxication is very rare and is often lethal. We 68 ml/min with normal lactate (3.0 mmol/l). Moreover, presented a patient who recovered from this intoxication she was normovolemic, did not use paracetamol, and by supportive treatment.

46 educational value of case reports in therapeutic reasoning, C081 An unusual cause of fever during pregnancy we analyzed to what degree pharmacotherapeutic reasoning was discussed. V.L.M.N. Soomers, E. Waizy Methods: Review of clinical cases published in two high Elisabeth-TweeSteden Hospital, location TweeSteden Hospital, impact medical journals (BMJ and Lancet). For every Department of Internal Medicine, Tilburg, the Netherlands drug therapy started in these case reports, information regarding the choice and argumentation was assessed. We Introduction: Adult Still’s disease is uncommon, and used a score form based on the WHO 6-step, a method rarely seen throughout pregnancy. We describe a case of a used in medical schools to train students therapeutic pregnant woman with fever of unknown origin. reasoning in a step-by-step approach. Case: A 29-year old woman, 16 weeks pregnant, was Results: PubMed database was searched for articles admitted because of persistent fever without cause. Her classified as case report and published in the first half year medical history was uneventful. of 2014. We identified 58 articles, 44 of which we qualified Four weeks earlier her complaints had started with an itchy as clinical case report. In 24 of these reports a total of 43 rash. Later she developed painful, stiff joints, daily fever drugs were started. The drug name was mentioned in 65% and a sore throat. An elaborate anamnesis did not provide and in < 10% general drug information (contraindications, any other clues. adverse effects and interactions) was given. In < 3% the On physical examination a moderately ill woman was presence/absence of contraindications/interactions and seen with a temperature of 38.9°C. Besides painful joint suitability for the patient was discussed. movement without arthritis, there were no abnormalities. Conclusion: Although case reports could play a role in Laboratory results showed marginally raised liver enzymes developing clinical reasoning skills, this opportunity is an a normocytic anaemia. not fully utilized for pharmacotherapeutic reasoning. Furthermore, inflammation was present with a CRP of Drug choices were frequently not described properly and 210 mg/l (0-10 mg/l), leukocytes of 17.4 * 10^9/l (0-10 argumentation for these choices was hardly mentioned. *10^9 /l), ESR 51 mm/h (0-17 mm/h). We propose a more detailed description of pharmacothera- Serology testing, blood and urine cultures were negative. peutic reasoning in case reports, e.g. by using some steps An ultrasound of the abdomen showed splenomegaly. of the WHO-6-step method. After revising the case, we concluded that she met the Yamaguchi criteria for Still’s disease. Her ferritin level C083 Mechanisms of ecstacy-induced hyponatremia: appeared to be 11257 mg/l. We prescribed diclofenac polydipsia and inappropriate antidiuretic hormone and later prednisolon was administered. Eventually she secretion received anakinra. After delivery her complaints improved and treatment could be discontinued. C.L.M. Krieckaert, S. Slot, T. Smissaert van de Haere, Discussion: Adult Still’s disease is uncommon, charac- D. ten Oever, F. Stam terized by quotidian fever, arthritis and a rash. Both onset MC Alkmaar, Department of Internal Medicine, Alkmaar, and illness are rarely seen throughout pregnancy. Even in the Netherlands pregnant women presenting with these complaints, inflammatory diseases like Still’s disease should be considered if Introduction: Each year young people die of 3,4-methyl- more common diagnosis have been ruled out. enedioxymethamphetamine (MDMA) use, also known as ecstasy (XTC). MDMA causes mental stimulation and C082 Little argumentation regarding therapeutic decision euphoria, however potentially lethal side effects include making in case reports: A case report review in hyperthermia, rhabdomyolysis and hyponatremia. high-impact medical journals Case: A 26-year-old female was admitted to our emergency department. She had been vomiting large amounts of R.J. van Unen, T. Schutte, J. Tichelaar, T.h.P.G.M de Vries, water after polydipsia, and her consciousness was low. M.C. Richir, M.A. van Agtmael Medical history was of insignificance and she did not VUmc, Department of Internal Medicine, Amsterdam, the use any medication. An accompanying friend reported Netherlands that they had visited a festival the day before. There, our patient had taken 3/4 tablet of MDMA, without alcohol Background: Reading case reports is a method to train or other recreational drugs. At physical examination, clinical reasoning in general, however they seem to be equally enlarged pupils and low consciousness with focused at diagnostics rather than therapeutics. Doctors motor agitation (E4M5V1) were observed, without other in training indicate they experience a deficit in education abnormalities. Laboratory testing revealed plasma sodium in pharmacotherapeutic reasoning. To determine the 113 mmol/l, serum osmolality 239 mOsm/kg, urine

47 sodium 148 mmol/l, and urine osmolality 702 mOsm/ due to elevated hepcidin levels, but the awareness kg, compatible with inappropriate antidiuretic hormone that heterozygous mutations can be linked to IRIDA secretion. Computertomography of the brain was is low. This case illustrates the clinical setting where performed, which showed mild edema. Our patient was bleeding combined with a heterozygous pathogenic monitored at the Intensive Care Unit where she was treated TMPRSS6 mutation results in symptomatic IRIDA. with infusion of a 3% saline-solution. Several hours after The clinical implications of diagnosing and understanding resuscitation plasma sodium levels increased rapidly, urine the pathophysiology of IRIDA are avoidance of oral iron sodium was < 10 mmol/l, urine osmolality 79 mOsm/kg supplementation and undeserved suspicion of noncom- and symptoms decreased, pointing towards a terminated pliance, restricting work-up for gastro-intestinal bleeding effect of MDMA on vasopressin production. to the most relevant causes and i.v. iron supplementation Conclusion: We described a case of severe symptomatic in a frequency dependent on the Hb level. hyponatremia after the use of MDMA. Our patient experienced a drug-induced inappropriate vasopressin C085 Porphyria cutanea tarda in a patient presenting with production, leading to water reabsorption at the collecting increased ferritin levels tubules of the kidney. Water ingestion (generally advised when using XTC) contributed to the severity of the hypona- C.E.M. de Mooij, M. van Apeldoorn tremia in this case. Jeroen Bosch Hospital, Department of Internal Medicine, ’S-Hertogenbosch, the Netherlands C084 Bleeding and the presence of a pathogenic TMPRSS6 mutation can result in symptomatic Iron Case report: A 65-year old male was referred to our outpatient clinic because of increased ferritin levels. His Refractory Iron Deficiency Anemia (IRIDA) in medical history reported analysis seven years ago for the adulthood, necessitating intravenous iron same reason. After DNA analysis had shown no mutations supplementation in the HFE gene, he was discharged from follow-up. Upon referral, he had no physical complaints other than M. van Gelder1, A.E. Donker2, R. Olie1, D.W. Swinkels3 easily developing wounds, that left hyperpigmentated 1Maastricht UMC+, Department of Internal Medicine, scars. He reported smoking and drinking alcohol heavily. Maastricht, the Netherlands, 2Maxima Medical Physical examination showed multiple erythematous Centre,Department of Paediatrics , Veldhoven, the macules and hyperpigmentated scars on the hands. Netherlands, 3Radboudumc, Department of Laboratory Laboratory results showed an increased ferritin level Medicine, trans[wat moet dit zijn?], Nijmegen, the Netherlands (920 mg/l). Ultrasonography showed hepatic steatosis. On the working diagnosis of increased ferritin levels due Iron-deficient anemia (Hb 4.9 mmol/l, MCV 62 fl, ferritin to excessive alcohol consumption, he quit using alcohol. 3 mg/l, serum iron 2.6 mmol/l, transferrin saturation 2.8%) However, ferritin levels did not decrease. On suspicion of was coincidentally diagnosed in a 40 year old Creole female porphyria cutanea tarda (PCT), we performed urinalysis, with pulmonary embolism. Gastrointestinal bleeding, HP showing elevated levels of uroporphyrines. Hepatitis infection and celiac disease were excluded. B, C, and HIV serology were negative. A skin biopsy Treatment with 200mg ferrous fumarate tid for 8 months showed findings consistent with porphyria. Treatment did not increase Hb and ferritin. Noncompliance was with phlebotomies was initiated, after which ferritin levels denied. After i.v. iron Hb and ferritin increased, but decreased. ferritin dropped (13 mg/l) within a few months. Biannual Discussion: PCT is a metabolic disorder caused by i.v. iron kept Hb constant at 6.5 mmol/l, until the onset of decreased activity of uroporphyrinogen decarboxylase, menorrhagia (5.3 mmol/l). GnRH-induced amenorrhea and and is characterized by skin photosensitivity and potential continued biannual i.v. iron increased and stabilized Hb liver damage. It is associated with alcohol consumption, (6.5 mmol/l). When menorrhagia re-appeared, restart of iron overload, hepatitis C, and HIV. PCT is diagnosed by anticoagulant therapy was coincidentally required because demonstration of increased urinary and fecal porphyrin of deep-venous thrombosis. Hb dropped to 4.2 mmol/l excretion. Management includes phlebotomies, hydrox- necessitating more frequent i.v. iron. ochloroquine, and alcohol avoidance. In this patient, PCT Iron Refractory Iron Deficiency Anemia (IRIDA) was was associated with excessive alcohol consumption and considered. As the increased hepcidin level was not iron overload. fully reliable because of slightly elevated CRP levels, Conclusion: This case illustrates that in patients presenting genetic testing was ordered and revealed a heterozygous with elevated ferritin levels and skin lesions, secondary pathogenic TMPRSS6 mutation. Homozygous pathogenic causes of iron overload, such as PCT, should be considered. TMPRSS6 mutations cause anemia in childhood

48 C086 Nutritional deficiencies after gastric bypass surgery to normalize ferritin but this therapy is controversial. The aim of the literature review is to determine if hyperferri- S.R. Verhoeff, A. Herbers tinemia is a marker of inflammation or iron accumulation, Jeroen Bosch Hospital, Department of Internal Medicine, causing liver inflammation referred to as DIOS. Methods: ’S-Hertogenbosch, the Netherlands A systematic search in Embase, Pubmed, Medline and Cochrane was conducted using the key words; hyperfer- Case: A 33-year-old female patient presented with ritinemia, iron overload, Non-alcoholic fatty liver disease, complains of fatigue since 2,5 years. Her medical history NAFLD, dysmetabolic iron overload syndrome and DIOS. consisted of morbid obesity and a gastric bypass surgery Results: Thirty eligible studies on the relationship (Roux-en Y) was performed in Belgium 3 years ago. She between hyperferritinemia and NAFLD were included. had no signs of blood loss, besides a regular menses, no The combination of hepatic steatosis and iron overload hypermenorroe. The patient looked pale. She had normal may initiate an oxidative stress cascade which causes the vital signs and no abnormalities at physical examination. progression to NASH. However, increased hepatic iron in Her laboratory results showed: hemoglobin 5.1mmol/l, NAFLD patients is less common than hyperferritinemia. mean cell volume 61 fl, white blood cell count 9.5 109/l, Ferritin, as an acute phase protein, could be increased ferritin 3.4 mg/l, vitamin B12 181pmol/l and folic acid secondary to the inflammatory state in obesity or diabetes 3.5nmol/l. mellitus type 2 often associated with NAFLD. Our primary working diagnosis was a combined iron-, folic Conclusions: Although conflicting results, hyperferri- acid and vitamin B12 deficiency microcytic anaemia due to tinemia seems to be a phenomenon of inflammation. inadequate uptake of vitamins and minerals after gastric Serum ferritin could be used to identify NAFLD patients bypass surgery. The patient was treated with folic acid, at risk of progression toward NASH and advanced fibrosis. vitamin B12 and iv. iron suppletion. Phlebotomies do improve histological findings in some Discussion: Anemia is the most common late-complication cases of NAFLD but further research is necessary to of a gastric bypass and is estimated to occur in 20%-49% elucidate its role as a therapeutic option in NAFLD. of patients. This is mostly due to iron, folate and vitamin B12 deficiencies like in this case. Major deficits were also C088 Hyperammonemia due to very late-onset noted in magnesium, calcium, 25-hydroxyvitamin D and N-acetylglutamate synthase deficiency thiamine (all normal in this case). Often patients who receive gastric bypass surgery outside the the Netherlands A. van de Logt, M. Janssen do not have any follow up. Radboudumc, Department of Nephrology, Nijmegen, the Recommendations: multidisciplinary management of Netherlands expected vitamin/mineral deficiencies is recommended after gastric bypass surgery. Also when performerd outside Case description: A 59-year old woman, with a medical of the the Netherlands, blood tests should be performed on history of mental retardation, was referred because of coma a regular basis to detect and monitor vitamin and mineral due to hyperammonemia after a fracture of the pelvis. The deficiencies. Patients require a referral to a dietitian ammonia level was 280 mmol/l. Laboratory investigation for nutrition counseling, lifelong vitamin and mineral showed normal liver enzymes and coagulation factors. She supplementation. was treated with a high caloric/low protein diet, lactitol, and later citrulline and sodium benzoate. She became fully C087 Hyperferritinemia in Nonalcoholic Fatty Liver conscious at an ammonia level of 100 mmol/l. Acquired Disease, a representation of iron overload or disorders as explanation for the hyperammonemia were inflammation? excluded. Metabolic investigations showed an elevated glutamine and alanine level, whereas citrulline was low. W. Moris, P.L.M. Verhaegh, G.H. Koek Orotic acid could not be demonstrated in urine. DNA Maastricht UMC+, Department of Internal Medicine, investigation revealed a novel homozygous mutation in Division of Gastroenterology, Maastricht, the Netherlands the N-acetylglutamate synthase (NAGS) gene, a cofactor involved in the urea cycle. Background: Non-alcoholic fatty liver disease (NAFLD), Discussion: This is the first patient in literature in whom the hepatic manifestation of the metabolic syndrome, the diagnosis of NAGS deficiency is made at this age. She ranges from hepatic steatosis to non-alcoholic steato- had no medical history of coma, but was mentally retarded. hepatitis (NASH). Hyperferritinemia is seen in 30% of This was always considered due to perinatal asphyxia. A NAFLD patients and when associated with mild hepatic part of patients becomes symptomatic later in life and iron accumulation, it is referred to as dysmetabolic iron symptom onset coincides with a precipitating factor such overload syndrome (DIOS). Phlebotomies are performed as a trauma in this case. The diagnosis of a urea cycle

49 defect is suspected when plasma amino acid analysis 1MC Leeuwarden, Department of Internal Medicine, reveals elevated glutamine and a decreased citrulline Leeuwarden, the Netherlands, 2Izore, Centre for Infectious level. The diagnosis can be confirmed by molecular diseases Friesland, Department of Medical Microbiology, genetic studies. Management consists of protein restriction Leeuwarden, the Netherlands and adjunct pharmacologic treatment to reduce plasma ammonia levels. It remains important for the internist to A 54-year old Negroid woman, with unremarkable medical consider a metabolic disorder at every age. history, was admitted with unexplained high fever and cold chills four weeks after her holiday in Turkey. At admission C089 Refeeding syndrome, an underestimated, but physical examination was unremarkable, but in hospital potential life-threatening diagnosis cervical lymphadenopathy developed. Laboratory testing revealed elevated CRP (249 mg/l), WBC (6.7x109/l), ESR G. Prins, H.S. Brink, J.H. Assink, I.J.A.M. Verberk-Jonkers (120 mm) and LDH (527 U/l). Repeated blood cultures, Maasstad Hospital, Department of Internal Medicine, microbiological and auto-immune serological evaluation Rotterdam, the Netherlands were negative. Additional PET-CT scanning showed generalised PET-positive lymphadenopathy. Case: A 22-year-old woman was admitted to the medical During admission patient developed peripheral oedema psychiatric unit with suspected anorexia nervosa (BMI and proteinuria (8.6 g/day) due to a nephrotic syndrome. 9.2). Refeeding was started at 10 kcal/kg, vitamins were Kidney biopsy showed an acute tubular necrosis. Because given and electrolytes were checked daily. On day four of rapidly rising liverenzymes, including a hyperferri- after admission she complained of a painful abdomen, tinemia (47147 mg/l), a liver biopsy was performed showing dyspnea and edema. On examination she had a septic cellular necrosis. Bone marrow examination revealed profile, a distended abdomen and peripheral edema. extensive hemophagocytosis, with fulfillment to all criteria Laboratory investigations showed slightly increased CRP, of an hemophagocytic syndrome. Examination of a lymph pancytopenia and electrolyte disturbances with hypophos- node showed reactive lymphadenitis without signs of phatemia, hypomagnesemia, hypokalemia, hypoalbumi- malignant lymphoma. After additional staining, Kikuchi naemia and a normal vitamin B1 level. Chest X-ray revealed disease was diagnosed. In the meantime, patient recovered bilateral pleural effusion. Abdominal ultrasound showed with normalisation of both temperature and laboratory ascites. Cardiac echo revealed a poor left ventricular abnormalities and without residual organ damage. No function with a diffuse hypokinetic left ventricle. She treatment of corticosteroids was administered. was diagnosed with fulminant refeeding syndrome In conclusion, this patient had an impressive presentation with clinical manifestations of cardiac and respiratory and course of Kikuchi disease (histiocytic necrotizing failure, for which admission to the Intensive Care Unit lymphadenitis) with nephrotic syndrome, liver disease was required for intubation, ventilation and vasopressor and an extensive hemophagocytic syndrome, which has therapy. After a few days diuretics could be started, never been reported in literature. Kikuchi disease is a resulting in detubation at day 10. At day 29 she could be rare, benign, self-limiting condition characterized by fever discharged. Repeat cardiac echo 4 weeks later showed and lymphadenopathy. Pathogenesis is unknown, but an marked improved left ventricular function. immune response of T-cells and histiocytes to an, not Conclusion: This case-report illustrates that refeeding yet specified, infectious agent is suggested. This disease syndrome is a life threatening and an underestimated mimics several other serious malignant and infectious condition with possible full-blown clinical manifesta- conditions and must be considered in case of lymphad- tions. Refeeding syndrome is often not recognized or, enopathy and fever. when recognized, treated inappropriately. It is therefore relevant to raise awareness about what refeeding syndrome C091 An Escherichia coli pyogenic liver abscess with an entitles, the identification of patients at risk and the unusual clinical presentation multidisciplinary management, which is needed to treat this preventable condition. We aim to give a structured N. Goos-Peek, J.J.J. de Sonnaville overview of the management and treatment of refeeding Tergooi, Department of Internal Medicine, Hilversum, the syndrome. Netherlands

C090 Lymphadenopathy and fever: a rare course of a rare Introduction: The Clinical manifestations of liver abscesses disease usually include fever (90-100%) and abdominal pain (50-75%). We describe a patient with severe weight loss H.A. Hoogstins1, F.L. Ubels1, M. Hoogendoorn1, without fever, caused by a liver abscess. E.A.N.M. Mooi2

50 Case report: A 65-year old man presented with dyspnoe relapsed and we started treatment with intravenous high and weight loss of 15 kilograms. He has had surgery two dosage Methylprednisolone followed by intraveneous years before, because of an acute perforated T3N1c-sigmoid Cyclophosfamide and oral steroids. After three months the carcinoma with fecal peritonitis. The patient had rejected treatment respons will be evaluated. adjuvant chemotherapy. He had no fever nor abdominal Conclusion: Behcet’s disease with multiple organ pain. CRP (98 mg/l) was elevated. Chest X-rays showed no involvement including oral and genital ulcera, skin infiltrates. Because malignancy, possibly with pulmonary laesions, bilateral granulomatous panuveitis and embolism, was highly suspected, a CTA of the thorax and neuro-Behcet. CT-scan of the abdomen was performed. This showed a Discussion: Behcet’s disease can occur in non-Mediterra- large mass in the liver with a diameter of 16 centimetres neans and can cause neurological disorders. In our case, and some pleural effusion. No signs of malignancy or discrimination between sarcoidosis and Behcet’s disease pulmonary embolism were found. Ultrasound guided was difficult. puncture and drainage of 1 litre of pus was performed. The culture revealed Escherichia coli. With drainage of the abscess and intravenous antibiotic therapy the patient VIII GERIATRIC MEDICINE recovered, his appetite returned to normal and inflammation parameters decreased fast. Conclusion: This patient had an unusual clinical presen- C093 Heartfailure in an elderly women: not always all tation of a pyogenic liver abscess with symptoms and a about the coronaries history that initially made the case highly suspected for a malignant origin.It shows that another cause of severe I.W. Custers, N.M.J. Hanssen, E.G. Gerrits, P.M. Stassen weight loss without fever, besides cancer, must not be 1Maastricht UMC+, Department VED5, Maastricht, the overlooked. Netherlands

C092 Behcet’s disease in the Dutch Antilles? Introduction: Takotsubo cardiomyopathy is an underdiagnosed, reversible form of heart failure, presumably caused M.W.L. van Geffen, H.P.J. Willems by release of catecholamines. Through poorly understood Máxima Medical Centre, Department of Internal Medicine, mechanisms, this will lead to ballooning of the apex of Veldhoven, the Netherlands the left ventricle, which resembles Japanese octopus traps (called Takotsubo). Here, we describe a case of Takotsubo Introduction: Behcet’s disease is a systemic auto-immune in the context of bacterial dissemination from a rectal disease characterized by recurrent oral ulceration, genital carcinoma. ulceration, skin lesions and eye lesions. The disease equally Case report: An 84-year old woman with an unremarkable affects males and females from the Mediterranean and medical history, was admitted with diarrhea, lower Middle Eastern region. back pain and weight loss. After three days, she went We present a non-Mediterranean patient with Behcet’s into (cardiogenic) shock. Electrocardiography showed disease with oral and genital ulceration, bilateral panuveitis atrial fibrillation (168 bpm) and signs of ischaemia. Our and neurological involvement. patient had no clinical signs of myocardial infarction. Case: A 24-year old Antillean man was seen in the Echocardiography showed akinesia of the apical outpatient clinic because of recurrent oral and genital segment and hyperdynamic basal segments of the left ulcerations, a pustular skin erupion, impairment of vision ventricle. Left ventricular ejection fraction was 30%, and and loss of short memory. Fundoscopic examination troponin T levels were increased (179ng/l; hsTnT “14 showed a bilateral granulomatous panuveitis. An MRI ng/l). However, emergency coronary angiography did not cerebrum revealed multiple lesions in the capsula show any significant coronary obstruction. The diagnosis interna. Further examination showed a positive pathergy of Takotsubo was made and improvement of ejection reaction. Laboratory tests showed a normal ESR, CRP, fraction and electrocardiography occurred with supportive calcium and blood smear. A chest X-ray showed no hilair care. Previously obtained blood cultures revealed fecal lymfadenopathy. bacteremia. Further evaluation by CT scan showed spondy- Our patient had a granulomatous panuveitis. However, lodiscitis which explained her backpain and colonoscopy favouring the diagnosis Behcet’s disease over sarcoidosis, showed a rectumcarcinoma, explaining diarrhea and he was treated with oral Prednisolone and Azathioprine. bacterial dissemination. The ulcera diminished and the MRI cerebrum showed Conclusion: Not all episodes of acute heart failure in improvement of the lesions in the capsula interna. A the elderly are due to coronary artery disease. In fact, few weeks after sessation of the therapy, his disease Takotsubo may occur as a rare complication of sepsis.

51 The condition is difficult to differentiate from myocardial infarction; its major distictinctive features are spontaneous Introduction: Myeloproliferative disorders (MPDs) are resolution of cardiac abnormalities and absence of diseases in which the bone marrow produces too many significant coronary artery stenosis. blood cells or platelets. MPDs are relatively rare and most commonly found in patients aged 50 years and above. Men are more likely to be affected. The cause is unknown. IX HAEMATOLOGY One of the major complications is venous thromboembolism. Philadelphia-negative (Ph-) MPDs are the most common cause of portal and mesenteric vein thrombosis C094 An elevated aPTT: further testing allowed (PVT/MVT). In some cases the blood count is normal. JAK2V617F and Calreticuline (CALR) mutations represented A. Breedijk, M.M.C. Hovens a crucial advance in the diagnostic approach to MPDs. Rijnstate, Department of Internal Medicine, Arnhem, the These mutations can precede the actual thrombocytosis or Netherlands erythrocythosis in the peripheral blood. Cases: Patient A, a 51-year old male, was admitted with Case: a 60-year old woman was admitted to our hospital melaena. Gastroscopy showed esophageal varices caused with a 1-day history of abdominal pain and hematoma of by portal vein thrombosis, for which no clear cause was the left loin. She was known with allergic bronchopul- found. Except for mild anemia, he had a normal blood monary aspergillosis for which she was using prednisolon count. A year later he was referred to the internist for and itraconazol. Imaging of the abdomen revealed a subcu- thrombocytosis. A JAK2V617F mutation was found and the taneous hematoma of the right loin and a large retroperi- patient was diagnosed with Essential Thrombocythemia toneal hematoma. Laboratory investigation showed anemia (ET). (hemoglobin 3.7 mmol/l) and an increased activated partial Patient B, a 54-year old male, presented with abdominal thromboplastin time (aPTT; 54 seconds). Prothrombin pain and was diagnosed with PVT and MVT. Blood work time (PT) was normal. The aPTT did not correct with showed leukocytosis and thrombocytosis and a JAK2V617F normal plasma. The levels of factor VIII activity and factor mutation was found. ET was diagnosed with bone marrow VIII-inhibitory activity were respectively 14% and 2 BU/ biopsy. ml, thus confirming the presence of acquired factor VIII Conclusion: These cases describe PVT as the first inhibitor. Lupus anticoagulant was positive. A diagnosis and single presenting symptom of MPD. In medically of acquired hemophilia A was made. Our patient was unexplained abdominal vein thrombosis, Ph-MPD must treated with recombinant factor VIIa, a higher dose of be considered, even with normal blood count. It is the prednisolon (1 mg/kg/day) and cyclofosphamide. With this most common cause of PVT/MVT. JAK2V617F and/or treatment the level of hemoglobin en factor VIII activity CALR mutations belong in the work-up of abdominal vein increased. Factor VIII-inhibitory activity decreased. Despite thrombosis. extensive investigation there was no underlying cause found. Our patient was discharged with the combination C096 Anaemia in general practice: causes and survival of prednisolon and cyclofosphamide. Discussion: acquired hemophilia A is a rare auto-immune K. Stouten1, J.A. Riedl1, P. Sonneveld2, M.D. Levin1 disease caused by an inhibitory antibody to factor VIII. 1Albert Schweitzer Hospital, Departments of Clinical Patients with this disease are at risk for life threatening Chemistry and Internal Medicine, Dordrecht, the Netherlands, bleeding. Therefore, it is important to perform further 2Erasmus MC, Department of Haematology, Rotterdam, the investigation when an isolated increased aPTT is Netherlands found. There is association with autoimmune diseases, malignancy, pregnancy and dermatological disorders. Background: Anaemia is a common finding in the elderly However, in about half of patients no underlying case population and for many years it was assumed to be a is found. In our patient there may be association with normal consequence of aging. Recently anaemia has itraconazol. been shown to be associated with increased mortality and morbidity and with decreased quality of life. However, C095 Myeloproliferative diseases as a, often forgotten, information on the causes of anaemia in general practice cause of abdominal vein thrombosis is limited. Methods: For six years, patients aged 50 years or older and L.M. van der Burg presenting with a newly diagnosed anaemia were included. Isala, Department of Internal Medicine, Zwolle, the A wide range of laboratory parameters was analysed for Netherlands each patient and used to establish one or multiple causes

52 of anaemia. The survival in months after entry was A healthy boy (birth weight 1263 gram, p20-50) was determined. born. Histopathological examination of the placenta (237 Results: We included 2513 patients, 1238 men and 1275 gram, < p10) showed multiple peripheral infarctions due women, of which 229 presented with two or more causes to thrombotic events. One year after delivery, the patient for their anaemia. Anaemia of chronic disease was and her child are doing well. Eculizumab treatment is established in 823 patients (29.8%), haemoglobinopathy continued. in 17 (0.6%), renal anaemia in 340 (12.3%), haemolysis in Conclusion: PNH during pregnancy may mimic the 16 (0.6%), possible bone marrow disease in 105 (3.8%), clinical course of pre-eclampsia. Prompt commencement iron deficiency in 516 (18.7%), vitamin B12 deficiency in 115 of Eculizumab might prolong pregnancy whilst in a (4.2%), folic acid deficiency in 23 (0.8%) and other causes critical premature phase. The diagnosis of PNH must be in 106 (3.8%), while in 703 patients (25.4%) no cause could considered in pregnant women with haemolysis. Hemolytic be elucidated. PNH in pregnancy is an indication for Eculizumab. Overall survival of the cohort was 70.8 months (95% CI 69.3-72.2) after entry into the study. There was no C098 Ultrasound-guided percutaneous biopsy of the significant difference between the mean survival of men spleen: safer than assumed and women (p = 0.083). Conclusion: Using a standardised laboratory protocol, R.M.M. van Aerts1, G. Belle-van Meerkerk1, H.R. Koene2, it was possible to establish a cause in 1810 (72%) of the R. van der Griend1 included patients. The influence of each cause on survival 1Diakonessenhuis, Department of Internal Medicine, Utrecht, will be determined. the Netherlands, 2St. Antonius Hospital, Department of Internal Medicine, Nieuwegein, the Netherlands C097 Paroxysmal Nocturnal Hemoglobinuria in pregnancy mimicking pre-eclampsia Introduction: Ultrasound-guided percutaneous biopsy of the spleen is not a widely performed diagnostic procedure, D. Evers1, O.W.H. van der Heijden2, C.J. Halkes1, P. Muus2 due to the assumed major risk of bleeding. Our clinical 1Leiden University Medical Centre, Department of case demonstrates that this technique can be of significant Haematology, Leiden, the Netherlands, 2Radboudumc, value in the (hematological) diagnostic process. We did a Department of Gynaecology and Obstetrics, Nijmegen, the literature search to find out whether the restraint on spleen Netherlands biopsy is reasonable. Case description: We describe a 75-year old man who Background: Paroxysmal nocturnal hemoglobinuria (PNH) was staged for rectal cancer (histology: adenocarcinoma). is characterized by intravascular haemolysis and a high Abdominal CT-scan showed five hypodense abnormalities thrombosis incidence. Because of increased maternal (max diameter 2.9cm) in the spleen and the PET-scan and fetal mortality, pregnancy has historically been showed high-FDG-avidity in both the spleen and rectum. discouraged. Eculizumab decreased complications of 70 Bone marrow biopsy was normal. Uncomplicated ultra- pregnancies in 57 PNH patients compared to historical sound-guided percutaneous biopsy of the spleen was controls. performed using an 18-Gauge needle. Based on this Methods: A 32-year old, 28 weeks pregnant, patient was histology, a diffuse large B-cell non-hodgkin’s lymphoma admitted with presumed pre-eclampsia based on: asymp- (NHL) was diagnosed. The patient underwent transanal tomatic hypertension, mild proteinuria (0.4 gr/l) and fetal endoscopic microsurgery (radical resection pT3), followed growth restriction (estimated fetal growth < p10). Her by eight cycles of chemo-immunotherapy with curative medical history listed chronic haemolysis of unknown intent for NHL, after which remission was achieved. origin, unresponsive to oral corticosteroids. Laboratory Conclusion: This case demonstrates that ultrasound- results revealed: DAT-negative haemolysis (Hb 5.7 mmol/l, guided percutaneous biopsy of the spleen can be of great reticulocytes 252x10^9/l, LDH 1500 IE/l, haptoglobin < 0.1 diagnostic value. Conducting splenic biopsy accelerated g/l and 4% fragmentocytes). Coagulation parameters and the diagnostic process and prevented splenectomy with liver enzymes were normal. Flow cytometry revealed the well-known long-term immunologic negative impact . In diagnosis PNH (70% clone size). Fetal growth restriction addition, recent literature shows that the major risks of in an otherwise normal fetus in PNH, suggesting placental splenic biopsy is comparable with those of widely accepted thrombosis, prompted to immediate commencement of techniques such as liver (0,5%-3,3%) and kidney biopsy Eculizumab and low-molecular weight heparin. (0,7%-6,3%) . Furthermore, compared with splenectomy Results: Haemolysis parameters and proteinuria , the comorbidity is less and the diagnostic accuracy of markedly decreased. The pregnancy was temporized splenic biopsy is very acceptable. We therefore recommend until fetal distress urged caesarean section at 31+1 weeks.

53 to consider ultrasound-guided percutaneous biopsy as an revealed Raynaud’s syndrome and loss of libido and erectile alternative in the diagnostic work-up of splenic diseases. function. Physical examination was unremarkable except for mild ascites, edema and diminished reflexes. He had C099 The difficulty of reading poems clubbing and cyanotic fingers. Initial laboratory results showed diminished vitamin B12 and albumin levels with K. Goossens, A. Broijl, J. Alsma normal blood count, kidney function, liver chemistry. Erasmus MC, Department of Internal Medicine, Rotterdam, EMG indicated axonal polyneuropathy. A CT-scan revealed the Netherlands ascites, pericardial effusion and osteosclerotic bone lesions in his iliac bone. The presence of polyneuropathy, osteo- Case report: A 46-year-old patient presented with malaise, sclerotic bone lesions and ascites led to suspicion of muscle weakness in both legs and pins-and-needles POEMS syndrome. This was confirmed by a M-protein of 2 sensation in his toes. He also had night sweats, periods of grams/l (IgA-lambda), a hypergonadotrope hypogonadism fever and weight loss. General physical examination and and raised levels of vascular endothelial growth factor initial laboratory testing, including an ESR, were despite a (VEGF). mild trombocytosis unremarkable. He was referred to the The acronym POEMS is formed in 1980 by the symptoms neurologist who diagnosed demyelinating polyneuropathy. of polyneuropathy, organomegaly, endocrinopathy, The combination of polyneuropathy and B-symptoms was monoclonal gammopathy and skin changes. Nowadays cause for additional examination. Blood result showed a POEMS is recognized as a paraneoplastic syndrome mild paraproteinemia (6 g/l). Bone marrow biopsy and leading to endocrinopathies, extravascular volume aspiration were without abnormalities. Imaging of the overload, skin changes and osteosclerotic bone lesions. abdomen, including ultrasound and CT-scan, was normal. VEGF is found to have an important role in the patho- Surprisingly we found three sclerotic lesions in the genesis. Treatment is based on the eradication of the ileum. Targeted biopsy showed a monoclonal plasma-cell monoclonal gammopathy by mostly chemotherapy population. The diagnosis POEMS-syndrome (polyneu- followed by autologous stamcell transplantation, or ropathy, organomegaly, endocrinopathy, monoclonality radiation of the osteoslerotic lesions. Our patient is treated and skin lesions) was made based on the criteria present; with lenalidomide/dexamethasone followed by high-dose polyneuropathy and a clonal lambda plasma cell disorder melfalan which resulted in remission of the disease. (required criteria), sclerotic bone lesions (major criteria) POEMS syndrome is a rare paraneoplastic disorder and thrombocytosis (minor criteria). He was treated resulting in debilitating symptoms as presented. It is with lenalidomide and dexamethasone induction therapy important to be aware of rare monoclonal gammopathies followed by high dose melphalan and autologous stem cell in order to start treatment on short notice. transplantation, from which he is still recovering. Discussion: POEMS-syndrome should be considered C101 Early and rapid increment of CRP and IL-8 levels in patients with a combination of polyneuropathy and together with faster and deeper dipping of leukocytes B-symptoms. Even though initial workup was without predict for typhlitis development in treated AML abnormalities, perseverance led to the diagnosis. POEMS- patients syndrome is a rare paraneoplastic syndrome due to an underlying malignant plasma cell disorder. The acronym L.F.R. Span1, A.B. van den Hengel1, B. Roerig2, G. Dijkstra1, refers to several, but not all, of the features of the G. Huls3, E. Vellenga1 syndrome. Appropriate additional testing is necessary 1UMC Groningen, Department of Haematology, Groningen, to make the diagnosis. This case also illustrates that the Netherlands, 2Ommelander Hospital Group, Department malignant plasma cell proliferative disorders can present of Hemato-oncology, Delfzijl, the Netherlands, 3Radboudumc, with apparently normal laboratory results. Department of Haematology, Nijmegen, the Netherlands

C100 A debilitating weakness in the legs due to a poetic Background: Typhlitis is an important and severe compli- disease cation in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy. In this study, we H. de Vries, B.W. Schot evaluated serum C-reactive protein (CRP) and interleukin ZGT, Department of Internal Medicine, Almelo, the (IL)-8, fecal calprotectin, and oral mucositis score as Netherlands possible time-dependent predictors of developing typhlitis. Methods: Adult patients with AML treated with intensive A 43-year old Caucasian male was hospitalized with chemotherapy (with cytarabine) were included. Serum IL-8 debilitating weakness, loss of weight and fatigue, which and CRP levels were measured daily during 14 days after aggravated in the past two months. Further enquiry cessation of chemotherapy, as well as calprotectin in the

54 stool. Oral mucositis was also scored daily. Furthermore, Discussion: Levamisol is an immunomodulatory agent CT scan of the abdomen at day 21 was performed to initially developed as an anthelmintic agent and later objectively define typhlitis patients. utilized in humans in treatment of various auto immune Results: In total, 34 patients were included and 11 episodes diseases and colorectal cancer. It was withdrawn of the of typhlitis were diagnosed. All patients with typhlitis market because of the frequent side effect of neutropenia. received conservative treatment and only one patient with Since 2003 there is a significant increase in the use of typhlitis died with Enterococcus faecium sepsis. From day levamisol as an adulteration of cocaine. Therefore, a rise 5 onward (after cessation of chemotherapy), median IL-8 in the prevalence of cocaine-associated agranulocytosis is and CRP levels increased more rapidly to significantly expected, which underscores the importance of a thorough higher levels in patients with typhlitis, whereas white drug abuse history. blood cell (WBC) counts decreased faster to significantly lower levels as compared to the non-typhilitis patients. C103 Abducens nerve palsy: there is more than meets the As was corrected for bacteraemia, no differences were eye seen between both groups. Oral mucositis score and fecal calprotectin levels failed to be different in both groups. F.O. Meeuwes, J.L.L.M. Coenen Cytarabine dose was of no influence. Isala, Department of Internal Medicine, Zwolle, the Conclusion: Pattern recognition of early and rapidly Netherlands increasing IL-8 and CRP levels with significantly lower WBC counts after cessation of chemotherapy can identify Introduction: Abducens (sixth) nerve palsy is an AML patients developing typhlitis. Early recognition of uncommon condition, with many different causes. We developing typhilitis can potentially decrease the high present a case where this condition was the first presen- mortality rate (25-50%) of this complication. tation of acute myeloid leukemia (AML). Case: A 63-year old male presented with diplopia and C102 Cocaine-associated agranulocytosis blurry vision of his left eye. A sixth nerve palsy was apparent without other neurological deficits. There was A.M. Koopen, F. Stam, M. Westerman, W.A.T. Slieker, an abscess on the occiput and a blueish node on the S. Simsek forearm. Laboratory tests showed anemia (Hb 5.4 mmol/l), MC Alkmaar, Department of Internal Medicine, Alkmaar, thrombocytopenia (56 x 10^9/l) and 29% blasts in the the Netherlands peripheral smear. Bone marrow biopsy showed AML, best compatible with a myelomonocytic type. Skin biopsies Introduction: Agranulocytosis is a rare condition that can revealed chloromas. In the liquor no malignant cells were be complicated by potentially life threatening infections. A seen. An MRI-cerebrum was without abnormalities. The variety of causes has been implicated, including congenital patient was treated with idarubicin and cytarabin intrave- diseases, infections, autoimmune disorders and bone nously, and cytarabin once intrathecally. The palsy resolved marrow diseases. We present a rare, but possibly under in two weeks and he regained his eyesight. Unfortunately, recognized cause. he died after a massive intracranial hemorrhage due to Case: A 38-year-old Caucasian man was referred because refractory thrombocytopenia. of fever and pharyngitis. His medical history reported an Discussion: In AML, CNS involvement is uncommon. It agranulocytosis in 2008, for which no cause was found occurs mostly in patients with acute monocytic or myelo- after extensive analysis. Laboratory tests showed again an monocytic leukemia, acute promyelocytic leukemia or agranulocytosis, with no detectable neutrophilic granu- AML with inv16 or chromosome 11 defects. The fact that locytes. Virus serology was negative and chest X-ray was the sixth nerve palsy resolved after one round of induction normal. He was not using any medication but admitted chemotherapy combined with intrathecal chemotherapy, to snort cocaine almost weekly. No urine toxicology on is highly suggestive of CNS involvement. Furthermore, cocaine nor levamisole was done, although of the latter in myelomonocytic or monocytic leukemias, cutaneous is known that the detection is challenging. Autoimmune manifestations (i.e. chloromas) are more commonly seen workup was positive for ANCA-MPO, ANCA-PR3, anticar- as well. diolipin and lupus anticoagulant. Also the ANCA-HNE Conclusion: Serious underlying pathology can be present was positive. He was treated with parenteral antibiotics, in patients with an abducens nerve palsy. Although CNS antifungals and antivirals and eventually with G-CSF involvement in AML is rare, patients with neurological because he was not clinically improving. After the symptoms should be evaluated for CNS involvement. initiation of G-CSF his neutrophil count increased and the patient recovered. C104 The protein gap

55 T.M. Boertien, M.N. Klaver, W. Deenik, M.E.M. Rentinck compatible blood . All tests were positive, indicating Tergooi, Department of Internal Medicine, Hilversum, the the presence of irregular antibodies. Her transfusion Netherlands history revealed a recent erythrocyte transfusion, matched according to the current guidelines. No irregular Case: A 79-year-old female was admitted with complaints antibodies were found then. of fatigue and malaise. Medical history included To specify the new antibodies, various identification essential thrombocythemia with vascular complica- panels were used. Unfortunately, all test panel showed tions. Treatment with hydroxycarbamide (Hydrea) had cross reactivity. Because of this pan-reactivity blood was been ceased recently because ofsuspicion of myelosup- sent to Sanquin Blood Supply. After time consuming pression withthe occurrence of anemia. At the time of identification tests, an antibody could be identified: admission laboratory tests showed acute on chronic kidney anti-Duffy 3. This is an antibody against a high-frequent disease and progression of anemia despite the ceasing antigen (> 99.9% Caucasians express Duffy-3). Therefore, of Hydrea. The finding of splenomegaly, and erythro- Duffy-3 antigen negative blood units were selected from blasts in the peripheral blood smear raised suspicion of the Sanquin Bank of Frozen Blood. Nevertheless cross progression of essential thrombocythemia to myelofibrosis. matching still gave positive tests. Additional analysis However, an extremely high ESR in relation to CRP and a revealed anti-Dombrock(a) antibodies (another clinically strongly raised total protein were suggestive of multiple relevant, high-frequent antigen). The combination of these myeloma. Additional tests showed a surprisingly normal antibodies made it impossible to select suitable blood. to suppressed IgA-G-M spectrum. This ‘protein gap’ was Both antibodies can cause serious hemolytic transfusion resolved with supplementary immunofixation electropho- reactions. resis revealing a monoclonal IgD-lambda – one of the more In the meanwhile, she developed fever and the curettage rare subtypes of multiple myeloma. Further evaluation of had to be done without transfusion support. The course of contemporaneous myelofibrosis is ongoing. the procedure was uncomplicated with additional support Discussion: Multiple myeloma (MM) entails the via inotropic agents and antibiotics. Postoperative Hb was development of uncontrolled proliferation of clonal plasma 3,4 mmol/l. cells within the bone marrow producing monoclonal Conclusion: Development of irregular antibodies is immunoglobulines. It accounts for approximately 10% possible after selecting blood conform recent guideline. of all hematological malignancies. There are several Identification of these antibodies is crucial for transfusion subtypes depending on the type of immunoglobulin support. that is overproduced. Of these, IgG is the most common. IgD-MM is rare and represents about 2% of all MM. It is C106 Intra-abdominal vein thrombosis in a patient with a associated with faster progression and advanced disease myeloproliferative disorder presenting with a normal at diagnosis. Coexisting MM with myeloproliferative blood cell count: a case report disorders (including essential thrombocythemia) has been described. However, there is no concluding evidence that B.D.C. Baake, D. Walter, R. Fijnheer these two entities arise from a common-ancestor hemat- Meander Medical Centre, Department of Internal Medicine, opoietic stem cell. Amersfoort, the Netherlands

C105 Life-threatening situations: No compatible A 64-year old female with a history of thrombosis transfusion for a sickle cell patient with a fluxus presented with complaints of progressive abdominal pain since a week. CT-angiography revealed extensive E.J. Huijssen-Huisman1, H. Russcher2, Y.B. de Rijke2, thrombosis of the portal- and splanchnic veins. Full P.A.W. te Boekhorst2 blood count was not suggestive of a myeloproliferative 1Erasmus MC – SKZ and Sanquin, Department of disorder (MPD), however a JAK2 mutation was found. Haematology, Rotterdam, the Netherlands, 2Erasmus The prognosis seemed poor at first, but then things took MC, Department of Clinical Chemistry, Rotterdam, the a turn for the better. MPDs, like polycythemia vera and Netherlands essential thrombocythemia, are a known risk factors for intra-abdominal vein thrombosis and not rarely such a A 14-weeks pregnant sickle cell patient, presented herself thrombosis is the presenting symptom of a MPD. These with vaginal blood loss secondary to a spontaneous cases can present with normal blood cell counts, making abortion (Hb at admission: 4.3 mmol/l). A curettage the diagnosis more difficult. Terms like ‘latent’ or ‘occult’ was urgently needed to stop the fluxus and to prevent MPD have been used in the past and a bone marrow biopsy intra-uterine infections. ABO-blood group typing and was needed for diagnosis. Nowadays genetic screening for irregular antibody screening were routinely done to select JAK2(V617F) mutation can prove the diagnosis of MPD.

56 This case showed us that patients presenting with intra- Case: A 70-year old Caucasian female presented with abdominal vein thrombosis should always be screened for persistent bleeding gums after a dental procedure and JAK2(V617F) mutation and that a case of extensive intra- low von Willebrand Factor (VWF) levels. She never had abdominal thrombosis with a very poor prognosis at first bleeding problems before and her medical history was can be successfully treated. unremarkable besides hypertension treated with valsartan. Physical examination showed no abnormalities, particu- C107 Plasmacytoma as part of presenting symptoms for larly no cardiac murmurs. Laboratory investigation showed multiple myeloma a factor VIII of 10%, VWF antigen of 12% and VWF activity of 6%. DNA mutational analysis was done. Three J.W.H.J. Geerts, A.M. Schrander – v.d. Meer months later, DNA analysis showed a normal VWF and Alrijne Hospital, Department of Internal Medicine, factor VIII gene. Meanwhile she developed increasing Leiderdorp, the Netherlands pain in her right hip, right leg and spine. Further analysis revealed an IgA lambda of 37.7 g/l, beta-2-microglobulin Introduction: Multiple myeloma is a neoplastic prolif- 3.5 mg/l, albumin 30 g/l, haemoglobin 6.2 mmol/l and eration of a single clone of plasma cells producing a a calcium of 2.61 mmol/l. Skeletal imaging with CT monoclonal paraprotein. The presenting symptoms can be: showed multiple lytic lesions of the skull and spine. Bone bone pain, systemic symptoms suggestive of malignancy, marrow examination revealed 60% pathologic plasma symptomatic hypercalcemia, acute renal failure or cells. Thus, a symptomatic multiple myeloma, ISS stage increased total serum protein. The patient described in 2, with an acquired von Willebrand disease (VWD) was this case had a lump on his back as part of his presenting diagnosed. After 3 courses of MPV chemotherapy IgA symptoms. lambda was < 2.0 g/l and VWF antigen and activity Case: The patient was a previously healthy 64-year old completely normalised: VWF activity 181%, VWF antigen male, who was monitored as an outpatient for microscopic 172%. glomerular hematuria with normal kidney function. At Discussion: Rarely, low VWF levels can be secondary to a routine check-up the patient complained of a lump of 8 cardiovascular, autoimmune, lymphoproliferative, plasma cm on his back, just behind his armpit. Also the patient cell and other disorders. VWF abnormalities in these unwillingly lost weight. Further physical investigation disorders can result from antibody-mediated clearance was normal. Laboratory investigations showed a normal or functional interference, adsorption to surfaces of kidney function, low albumin, decreased haemoglobin and transformed cells or platelets, or increased shear stress proteinuria. X-ray of the chest showed destruction of the and subsequent proteolysis. We demonstrate a patient with bone and a soft tissue mass, where the lump was located. multiple myeloma and acquired VWD probably by inter- Echography of the abdomen was normal. Paraprotein was ference of VWF with myeloma cells or the IgA lambda. elevated. PET-CT showed multiple lytic bone lesions and multiple pathologic lymph nodes. A biopsy was taken from C109 The chicken or the egg: neutropenia during infection the lump, which showed a plasmacytoma of IgG lambda type. The patient was diagnosed with multiple myeloma I. Maijers, H.T.J. Roerdink, J.K. Olijhoek and started with Pamidronic acid. The patient is still Elisabeth-TweeSteden Hospital, Department of Internal contemplating if he wants to start chemotherapy for his Medicine, Tilburg, the Netherlands condition. Discussion: Solitary plasmacytomas can be divided in two A 67-year old man was admitted to the surgical ward groups: solitary bone plasmocytoma or extramedullary because of a peri-anal fistel. The internist was consulted plasmacytoma. In this case the plasmacytoma was part of because of neutropenia and ongoing fever. In the previous the presenting symptoms of multiple myeloma. Only seven seven months our patient had suffered from multiple percent of the patients with multiple myeloma have this as infections: axillary furunkel, parotid gland infection, a presenting symptom. pneumonia and a muscular abcess in his upper leg with staphylococcus aureus. No previous cultures were positive. C108 Bleeding gums and bone pain We noticed that the neutrophil count was low at every blood sample for the previous nine years. A previous CT P.A.F. Geerts1, F. van der Graaf1, E. Jacobs2, M.R. Nijziel1 scan, performed because of fatigue and pancytopenia, had 1Máxima Medical Centre, Department of Internal Medicine, shown splenomegaly.We suspected a case of large granular Veldhoven, the Netherlands, 2Elkerliek Hospital, Department lymphocytic leukemia (LGL), for which we requested an of Internal Medicine, Helmond, the Netherlands immunophenotyping of peripheral blood. This showed an increase of non-monoclonal B-lymphocytes, which could be reactive to infection, but no sign of LGL.Meanwhile

57 our patient suffered from progressive sepsis, treatment myeloid sarcoma, defined as without systemic evidence of in intensive care was necessary. Because LGL was still AML, has only been described in case reports. Untreated in our differential diagnosis, prednisolon and G-CSF isolated myeloid sarcoma may progress to AML within were added to the antibiotics and our patient recovered. 5-12 months and intensive AML induction chemotherapy Bonemarrow showed hypercellularity, probably reactive is strongly advised. Post-remission treatment may consist to septicaemia, no monoclonal cells were seen. Finally, of radiotherapy or allogeneic transplantation, although repeated peripheral immunophenotyping now combined data is limited. with T-cell re-arrangement revealed monoclonal T-cells, compatible with LGL.LGL is a clonal disease of the large C111 Nonspecific pulmonary lesions after R-EPOCH granular T-cell lymphocyte characterized by peripheral therapy in a double hit lymphoma blood and bone marrow infiltration with LGLs, splenomegaly and cytopenias, most commonly neutropenia. Fever A.J.W. Gulpen, L.W. Tick with recurrent bacterial infections is common, typically Máxima Medical Centre, Department of Internal Medicine, of skin, oropharyngeal and perirectal areas. Severe sepsis Veldhoven, the Netherlands and pneumonia may also occur. In this case, making the diagnosis was challenging because during sepsis the Case: We present a 54-year old woman, who was recently diagnostic tests were difficult to interpret. diagnosed with an double hit lymphoma with extensive lymphadenopathy and central nervous system involvement. C110 Sometimes it is not so lonely at the top: an unusual She received R-EPOCH (rituximab, etoposide, doxorubicin, localization of Myeloid Sarcoma vincristine, cyclophosphamide, prednisolone) therapy with intrathecal methotrexate. Ten days after the second J. Versluis, A.A.M. Ermens, M. van der Klift, cycle she developed an severe oropharyngeal candida R.S. Boersma, J.W.J. van Esser infection, which was successfully treated with fluconazole. Amphia Hospital, Department of Internal Medicine, Breda, A few days later she developed fever with multiple, the Netherlands bilateral consolidations with apical dominance on a thorax CT-scan. She was treated with broad-spectrum antibiotics Introduction: Acute myeloid leukemia (AML) is for a hospital acquired pneumonia. Because of lasting a malignant disease of the bone marrow and can be fever, respiratory difficulties and progressive pulmonary accompanied with extramedullary involvement. We present lesions, aspergillus pneumonia was suspected and voricon- a patient with extramedullary AML without bone marrow azole was started. An broncho-alveolar lavage (BAL) localization. was performed and showed no microorganisms. Three Case description: A 57-year old female was referred to the days later, she developed progressive respiratory failure, gynecologist because of post-menopausal vaginal blood pneumocystis jerovici (PJP) was considered and high dose loss. Medical history revealed breast cancer at age 36, trimethoprim-sulfamethoxazole and prednisolone was treated with adjuvant chemotherapy (6 cycles of cyclofos- started. Other causes of respiratory failure in the differ- phamide, methotrexate and fluorouracil), mastectomy and ential diagnosis were cryptogenic organizing pneumonia radiotherapy. Subsequent genetic analysis showed mutated due to the chemotherapeutic agents. The patient showed a BRCA1 and therefore patient underwent a contralateral significant improvement after starting the trimethoprim- mastectomy and ovariectomy at age 42. On physical sulfamethoxazole and prednisolone. A new CT-thorax was examination, a tumor of six by four centimeter was found performed and showed total recovery. The test results of at the top of the vagina, suggestive for cervical cancer. the BAL where reconsidered and extended. Pneumocystis Surprisingly, histology showed CD117 and myeloperoxidase Jerovici PCR tested positive. The third R-EPOCH cycle positive blasts indicating myeloid sarcoma. Peripheral started successfully in a good clinical condition. blood count was unremarkable, while lactate dehydro- Discussion: Patients with hematological malignancies are genase was elevated (410 U/l; normal range 0-247 U/l). A highly susceptible to PJP due to treatment related immuno- PET-CT-scan revealed a highly FDG-intense cervical mass suppression. PJP should always be considered in case of and para-iliac and para-aortic lymph node enlargement. fever and respiratory symptoms since PJP is associated Bone marrow morphology, immunophenotyping, and with high morbidity and mortality. The main question in cytogenetics showed no localization of AML. Our patient this case remains: is PJP prophylaxis recommended in this was diagnosed with an isolated myeloid sarcoma and chemotherapy? intensive AML induction chemotherapy was initiated. Discussion: Myeloid sarcomas have been reported in C112 Clinical consequences of lymphocytosis with buttock 2.5-9.1% of patients with AML occurring concomitantly, cells before, or after the onset of systemic AML. Isolated

58 A.J.W. Gulpen, L.W. Tick, P.H.M. Kuijper negative.Complement factors C3 and C4 were decreased. Máxima Medical Centre, Department of Internal Medicine, Serum immunofixation was positive for a noncryopre- Veldhoven, the Netherlands cipitating IgG kappa biclonal protein and M-protein was detectable in the urine without being quantifiable. A renal Case: A 30-year-old woman was evaluated for a lymphocy- biopsy revealed a cryoglobulinemic membranoproliferative tosis identified during a routine check. Patients medical glomerulonephritis.The patient was treated with cyclophos- history mentioned psoriasis, for which she uses dimethyl phamide and prednisone, with almost complete normali- fumarate. At presentation, patient had no complaints, sation of kidney function and abrogation of proteinuria. especially no B-symptoms. She has a 6 pack-years history Four years after initial presentation kidney function of smoking. Physical examination was unremarkable, no worsened, erytrocyturia and proteinuria developed again. lymphadenopathy or hepatosplenomegaly was observed. A A monoclonal IgG kappa and cryoglobulinemia type I were chest X-ray showed no abnormalities. An ultrasound of the detected. A second renal biopsy was performed and showed abdomen showed a mild splenomegaly of 12 cm. again a cryoglobulinemic membranoproliferative glomeru- Laboratory examination showed hemoglobin 8.6 mmol /L, lonephritis. Rituximab treatment was started. leukocytes 12.7*109/l (39% neutrophils, 58% lymphocytes), Discussion: Glomerular disease secondary to CLL is rarely platelets 252*109/l. Other laboratory findings were reported in the literature and may be caused by deposition unremarkable, with the exception of a polyclonal elevation and possibly processing of cryoprecipitating or noncryo- of IgM (5.1 g/l). Earlier laboratory studies showed also precipitating M-components. Urinalysis can demonstrate a leukocytosis of 11.8*109/l with 41% lymphocytes. renal disease and should be performed in the standard Examination of the peripheral blood smear showed 5% work up for CLL patients. Depending on the renal histology binucleated lymphocytes. Immunophenotyping demon- treatment of the glomerulonephritis is usually indicated. strated a polyclonal population of B lymphocytes (CD19+, Whether treatment of the underlying hematologic disease CD20+, CD10-, CD5-), with k/λ ratio of 1.8 (ref.0,8-3,5). is indicated is questionable, but most renal diseases Viral serology tests of Epstein Barr virus showed a previous that are a consequence of CLL respond to the standard EBV infection (IgG VCA+, IgG EBNA+, IgM VCA-). treatment of the glomerulonephritis. Conclusion: The above findings established the diagnosis persistent polyclonal B-cell lymphocytosis (PPBL). PPBL C114 A long term complication of breast implants: is a benign, chronic disorder of B-lymphocytes which anaplastic large cell lymphoma occurs mainly in young women with an smoking history. It is characterized by increase of polyclonal B-lymphocytes A. Nijhof, K.E.M. Cox, M. Meesters, R.J.W. van Kampen in the peripheral blood, binuclear lymphocytes in the Atrium-Orbis Medical Centre, Department of Internal microscopic differentiation and an increase of polyclonal Medicine, Sittard-Geleen, the Netherlands IgM. Morphology is distinctive with polyclonal binucleated Introduction: Non-Hodgkin lymphomas of the breast lymphocytes (Buttock cells). Buttock cells are also present are rare, mostly distinct clinical entities. In recent years in aggressive or indolent lymphomas; these are monoclonal anaplastic large cell lymphoma (ALCL) has been associated B-cell populations. The polyclonal B-cell population very with the presence of breast implants. We report two cases rarely degenerate into a malignant lymphoma. of this rare and possibly underestimated condition. Case report: Patient A (48 yr.) and patient B (40 yr.) C113 An unusual cause of renal failure in a patient with both presented with swelling and pain in one of their chronic lymphocytic leukaemia breasts (due to seroma and masses). Both had undergone aesthetic breast augmentation with implants more than L.W. de Bont, G.W. Feith, G.A. Velders ten years before presentation, which were still in place. Gelderse Vallei, Department of Internal Medicine, Ede, the We diagnosed both patients with a localized ALK negative Netherlands ALCL. Breast implants were removed in both patients and both started chemotherapy (CHOP-regimen). Case report: A 65-year old man was diagnosed in 2009 In patient A complete remission was reached. Five years with B-cell chronic lymphocytic leukaemia Rai stage 0, after her last treatment however, disease relapse occurred without treatment indication. At the time, the leukocyte and she was treated with reinduction chemotherapy with count was 20.0 x 109/l with 57% lymphocytes. In five autologous stem cell transplantation. In patient B, initial months he developed renal failure with a serum creatinine response on therapy was obtained, but early and aggressive of 160 mmol/l. Urinalysis showed dysmorphic eryth- relapse of her lymphoma after five cycles of chemotherapy rocytes and nephrotic range proteinuria of 8.6 gram. occurred. Salvage chemotherapy was given complicated ANCA, ANA, cryoglobulins and anti-GBM tests were by end stage renal failure, respiratory insufficiency and

59 fulminant relapse after initial short lasting response to supportive care. Accrual into clinical trials decreased with therapy. age, with no trials available for ≥70 years. Novel treatment Conclusions: aesthetic or reconstructive augmentation may options with an acceptable toxicity profile are warranted have severe consequences. Implant related ALCL is one of to further improve outcome, particularly in older patients. these. The exact number of patients, the relation to type of implant and the relation to reason for implant remain C116 The T cell leads the way to a diagnosis unclear. Besides awareness, a need for long-term clinical follow-up to better define natural history and outcome A. Magro exists. A nationwide implant registry and extensive Amphia Hospital, Department of Internal Medicine, Breda, information to patients could reveal these causes and the Netherlands relations. Introduction: Bone marrow biopsies play a central role in C115 Improved survival in adult Acute Lymphoblastic the diagnosis of haematological conditions. We present a Leukemia (ALL) in the the Netherlands from 1989 patient with transfusion-dependent anaema with incon- to 2012: a population-based study on incidence, clusive bone marrow examinations leading to delayed treatment, trial participation and survival diagnosis. Case description: A 62-year old male presented with A. Szabó1, A.G. Dinmohamed1, M. van der Mark2, a 2-month history of fatigue and shortness of breath. O. Visser2, P. Sonneveld1, J.J. Cornelissen1, Physical examination revealed no abnormalities. M. Jongen-Lavrencic1, A.W. Rijneveld1 Laboratory tests showed a macrocytic anaemia of 1Erasmus MC Cancer Institute, Department of Haematology, 3.3mmol/L (MCV: 112fl) and thrombocytopenia of 60x109/l Rotterdam, the Netherlands, 2Comprehensive Cancer Centre with low reticulocyte count (4x109/l). Deficiencies, viral the the Netherlands, Department of Registration and Research, infections and haemolysis were excluded. The initial bone Utrecht, the Netherlands marrow biopsy revealed normal cellularity including normal erythropoeisis. The patient was transfusion- Population-based studies among unselected adult ALL dependent, needing 2 units of blood two weekly with patients are scarce. We conducted a nationwide population- secondary haemochromatosis, and progressive thrombocy- based study to assess trends in treatment, trial partici- topenia. A second bone marrow biopsy showed an increase pation and survival. in lymfocytes. Peripheral blood flowcytometry showed a We identified 1833 over 18-year-old ALL patients (average small clonal T-cell population and a larger polyclonal T-cell annual age-standardized incidence, 0.6/100,000) population, leading to the possibility of a lymphoma. A diagnosed between 1989-2012 from the the Netherlands CT scan showed a 7 cm-large lobular anterior mediastinal Cancer Registry (NCR). Patients were categorized into mass. The mass was surgically removed, and the diagnosis 4 periods and 5 age groups (18-24, 25-39, 40-59, 60-69, thymoma was made. Unfortunately, blood counts did not ≥70 years). Primary treatment was defined as supportive improve after thymectomy. Bone marrow morfology after care, chemotherapy (CT) and chemotherapy followed by thymectomy showed absent erythropoeisis and slightly autologous/allogeneic stem cell transplantation (CT+SCT). reduced megakaryocytes, finalising the diagnosis aplastic Linking the NCR to HOVON and EORTC databases anaemia. Currently transfusion dependancy persists, so provided trial participation data. Relative survival rates immunosuppressive therapy is considered. (RSRs) were calculated as a measure of disease-specific Discussion: Thymomas are well known to be accompanied survival. by immune-mediated conditions like myastenia gravis. Overall, 98%, 97%, 91%, 83% and 43% of the patients in The association with aplastic anemia is rare. Thymectomy the 5 age groups received intensive treatment (CT±SCT), can, but often does not lead to a resolution of anaemia. while 2%, 3%, 9%, 17%, 57% received supportive care Aplastic anemia can occur years after thymoma resection. only, respectively. Clinical trial inclusion rate was 67%, Treatment of thymoma related aplastic anemia is similar 66%, 55%, 45% and 0% for the 5 age groups, respectively. to other aplastic anemias. Five-year RSRs improved over time from 19% in 1989-1994 to 37% in 2007-2012. Relative survival deteriorated consid- C117 Cryoglobulinemic vasculitis in two patients with erably with age as 5-year RSRs were 75%, 57%, 37%, 22% multiple myeloma and 5% for the five age groups in 2007-2012, respectively. Survival of unselected Dutch adult ALL patients improved L. Nieuwenhuizen, M. Minnema over time. This improvement might be explained by UMC Utrecht, Department of Haematology, Utrecht, the increased application of allogeneic-SCT, intensification of Netherlands chemotherapy based on pediatric protocols and improved

60 Introduction: Precipitation of cryoglobulin, which consists chronic xanthogranulomatous inflammation suggestive of of immunoglobulins and complement components, at Rosai-Dorfman disease. Treatment with prednisone gave a temperatures lower than 37ºC is referred to as cryoglo- partial response. bulinemia. Type I cryogloblinemia indicates the presence Five years later she presented with relapsing ocular of isolated monoclonal Ig (typically IgG or IgM, less complaints. Laboratory results showed similar abnor- commonly IgA or free immunoglobulin light chains) and malities as before in addition to an acute on chronic kidney is associated with Waldenström’s macroglobulinemia and disease with nephritic syndrome. Bone marrow aspiration multiple myeloma. showed no abnormalities. Renal biopsy revealed tubuloint- Case description: A 61-year old Caucasian female and erstitial nephritis and secondary FSGS together with a a 67-year old Caucasian male presented both at our large number of IgG4-positive plasma cells in accordance outpatient clinic with generalized erythematous macules, with IgG4 related disease. Treatment with prednisone purpuric papules, and necrotizing lesions. Skin biopsies was reinduced after which the ocular complaints and revealed leukocytoclastic vasculitis. Laboratory results kidney function improved. The elevated serum IgG4 levels showed a type I cryoglobulin with a IgG kappa monoclonal declined. Retrospectively biopsy material of the ocular peak on protein electrophoresis of 6 g/l and 7 g/l respec- mass also showed IgG4 positive plasma cells thereby tively. HIV, HBV, HCV, EBV, CMV, rheumatoid factor, adding Rosai Dorfman disease to the spectrum of IgG4 anti-nuclear antibody, antineutrophil cytoplasmic and associated disorders. antiphospholipid antibodies were negative and C3 levels Conclusion: We described a patient diagnosed with were normal. Calcium and renal function were normal relapsing Rosai-Dorfman disease accompanied by an and there were no osteolytic lesions. Bone marrow biopsies IgG4 mediated nephritic syndrome. Literature describes a demonstrated a clonal plasma cell population of 10% relationship between these diseases especially in patients and 15% respectively. Both patients were diagnosed with of Asian descent. a IgG kappa multiple myeloma, ISS I with a cryoglobulinemia type I and treated with chemotherapy with clinical remission of the cutaneous manifestations. X IMMUNOLOGY/ALLERGOLOGY Conclusion: We describe two patients with a cryoglobulinemia type I in the presence of a multiple myeloma. Cryoglobulinemia type I is associated with significant C119 Deep venous thrombosis as first presentation of morbidity and the underlying multiple myeloma needs celiac disease to be treated for, even at low M-proteine levels or in the absence of CRAB criteria. N.A.F. Verheijden1, P. van Wijngaarden2, C. van Guldener2 1Erasmus MC, Department of Internal Medicine, Rotterdam, C118 Periorbital extranodal Rosai-Dorfman disease the Netherlands, 2Amphia Hospital, Department of Internal associated with IgG4 disease Medicine, Breda, the Netherlands

J.M.W.E. Willems, C.R. Susanto, H.A.D.M. van Herk, Celiac disease (CD) is an auto-immune disorder with E.M.G. Jacobs chronic inflammation of the small intestine leading to Elkerliek Hospital, Department of Internal Medicine, villous atrophy and malabsorption. In this case report Helmond, the Netherlands we highlight a patient with an extensive DVT continuing into the iliac vein up to the inferior vena cava. She had no Case description: We describe a combination of extranodal known thrombogenic risk factors besides the use of oral Rosai Dorfman and IgG4 mediated disease; two rare, contraceptives. Because of the presence of iron-deficiency though related diseases. anaemia in addition to the thrombosis we searched for A 68-year old Asian female presented with bilateral an underlying condition. CD was diagnosed, which was periorbital swelling, partial loss of vision and anosmia. presumed to be the cause of the anaemia, and possibly had Her medical history included diabetes mellitus with played a role in the occurrence of the DVT through a link micro- and macrovascular complications and osteomyelitis with the antiphospholipid syndrome. Next to the classical of her left foot. Physical examination showed solid masses clinical picture of CD, the extra-intestinal presentations are in both upper eyelids. There were no palpable lymph emerging. Literature describing the association of CD with nodes or signs of hepato-splenomegaly. Laboratory results other autoimmune diseases, namely those with hyperco- showed a normocytic anemia, mild kidney dysfunction, an agulability, is growing. Therefore, it is important to create elevated ESR and ferritin. MRI showed bilateral extraocular awareness of these associations. masses which extended into the glandulae lacrimales. Histopathology showed reactive lymfoïd hyperplasia with

61 C120 Haemophagocytic lymphohistiocytosis as presenting cultured.A diagnosis of idiopathic hypophysitis was symptom of SLE supposed, iv solumedrol initiated and she was referred to an university hospital. Despite the immunosuppressive B. Santbergen, J.A.M. van Laar, P.L.A. van Daele, treatment, left-sided blindness remained, and visual P.M. van Hagen impairment of the right eye (OD) was also observed. Erasmus MC, Department of Haematology, Rotterdam, the Optical coherence tomography showed a thin retina, Netherlands suggesting temporary ischemia. A new MRI revealed aspecific thickening of the dura. The differential diagnosis A previously healthy 17-year old girl with persisting was expanded to lymphoma, sarcoidosis, tuberculosis fever, pancytopenia, elevated serum levels of triglyc- or vasculitis. Subsequently pulmonary nodular lesions erides, ferritin and soluble IL2-receptor, splenomegaly were demonstrated on a chest CT. Histology showed and haemophagocytosis in the bone marrow was aspecific neutrophillic para-capillary inflammation without transferred to our university hospital. Based on these signs of tuberculosis. Elevated c-ANCA and anti-PR3 findings, haemophagocytic lymphohistiocytosis (HLH) titers confirmed granulomatosis with polyangiitis(GPA). was diagnosed. Further evaluation revealed a subtle Cyclophosphamide and low molecular heparine were butterfly rash, increased ANA and anti-dsDNA- levels added to corticosteroids. Despite high dose corticosteroids, and lupus nephritis class IV. Molecular analysis demon- immunoglobulins and plasmaphereses, the visual acuity strated heterozygosity for the c.2679G > C variant in exon of OD detoriated to < 1%. A new MRI showed optical 28 of the UNC 13D gene. We concluded that systemic nerve compression by progressively thickening dura. lupus erythematosus (SLE) triggered HLH in our patient, However, the pulmonary lesions and ANCA’s diminished. possibly enabled by a minor defect in a gene known to be Neurosurgical decompression of the right optical nerve, associated with primary HLH. combined with rituximab, resulted in normalization HLH is an inflammatory syndrome characterized by of visual acuity (1.0). Histology of the affected dura exaggerated cytokine release due to an imbalance between demonstrated active vasculitis. Cyclophosphamide followed CD8+ cells and macrophages. HLH can be primary or by azathioprine conserved the right-sided vision and secondary. Secondary HLH is mostly associated with remission of the pulmonary lesions and ANCA’s. We here infections malignancies, or seldomly auto-immunologic demonstrate the importance of teamwork and illustrate diseases. Of those, the macrophage activating syndrome in the difficulty of diagnosing and treating ANCA-associated Stills disease is most known. SLE is second most reported. vasculitis, in this case GPA presenting with visual loss due HHoHowever, only few cases of SLE presenting as HLH to a hypertrophic pachymeningitis. have been reported. The relation with the heterozygous UNC13D mutation is unclear and not been described C122 A 21-year-old Congolese female with a rare cause of previously. progressive extensive skin granuloma of hands and Our patient started with steroids and mycofenolic acid. legs, and nodular respiratory tract lesions Within 2 weeks, she recovered completely and blood levels improved. Up till now, mycofenolic acid is used as H. Ytredal, E.F.H.I. Peeters, C.M.J. Steendam, maintenance therapy and prednisone is tapered. A.S.R. van Lindert, C. Sanders, H.L. Leavis This case demonstrates how a systemic disease can UMC Utrecht, Department of Internal Medicine, Utrecht, the commence in many different ways and that one must Netherlands always be prepared for unexpected causes in patients with persisting fever. Introduction: Granulomatous disease is typically caused by infections and conditions like sarcoidosis and granu- C121 Multidisciplinary approach to save the day-light lomatosis with polyangiitis. Less frequent are immuno- deficiencies. We describe a suspected extremely rare R. Otten, P. van Biezen, J. de Hoog, P.M. van Hagen, case of primary immunodeficiency, leading to significant R. Dammers, J.A.M. van Laar morbidity. Erasmus MC, Department of Internal Medicine, Rotterdam, Case: A 21-year-old Congolese female was admitted with the Netherlands extensive hyperpigmented, active ulcerative skin lesions and peripheral bone and joint deformities, progressive A 67-year old woman presented to the neurologist during the past 11 years. Her medical history revealed with visual loss of the left eye, headache, diplopia and recurrent respiratory tract infections, exacerbations ataxia. Ocular examination, angiography and MRI of skin and stomach symptoms. Blood tests showed revealed no abnormalities. A cerebrospinal fluid tap anemia, chronic inflammation and immune activation,an showed pleocytosis, but micro-organisms were not unremarkable phago cyticoxidative burst and negative

62 ANCA. Skin biopsies showed ulcerating granulomatous of Reumatology, suggestive of the diagnosis of SLE. High inflammation. Repeated cultures were negative for dose prednisone, combined with hydrochloroquine was mycobacteria including M.leprae, fungi, histoplasmosis started. Her treatment was complicated by prednisone- and leishmania. HIV and TBC-screening because of induced delirium, for which we switched treatment to brochopathy and tree-in-bud lung deformations was azathioprine. Full recovery was noticed within 4 weeks of negative. Without classifying diagnosis, TAP deficiency admission. syndrome was considered. MHC class I was absent from Conclusion: Serositis with pleural and cardiacl effusion is peripheral blood lymphocytes on flow cytometry and needs a well known presentation of SLE. However, there can be a repeated testing. MHC class I immunohistochemical significant delay in diagnosis. Pathology results can guide staining revealed expression in skin, yet quantification was the search for a diagnosis and prevent extensive diagnostic unavailable. Genetic testing for Tap deficiency is currently investigations. performed. Azithromycin prophylaxis and local skin therapy, have improved her medical condition. C124 Local and systemic signs of chronic B-cell responses Discussion and conclusion: In TAP1-deficiency a defective in Crohn’s disease- New opportunities in treatment TAP complex results in reduced surface expression of and therapeutic monitoring? MHC class I. Only 10 cases surviving into adulthood have been described. It is characterized by recurrent W.M.C. Timmermans1, J.A.M. van Laar1, T.B. van der Houwen1, bacterial respiratory infections, chronic granulomatous L.S.J. Kamphuis1, S.J. Bartol1, K.H. Lam1, R.J. Ouwendijk2, skin lesions and sometimes non-erosive symmetrical P.M. van Hagen1, M.C. van Zelm1 polyarthritis. Therapy focuses on reducing infectious 1Erasmus MC, Department of Internal Medicinee, burden. Immunosuppressive medication might worsen Rotterdam, the Netherlands, 2Ikazia Hospital, Department of clinical symptoms. Allogeneic bone marrow or lung trans- Gastroenterology, Rotterdam, the Netherlands plantation might prove beneficial, but has yet never been performed. Background: Patients with Crohn’s disease show B cell infiltrates around granulomas and impaired IgM B cell C123 Cardiac tamponade as presenting symptom of memory. These contradictory observations prompted us to systemic lupus erythematosus study the B-cell involvement in chronic inflammation in patients with Crohn’s disease. V. de Jonge, A. Dees Methods: B-cell infiltrates in intestinal biopsies were Ikazia Hospital, Department of Internal Medicine, studied in 5 patients. Serum immunoglobulins and Rotterdam, the Netherlands blood B-cell subsets were studied in 21 patients not receiving immunosuppressive medication and 5 patients A 57-year old lady presented to the Emergency Department who responded well to infliximab. because of progressive dyspnea. Besides significant weight Results: Granulomatous tissue showed infiltrates of loss of 10 kg in 3 months our patient had no other B lymphocytes rather than Ig-secreting plasma cells. complaints. Circulating IgM memory B cells were reduced and showed Her medical history revealed fibromyalgia diagnosed 2 decreased replication history and low levels of somatic years before presentation, furthermore she had hyper- hypermutation. Transitional B cells and CD21low B cells tension, an anxiety disorder, paroxysmal atrial fibrillation were elevated. IgG and IgA transcripts carried increased and an aortic valve sclerosis. She was recently analysed mutation levels and large fractions of switched memory B because of a pleural effusion. Drainage of the transudate cells carried low CD21 expression. The numbers of transi- and pleural biopsies showed no diagnosis so far. tional and natural effector cells normalized in patients At presentation our patient was hypotensive and tachycard. responding to infliximab. Bibasal crackles were heard. X-ray showed persisting Conclusion: The large numbers of B cells present in granu- pleural effusion. Electrocardiography showed expect atrial lomatous tissue and the increased mutation levels in class fibrillation without signs of ischemia. Echocardiography switched memory B cells suggest their involvement in was performed because of a threatening cardiac tamponade chronic inflammation in Crohn’s disease. These concern and showed besides pleural effusion also pericardial switched memory B cells that show signs of chronic effusion. This was punctured and revealed a hemorrhagic activation with increased somatic hypermutations and punctate. Pathology results on the pericardial effusion elevated CD21low fractions. In contrast, IgM memory B raised suspicion of systemic lupus erythematosus. cell production is impaired. Still, their levels normalize Serology was subsequently performed, which demon- in response to TNFa-blockers making them potential strated anti-ds DNA (117 IU/ml) and anti-SSA. She markers for treatment monitoring. Together, these results sufficed now to 4 of 11 criteria of the American College suggest a chronic and aberrant B cell response in Crohn’s

63 disease in which new therapeutics regulating B cells could potentially target inflammation in Crohn’s disease. Background: Behçet’s disease (BD) is an autoinflammatory disease characterized by recurrent orogenital ulcerations, C125 Plasma cell dyscrasia and vasculitis: the clue is in the skin lesions and uveitis. The inflammatory nature of BD is kidney thought to be a result of a hypersensitive innate immune reaction; this is stressed by the association of human L.T.H. Broeren1, M.A. Hamid2, C.J.A.M. Konings1, leukocyte antigen (HLA)-B51 with BD and the pathergy P. Paassen2 reaction. 1Catharina Hospital, Department of Internal Medicine, Methods: To study the possibility of an increased innate Eindhoven, the Netherlands, 2Maastricht UMC+, Department immune response to pathogen associated molecular of Pathology, Maastricht, the Netherlands patters we analyzed the Toll-like receptor (TLR) response of 7 immunosuppressivetherapy naïve BD patients Both plasma cell dyscrasia and vasculitis present with a and 3 healthy controls. We incubated whole blood with highly variable clinical phenotype, in many cases resulting TLR-agonists for 6 hours at 37 °C 5% CO2 and measured in diagnostic and therapeutic dilemmas. TNF-a response with ELISA. Case: A 69 year old female presents with severe leuco- Results: We found a significant higher level of TNF-a cyoclastic vasculitis of the skin, and acute kidney injury in BD patient in response to TLR-2 stimulation with (creatinine 680 umol/l), initially explained by E. Coli pyelo- Streptococcus pneumoniae derived LTA (p = 0.02). After nephritis. Kidney function restores after antibiotics, but stimulation with Flagellin (TLR-5) we demonstrate an subsequently she develops pleura effusion and progressive even more potent TNF-a response (p = 0.02). In addition dyspnoe. She has arthralgias and Raynaud’s phenomenon. to this we showed a trend in increasing TNF-a levels after The laboratory shows strongly elevated reumatoid factor, stimulation with PAM3CSK4 (TLR-1/2). Both controls and and presence of cryoglobulins, predominant IgM kappa, patients showed a strong TNF-a response after TLR-4 and IgG lambda. There is complement C4 consumption. stimulation with (LPS). Bone marrow aspirate showed normal hematopoiesis, Conclusion: This pilot study presents elevated TNF-a and no clonal proliferation of plasma cells. A differential response after stimulation of especially TLR-2 and TLR-5 diagnosis of lupus is considered. in a small group of BD patients. After stimulation of TLR-4 Remarkably, kidney biopsy showes normal glomeruli, with LPS no difference is found, which could be the result but a lymphoplasmacellular tubulointerstitial infiltrate of overstimulation with high doses of potent LPS. This data with predominance of kappa light chains. There is no suggests a hyperreactivity of TLR-2 and TLR-5, as possible sign of viral infection. Congo red staining is negative. clue for the inflammatory nature of BD. These findings Ultrastructural analysis also showes no deposition of need to be confirmed and further explored, especially in amyloid, light chains nor cryoglobulins. Total body PET-CT the direction of TLR-expression and other inflammatory did not show signs of lymphoma. cytokines. In conclusion: Our case shows the rare combination of a localized (pre)malignant clonal lymphoplasmacellular C127 Retrospective assessment of immunosup- proliferation within the kidney, and type II cryoglo- pressive agents in virus-negative inflammatory bulinemia mediated systemic vasculitis, with normal cardiomyopathy bone marrow examination. In such a case, it is quite important to consider the cost-benefit of a far more J.J. Merken, M. Hazebroek, P. van Paassen, S.R.B. Heymans, toxic hematological treatment regime, as compared to an P. van Paassen immunological approach. Patient was treated with plasma Maastricht UMC+, Department of Cardiology, Maastricht, exchange, corticosteroids, and mycophenolate, subse- the Netherlands quently followed by 4 cycles of rituximab. Her clinical response was favorable. Background: The WHO defines non-ischaemic virus- negative inflammatory cardiomyopathy as a disease of the C126 Behçet’s disease patients show a more potent heart associated with cardiac dysfunction, with at least 14 response to TLR-2 and TLR-5 stimulation in human CD45-positive leucocytes (4 CD68-positive leucocytes can whole blood be added to reach these 14 inflammatory cells) or at least 7 CD3-positive leucocytes per mm2 on endomyocardial T.B. van der Houwen, M. Goeijenbier, E.C.M. van Gorp, biopsy, and no viruses (or < 500 copies/microgram) J.A.M. van Laar revealed by PCR. Up to the present, no studies evaluated Erasmus MC, Department of Clinical Immunology, the effect of immunosuppression on patients who fulfilled Rotterdam, the Netherlands this definition.

64 Methods: Within the Maastricht Cardiomyopathy Registry, Results: 214 physicians completed the questionnaire, and a total of 487 DCM patients underwent endomyocardial 580 comments were given. Seven barriers were identified, biopsy (EMB) between 2008 and 2014, of which 93 namely: expectation of little improvement of antibiotic use; fulfilled the WHO and ESC guideline criteria for virus- expectation of little patient’s satisfaction for checklist use; negative inflammatory cardiomyopathy. Sixty-eight patients low expectation of colleagues’ checklist use; low estimated did not and 25 did receive immunosuppressive therapy. supervisors’ and nurses’ expectation of checklist use; To correct for possible selection bias, 2:1 propensity score negative previous experiences with checklists, and lack of matching was performed, consisting of 50 untreated financial resources. A comparative analysis showed that the (Group 1) and 25 treated patients (Group 2). Primary feasibility of the checklist was significantly lower according outcome was the assessment of left ventricular ejection to surgeons than to medical doctors. fraction (LVEF) after one year follow up. Conclusion: Barrier identification is necessary for adequate Results: A higher increase of LVEF was revealed in group preparation of checklist implementation. Restructuring of 2 compared to group 1. Group 1 had a mean absolute the contents is necessary to make the checklist workable. LVEF incline of 8,8%, compared to 15,3% in group 2 Implementation activities will focus on teamwork and (p-value = 0,041). Both groups demonstrated a significant education about the possible improvement of antibiotic use. increase in LVEF (p < 0.001) after one year. Baseline characteristics did not show significant differences C129 A patient with rheumatoid arthritis and five times between both groups. aortic valve replacement Conclusion: This retrospective study shows that immunosuppression leads to a higher increase of left ventricular E.M. van Soest1, J.G.M. Koeleman1, M.E.I. Schipper2, function in patients with virus-negative inflammatory D. van Zeben1 cardiomyopathy. This conclusion triggers further 1Sint Franciscus Gasthuis, Department of Internal Medicine, prospective trials. Rotterdam, the Netherlands, 2Erasmus MC, Department of Clinical Pathology, Rotterdam, the Netherlands

XI INFECTIOUS DISEASES A 67-yr old male with rheumatoid arthritis and four times an aortic valve replacement (1998, 2x 1999 and 2012), was at the rheumatology outpatient clinic for routine C128 Barriers to implementation of an antibiotic checklist check-up in January 2013. Laboratory testing showed an elevated ESR and increased gamma-glutamyl transferase F.V. van Daalen1, S.E. Geerlings1, J.M. Prins1, and alkaline phosphatase without evident cause. Later that M.E.J.L. Hulscher2 year he was admitted twice with fever and progressive rash. 1AMC, Departments of Internal Medicine and Infectious Liver chemisty abnormalities and ESR further increased. Diseases, Amsterdam, the Netherlands, 2Radboudumc, Centre Blood/urine/joint cultures, CT,- PET scans and echocar- for Quality of Care Research, Nijmegen, the Netherlands diography showed no abnormalities. Coxiella burnetii fase I serology turned out highly positive, indicating Background: To curb antimicrobial resistance, a better use chronic Q fever. Chronic Q fever is rare condition (< 5% of of current agents is necessary. Guideline-based quality patient with acute Q fever). It may present as endocarditis, indicators (QIs) have been developed to define appropriate especially in patients with pre-existent valve abnormalities, antibiotic use for the treatment of bacterial infections in however with negative blood cultures and negative echocar- the hospital. A checklist based on these QIs can be a useful diography results. Because of non-specific symptoms the tool to stimulate appropriate use. We aimed to identify diagnosis is often delayed. The patient was started on barriers to the implementation of an antibiotic checklist for doxycycline and hydroxychloroquine. Revision of aortic patients with suspected bacterial infections who are treated valve tissue from 1998/1999 revealed an plasmocellulair with intravenously antimicrobial therapy in the hospital. inflammatory reaction possibly due to Coxiella infection, Methods: We developed a questionnaire to determine but PCR for Coxiella burnetii DNA was negative. In barriers related to the checklist, the professional and to October 2014 the patient again underwent aortic valve his/her social and organisational setting. It consisted of replacement because of aortic valve insufficiency. Now 23 statements. Participants could add comments. The PCR for Coxiella was positive. Additionally, he was started questionnaire was sent to physicians in seven Dutch on moxifloxacine. It remains uncertain whether the patient hospitals. If ≥ 25% of the participants indicated that was infected already in 1998 and his aortic valve failure has the determinant hindered use of the checklist, this been due to chronic Q fever infection all along, or whether determinant was labelled a barrier. he has been infected later, being at higher risk because of

65 etanercept use for his rheumatoid arthritis and prosthetic Background: Hepatitis E can develop to a chronic infection aortic valve in situ. in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that C130 Clinical practice of darunavir/ritonavir (DRV/r) treatment with ribavirin or pegylated interferon-a can monotherapy in HIV patients result in viral eradication. This systematic review aims to evaluate efficacy and safety of both treatments in chronic H. Visser1, M. Martinez-Rebollar2, J. Mallolas2, M. Laguno2 hepatitis E. 1VUmc, Department of Internal Medicine, Amsterdam, Methods: A systematic literature search was performed on the Netherlands, 2Hospital Clínic, IDIBAPS University of PubMed, Web of Science and clinicaltrials.gov for articles Barcelona, Department of Infectious Diseases, Barcelona, and abstracts. The keywords ´”Hepatitis E”or HEV’ AND Spain ‘ribavirin or Rebetol or Copegus’ OR ‘pegylated interferon OR peginterferon’ were combined. The primary outcome Background: Combined antiretroviral therapy is the was sustained viral response (SVR). Secondary endpoints standard of care for HIV patients. Simplifying treatment include rapid viral response (RVR), relapse rates and side to monotherapy has been proposed to avoid side effects and effects. Descriptive statistics and intention-to-treat analysis lower costs. However, monotherapy is still controversial. were performed. Here we analyze retrospectively the efficacy and safety of Results: Twenty-four studies matched our criteria, repre- DRV/r monotherapy in a clinical setting. senting a total of 105 ribavirin treated and 8 pegylated- Methods: Hospital Clínic has 3,500 HIV patients in interferon treated patients. The majority of patients had follow-up. From January 2010 to September 2013, all a solid organ transplant. Sixty-three percent of ribavirin patients who received DRV/r were analysed. Follow up treated patients achieved a SVR at 6 months after was at least 48 weeks. Virological failure (VF) was defined treatment cessation compared to 2/8 peg-interferon treated as two consecutive times a detectable viral load (VL). patients. Ribavirin was relatively well tolerated with the Therapeutic failure (TF) was considered as a change of main side effect being anemia, requiring dose reduction monotherapy because of VF, side effects or lost to follow in 28% of patients. Peg-interferon lead to acute transplant up. rejection in 2/8 patients. Results: DRV/r was prescribed to 299 patients, 51% had a Conclusions: Ribavirin monotherapy appears to be an nadir CD4 > 100 cells/mm3, 81% had no previous failure effective and safe treatment in all immunocompromised to protease inhibitors (PI) and 85% had undetectable VL patients with chronic hepatitis E. The use of pegylated >6 months before starting monotherapy and 10% was interferon in transplant patients may lead to transplant coinfected with hepatitis C. rejection and is not recommended. Ribavirin should TF occurred in 18% of the patients. Eleven percent showed therefore be the antiviral treatment of choice in chronic VF, of which 7 % changed antiretroviral therapy. Other hepatitis E. reasons to change monotherapy were adherence (3%) and side effects (2%). Out of 32 patients with VF, drug C132 Tuberculous Peritonitis resistance was tested in 18 and in one patient a minor resistance due to L33F mutation occurred. Age, gender, M. Koning, L.M. van der Pol, E.F. Schippers nadir CD4 count nor previous failure to PI were associated HagaZiekenhuis, Department of Internal Medicine, Den with TF. Haag, the Netherlands Conclusion: DRV/r monotherapy is safe and effective in a clinical setting with similar results to that published in Introduction: Tuberculous peritonitis (TP) frequently clinical trials. Virological failure due to drug resistance presents with nonspecific symptoms which often lead to was very low. delayed diagnosis. We describe a case of TP in a native Dutch patient. C131 Chronic hepatitis E: A systematic review of antiviral Case: a 42-year-old patient was referred to the outpatient therapeutics clinic because of weight loss. He had no other complaints and no medical history. Physical examination, laboratory T.J.G. Gevers1, A.M. Peters van Ton2, J.P.H. Drenth2 tests, abdominal ultrasound and CT-scan showed no abnor- 1Rijnstate/Radboudumc, Departments of Gastroenterology/ malities. A watchful waiting strategy was adopted. Internal Medicine, Nijmegen, the Netherlands, 2Radboudumc, Six months later, he was referred again because of Departments of Gastroenterology and Hepatology, Nijmegen, progressive weight loss, accompanied by night sweats and the Netherlands myalgia. A submandibular swelling was noted. Cytology was consistent with a lateral or median neck cyst.

66 Three months later, a CT scan was performed because Background: Hantavirus infection is frequently confused of clinical suspicion of pulmonary embolism. Strikingly, with leptospirosis and tropical diseases and remains it showed lymphadenopathy in the epigastrium and undiagnosed in expectedly 50% of cases. Hantavirus is liver hilum. Subsequent abdominal CT-scan revealed believed to infect humans via aerosols from rodent excreta. ascites, omental lymphadenopathy and a diffusely Infection can be asymptomatic or cause hemorrhagic fever, thickened mesentery. Malignancy and tuberculosis were a cardiopulmonary syndrome, and/or a renal syndrome. considered and a diagnostic laparoscopy was performed. The current case demonstrates that hantavirus infection Laparoscopic findings were consistent with miliary tuber- should be considered in patients with fever and possible culosis and culture of a peritoneal biopsy was positive for rodent contact, particularly when renal insufficiency Mycobacterium tuberculosis. The patient had frequently and thrombocytopenia are present. It also shows that travelled to Asia until 3 years before presentation. He was hantavirus infection does occur in The the Netherlands treated with tuberculostatics for 6 months and slowly (seroprevalence 1.7%). recovered. Discussion: TP represents a diagnostic challenge C134 Rickettsiosis: a souvenir from Vietnam and because of the lack of specific symptoms and absence of Cambodia non-invasive diagnostic tests. Treatment delay is especially common in countries with a low prevalence of tuberculosis I.M. Celis, C. Richter and leads to high morbidity and mortality. Rijnstate, Department of Internal Medicine, Arnhem, the TP should be considered in patients with weight loss, Netherlands abdominal pain and ascites. Laparoscopy with peritoneal biopsy is the diagnostic tool of choice. A 48-year-old woman presented to the emergency department with five days of fever, headache, abdominal C133 Acute renal insufficiency, thrombocytopenia, and pain, backache and dyspnea. She had just returned from fever after a swim in open water a three weeks’ holiday to Vietnam and Cambodia. One day ago she noticed a disseminated skin rash. Physical W.E. van Spil, A.W.A. Koot, C. Richter examination revealed a temperature of 40 °C and diffuse Rijnstates, Department of Internal Medicine, Arnhem, the small red spots on the trunk and extremities. Laboratory Netherlands results showed a CRP of 240, mild leukopenia, thrombopenia and slightly raised liver enzymes. Chest X- ray Case: A 46-year old man was admitted because of showed a consolidation in the right upper lobe. Differential high-grade fever, headache, and myalgia and arthralgia diagnosis included meliodosis, dengue, chikungunya since a few days. He had swum in open water the week and rickettsiosis. Treatment with meropenem (possible before in Babberich, near the German border. Physical meliodiosis) and doxycycline (possible rickettsiosis) was examination was unremarkable. Blood tests showed mild started. After three days she slowly recovered and became neutrophilia (8.1*10^9/l), thrombocytopenia (55*10^9), and afebrile. She was discharged six days after admission with a high C-reactive protein level (190 mg/l). Renal function, cotrimoxazole and doxycycline. Blood and stool cultures liver enzymes and function, and a chest X-ray were remained negative. There was no serological evidence of normal. Urinalysis showed mild proteinuria and some Dengue and Chikungunya.A couple of weeks later serology non-dysmorphic erythrocytes, but no leukocytes or nitrite. showed very high IgM and IgG antibody titers to Rickettsia Intervention: Amoxicilline/ciprofloxacine treatment Ricketsii and Rickettsia Typhi. We discussed these results was initiated under suspicion of atypical pneumonia. with the RIVM. Since there is cross-reactivity between Antibiotics were stopped when cultures and antigen tests different rickettsia species and because not all species for atypical pathogens all appeared negative. CRP levels can be tested, it is difficult to identify the exact causative decreased and the patient’s clinical status improved. agent. Because the patient had visited Cambodia and Surprisingly, the patient gradually developed acute Vietnam, she most likely had been infected with Orientia renal insufficiency (minimum GFR 45 ml/min) that Tsutsugamushi (a rickettsia species that causes scrub did not respond to intravenous fluid administration. typhus).Delay in antibiotic treatment is the main factor Ultrasonography showed normal-sized kidneys without for poor prognosis in patients with rickettsial diseases postrenal obstruction. Renal function did stabilize and the and doxycycline should be administered upon suspicion patient was discharged. of rickettsiosis without waiting for serologic confirmation, Diagnosis and clinical course: During follow-up, serology which can take weeks. appeared positive for hantavirus infection. All laboratory tests normalized spontaneously. C135 Leishmania infantum relapse in a renal transplant patient 8 years after treatment

67 bacteriological spectrum of these occurring post-surgical M.A.H. Berrevoets, M. Keuter infections, leading to inappropriate empirical antibiotic Radboudumc, Department of Infectious Diseases, Nijmegen, therapy. the Netherlands Methods: In this retrospective mono-center study we analysed the surgical and bacteriological data of all Case report: A 75-year-old man, who received a kidney consecutive patients who developed an infection between transplant in 2003, was admitted because of fatigue, January 2010 and April 2014 after surgical resection of a general weakness, weight loss and swelling of his left malignant BT or STT. forearm and hand. In 2005 visceral leishmaniasis (L. Results: 72 consecutive patients undergoing surgical infantum) was diagnosed after travelling to France treatment for a BT (n = 42) or SST (n = 30) were included. and Spain. In 2006 a relapse was diagnosed, necessi- A multimicrobiological flora was frequently present, tating repeated treatment. Current immunosuppressive more often in STTs (83%) than in BTs (48%) (p = 0.002). medication consist of prednisolone and tacrolimus. Gram-negative bacteria were more frequently isolated in Physical examination revealed a weak, cachectic patient. STTs (55%) than in BTs (26%) (p = 0.013), Staphylococci Body temperature was 36.8 °C. His left forearm and hand were more frequently found in BTs (76%) than in STTs were swollen and showed some skin interruptions but no (52%) (p = 0.032). ulcera. Ultrasound of the abdomen showed hepatosple- Conclusions: Post-surgical infections in patients who nomegaly. Laboratory results were as follows: C-reactive underwent surgical resection of a malignant BT or STT protein 31 mg/l, haemoglobin 6,7 mmol/l, leucocytes 4,3 were often of multimicrobial origin, especially STTs. x109/l, thrombocytes 107x109/l. The diagnosis of dissemi- Causing bacteria were often Gram-negatives in STTs, while nated visceral leishmaniasis was made by a positive PCR staphylococcipredominated in BTs. Antibiotic treatment for on blood and skin biopsy. Treatment with liposomal infections after surgical resection of BTs or STTs should amphotericin B was started. There is no literature about be based on these microbiological findings covering both treating relapsing leishmaniasis in this patient category, so Gram-positives and Gram-negatives. we asked the European LeishMan group for their opinion. They advised to give pentavalent antimonials for 28 days, C137 Evaluation of management of Staphylococcus aureus followed by monthly infusions, as long as immunosup- bacteraemia in a Dutch university medical centre pressive drugs are continued. Treatment with sodium stibogluconate was started and until now our patient is M. Cobussen, S.H. Lowe, F. van Tiel, A.M.L. Oude Lashof improving. Maastricht UMC+, Departments of Medical Microbiology and Conclusion: Visceral leishmaniasis in immunocompro- Infectious Diseases, Maastricht, the Netherlands mised patients is a potentially fatal disease. Due to the increasing use of immunosuppressive drugs and the Background: Staphylococcus aureus is an important cause ease of travelling, the incidence in immunocompromised of bacteraemia and associated with a high mortality. It has travelers will increase and doctors should be aware of previously been shown that consultation by an internist- the consequences of this disease. Once infected, relapses infectious diseases specialist (IDS) improves the outcome after treatment are common and doctors should consider of the patient. In this study, we evaluated the differences multidisciplinary treatment in a center with an infectious in management and outcome between patients with, and disease specialist. those without consultation by an IDS. Methods: All adult patients with a positive blood culture C136 High frequency of multimicrobial infections after for S. aureus from January 2010 to December 2013 were surgical resection of malignant bone and soft tissue retrospectively identified with the electronic registration tumors system of our Laboratory for Medical Microbiology. Clinical and microbiological characteristics were retrieved from the L.M. Vos1, P.C. Morand2, J.E. Arends3, D. Salmon2 electronic patient files, as well as information whether a 1Diakonessenhuis, Department of Internal Medicine, consultation by an IDS took place. Utrecht, the Netherlands, 2Hopital Cochin, Department of Results: A total of 245 patients with S. aureus bacteraemia Microbiology, Paris, France, 3UMC Utrecht, Department of were included in the study, of whom 77.8% were consulted Internal Medicine, Utrecht, the Netherlands by an IDS. Management of patients with IDS consultation was more often according to guidelines, compared to those Background: Surgical resection of a malignant bone without consultation by an IDS; follow up blood cultures tumor (BT) or soft tissue tumor (STT), with or without were taken more often (97.8% vs. 80.8%, p < 0.001), prosthetic replacement, carries a high risk of developing patients received more often echocardiography (70.9% postoperative infections. There is limited knowledge on the vs. 50.0%, p = 0.007), and they were more often treated

68 adequately (86.6% vs. 59.2%, p < 0.001). Although the C139 Coagulase Negative Staphycolococcus lugdunensis; detection rate of complications in the IDS group was higher not a contamination (59.3% vs. 32.7%, p = 0.001), 30-day mortality rate was lower (12.1% vs. 23.1%, p = 0.04). E.C.F. Wagenaar, R.W. van Etten Conclusion: In patients with a S. aureus bacteraemia, Amphia Hospital, Department of Internal Medicine, Breda, consultation by an IDS resulted in better adherence to the Netherlands diagnostic and treatment guidelines, with higher detection of complications and a higher survival rate. A 71-year old man is admitted because of fever and reduced vision and a painfull, red right eye. Laboratory research C138 Pretreatment HIV drug resistance increases regimen shows elevated CRP and leucocytosis but further regular switch in sub-saharan Africa research does not indicate a focus. Cefuroxime and tobramycin is started intravenously. K.C.E. Sigaloff1, T.S. Boender2, R.L. Hamers1, Bloodcultures show growth of coagulase negative staphy- B.M. Hoenderboom2, M. Siwale3, M. Wellington4, lococci (CNS), initially interpreted as contamination. C. Kityo5, S. Akanmu6, M. Botes7, T.F. Rinke de Wit2 The reduced vision is caused by endogenous endoph- 1AMC/AIGHD, Department of Internal Medicine, thalmitis and is treated with vitrectomy and intra-ocular Amsterdam, the Netherlands, 2AIGHD, Department of Global vancomycin, ceftazidim and amikacin. Health, Amsterdam, the Netherlands, 3Lusaka Trust Hospital, It is strongly suspect to endocarditis with embolic Lusaka, Zambia, 4Newlands Clinic, Harare, Zimbabwe, dissemination to the eye. A trans-esophageal echo shows 5Joint Clinical Research Centre, Kampala, Uganda, 6Lagos vegetations on the mitral valve. The CNS appears a University Teaching Hospital, Lagos, Nigeria, 7Muelmed Staphylococcus Lugdunensis (SL). A mitral valve Hospital, Pretoria, South Africa replacement is done and he is treated with flucloxacillin, gentamycin and rifampin for six weeks and recovers. After the scale-up of antiretroviral therapy (ART) in Africa, CNS are often interpreted as contamination and are there are concerns about emerging drug-resistant HIV and mostly not very virulent. SL however can cause serious an increasing need for more costly second-line regimens. invasive disease. 46% of the bloodstream infections with We investigated the impact of pretreatment drug resistance SL is complicated with endocarditis, meningitis, abscesses, (PDR) on switch to second-line within the Pan-African spondylodiscitis, infection of foreign material etc. SL Studies to Evaluate Resistance (PASER) cohort. endophthalmitis is rare and sometimes complicates eye The PASER cohort followed HIV-infected individuals surgery and has never been published as a first expression initiating ART for 3 years in 6 African countries. Viral of a bacteremia. An endocarditis with an indication to load (VL) and genotypic testing was performed at ART cardiac valve replacement has a very high mortality rate of initiation and annually thereafter. PDR was defined as a 23-45%, comparable to S. Aureus endocarditis. decreased susceptibility to ≥1 prescribed drug, using the SL is good sensitive to a broad range of antibiotics, but final Stanford algorithm. The effect of PDR on (I) switch to treatment should be led by its sensitivity spectrum. second-line, (II) virological failure and (III) acquired drug The challenge for the attending physician is to determine resistance was assessed using cumulative incidence plots, whether CNS in the bloodculture is a contamination, or an multivariate cox-models and multilevel logistic regression. infection. Beware of SL, it is a very serious CNS. Among 2,737 participants, PDR was present in 5% (n = 139). After 3 years, 112 (4.3%) participants had switched C140 Peginterferon alfa-2a and Ribavirin induced Graves to second-line regimen; 33.3% switched unnecessarily (with ophthalmopathy in an euthyroid patient without VL < 1,000 cps/ml). PDR increased the risk of: (I) switch thyroid autoantibodies to second-line, subhazard ratio 7.8 (95%CI 3.9-15.6); (II) virological failure, odds ratios (OR) 2.8 (95%CI 1.1-7.2, E.C.F. Wagenaar, S.W. van Thiel, P. van Wijngaarden and (III) acquired drug resistance, OR 5.0 (95%CI 1.8-14.3) Amphia Hospital, Department of Internal Medicine, Breda, after 3 years of first-line ART. PDR was not associated with the Netherlands mortality or new AIDS events. After 3 years, PDR was strongly associated with switch to A 41-year old man, known with Hepatitis C Virus (HCV) second-line ART, but it did not cause excess mortality or infection genotype 3a, was treated with Peginterferon AIDS events. VL monitoring can enable timely detection of alfa-2a and Ribavirin. Duration of treatment was planned therapy failure and avoid unnecessary switches. In view of for 24 weeks. In the twentieth week of treatment he rising PDR levels in Africa, these findings have important developed severe Graves’ ophthalmopathy. TSH/FT4 were implications for allocation of ART resources. normal, thyroid-stimulating hormone receptor antibodies (TRAb) were not elevated. Because of the severity of the

69 exophthalmus treatment was discontinued and he was bacilli and was finally determined as a Mycobacterium successfully treated with prednisolone. Bovis of the BCG-stem. Serological testing for Q-fever HCV-RNA was not detectable until he developed the and Quantiferon remained negative. After four weeks Graves’ ophthalmopathy. Four weeks after discontin- of treatment patient clinically deteriorated and CT-scan ation of treatment a relapse occured with high levels of showed progression of the aneurysm. An aortic-repair was HCV-RNA. performed. PCR showed Mycobacterium tuberculosis DNA Peginterferon alfa/Ribavirin is the regular treatment on aortic wall material. Auramine-stain was negative. of HCV. It can cause several side effects like influenza- Cultures of aortic material have not yet grown until now. like symptoms, hematological side effects and neuro- After discharge with a no-return policy from the ICU to the psychiatric symptoms. The main side effects described surgical ward patient deteriorated despite adequate anti- regarding the thyroid gland are the development of mycobacterial therapy, abscess drainage and aortic-repair antithyroid antibodies in 5 to 40 % of the patients. and eventually died. Main antibodies described are the thyroid peroxidase Mycotic aneurysm due to BCG is a rare but severe compli- antibodies (TPO-ab) and thyroglobuline antibodies cation of adjuvant BCG instillations for bladder carcinoma. (Tg-Ab). Only a minority develops clinical thyroid disease, most commonly Hashimoto’s hypothyroidism. Graves’ C142 Double plasmodium infections in two travelers from disease is uncommon and Graves´ opthalmopathy is rare. Kenya Patients having antithyroid antibodies at the beginning of the treatment with Peginterferon and Ribavirin will have a I.G. Manders1, C.E. Delsing1, L. Mulder2, G.J. Kootstra1 higher chance of developing thyroid dysfunction. Nearly all 1Medisch Spectrum Twente, Department of Internal Medicine, Graves´ patients have elevated TRAb level and the severity Enschede, the Netherlands, 2Labmicta, Department of Medical is correlated with the TRAb concentration. However our Microbiology, Hengelo, the Netherlands patient had no elevate levels and was euthyroid. This uncommon presentation of a known side effect of HCV Despite increased travel to malaria endemic areas, reported treatment indicates that clinical evaluation of side effects cases of malaria in The the Netherlands have decreased of HCV treatment is required next to laboratory results. from 535 patients in 2000 to 164 in 2013. Patients mainly present with Plasmodium falciparum (74.8%) and less C141 Mycotic aortic aneurysm and multiple abscesses; frequently with P. vivax (15.4%), P. ovale (7.3%) and a rare but fatal presentation of disseminated P. malariae (2.5%) infections. Among travelers double Mycobacterium bovis infection after adjuvant intra- malaria infections within one patient are rarely seen and vesical BCG-instillation for bladder cancer therefore easily missed. We describe a Dutch couple who initially presented with P. falciparum, for which they were A.J.J.M. Cloïn, D. Posthouwer adequately treated. However, both showed relapse based Maastricht UMC+, Departments of Internal Medicine/ on P. ovale, for which additional therapy is required. We Infectiology, Maastricht, the Netherlands discuss the diagnostic pitfalls and clinical and therapeutic implications of infections with multiple malaria species. A 80-year-old man was treated for bladder cancer with Double malaria infections should be considered in patients intravesical instillation with Bacillus Calmette-Guerin with recurrent fever after P. falciparum treatment, which is (BCG). Six weeks after the last instillation he was admitted inadequate for P. ovale and P. vivax hypnozoites. because of back pain and a chest wall mass. He reported loss of appetite, nausea, and weight loss, but no fever or C143 Early hepatic flares during ETV treatment are rare night sweats. Medical history revealed no tuberculosis or and do not require immediate treatment adaptation contact with tuberculosis. Physical examination showed no in chronic hepatitis B without cirrhosis abnormalities apart from the chest wall mass. Laboratory testing showed a normocytic anemia and P. Arends1, H. Chi2, I. Carey3, A. Brown4, elevated C-reactive protein. CT and consecutive PET/ M. Fasano5, D. Mutimer6, K. Deterding7, Y. Oo6, CT showed a mycotic saccular aneurysm and a chest J. Petersen8, F. Bommel9, R.J. Knegt2, J.G.P. Reijnders2, wall abscess. The abscess was surgically drained and T. Berg9, T. Wezel10, H. Wedemeyer7, M. Buti11, P. Pradat12, cultured, but Auramine-stain was negative. PCR on the F. Zoulim12, B.E. Hansen2, H.L.A. Janssen2 material was positive for Mycobacterial Species DNA 1Sint Lucas Andreas Hospital, Departemnt of Internal (CT 30) and Mycobacterium tuberculosis DNA (CT 27). Medicine, Amsterdam, the Netherlands, 2Erasmus MC, Tuberculostatic therapy consisting Isoniazide, Rifampicine, Departments of Gastroenterology and Hepatology, Rottedam, and Ethambutol was started. 2 weeks after incubation the Netherlands, 3Kings College London, Departments of the mycobacterial culture became positive with acid-fast Gastroenterology and Hepatology, London, United Kingdom,

70 4Imperial College London, Departments of Gastroenterology and Hepatology, London, United Kingdom, 5Clinic of Case description: A 53-year-old man was recently admitted infectious diseases, Departments of Gastroenterology and to our hospital. He had a history of HIV on cART (hiv Hepatology, Foggia, 6Queen Elizabeth Hospital, NIHR load undetectable and CD4-count 600/mm3) and chronic Biomedical Research Unit and Centre, Birmingham, United hepatitis C-1a, with cryoglobulinemia and polymyositis. Kingdom, 7Medical School Hannover, Departments of Since initial hepatitis C treatment failed twice, he had Gastroenterology and Hepatology, Hannover, Germany, started Sofosbuvir and Daclatasvir two months earlier, with 8Asklepios Klinik St. Georg, Ifi Institute, Hamburg, Germany, full suppression of the HCV load. 9University Clinic Leipzig, Department of Hepatology, He presented with severe thoracic pain, dyspnea and Leipzig, Germany, 10Klinikum der Johann Wolfgang Goethe- spiking fever since three days. He had no (productive) Universität, Frankfurt Am Main, Germany, 11Hospital coughing, provoking factors or recent travels. Physical Vall de Hebron, Department of Hepatology, Barcelona, examination showed no abnormalities except a Spain, 12Hôpital de la Croix-Rousse Hospices Civils de Lyon, temperature of 39 °C. Department of Hepatology, Lyon, France Laboratory results showed mild inflammation and elevated transaminases. Both ECG and transthoracic echocardiog- Background: Flares during NA therapy are associated raphy were normal. CT-thorax did not reveal pulmonary with resistance or cessation of therapy. We investigated embolism, or dissection of the aorta, but showed marked the frequency and outcome of flares during ETV therapy mediastinal lymfadenopathy, turning out to be highly in CHB. active on the PET-scan. On microscopy, a thoracoscopi- Methods: HBV patients treated with ETV from 11 European cally removed paracardiac lymphnode showed necrotizing centers (VIRGIL Study Group) were studied. Flares were lymphadenitis, with no signs of lymphoma. The differ- defined as an ALT level >3xULN compared to baseline with ential diagnosis of necrotizing lymphadenitis includes an absolute ALT level >3xULN. Bartonellosis, Q fever and tuberculosis. Results: 733 patients were treated for a median of 168 PCR confirmed the presence of Bartonella henselae and (84-213) weeks with ETV. Nineteen patients (3%) developed proved negative for Coxiella burnetii and mycobacteria. He a flare after a median of 26 (10-83) weeks. None of turned out to have several cats and kittens. During further the patients developed genotypic resistance and in only admission, both his thoracic pain and fever resolved one case non-compliance was documented. Flares were without antibiotic therapy. relatively mild with a median ALT peak of 7.3xULN Conclusion: We describe an extraordinary clinical (4.5-10.1). Among patients with flares, one developed presentation of an HIV/HCV infected patient with HBeAg-seroconversion, and one HBeAg-loss. HBeAg PET-scan positive mediastinal lymphadenopathy, due to status (HR 2.91, 95%CI 1.17-7.23, p = 0.02), HBVDNA (HR a Barthonella henselae infection, without a malignant 1.31, 95%CI 1.06-1.63, p = 0.01), platelet count (HR 1.0, lymphoma. 95%CI 0.98-1.00, p = 0.04) and albumin (HR 0.91, 95%CI 0.84-0.99, p = 0.03) were associated with development of C145 An unwelcome companion following a beautiful flares. Nine patients (47%) had a flare during decline of holiday; an unknown danger of the desert? HBVDNA, three patients (16%) with a stable and seven (37%) with an increase of HBVDNA. Flares during a L. Nieuwenhuizen, B.P.M. Imholz decline of HBVDNA occurred after a median of 10 weeks Elisabeth-TweeSteden Hospital, Department of Internal (4-21), which was significantly earlier compared to flares Medicine, Tilburg, the Netherlands during a stable or increase in HBVDNA (76 weeks, 29-149) (p < 0.001). A 62-year old woman without relevant history, was Conclusion: Flares during ETV are rare. Flares occurring admitted with fever, malaise, pain in the right flank, before week 26 of therapy were almost exclusively present dyspnea and erythematous rash on the medial side of during continued decline of HBV DNA. In these patients legs and arms. Laboratory findings showed inflam- ETV can be continued under strict monitoring as the mation , a mild hyponatremia, respiratory alkalosis, and majority have a good biochemical- and virologic outcome. pulmonary infiltrate on a chest X-ray. Under suspicion of a pneumonia penicillin intravenous and ciprofloxacin were C144 A patient with HIV/HCV co-infection, presenting started. Despite the antibiotic regimen, fever persisted with spiking fever and mediastinal lymphadenopathy and infection parameters increased. Considering atypical pathogens, antibiotics were switched to amoxicillin/ J. van Es, P.H.J. Frissen, Y.F.C. Smets, K. Brinkman clavulanic acid and doxycyclin. Additional test showed Onze Lieve Vrouwe Gasthuis, Department of Internal progressive infiltrative abnormalities on ct-thorax. Medicine, Amsterdam, the Netherlands Bronchoscopy, blood cultures and auto-immune serology

71 remained negative. Her travel history revealed a tour widely known and this may lead to inappropriate treatment in the west of USA of which she had returned nine for suspected vasculitis or microemboli. In the occurrence days before admission. Additional viral and atypical of blue toes, thrombopenia and the presence of a dog, bacterial pathogens, like HIV-screening and Rickettsia, fulminant infection with Pasteurella should be suspected. were negative. Nine days after admission banal sputum culture became positive for Coccidioides immitis. These C147 Protease-Activated Receptor 2 facilitates bacterial fungi are found in the sand and dust of some desert dissemination during pneumococcal pneumonia areas on the Western Hemisphere, like in California and Arizona. When spores of this fungus are inhaled F.E. van den Boogaard1, X. Brands2, S.F. de Stoppelaar3, pulmonary symptoms occur after 1-4 weeks. The conse- J.W. Duitman2, J.J.T.H. Roelofs2, M.J. Hollenberg4, quences range from very mild symptoms to life-threat- M.J. Schultz2, C. van ‘t Veer2, T. van der Poll2 ening pneumonia and disseminated coccidioidomycosis 1Tergooi, Department of Internal Medicine, Hilversum, the in the course of months to years. Also, erythematous rash Netherlands, 2AMC, Department of Internal Medicine, is described. Both immune-competent and immunocom- Amsterdam, the Netherlands, 3Flevo Hospital, Department promised patients can become infected. Our patient was of Internal Medicine, Almere, the Netherlands, 4University of treated for 3 months with fluconazole and recovered fully. Calgary, Department of Physiology & Pharmacology, Calgary, Follow-up after 3 months only showed minimal residual Canada abnormalities on the chest X-ray. The case highlights the importance of a properly conducted travel history and the Background: Streptococcus (S.) pneumoniae is the most possibility of a fungus induced pneumonia. common causative pathogen in community-acquired pneumonia and a major cause of sepsis. Protease-Activated C146 Blue toes and thrombopenia, cave canem Receptor 2 (PAR2) is expressed by different cell types in the lungs and can mediate a variety of inflammatory A. van Norel, C.L. Doorenbos responses. We sought to determine the role of PAR2 Deventer Hospital, Department of Internal Medicine, during pneumococcal pneumonia. Deventer, the Netherlands Methods: Pneumonia or sepsis was induced by intranasal or intravenous inoculation with S. pneumoniae in wild A 52-year old woman with borderline personality disorder type (WT) and PAR2 knock-out (Par2-/-) mice. To obtain and a dog presented with weakness and painful feet. insight in the proteases involved in PAR2 activation WT Examination showed BP 137/89 mmHg, HR 99/minute, and/or Par2-/- mice were treated with specific inhibitors warm extremities, automutilation wounds on her left arm of the tissue factor pathway or tryptase. The capacity of and markedly blue toes, fingers and ears. S. pneumoniae to directly activate PAR2 was studied in a Laboratory investigation revealed severe thrombopenia 9/nl human alveolar epithelial cell line and HEK293 cells stably (150-400), leukocytosis 13.4/nl (4.0-10.0), the differential transfected with PAR2. showed bacteria, fibrinogen 5.7 g/L (2.0-4.5), CRP 338 mg/l Results: Par2-/- mice demonstrated an improved host (< 10), creatinine 104 mmol/l and elevated liver enzymes. defense during pneumococcal pneumonia as reflected by She was given ceftriaxon and platelets. Unfortunately blood lower bacterial loads in lungs, markedly reduced dissemi- cultures were not taken, but on the 4th day Pasteurella nation of pneumococci, a largely preserved lung barrier species had grown from a wound culture. integrity and reduced mortality. PAR2 deficiency did not On the 6th day she was transferred to the intensive care influence bacterial growth after intravenous infection. unit in respiratory failure. A CT-scan showed ARDS and Inhibition of the PAR2 activating proteases tissue factor/ complete ischemia of the spleen. Vasculitis was suspected factor VIIa or tryptase did not impact on bacterial burdens and prednisolone was started, but ANCA, ANA/ENA and during pneumonia. Furthermore, S. pneumoniae was RFaCCP were normal. Suspecting microembolisation, unable to directly activate PAR2 in a human alveolar anticoagulation was started. She recovered and returned epithelial cell line and HEK293 cells stably transfected to the ward, but developed severe pain and necrosis of her with PAR2. toes and fingers. Then the significance of the Pasteurella Conclusion: S. pneumoniae uses PAR2 in the airways to was recognised and prednisolon and anticoagulation were cause systemic dissemination during pneumonia. stopped. Pasteurella inhabits the oral cavity of dogs and her dog had licked the automutilation wounds. Infection C148 Complicated Pseudomonas aeruginosa meningitis may cause severe disseminated intravascular coagulation, after a visit to the swimming pool? multi organ failure and is associated with severe necrosis of the extremities sometimes necessitating amputation. D.G. Knapen1, B. Mulder2, F. Sousa1, T.h.F. Veneman1 Several case reports describe this phenomenon but it is not

72 1ZGT, Department of Intensive Care, Almelo, the Netherlands, 5 kilograms in bodyweight. After omeprazol was started 2ZGT, Laboratory for Medical Microbiology, Hengelo, the a non-pruritic rash developed on his trunk. He had no Netherlands fever, but nocturnal perspiration had developed in the past weeks. On physical examination he was afebrile. Multiple Case: A healthy 75/year old male was admitted to the small, non-tender lymph nodes were found. His trunk Emergency Department with fever, vomiting and showed an erythematous, non-squameous rash. Laboratory confusion since 8 hours, which started shortly after a results showed a normal blood count, C-Reactive Protein, visit to a public swimming pool. His medical history renal function and liver tests. Serological testing for HIV, revealed no underlying disease. Physical examination Toxoplasma, Parvovirus was negative. A CT-scan showed a revealed a lethargic patient with evident nuchal rigidity. granulomatous lesion in the liver with central necrosis. A His vital signs were normal, his body temperature 39 °C. skin biopsy was performed, which showed stage II syphilis. Laboratory investigation showed an elevated C-reactive The patient was treated with penicillin after which his protein of 324 mg/l and 18 x 109 leucocytes/l, without symptoms resolved. Furthermore, the lesion in the liver other abnormalities. Analysis of cerebrospinal fluid (CSF) resolved. revealed a glucose concentration of 3.2mmol/l and 126.7 Conclusion: We describe a patient with stage II syphilis x 106 leucocytes/l (93% PMNL). After taking blood and who presented nonspecific symptoms as malaise, fatigue, CSF cultures, treatment with ceftriaxone and amoxicillin weight loss and a skin rash which was in retrospective was started according to the Dutch meningitis-guidelines. a typical combination. Syphilis has a broad variety of Aciclovir was started since a viral origin could not be signs and symptoms and its clinical presentation can excluded. CSF and blood cultures yielded the bacterium be misleading. Due to its increasing prevalence syphilis Pseudomonas aeruginosa, not sensitive to ceftriaxone nor deserves a spot in nearly all differential diagnoses. amoxicillin. Aciclovir and ceftriaxone were replaced by ceftazidime after which the patient clinically improved. C150 Bilateral swelling of the eyelids in EBV (Hoagland However, a secondary endopthalmitis caused complete sign) blindness of his right eye. Enucleation will be necessary. Conclusion: A community-acquired spontaneous C. Snackey meningitis caused by P. aeruginosa is rare but has a very Kennemer Gasthuis, Department of Internal Medicine, high mortality rate. Swift recognition and treatment is of Haarlem, the Netherlands paramount importance. However, treatment according to Dutch meningitis-guidelines does not cover infection A 20-year old woman presented at our emergency with P. aeruginosa, causing an important treatment-delay. department with bilateral swelling of the upper and lower Patients with a history of contact with service water, hot eyelids which existed for about ten days. Her GP prescribed tubs, whirlpools or swimming pools should receive a her anti-histamines without effect. She did not have fever, different empiric antibiotic therapy. We suggest a regimen but felt sick, noticed a nasal speech and had an aching containing ceftazidime 3x2000mg instead of ceftriaxone throat since two days. There were no symptoms of allergic as empiric treatment until culture results are available. reaction. On physical examination we saw bilateral edema of C149 Progressive fatigue, malaise, weight loss and a skin the eyelids and painful submandibulary and cervival rash: A classical presentation lymphadenopathy. Body temperature, blood pressure and pulse rate were normal. Examination of the heart, lungs C.E. Tazelaar, E.M.G. Jacobs, Y.E.P. Soethoudt and abdomen was normal. Laboratory testing showed a Elkerliek Hospital, Department of Internal Medicine, lymphocytosis with atypical lymphocytes and elevated Helmond, the Netherlands liver-enzymes. Flexible laryngoscopia revealed swelling of the mucous Introduction: Our case reports a patient with progressive membranes of the larynx and the upper part of the symptoms due to stage II syphilis. Although he presented oropharynx. Serologic testing showed elevated EBV-IgM with nonspecific symptoms, retrospectively seen, his and EBV-IgG antibodies, which indicates a current presentation was highly applicable. infection with the Epstein Barr virus. Bilateral swelling Case description: A 47-year old Caucasian male with of the eyelids in EBV (Hoagland sign) is a rare but typical no medical history was referred to the outpatient clinic feature which helps to distinguish EBV from other viral because of weight loss and malaise. Six months prior to infections. It is usually only seen in the acute stage of presentation he visited Southeast Asia in good health, fully infection. vaccinated and using malaria prophylaxis. After his return After discharge she developed a peritonsillar abscess which he experienced progressive fatigue and malaise, and lost was treated with surgical incision and antibiotics. The

73 patient made a full recovery and the lymphocytosis and and supraclavicular. Laboratory results showed a high elevated liver-enzymes normalized within a month. erythrocyte sedimentation rate, microcytic anemia and low haptoglobin. No further abnormalities were found. C151 Massive hemolysis in sepsis Blood smear detected Plasmodium falciparum gametocytes. We diagnosed the patient with malaria tropica. She was A.J. Meinders, I. Dijkstra treated with atovaquon/proguanil 250/1000 mg for three St. Antonius Hospital, Department of Intensive Care, days. Afterwards, no signs of malaria were found and her Nieuwegein, the Netherlands anemia had vanished. Discussion: The incubation period for malaria tropica A 61-year old female patient with an uneventful medical is generally less than two months. Presentation four history was admitted to the emergency department because months after exposure is rare. It is known that sickle of icterus and abdominal discomfort. At arrival she was cell trait is associated with delayed onset of malaria. haemodynamically stable. No laboratory tests could be Also longer incubation periods and a non-specific and performed because of massive haemolysis, [panel A], vague presentation are more likely in individuals taking reason to perform a direct blood smear. This smear showed ineffective malaria prophylaxis. Therefore, physicians two species of bacteria and erytrophagocytosis,[panel B] should always consider malaria in patients who were Patient detiorated acutely and was admitted to the ICU visiting malaria-endemic regions, especially in those who were she was intubated and was started on massive could be semi-immune or have sickle-cell trait, even when inotropes and broad spectrum antibiotics with the the patient does not experience fever. hypothesis of a septic shock. Repeated blood samples showed severe haemolysis with no possibility of chemical C153 A cerebral abscess, again?! or haematological testing. Patient died within one hour due to an overwhelming sepsis. C.H.S.B. van den Berg, A. Huurnink, W.R. van Furth, Post mortem blood cultures showed a clostridium Difficile J.M. Prins and an escherichia Coli bacteremia. Autopsy showed an AMC, Department of Internal Medicine, Amsterdam, the infected hematoma in the liver hilum as source of the Netherlands sepsis Clostridium septicemia is known for its massive A 42-year old female was admitted to the department of haemolysis and poor prognosis. The case shows that neurosurgery for the treatment of a right frontal cerebral a direct blood smear can be a fast and relevant test in abscess. She had an extensive medical history with a severely ill patients. Budd-Chiari syndrome since childhood, complicated by livercirrhosis and esophageal varices, hypercoagulability, C152 Hemolytic anemia after visiting Nigeria: delayed and a cerebral abscess (right occipital) 5 years before this onset of malaria without fever in a patient with sickle episode (Streptococcus constellatus and S. intermedius). Her cell trait presenting symptoms were progressive headache and falling. On physical examination she was tachypnoeic and J. van Heek, M.J. van Apeldoorn, A.H.E. Herbers hypoxemic, which improved partly with supplemental Jeroen Bosch Hospital, Department of Internal Medicine, oxygen. There were no signs of a systemic infection that ’S-Hertogenbosch, the Netherlands could be a source of metastatic abscesses or an infection that could explain the brain abscess by continuity. Culture Introduction: Almost 2 million immigrants of non-Western of the abscess showed S. constellatus. Because of the origin are living in the the Netherlands. Many of them recurrent nature of the brain abscesses we started an travel to their family abroad. Therefore tropical infections investigation for (intracardiac) right-left-shunts. An earlier are likely to occur. Our case reports a traveller with malaria performed agitated saline echocardiography did not show tropica after visiting Nigeria. intracardiac or pulmonary right-left shunting. However, Case description: A 44-year old woman from Nigeria lung perfusion scintigraphy with 99mT-labelled macroaggre- presented herself four months after she visited her gated albumin showed intrapulmonary functional vasodila- family in Nigeria. She used inconsistent malariaprophy- tation with a right-left shunt (shunt fraction 25%). She was laxis during her stay. In Nigeria she was tired, but she treated with antibiotics and drainage of the abscess. In experienced no fever. After travelling back home she conclusion, the diagnosis was a recurrent bacterial brain remained tired and she experienced chills and headaches abscess in a patient with a hepatopulmonary syndrome. without fever. She did not take acetaminophen. Medical (Recurrent) bacterial cerebral abscesses are usually history revealed sickle cell trait. On physical examination associated with a systemic infection (e.g. endocarditis), we noticed left-sided lymfadenopathy in axilla, neck an infection by continuity from the ENT region, or

74 bacteremia in a patient with an (intracardiac) right-left T.B. de Vries, M.G. Vloedbeld, A.A.J. Ramdhani-Joosten shunt. However, in patients with livercirrhosis, one should ZGT, Department of Internal Medicine, Almelo, the also consider hepatopulmonary syndrome (prevalence Netherlands in literature up to 30%). The only curative treatment for hepatopulmonary syndrome is a liver transplantation. Introduction: Infection with the Epstein-Barr virus (EBV) is very common. Approximately 95% of the adult C154 A challenging cause of ongoing fever of unknown population have been infected with EBV. In most cases origin: down the drain or from the tap? EBV infection is asymptomatic. Occasionally neurologic symptoms occur, such as Guillain-Barré syndrome, facial H. Ytredal, M.J.A. de Regt, R.J. Rentenaar, H.L. Leavis nerve palsy, meningo-encefalitis and transverse myelitis. UMC Utrecht, Department of Internal Medicine, Utrecht, the We present a patient with an EBV infection complicated by Netherlands myeloradiculitis. A case report: A 55-year old, previously healthy, Caucasian Introduction: Fever of unknown origin can be challenging. man was admitted to our hospital with fever, malaise Systematic reassessment with repeated testing for and hepatitis as a result of an EBV infection. During pathogens previously not detected can be valuable. the hospitalization he developed progressive neurologic Case: A 77-year-old-man, previously in good health, symptoms. Physical examination showed an alert man was referred because of ongoing fever, polyarthritis and with gait disturbance due to sensory impairment with migratory pulmonary opacities during the last 9 months. hyperaesthesia in both legs and trunk and areflexia of Past medical history revealed rheumatoid arthritis, treated the lower limbs. Laboratory findings revealed a C-reactive with prednisone and methotrexate, and artificial knee protein of 12 mg/ml (< 10 mg/ml) and white blood joints. Previously extensive diagnostic examinations count of 12.6 x 109/l (4.0-10.0 x 109/l). Differential count (including joint aspirations, PET-scanning, BAL) were included 2+ atypical lymphocytes. Cerebrospinal fluid insufficient. Because of ongoing polyarthritis despite contained an elevated white blood count and protein was high-dose glucocorticoids, TNF-alfa-inhibition was admin- elevated. Culture of the CSF showed no pathogens, but istered, but discontinued since his condition worsened. polymerase chain reaction was positive of EBV. MRI of Before current admission, Abatacept had been initiated. the spine showed no abnormalities of the myelum. EMG Nevertheless, daily periodic fever until 40°C persisted with results were compatible with a polyradiculitis. Despite the concurrent worsening of joint pain and stiffness. absence of MRI-abnormalities there clinically also seems Repeated PET-scan showed FDG-uptake in wrists, elbows, to be myelum involvement. Myeloradiculitis due to EBV shoulders, knees, testis and subcutaneous abscesses. infection was diagnosed. Patient recovered partially during Aspiration of joint fluids and subcutaneous abscesses the admission and he was referred to a rehabilitation centre now revealed auramine-positive rods, confirmed as for further rehabilitation. Mycobacterium kansasii by 16S-sequencing. Rifampicin, Discussion: Although EBV infections very frequently ethambutol and isoniazid were started. Repeatedly intra- occur, neurologic complications of EBV infections, such articular debridement of affected joints was performed as the development of myeloradiculitis have rarely been because of septic periods. Currently the patient is reported. still critically ill and infection of the joint prostheses complicates long-term management. C156 Fatal nocardia pneumonia caused by treatment of a Discussion: M.kansasii is a slow-growing nontuberculous- paraneoplastic polymyositis mycobacterium (NTM) mostly causing pulmonary disease. Disseminated disease is rare. M.kansasii is an environ- A.J.C. Overgaauw, M.W.A. Kamermans, F.C.P. Frerichs mental microorganism (e.g. tap water), and constitutes 7% MC Alkmaar, Department of Internal Medicine, Alkmaar, of NTM cultured from Dutch pulmonary samples. Despite the Netherlands repeated culturing for NTM in this case, only after months with severe disseminated disease the microorganism was Introduction: Polymyositis is an inflammatory myopathy identified and treated. that causes symmetrical proximal muscle weakness. Conclusion: Detection and treatment of NTM infections Polymyositis is rarely seen as isolated entity and more can be notoriously difficult, as demonstrated in our case of commonly associated with autoimmune or connective disseminated disease in an immunocompromised patient. tissue disease. It is also seen with infection or paraneoplastic phenomenon. C155 Myeloradiculitis – a rare complication of a very Case: A 78-year old woman was admitted to our hospital common infection with proximal muscle weakness. Her medical history revealed morbid obesitas and an uterus extirpation among

75 others. The complaints started six weeks ago and were year after first presentation, referred to an infectiologist. progressive. Under suspicion of polymyalgia rheumatica Because of the history of BCG therapy additional PCR test she already used prednisone 10 mg for 4 days. On physical for Mycobacterium tuberculosis complex (including M. examination there was no rash or calcinosis. Laboratory bovis) on the previously taken bone biopsy was found to test revealed decreased kidney function, elevated liver be positive. Treatment with tuberculostatics was started enzymes and an increased creatinine-kinase of 4288U/l. immediately and four weeks later our patient was pain free. Additional laboratory tests showed no clues of underlying Discussion: M. bovis spondylodiscitis is a rare complication autoimmune disease or viral infection. A computed of intravesical BCG therapy. It is essential to consider an M. tomography of thorax and abdomen showed no malignancy bovis infection even years after treatment. or infection and electromyographic findings showed myopathic potentials. A muscle biopsy was planned and C158 Sleeping beauty prednisone 1mg/kg was started. After 2 days the patient became septic and hemodynamic unstable and admission T. ten Doesschate, A.J. Meinders, H.S. Moeniralam to the ICU was necessary. Despite broad-spectrum St. Antonius Hospital, Department of Internal Medicine, antibiotics and resuscitation patients condition decreased. Nieuwegein, the Netherlands After consulting the family, treatment was stopped and she died. Obduction showed a nocardia pneumonia with A 57-year old man was referred to the hospital with a diffuse septical localizations in the liver. There was also an stupor. In three days he gradually became somnolent and adenocarcinoma of the ovary and a paraneoplastic T-cell finally stuporous. He used prednisolon for an interstitial mediated myositis. nephritis and later for suspicion of sarcoidosis. Four Conclusion: This case illustrates the difficulty of diagnosis weeks before he underwent a hemicolectomia because and treatment of polymyositis. Nocardia is typically an of an adenocarcinoma. There was no suspicion of an infection of the immunocompromised patient. While intoxication. Physical examination showed a decreased treating polymyositis or other immunocompromised mental status (E4M5V2). Laboratory showed a leucocy- patients, think about nocardia as potential cause of sepsis. tosis of 9.7 x10^9/l, a CRP of 69 mmol/l, an anemia and trombocyopenia (Hb 7.4mmol/L, T 101 x10^9/l), an renal C157 Culture Negative Spondylodiscitis after Intravesical insufficiency (kreatinine 295 mmol/l) and a respiratory BCG Therapy? Think of Mycobacterium Bovis alkalosis (pH 7.64, pO2 14.0kPa, pCO2 2.8kPa, bic Spondylodiscitis 22.2mmol/l). The CT cerebrum was normal. EEG was typical for a metabolic encephalopathy. The ammonia level M.C.E. van den Heuvel, H.S.M. Ammerlaan was strongly elevated (169 mmol/l; normal 10-45 mmol/l). Catharina Hospital, Department of Internal Medicine, As consciousness declined, patient was admitted to ICU. Eindhoven, the Netherlands To lower ammonia, RRT was started, protein diet was minimized and ammonia lowering medicines were Introduction: Intravesical Bacillus Calmette-Guerin (BCG) started. Underlying disorders were investigated. All therapy has proven to be effective for superficial bladder medication was stopped. Liver failure and a portosystemic cancer. This immunotherapy consists of an attenuated shunt were excluded. Cultures stayed negative. Underlying strain of Mycobacterium bovis causing a local antitumor urea cycle disorders were excluded. A PET scan showed activity.2 Complications appear in less than five percent of generalized mesenteric lymphadenopathy with ascitis. patients, ranging from mild irritative cystitis until severe We aspirated and cultured the milky looking ascites. systemic infections. Only six case reports were published After 4 days a Mycobacterium simiae was cultured, an describing spondylodiscitis as a late complication. urease producing species. Bone marrow, sputum and the Case report: We report a 75-year old man who received hemicolectomy preparate demonstrated acid fast bacteria, intravesical BCG therapy for bladder cancer two years which proves a disseminated M. simiae infection causing before presentation. He presented in another hospital the hyperammoniemia. Antibiotics were started and subse- with back pain since six months due to a spondylodis- quently the ammonia level declined. After 35 days of coma, citis and was treated with flucloxacilline for six months the patient awoke. He recovered fully. without obtainment of vertebral bone cultures. An MRI six months later showed progression of infection. He was C159 A different cause of an acquired immunodeficiency? referred to our hospital where antibiotics were stopped and three months later a vertebral bone culture for regular E.E. Vink, A.J. van Vuren, C. Linthorst, C.G. Schaar, microorganisms was performed. A tuberculin skin test G.W.D. Landman and bronchoalveolar lavage culture were both negative Gelre Hospitals, Department of Internal Medicine, Apeldoorn, for Mycobacterium tuberculosis. The patient was, one the Netherlands

76 copies/ml). At this stage a differential diagnosis of Still’s A 40-year old man without relevant medical history, disease or a hemophagocytic lymphohistiocytosis (HLH) presented to the ER with dyspnea. Eight weeks before remained. Bone marrow biopsy confirmed hemophago- presentation he noticed weight loss (-30kg) and since two cytosis, combined with the presence of splenomegaly, weeks intermittent fever and chills. pancytopenia, hypertriglyceridemia, increased serum On examination, he appeared moderately ill and cachectic. ferritin (18998 mg/l) and sIL-2R (> 50000), there were Laboratory-analyses showed pancytopenia (leukocytes 6 out of 8 criteria present while 5 needed to make the 0.69/nl; Hb 3.3mmol/l; trombocytes 51/nl). Laryngoscopy diagnosis of HLH. HLH is an aggressive, life-threatening revealed candida esophagitis and CT-scan showed diffuse syndrome of excessive immune activation. In this patient, miliary size pulmonary nodules, splenomegaly and the trigger for the HLH was a CMV reactivation, which abdominal lymphadenopathy. His CD4 T-cell count was could occur due to the immunosuppressive treatment the 130/nl, HIV tests were negative. Bone marrow biopsy patient was receiving for ulcerative colitis. The patient showed evidence for hairy cell leukemia (HCL). Auramine started Dexamethasone, Etoposide and Cyclosporine, staining of bronchoalveolar lavage fluid initially was following the HLH-2004 protocol. This therapy resulted negative. Auramine staining of a histologic lymphnode in a rapid partial remission of the HLH and control of the biopsy was positive for acid fast bacilli. CMV reactivation. However, the treatment was and is still Severe cellular immunodeficiency due to HCL was hampered by several serious infectious complications, due suspected, we decided that empirical therapy for to which the patient is still hospitalized. Mycobacteria tuberculosis and avium were indicated with a clinical picture best compatible with disseminated avium C161 A possible and novel case of HIV-induced serious infection. Rifampicin, ethambutol, isoniazid, pyrazi- hepatitis, resolved after starting cART namide and azithromycin, later converted to clarithro- mycin, were started. After three weeks, bronchoalveolar V.C. Harris, U.H. Beuers, J.M. Prins, S.E. Geerlings lavage fluid, lymph node biopsy and blood cultures AMC, Department of Internal Medicine, Amsterdam, the tested positive for Mycobacterium avium, confirming the Netherlands diagnosis. By then, he developed an cutaneous leukocytoclastic vasculitis, possibly due to a drug reaction or HCL. A 27-year old man presented to our outpatient clinic Steroids were started, pyrazinamide and isoniazid were with a serious hepatitis and a newly diagnosed, advanced discontinued. Thereafter, fever and sweating diminished. HIV-1 infection. The patient had been healthy till one year After four weeks of antibiotic therapy his pancytopenia prior to presentation, when he noted white oral plaques resolved, after eight weeks cladribine was started. requiring treatment with fluconazole. Two months prior to Cladirabine is recommended soon after adequate therapy presentation, he developed early satiety, nausea, and icterus for opportunistic infections is started. A single course of and noted a 10 kg weight loss. cladribine results in high response rates (85%) and the The patient used no medications and his past medical 12-year overall survival rate varies between 75-87%. history was negative. He was heterosexual, used marijuana sporadically, and repeatedly denied using any over- C160 Immunological chaos triggered by CMV reactivation the-counter-drugs, food supplements, or recreational drugs. Travel history was negative. B. de Klerk, Y. Eling, J.C. Regelink On examination, the patient was afebrile, cachectic and Meander Medical Centre, Department of Internal Medicine, his liver was palpable. Initial laboratory analysis revealed: Amersfoort, the Netherlands total bilirubin 341 mmol/l, conjugated bilirubin 272 mmol/l, ASAT 1953 U/l, ALAT 472 U/l, albumin 39 g/l, PT 14.3s, A 58-year-old female, suffering from ulcerative colitis, APTT 30s; HIV antigen/antibody tests positive, plasma for which she received mercaptopurine treatment, was HIV-RNA load 4,028,639 copies/ml and CD4 count 13 x admitted to the Internal Medicine ward with fever and 10E6/l. headaches for more than ten days. Subsequently she Repeated testing for immunologic, viral, bacterial, and developed pancytopenia, a diffuse rash and abnormal liver parasitological etiologies of the hepatitis was negative. Liver function tests. A severe systemic infection was suggested, biopsy revealed minimal inflammation and a predominant however intensive diagnostic testing did not reveal any parenchymal bilirubinostasis. clues for a diagnosis. Therefore a PET-CT scan was Two weeks following presentation, his hepatic synthetic obtained, revealing pulmonary consolidations, activated function deteriorated significantly, and the patient bone marrow, splenomegaly and lymphadenopathy. was admitted. cART was initiated and within one day Broncho-alveolar lavage showed CMV activation. Systemic the patient had a significant drop in ASAT and ALAT. CMV reactivation was confirmed by PCR of serum (1.1e5

77 By 4 months of cART treatment, liver enzymes had Rijnstate, Department of Internal Medicine, Arnhem, the normalized completely. Netherlands This report describes a case of possible HIV-induced, serious hepatitis. We have not found similar cases in the This report describes a 68-year-old patient with infectious literature. In patients with advanced HIV, a high viral load tenosynovitis caused by Mycobacterium abscessus after and an unexplained hepatitis, early cART can be effective traumatic laceration on a thorn bush. Mycobacterium and safe. abscessus is a rare causative organism of tenosynovitis, however with increasing incidence. It can generate skin C162 A rare extrahepatic manifestation of acute hepatitis B and soft tissue infection after trauma or through haema- togenous spread and can be very destructive. Recognition H. Bieze, M.G.A. van Vonderen, F.H. Woudstra is often delayed. Mycobacterium abscessus is also known MC Leeuwarden, Department of Internal Medicine, for its extensive drug resistance which limits chemothera- Leeuwarden, the Netherlands peutic options. Success rate of treatment is limited. Often treatment is not finished because of severe side effects Introduction: Hepatitis B (HBV) can be associated with or the burden of long term (intravenous) administration extrahepatic manifestations involving the skin, haema- of drugs. Our patient was successfully treated with a tological, renal, and nervous systems. Neurological combination of amikacin, cefoxitin intravenously and manifestations in hepatitis B may present as Guillain- clofazamin orally for six months in an ambulant setting, Barré syndrome and secondary systemic vasculitis-related necessitating extensive participation and collaboration mononeuritis multiplex. We report a patient with acute of several healthcare professionals. This article aims to HBV-associated subacute severe distal asymmetric senso- increase the awareness of atypical bacteria as causative rimotor vasculitic polyneuropathy. agents of infectious tenosynovitis and to provide an Case: A 42 year old Caucasian homosexual male example of effective ambulant long term treatment for presented with malaise, anorexia and weight loss. He also this condition. complained about slowly progressive diffuse sensory loss and decreased muscle strength of both hands and feet. On C164 The diagnostic accuracy of procalcitonin for physical examination there was a claw-like hand shape. We bacteraemia: a systematic review and meta-analysis confirmed a severe polyneuropathy with muscle weakness and sensory loss of the distal extremities. There were no S. Hoeboer1, P. van der Geest2, D. Nieboer2, other abnormalities, especially no skin lesions. Laboratory A.B.J. Groeneveld2 data showed raised inflammation parameters and elevated 1Erasmus MC/Tergooi, Departments of Intensive Care/ liver enzymes. Viral serology showed acute HBV. With Internal Medicine, Hilversum, the Netherlands, 2Erasmus MC, initially suspicion of Guillain- Barre syndrome related Department of Intensive Care, Rotterdam, the Netherlands to the HBV, the patient was treated with intravenous immunoglobulin. There was no improvement, on the Background: The diagnostic use of procalcitonin for contrary, the patient experienced increasing pain with bacterial infections remains a matter of debate. So far most muscle cramps. Autoimmune parameters were slightly studies used ambiguous outcome measures such as sepsis elevated (ANA, SSA60, Ro60). Because the clinical presen- syndrome instead of proven infection. tation was suspect for a HBV associated vasculitis related Methods: We performed a systematic review and meta- mononeuritis multiplex we started prednison combined analysis to investigate the diagnostic accuracy of procal- with antiviral therapy (tenofovir). The patient responded citonin for bacteraemia, a proven bloodstream infection. well to the therapy and started a revalidation programme. We searched all major databases from inception to June The association between acute HBV and vasculitic 2014 for original, English written, research articles that peripheral neuropathy is seldomly reported. Nevertheless, studied the diagnostic accuracy between procalcitonin and the early recognition of the diagnosis is important as the positive blood cultures in adult patients. We calculated the clinical outcome may be influenced by early therapeutic area under the summary receiver-operating characteristic intervention. Elevated liver enzymes and sexual risk curves (SROC) and pooled sensitivities and specificities. To behaviour are clues to the diagnosis. minimise potential heterogeneity we performed subgroup analyses. C163 Infectious tenosynovitis caused by Mycobacterium Results: In total 58 of 1,567 eligible studies were included abscessus, a case report in the meta-analysis and provided a total of 16,514 patients of whom 3,420 suffered from bacteraemia. In the overall R.F. Stolk, J.L.M. de Kanter, P.M.G. Filius, J. van Ingen, analysis the SROC was 0.79. The optimal and most widely E.H. Gisolf used procalcitonin cut-off value was 0.5 ng/mL with a

78 corresponding sensitivity of 76% and specificity of 69%. W.J.A.R.M Valckx, S.P.M. Lutgens, H.E. Haerkens-Arends, In subgroup analyses the lowest SROC was found in P.C. Barneveld, J.J. Beutler, E.K. Hoogeveen immunocompromised/neutropenic patients (0.71), the Jeroen Bosch Hospital, Departments of Internal Medicine/ highest SROC was found in intensive care patients (0.88), Nephrology, ’S-Hertogenbosch, the Netherlands sensitivities ranging 66-89% and specificities 55-78%. Conclusions: In spite of study heterogeneity, procalcitonin Case report: A 74-year-old haemodialysis patient, with a had a fair diagnostic accuracy for bacteraemia in adult history of atrial-septum defect closure, coronary artery patients suspected of infection or sepsis. In particular low bypass graft and aortic prosthetic valve, was admitted procalcitonin levels can be used to rule out the presence of to hospital because of coughing, chills and dyspneu. bacteraemia. Further research on the safety and efficacy of Pneumonia and volume overload were diagnosed. He was procalcitonin as a single diagnostic tool to withhold taking treated with antibiotics intravenously (ciprofloxacin and blood cultures is needed. penicillin) and extra ultrafiltration during haemodialysis. During hospitalization one blood culture yielded positive C165 Human granulocytic ehrlichiosis in the the for Listeria monocytogenes. Transthoracic echocardiog- Netherlands raphy showed no prosthetic valve dysfunction or valvular vegetations. The presence of infective endocarditis was D. Soonawala, M.B. Keur, M. Knoester considered unlikely since only three minor Duke criteria Leiden University Medical Centre, Department of Internal were present (one atypical positive blood culture, prosthetic Medicine, Leiden, the Netherlands valve, fever). Therefore, the patient was treated for two weeks with antibiotics (amoxicillin) with good clinical Case: A 25-year old Dutch male presented with a response. three day history of fever and fatigue. The complaints However, immediately after discontinuation of amoxicillin, started fourteen days after being bitten by thirty ticks, fever relapsed and we reconsidered the diagnosis endocar- while camping wild at Hoge Veluwe National Park in ditis. Because transesophageal echocardiography showed The the Netherlands. He had not been out of the the no valvular insufficiency or vegetations, we performed an Netherlands during the six months before presentation. On 18FDG-PET-CT scan. The scan showed activity at the aortic examination he was moderately ill. Physical examination root, proximal ascending aorta and inferior wall of the was unremarkable except for a temperature of 39.1 °C, and heart. Given the positive 18FDG-PET-CT scan, relapse of multiple unremarkable small scars on his legs, where the fever after discontinuation of amoxicillin, rise of CRP level ticks had been removed. He had a leucopenia (2.92 x10^9/l) and positive Duke criteria, we considered the diagnosis with lymphopenia (0.78 x10^9/l) and thrombocytopenia (87 Listeria monocytogenes endocarditis plausible. Amoxicillin x10^9/l). His haemoglobin was normal (10.2 mmol/l). He was given intravenously for six weeks with good clinical had elevated liver enzymes (ALAT 117 IU/l, ASAT 108 IU/l, result. Since the patient’s clinical condition did not allow gamma-GT 74 IU/l) with normal bilirubine. His creatinine an aortic valve operation, lifelong treatment with oral was 87 micromol/l and his sediment showed proteinuria amoxicillin was adviced. (1.3 gram/l) and mild leucocyturia and erythrocyturia. Listeria monocytogenes bacteraemia can be life-threatening, Based on his history and the febrile illness, with a mild especially in the presence of a prosthetic valve. Therefore hepatitis and a tentative diagnosis of tubulointerstitial treatment with ß-lactam antibiotic is important. However, nephritis, we suspected Anaplasmosis, Ehrlichiosis or establishing the diagnosis Listeria endocarditis can be early Lyme disease. He was treated with doxycycline for challenging and an 18FDG-PET-CT scan can be helpful. 7 days. After two days the fever subsided and after one month all serum and urine laboratory values normalised. C167 SVR12 results after a 12-week Boceprevir, Paired serology analysis for Borrelia burgdorferi and for Peginterferon and Ribavirin regimen in the Dutch Anaplasma phagocytophilum was negative. However, the Acute Hepatitis C in HIV Study IgM antibody titre for human granulocytic ehrlichiosis showed an increase from 1:128 to 1:1024. IgG was negative. S.J. Hullegie1, M.A.A. Claassen1, G.E.L. van den Berk2, A sample obtained at a later timepoint will be analysed for F. Lauw 3, P.P. Koopmans 4, J.E. Arends5, C. Richter6, IgG seroconversion. D. Posthouwer7, W.F.W. Bierman8, A. van Eeden9, Conclusion: This is probably the second documented case J.T.M. van der Meer10, B.J.A. Rijnders1 of human granulocytic ehrlichiosis in the Netherlands. 1Erasmus MC, Department of Internal Medicine, Rotterdam, the Netherlands, 2 Onze Lieve Vrouwe Gasthuis, Department C166 Listeria infection: a diagnostic challenge of Internal Medicine, Amsterdam, the Netherlands, 3Slotervaart Hospital, Department of Internal Medicine, Amsterdam, the Netherlands, 4Radboudumc, Department

79 of Internal Medicine, Nijmegen, the Netherlands, 5UMC the additional value of gentamicin in the empirical Utrecht, Department of Internal Medicine, Utrecht, the treatment of sepsis eci. Netherlands, 6Rijnstate, Department of Internal Medicine, Aim was to identify the antibiotic prescription behaviour in Arnhem, the Netherlands, 7Maastricht UMC+, Department community-acquired sepsis eci in our hospital and whether of Internal Medicine, Maastricht, the Netherlands, 8UMC concomitant treatment with gentamicin would have had Groningen, Department of Internal Medicine, Groningen, the additional value. Netherlands, 9DC Clinics, Department of Internal Medicine, Methods: In our retrospective cohort, 128 adult patients Amsterdam,the Netherlands, 10AMC, Department of Internal were included who were admitted to the Emergency Medicine, Amsterdam, the Netherlands Department between January 2011 and March 2014 with sepsis without focus. We registered the prescribed Background: The epidemic of acute hepatitis C virus antibiotics, the vital parameters and SIRS-criteria at (AHCV) spreads within HIV+ men having sex with admission. We evaluated in how many cases gentamicin men. The addition of boceprevir to peginterferon (P) and would have had additional value based on the antimi- ribavirin (R) may lead to higher cure rates and may allow crobial susceptibility pattern of blood cultures withdrawn for a shorter treatment duration. We present an interim at admission. analysis of the first 27 patients treated in the DAHH-Study. Results: There were no significant differences found Methods: HIV+ patients visiting the outpatient clinic between the groups with or without gentamicin regarding with a rise in ALAT were screened for the presence of patient characteristics, SIRS criteria or severity of sepsis. HCV RNA. If positive, stored historical plasma samples Concomitant gentamicin prescription dropped from 50% were tested to prove that the HCV infection was recent. in 2011 to 14% in 2014. We found in 8.1% (5 cases) Boceprevir, P+R for 12 weeks was started and was initiated resistance to first-choice guideline antibiotic (augmentin/ no later than 26 weeks after the presumed day of infection. ceftriaxon). But in only 3.2%, gentamicin would have had Primary endpoint is sustained viral response at week additional value since the other 4.8% showed resistance to 24(SVR24) in patients with no HCV RNA detected gentamicin as well. Most common pathogens were E. coli (Roche, CAP/CTM) at w4(RVR4) and in all patients (48.4), haemolytic streptococci (11.3%) and other coliform included(secondary endpoint). bacteria (11.3%). Results: We screened 117 HIV+ patients with a new HCV Conclusion: In patients with sepsis eci in Northern infection. We excluded 52 patients because of genotype 4 Limburg, the addition of gentamicin seems of little value. (n = 21), HCV infection > 6 months (n = 14), spontaneous In addition, no factor was identified which led doctors to clearance (n = 7) and refusal to participate (n = 10). prescribe gentamicin. The use of gentamicin combination Sixty-five were included of which 58 have started therapy. therapy is decreasing. RVR4 was reached in 23/33 (70%) patients with end of treatment responses being 26/29 (90%). SVR12 was 18/19 C169 Treatment of Varicella Meningoencephalitis with a (95%, 95% CI 72%-99%) in the RVR4 population. SVR12 combination of Acyclovir and Foscarnet was 21/27 (78%, 95% CI 57%-91%) in patients regardless of RVR4 results. C.A.M. van de Weg1, A.A. Baltissen-van der Eijck2, Conclusions: Addition of boceprevir to P+R for AHCV J. Droogendijk1, M. Durian1 treatment results in high SVR12 rates with a 50% shorter 1Elisabeth-TweeSteden Hospital, Departments of Internal therapy duration as long as HCV RNA has become negative Medicine/Haematology, Tilburg, the Netherlands, 2Erasmus at w4. MC, Department of Viroscience, Rotterdam, the Netherlands

C168 Gentamicin- a valuable component of the antibiotic A 60-year old female patient presented at the emergency regimen in the treatment of community-acquired department with complaints of malaise, headache, loss of sepsis eci in Northern Limburg? appetite and lethargy. The patient was immunocompromised due to prolonged leukopenia, caused by treatment C.M.Y. Sonnborn, T. Trienekens, L. Janssen, of a marginal zone lymphoma with rituximab-fludarabine- M.M.H. Hermans cyclophosphamide immunochemotherapy seven months VieCuri, Department of Internal Medicine, Venlo, the earlier. Moreover, valacyclovir prophylaxis was interrupted Netherlands and one month ago she had presented with a herpes zoster infection of the leg. Lumbar puncture was performed Background: Sepsis is a life-threatening condition. and Varicella Zoster DNA was detected in the liquor, Aminoglycosides (e.g. gentamicin) are advised as suggestive for Varicella meningitis. For four weeks she additional antibiotics in the treatment for sepsis eci. With was treated with high dose acyclovir intravenously. During potential oto- and nephrotoxicity in mind, we questioned treatment, her clinical condition detoriated and she became

80 more apathic and lethargic and developed loss of vision. culture of body fluids, antigen detection or serology. Mild Repetitive liquor samples tested positive for Varicella DNA, to moderate histoplasmosis can be treated with itraconazol. indicating the infection did not respond to treatment. Soil containing bird or bat droppings supports mycelial Magnetic resonance imaging was performed and showed growth. Bats can become infected with H. capsulatum inflammation of the whole brain and myelum, suggestive and subsequently secrete the organism in their feces. Our of a meningoencephalitis. Acyclovir was switched to patient used to have bats in his Brazilian house. He was foscarnet, but after a week of treatment the viral load in the treated successfully with itraconazol. liquor was still detectable at the same level. Next, acyclovir and foscarnet were both administered and eventually the C171 An exceptional Cluster-outbreak of Trichinellosis patient showed some clinical improvement. After three in Belgium: Clinical and Laboratory Features of 16 weeks of combination therapy, the Varicella infection was Patients successfully treated. There are no data from randomized controlled trials about P.E.A. Messiaen1, A. Forier2, S. Vanderschueren3, treatment of Varicella meningitis in immunocompromised C. Theunissen4, J. Nijs5, M. van Esbroeck4, E. Bottieau4, patients, but this particular case shows that aggressive K. de Schrijver2, I. Gyssens1, R. Cartuyvels1, P. Dorny4, treatment with both acyclovir and foscarnet is highly J. van der Hilst1, D. Blockmans3 indicated in case of patients not responding to acyclovir 1Jessa Hospital Hasselt, Department of Infectious Diseases monotherapy. and Immunology, Hasselt, Belgium, 2Agentschap Zorg en Gezondheid, Department of Infectious Diseases Prevention, C170 Unintended weight loss after immigration to Brazil Hasselt, Belgium, 3UZ Leuven, Department of Internal due to disseminated histoplasmosis Medicine, Leuven, Belgium, 4Institute for Tropical Medicine, Department of Clinical Science, Antwerp, Belgium, 5St L.C.J. de Bree, S.A. Gajadin Trudo Hospital, Department of Gastroenterology, St Truiden, Amphia Hospital, Department of Internal Medicine, Breda, Belgium the Netherlands Background: Trichinellosis is a rare zoonosis caused by Case report: A 66-year-old Caucasian man, known with ingestion of raw or undercooked meat containing larvae type II diabetes mellitus, presented with unintended of the genus Trichinella. In November 2014 an unprec- weight loss, fatigue and difficulties with swallowing. Six edented outbreak of trichinellosis occurred in the Belgian years before presentation he immigrated to Brazil. On Limburg/Antwerp region. We could identify 16 patients physical exam he appeared cachectic. Laboratory results who became ill after consumption of wild boar meat in one revealed an alevated C-reactive protein 11 mg/l, alkaline of three restaurants in two provinces. Here we report the phosphatase 114 U/l, gamma-glutamyltransferase 135 clinical and laboratory features of the patients from this U/l and calcium 2.68 mmol/l. Gastroduodenoscopy was exceptional cluster-outbreak. normal. Computed tomography showed reticulonodulary Methods: The medical records of 16 patients were lesions in the upper pulmonary fields. The differential reviewed. diagnosis consisted of a malignancy, mycobacterial, Results: The median time to first symptoms was 16 days parasitic or fungal infection, vasculitis, sarcoidosis and after exposure (range 4-24 days). All patients reported fever pneumoconiosis. Tuberculine skin test, HIV serology, and night sweats. Other major symptoms included peri- repeated sputum auramine and stool investigation orbital edema (14/16 patients), photophobia (6/16), mild to for parasites were negative. Bronchial lavage and lung moderate generalized myalgia (10/16) and conjunctivitis biopsy didn’t show any abnormalities. PET-CT showed (4/16). Only a minority of patients (6/16) reported initial FDG-uptake in the upper lung tissue and hilar and abdominal discomfort and diarrhea. There were signs of parajugulary lymph nodes. Patient developed nodular myocarditis in two patients. tongue lesions. Biopsy showed caseating granulomas. Laboratory analysis showed marked eosinophilia in all Histoplasma serology became positive. patients (mean 34% of white blood cells, range 7%-65%) Discussion: Histoplasmosis starts as a primary pulmonary and elevated serum creatinine kinase in all but two (mean infection after inhalation of microconidia of the fungus 666 U/l, range 101-1564 U/l). The diagnosis was confirmed Histoplasma capsulatum, after which reticuloendothelial by serologic testing. In addition, a muscle biopsy obtained dissemination follows. Although usually asymptomatic, from 3 patients revealed first stage Trichinella larvae. After it occasionally results in severe illness in immune treatment (Mebendazole or Albendazole 600mg to 1500mg compromised, or after inhalation of a large inoculum in daily with or without prednisolone), all but one patient had healthy individuals. Histoplasmosis, endemic in North- an uneventful recovery. America, does occur in Brazil. Diagnosis can be made by

81 Conclusion: Even in a non-endemic country, trichinellosis J. Maat1, K.P. Bouter1, C.P. Bleeker-Rovers2, should be considered in patients presenting with fever, M. van Apeldoorn1, M. Boulaksil1 blood eosinophilia, peri-orbital edema and/or myositis, in 1Jeroen Bosch Hospital, Department of Internal Medicine, particular if cases are clustered and/or have been exposed ’S-Hertogenbosch, the Netherlands, 2Radboudumc, to wild (boar) meat. Department of Internal Medicine, Nijmegen, the Netherlands

C172 Progressive coughing during the treatment of tuber- Case report: An 18-year old woman with a history of mild culosis; due to broncho-esophageal fistulae mitral valve insufficiency was admitted with fever and flu-like symptoms since one week. A viral infection was C.H.M. Leenen, J.M. Koorstra, C.E.H. Siegert, J. Veenstra, suspected and she was sent home. Two days later, she was C. Jie re-admitted because of three positive blood cultures with Sint Lucas Andreas Hospital, Department of Internal methicillin-sensitive Staphylococcus aureus. An abdominal Medicine, Amsterdam, the Netherlands ultrasound proved normal. She met one major and three minor Dukes criteria (Osler nodes and mitral valve Introduction: Broncho-oesophageal fistulae of benign prolapse) and intravenous flucloxacillin and gentamicin aetiology are rare. Tuberculous broncho-esophageal fistulae for endocarditis treatment was started. Transoesophageal (TBEF) are very rare complications of tuberculosis. echocardiography on days 2 and 10 proved negative. Case: a 70-year old Moroccan woman visited the outpatient Because of its potentially significant clinical consequence, clinic with a two week history of coughing, fever and we insisted on performing an 18F-FDG-PET/CT, although dyspnea. Physical examination revealed no abnormalities. this was debated, given a favorable clinical course and Laboratory tests showed an ESR 36mm, CRP 23mg/l. the potential drawback of radiation. An 18F-FDG-PET/ A right lower lobe infiltrate was seen on chest x-ray CT on day 8 revealed a large splenic abscess. An attempt for which she was treated with amoxicillin without to perform percutaneous drainage was unsuccessful. At improvement. Staining of sputum was dubiously positive this moment, she is still treated with flucloxacillin intrave- for Auramine, and negative for Ziehl Neelsen. However, nously and abscess size gradually decreased. PCR of sputum was weakly positive for Mycobacterium Discussion: Staphylococcus aureus bacteremia is a Tuberculosis and cultures showed Mycobacterium Bovis. potentially life-threatening condition with a mortality rate HIV serology was negative. Subsequently, tuberculo- up to 40 percent. Metastatic foci may remain asympto- static treatment was started. After the induction phase, matic or undetected by conventional imaging modalities. isiniazid and rifampicin were continued on the basis Known risk factors for dissemination are a community of sputum culture results. During treatment with good acquired infection and delayed treatment, both present compliance, dyspnea persisted. CT-scan demonstrated a in our case, resulting in a dissemination rate of up to growing calcified anterior mediastinal mass. Bronchoscopy 70%. Even though an initial abdominal ultrasound was showed enlarged antracotic lymph nodes with histological normal, 18F-FDG-PET/CT showed a large splenic abscess. inflammation. Therefore, a paradoxical response to tuber- In conclusion, 18F-FDG-PET/CT is a valuable imaging culostatic treatment was considered. After tuberculo- tool to visualize metastatic foci in Staphylococcus aureus static treatment she developed progressive coughing and bacteremia, which decreases mortality and relapse rate. dysphagia, especially after drinking liquids. A barium swallow illustrated TBEF to the middle lobe. Gastroscopy C174 Human metapneumovirus pneumonia: a stranger in confirmed the diagnosis, with two mucosal defects at 20 our midst? and 30cm (diameter>1cm) without options for endoscopic intervention. Repeated CT-scan showed reduction of the S. Slavenburg, C.H.M. Leenen, P.G.H. Peerbooms, mediastinal mass. L.P. Vos, A.M. de Kreuk Conclusion: Intractable cough and/or dysphagia in patients Sint Lucas Andreas Hospital, Department of Internal with tuberculosis should alert clinicians to the possibility Medicine, Amsterdam, the Netherlands of TBEF. TBEF may occur prior, during or after the treatment of tuberculosis. Tuberculostatic treatment alone Introduction: Human metapneumovirus (hMPV), may be sufficient in most patients. In non-responders belonging to the Paramyxoviridae family, has recently endoscopic intervention or surgery is indicated. been identified. It is commonly associated with mild to severe respiratory tract infections. Particularly in immuno- C173 Value of FDG-PET/CT in community-acquired compromised patients, it can cause life-threatening Staphylococcus aureus bacteremia pneumonia. hMPV appears to account for 9% of acute pneumonia in patients with hematological malignancies, mainly after hematopoietic stem cell transplantation.

82 Case: A 66-year old female started with R-CHOP of non-traumatic epilepsy. By eating infected pork meat, treatment for diffuse large B cell lymphoma localized ingestion of larval cysts can occur and these can develop in the spine. One week after the first cycle of chemo- into adult tapeworms in the human digestive tract. These therapy she presented herself in A&E with what seemed worms produce eggs which are transmitted to other to be neutropenic sepsis. Laboratory findings revealed humans by fecal-oral route. These ingested eggs develop a C-reactive protein level of 292 mg/l and white blood into cysts in all kind of tissues. Predominantly skin and cells < 0.1 E09/l. The chest radiograph showed diffuse brain, sometimes leading to serious complications, as was infiltrates in the right basal lung fields. The patient was shown in our patient. The diagnosis is made by serology, admitted to the ICU and treated with inotropic support, typical abnormalities on MRI of the brain and a travel antibiotics, corticosteroids and mechanical ventilation. history to endemic areas. Treatment comprises of several All cultures, as well as S. pneumonia and L. pneumo- options; surgery, anti-parasitic medication and supportive philia urinary antigen detections remained negative. care. Unfortunately, there was no improvement. Our primary differential diagnosis included acute respiratory distress C176 Extensive epidural abscesses in a patient with syndrome, atypical pathogens, transfusion-related acute Streptococcus intermedius bacteremia lung injury or R-CHOP related pulmonary toxicity. Therefore a bronchoalveolar lavage (BAL) fluid analysis L. van de Wijer, S.W. van Thiel was performed. Cultures did not show any bacterial of Amphia Hospital, Departement of Internal Medicine, Breda, fungal microorganisms. the Netherlands hMPV was detected in BAL fluid by reverse transcriptase PCR, by RespiFinder SMART 22 FAST assay. The patient We present a rare case of Streptococcus intermedius developed a bilateral pneumothorax and still requires bacteremia causing epidural abscesses in a patient with mechanical ventilation. diabetes. Discussion: This case illustrates that hMPV should also A 59-year old women with type 1 diabetes presented at be recognized as a potential life-threatening pathogen our emergency ward with progressive lower back pain and in patients with relatively mild immunosuppression. hyperglycemia. There was no history of sinusitis, dental Treatment still consists of supportive care. caries or prosthetic devices. On physical examination the patient was afebrile and, except for a systolic heart murmur C175 Pigs and people: more in common than we thought… grade 2/6, no abnormalities were found. Laboratory results showed glucose 19.7 mmol/l, ESR 104 mm/h, leukocytes E.H.C.C. Janssen, P. van Biezen, T.E.M.S. de Vries, 24.4 10e9/l with 87% bands and CRP > 00 mg/l. Renal V.A.S.H. Dalm, J.J. van Hellemond function was normal, liver tests were slightly elevated. Erasmus MC, Department of Internal Medicine, Rotterdam, X-ray and abdominal ultrasound were normal, endocar- the Netherlands ditis was excluded using cardiac ultrasonography. Under suspicion of bacteremia, treatment with broad-spectrum Case description: A 50-year old man, native from Cape antibiotics was commenced. After three days, blood Verde, without a relevant medical history was referred to cultures became positive for S. intermedius. Magnetic our hospital because of headache and vomiting. Physical resonance imaging (MRI) showed severe spondylodiscitis and laboratory examinations were unremarkable. However, of L5-S1 with widespread epidural abscesses, sparing the a MRI showed a lesion in the thalamus, leptomeningeal brain. Surgical drainage was considered too perilous, accentuation and hydrocephalus. The ophthalmologist given the extent and localization of the abscesses. An diagnosed papilledema. A ventriculoperitoneal drain was eight week treatment with intravenous antibiotics was placed and liquor was obtained, showing eosinophilia. started. Follow-up MRI’s showed clear response. Following Therefore serum and liquor were examined for infectious extended rehabilitation, the patient is now almost fully diseases. Both antibodies to and antigens of Taenia solium recovered. could be demonstrated in serum and liquor. Clinical and S. intermedius are member of the Streptococcus anginosus radiological symptoms matched the diagnosis. Our patient group and are most frequently found in the oral cavity and was treated with dexamethasone, albendazole and prazi- the gastro-intestinal tract. Though carriage is common, quantel. Within four weeks his clinical situation strongly bacteremia is rare. Once it occurs, however, S. intermedius improved. is known to form abscesses. In our case there was no Discussion: Neurocysticercosis is a parasitic disease, obvious site of infection and the only predisposing factor caused by Taenia solium. In the the Netherlands neuro- might be diabetes. Early recognition and prompt treatment cysticercosis is known as imported cases, whereas in Asia, with antibiotics remain crucial for a successful outcome. South America and Africa it is the most common cause

83 C177 A 32-year old man with mono-arthritis after visiting international recommendation is poor, and curiously it is South-East Asia unclear whether antibiotic streamlining may be harmful to individual patients. We investigated whether streamlining W.E. Boertien, B.B. Wintermans, K.C.M.C. Koeijvoets, in bacteraemic pneumococcal infections is associated with M.J. van Apeldoorn mortality. Jeroen Bosch Hospital, Department of Internal Medicine, Methods: Adults admitted to two Dutch hospitals between ’s-Hertogenbosch, the Netherlands 2001 and 2011 with bacteraemic pneumococcal infections were retrospectively included. Detailed clinical data on A 32-year old man, with no medical history, visited patient characteristics, comorbidities and severity and our emergency department because of a spontaneous outcome of disease were obtained in addition to data on progressive painful red swelling of his left sternoclavicular antibiotic treatment. Those eligible for streamlining were (SC) joint since one week, which extended to his neck. He selected for further analyses. returned to the the Netherlands 18 days ago after a holiday Results: In the 45.8% of cases (126 of 275) where antibiotic in South-East Asia. Seven days before his return he had treatment was streamlined, a lower mortality rate was unsafe oral and vaginal sexual intercourse. Five days later observed (6.3% versus 15.4%, p = 0.021). The decision he developed a sore throat, which lasted four days. to streamline was only marginally explained by the 38 Physical examination showed no abnormalities, except for determinants accounted for. After correction for potential a red, warm and painful swelling of the left SC-joint and confounders, the odds ratio for death while streamlining sternocleidomastoid muscle. No other joints were swollen was 0.45 (95% confidence interval: 0.18-1.11, p = 0.082) or painful. Blood analysis showed a mild leukocytosis (10.4 in all cases and 0.35 (95% confidence interval: 0.12-0.99, 10^9/l) and elevated C-reactive protein level (46 mg/l). p = 0.048) specifically in pneumonia cases. Ultrasound was performed which showed arthritis of the Conclusion: Our results suggest that streamlining in SC-joint and induration of the sternocleidomastoid muscle. eligible pneumococcal bacteraemia cases is safe, A needle aspiration was taken and intravenous amoxicillin/ irrespective of patient characteristics, severity of disease clavulanate was started. or empirical treatment regimen. Culture of the synovial fluid was hampered due to insufficient data supplied with the culture request, but after C179 Meningococcemia without meningitis: fever with four days bacterial colonies grew on the blood agar plate. myalgia not always a viral-infection These Gram-negative cocci were identified as Neisseria gonorrhoeae using mass spectrometry. PCR was used to J.W. Kroon test urine and throat to detect the primary focus. Urine Tergooi, Department of Internal Medicine/Nephrology, was tested negative and throat was positive. Blood culture Hilversum, the Netherlands and HIV combo test were negative. The patient was diagnosed with gonococcal arthritis and Case: A 61-year-old female was admitted at the emergency treated withintravenous ceftriaxone during one week department with symptoms of confusion, fever, vomiting because of ciprofloxacin resistance. This resulted in a and diarrhoea. Since one day she had severe myalgia, diminishing of the swelling and pain. especially of the lower extremity, headache and dyspnea. In conclusion our patient was diagnosed with a dissemi- Medical history included a lithium-induced nephropathy nated gonococcal infection after unsafe cunnilingus. treated with peritoneal dialysis. Laboratory tests at admission showed slightly raised CRP and WBC. On C178 Effect of antibiotic streamlining on patient outcome physical examination, the patient appears ill. Temperature in pneumococcal bacteraemia was 39.3 °C, blood pressure was 137/80 mm Hg, pulse rate was 147/min and respiration rate was 25/min. No signs of A.J.H. Cremers1, T. Sprong2, J.A. Schouten2, G. Walraven1, nuchal rigidity, rash, Kernig’s sign or Brudzinski’s signs. P.W.M. Hermans1, J.F. Meis2, G.F. Ferwerda1 Thorax x-ray, urine-dipstick were normal and gram-stain 1Radboudumc, Department of Pediatrics, Nijmegen, the of the peritoneal dialyse fluid was negative. Differential Netherlands, 2Canisius-Wilhelmina Hospital, Departments diagnosis include viral infection, urosepsis, abdominal of Medical Microbiology and Infectious Diseases, Nijmegen, sepsis or pneumosepsis. After blood- and urinecultures the Netherlands were taken, ceftazidim and amoxicillin was started. Rapid influenza tests were performed. After admission the Background: In blood culture-proven pneumococcal CRP-level raised rapidly to 479 mg/l.. Soon, the clinical infections, streamlining empirical therapy to monotherapy status improved, the fever disappeared and the myalgia with a penicillin is preferred in order to reduce the use of decreased. The CRP-level dropped quickly. Unexpected, broad-spectrum antibiotics. However, adherence to this the blood-cultures were positive for Neisseria menin-

84 gitides. The antibiotic therapy was switched to ceftriaxone. high sodium load is important: 1) in case of persistent The patient recovered well and left the hospital without psychic dysregulation, symptomatic hypernatremia need symptoms. to be considered 2) close monitoring of serum sodium is Discussion: Meningococcemia without meningitis is rare. necessary when patients are treated with high doses pGHB Severe myalgia has been overlooked and undervalued as and 3) NaCl 0.9% infusion should be avoided. an early clinical feature of meningococcemia. Although initial clinical features of patients with meningococcemia C181 A prospective study of QTc prolongation due to eryth- without meningitis are similar of common, self-limiting romycin used as prokinetic agent in ICU patients viral illnesses, signs of early sepsis should differentiate the patient who merits clinical monitoring. Early recognition R.B. Fiets1, J.M. Bos2, E.J. Lamfers1, R. Donders3, and prompt initial antibiotic therapy continue to be the J.A. Schouten2, C. Kramers1 cornerstones of the successful management of this disease. 1CWZ/Radboudumc, Department of Internal Medicine, Nijmegen, the Netherlands, 2CWZ, Department of Clinical Pharmacy, Nijmegen, the Netherlands, 3Radboudumc, XII INTENSIVE CARE Statistics, Nijmegen, the Netherlands

Background: High dose erythromycin used as antibiotic C180 Hypernatremia caused by GHB on doctor’s prolongs QTc. Low dose erythromycin is frequently used prescription as a prokinetic agent, especially in patients at the ICU. It is unknown whether low dose erythromycin prolongs QTc I.M. Rood, C.G.W. Seijger, M.M.R. de Maat, J.C. Verhave, and put patients at risk for torsades des pointes. M. Blans Methods: In this prospective study we included patients Rijnstate, Department of Internal Medicine, Arnhem, the at the ICU treated with erythromycin in a dose of 200 mg Netherlands bd. Electrocardiogram was registered before, 15 minutes and 24 hours after start of erythromycin. No new QTc Background: Requests for professional help with gamma- medication should be started during study. QTc was hydroxybutyric-acid (GHB) addiction have increased tenfold measured by 2 investigators. Electrolytes, renal function in recent years. Pharmaceutical GHB (pGHB) is used and hepatic function was measured in all patients. off-label to treat withdrawal symptoms. We present two Results: In a total of 51 patient, 3 ECGs were recorded patients, who developed a symptomatic hypernatremia that and no change in QTc prolonging medication was made. required Intensive Care admission. In these 51 patients QTc increased significantly from Case report: Patient 1: a 43-years old woman (chronically 430 ms at baseline to 439 ms (p = 0.03) after 15 minutes addicted to GHB) was referred to the emergency and 444 ms (p = 0.01) after 24 hours. After 15 minutes department because of psychic dysregulation, diagnosed and 24 hours upper limit of 95% confidence interval for as GHB withdrawal. She was admitted to the psychiatric prolongation of QTc was well above 10 ms. In 4 patients ward and administered two hourly pGHB according to the QTc increased to more than 500 ms and in 2 patients QT local protocol ‘GHB withdrawal/detoxification’. NaCl 0.9% was already above 500 ms. No QTc related arrhythmias infusion was also started. Within 24 hours the serum were seen. sodium increased from 147 to 165 mmol/l. Treatment Conclusion: Erythromycin in a dose of 200 mg bd prolongs was complicated because of agitation without acceptation QTc and ECG should be controlled when this is prescribed. of therapy. Sedation and consequently mechanical ventilation was necessary in order to treat the symptomatic C182 Milky lungs hypernatremia. Patient 2: a 41-years old man was admitted for clinical E.B.M. Keltjens, M.J. Blans detoxification of GHB-addiction. One day later he had Rijnstate, Department of Internal Medicine, Arnhem, the significant GHB withdrawal. Treatment was started (same Netherlands protocol as patient 1). NaCl 0.9% infusion was started. Within 24 hours, treatment resulted in a symptomatic A 49-year old Romanian woman who had been living on hypernatremia (141 to 160 mmol/l) and respiratory failure the street, presented to the emergency department with (needing treatment at the Intensive Care). progressive dyspnea for the last four weeks. There was no Discussion: Treatment with pGHB and NaCl infusion coughing and no fever. resulted in a sodium load of respectively 756 mmol/24h Physical examination revealed a tachypnoic patient with and 1040 mmol/24h. pGHB (sodiumoxybate) contains an oxygen saturation of 85% without oxygen suppletion. 4mmol sodium per ml. Awareness of the extremely

85 On pulmonary exam, bilateral crackles were heared. creatinine kinase level (1675U/l) which kept rising in the Cardiac exam was unremarkable and no edema was seen. first 24 hours (up to 3408U/l). Possible reasons for skeletal Chest X-ray showed severe bilateral pulmonary consoli- muscle destruction were taken into account but were dations, and computed tomography revealed bilateral considered unlikely. Creatinine kinase level normalized pulmonary consolidations with ‘crazy paving’. Almost no within 66 hours as plasma osmolality and glucose values healthy lung tissue could be recognized. normalized due to rehydration and insulin therapy. His Laboratory results only revealed a slightly raised C-reactive renal function improved until serum creatinine stabilized protein of 21 mg/L, a leukocyte count of 14.0 x 10^9/L and at 150-170mmol/l. a raised lactate dehydrogenase of 552 U/L. Conclusion: Although uncommon, rhabdomyolysis can Under suspicion of Pneumocystis pneumonia treatment occur in the diabetic state, which might be related to high with trimethoprim/sulfamethoxazole and prednisolone serum sodium, serum osmolality and blood glucose levels. was started. Furthermore the patient was treated with In this case the patiënt’s Studer pouch may have attributed amoxicillin and ciprofloxacin for community acquired to the metabolic complications. Management strategies are pneumonia. undefined yet, but adequate rehydration was shown in this PCR for Pneumocystis jirovecii was positive, but this case to be effective, and may prevent further complications. result was not confirmed by microscopy. HIV testing was negative. C184 Pneumorrhachis and pneumopericardium after During broncho-alveolar lavage (BAL) a milky fluid was ecstasy use; an uncommon complication seen. PAS staining on the fluid was positive and IgG anti-GM-CSF in serum was elevated (27 AE/ml (normal I.E. Kubbenga1, N. Postma2, B.P. Ramakers1 <12 AE/ml)) confirming the diagnosis of pulmonary 1Bernhoven, Emergency Unit/Department of Intensive alveolar proteinosis (PAP). Care, Uden, the Netherlands, 2Radboudumc, Department of The patient was treated with whole lung lavage in a Intensive Care, Nijmegen, the Netherlands specialized centre. After lavage, no oxygen suppletion was needed and the chest X-ray normalized. 2.5 weeks after Background: The use of ecstasy (active substance admission she was discharged in good clinical condition. 3,4-methyleendioxymethamfetamine; MDMA) rapidly PAP is a rare diagnosis and should be considered in increases among the Dutch population. The most common patients with bilateral diffuse lung consolidations. complication of ecstasy use is hyperthermia. Here we describe a patient with subcutaneous emphysema, C183 Hyperosmolar hyperglycemic state combined with pneumomediastinum, pneumopericardium and pneum- rhabdomyolysis and acute renal failure: a rare orrhachis (air within the spinal canal (either intra or extra presentation of type-2 diabetes mellitus de novo dural)) after ecstasy use. Case description: A 20 year-old man referred himself to J. Fehér, G.C. van Melsen the emergency department with swelling of his throat and MC Haaglanden, Department of Intensive Care, Den Haag, dyspnea. Physiological examination revealed subcutaneous the Netherlands emphysema and a CT scan demonstrated extensive subcutaneous emphysema, pneumomediastinum, pneumo- Introduction: Hyperosmolar hyperglycemic state (HHS) pericardium and pneumorrhachis. After exclusion of the is a serious acute complication of diabetes mellitus. We most common causes of subcutaneous emphysema, we present a rare case of HHS associated with rhabdomyolysis concluded that this clinical picture was due to volutrauma and acute renal failure. as a consequence of the combination of extensive activity Case report: A 66-year old man was admitted to our (dancing) with recurrent vasalva manoevres after ecstasy hospital because of abdominal discomfort, anorexia and use. After two days of observation in the ICU the patient fatigue. Laboratory test revealed the following results: fully recovered. plasma glucose 63.1mmol/l, corrected serum sodium Conclusion: Subcutaneous emphysema, pneumomedi- 159 mmol/l, potassium 6.0 mmol/l, urea nitrogen astinum, pneumopericardium and pneumorrhachis, are 36.0 mmol/l, creatinine 279umol/l and plasma osmolality rare, but potentially life-threatening complications after 423 mOsmol/kg. Urine ketone bodies were weak positive. drug use. In most cases treatment can be conservatively, Patient history included a radical cystoprostatectomy but cardiopulmonal monitoring is essential, given the risk with creation of a Studer Pouch and a non-functional of cardiovascular complications. left kidney (due to hydronephrosis). He was not known with diabetes mellitus. Diagnosis of hyperosmolar hyper- C185 CPR with an unusual cause glycemic state was made, as the first presentation of diabetes mellitus de novo. In addition, he had an elevated W. Kleinherenbrink, J. Dits, S. Stads

86 Ikazia Hospital, Department of Internal Medicine, lactic acidosis (pH 6.7, lactate 27 mmol/l) and acute Rotterdam, the Netherlands on chronic kidney injury (creatinine 720 mmol/l) were present. Intensive Care admission and intubation followed. Case report: A 71-year old woman was admitted to the Differential diagnoses were sepsis originated from the ICU after she was found comatose at home. Her vital abdomen or urinary tract and metformin intoxication. signs were BP 55/30 mmHg, pulse 70/min and SpO2 Broad spectrum antibiotics were started empirically. 97%. Medical history consisted of hypertension, treated The metformin concentration was 48 mg/l (therapeutic with metoprolol.After admission she developed Pulseless- < 2.0 mg/l) and haemodialysis was initiated. The Electrical-Activity. ROSC was achieved after 15 minutes metformin level decreased to 6.7 mg/l. Resuscitation of cardiopulmonary resuscitation. There was no evidence consisted of 30 liters of crystalloids and high dose of infection, metabolic or neurologic pathology after noradrenaline (0.9 ug/kg/min). In 8 days she improved to additional research. ECG and cardiac ultrasound showed full recovery. Blood cultures remained negative. normal rhythm, function and no pericardial effusion. The Diabetic nephropathy and metformin use is associated patient was vasodepressor dependent and antidotes were with metformin intoxication leading to lactic acidosis and administered (flumazenil, glucagon and naloxone) pending circulatory shock. Other risk factors are compromised toxicology results without any effect. After 24 hours cardiac function and use of ACE inhibitors or diuretics, she showed no neurologic or circulatory improvement. advised to be discontinued when acutely ill. This patient Repeated ultrasound showed reduced LV-ejection (37%). with multiple risk factors for developing metformin Metoprolol levels were 1.3 mg/l (normal: 0.1-0.6 mg/l) intoxication, presenting with extremely high levels and amitriptyline levels 0.65 mg/l (normal < 0.5mg/l). We of metformin, demonstrates the significance of started alkalinisation, weaning from vasopressors and her counseling patients taking ACE inhibition and diuretics consciousness normalized. in combination with metformin. It also illustrates the Discussion: Both amitriptyline and metoprolol levels importance of recognizing metformin intoxication as a were in toxic range. Elimination half-life for amitriptyline cause of distributive shock and the effectiveness of haemo- averages 36 hours with large inter-individual variability. dialysis in eliminating metformin. Tricyclic antidepressants can be fatal in doses from 10 times the daily dose. Early phase of tricyclic antide- C187 Neurogenic shock in a patient with Spinal Cord pressant intoxication is characterized by tachycardia Injury WithOut Radiographic Abnormality with rhythm and conduction abnormalities, in the late (SCIWORA) phase hypotension and cardiogenic shock predominates. Simultaneous use of metoprolol probably protected our N. van der Lubbe, D.J. Kamphuis, L. Dawson patient from rhythm disturbances in early phase, but Reinier de Graaf Gasthuis, Department of Intensive Care, aggravated cardiogenic shock in late phase. Delft, the Netherlands Conclusions: This case shows a patient developing PEA and subsequently severe cardiogenic shock, caused by an We report a case of SCIWORA, defined as spinal cord unexpected co-intoxication of amitriptyline and metoprolol. injury without radiographic abnormality. A 62-year-old Signs and symptoms can be masked by co-intoxication of male was admitted with pneumonia. He was known with medications and unpredictable deterioration may occur. atrial fibrillation for which he used oral anticoagulants. At admission he complained of neck pain after a recent fall. C186 Distributive shock: shockingly acid Neurological examination and a CT-scan of the cervical spine were unremarkable. His cervical pain was ascribed M.E.A.M. van Kleef, M. van Buren, P.L.J. van der Heiden to tendomyalgia. The next morning, unexpectedly, he HagaZiekenhuis, Department of Intensive Care, Den Haag, experienced asystolic cardiac arrest and cardiopulmonary the Netherlands resuscitation was initiated. After intubation he regained spontaneous circulation but remained hypotensive despite Determining the cause of acute distributive shock remains fluid resuscitation and inotropic drugs. Several causes of a challenge. The right diagnose, however, is extremely shock were excluded including hypovolemic/hemorrhagic important for the appropriate therapy. This is illustrated shock (normal urine production and hemoglobin concen- by our case of a 62-year old woman, known with diabetic tration), cardiogenic and obstructive shock (sinus rhythm nephropathy, hypertension and cardiomyopathy, presenting on EKG, normal chest radiograph and echocardiography) with symptoms of acute dyspnea and abdominal pain. and septic shock (normothermia, decreasing inflammatory Her medication included metformin, irbesartan and parameters while on antibiotics). Neurogenic shock was hydrochlorothiazide. She was hypotensive (85/27 mmHg), reconsidered because of the recent fall and the use of tachypnoeic (30/min) and hypothermic (32 °C). Severe oral anticoagulants together with unresponsiveness of

87 the patient, apnea and noteworthy bradycardia. Indeed, Jeroen Bosch Hospital, Department of Intensive Care, a new CT cervical spine showed an atlanto-axial (C1-C2) ’S-Hertogenbosch, the Netherlands dislocation with a relatively high position of the dens in the foramen magnum compromising the myelum and Introduction: Hantavirus is caused by an enveloped lower brainstem. He was withheld from further treatment Bunyaviridae virus, transmitted by secretions of infected because of a poor prognosis. He deceased soon after. rodents. Few hantavirus positive patients develop We believe that pre-existent spinal cord instability e.g. hantavirus cardiopulmonary syndrome; a febrile illness ligament injury, not discernable on the first CT scan, characterized by bilateral diffuse interstitial oedema, with led to the C1-C2 dislocation and shock. With this case respiratory failure requiring supplemental oxygen and we want to create awareness of SCIWORA and, when supportive care. suspected, suggest adding magnetic resonance imaging as Case: A 47/year old man was referred to the emergency a diagnostic tool to investigate spinal cord injury. department because of lower backpain and malaise since a few days. His medical history revealed only a lumbar C188 Respiratory insufficiency and coma after elective spine spondylodesis operation. He worked as a truck knee surgery driver and recently drove to Europe, Russia and Africa. Physical examination showed fever (38.8º Celsius) with no S.M. Rombach, A.C. Tukker, S. de Jager, E.R. Rijnsburger, other abnormalities. Laboratory evaluation revealed slight M. Hoeksema elevation of inflammation markers, raised lactate dehydro- Zaans Medical Centre, Department of Intensive Care, genase and thrombocytopenia. The next days he developed Zaandam, the Netherlands abdominal complaints, acute kidney injury and left-shifted granulocytic series with atypical lymphocytes. Serology A 78-year-old male with gonarthrosis of the left knee was tests were positive for both hantavirus antibodies IgG and admitted for elective knee arthroplasty. Despite a medical IgM class, revealing recent hantavirus infection. He was history of atrial fibrillation, coronary bypass grafting, treated with supportive care. Ten days after admission he and mitral valve reconstruction after endocarditis, he complained of acute dyspnea and showed deep hypoxia. was fit and still working at his farm. Surgery under We saw an anxious, agitated man with a oxygenation of general anesthesia was performed and uneventful. Upon 77% with maximum O2-supply. He was transferred to awakening he was confused and agitated, which was the ICU where he was intubated. The chest X-ray showed thought to be due to a delirium, and he was subsequently extensive bilateral diffuse interstitial oedema. Initially we treated with clonidine 75 mg in the recovery. A few hours needed high ventilation pressures and oxygen levels for later he developed respiratory distress and tachycardia. an adequate oxygenation. PICCO measurement showed Chest-X-ray showed pulmonary edema presumed to be a high extravascular lungwater, confirming pulmonary a result of congestive heart failure. With a presumed capillary leakage diagnosing hantavirus cardiopulmonary diagnosis of atrial fibrillation and congestive heart failure, syndrome. Within 3 days of mechanical ventilation diuretics, enoximon and bronchodilators were initiated and supportive care quick resolution of the cardiorespi- and he was admitted into the ICU. His neurological state ratory phase leaded to extubation. After ten days he was further deteriorated and 24 hours after surgery, he was discharged with complete recovery. found unconscious ( Glasgow Coma Scale: E2M4V2). After extensive assessments, including CT and MRI of the brain, liquor punction, EEG and laboratory investigations ruling XIII NEPHROLOGY out other causes, fat embolism syndrome was diagnosed. He was intubated and ventilated because of respiratory insufficiency and his comatose state. During his coma C190 Ticagrelor induced renal failure leading to statin- he sometimes opened his eyes but did not respond. At induced rhabdomyolysis day 27, he made eye contact and he responded to simple commands. At day 49 he was discharged from the ICU A.J. van Vuren1, B. de Jong2, H.P.R. Bootsma2, and was able to have a conversation, and regained strength M. van der Veen2, G.W. Feith2 in arms and legs. The prognosis in patients with coma due 1Gelre Hospitals, Department of Internal Medicine, Apeldoorn, to fat embolism syndrome is good in most patients and the Netherlands, 2Gelderse Vallei, Department of Internal complete recovery has been reported. Medicine, Ede, the Netherlands

C189 Hantavirus cardiopulmonary syndrome Introduction: Tuberculous peritonitis (TP) frequently presents with nonspecific symptoms which often lead to V. van Coenen, F.W. Rozendaal

88 delayed diagnosis. We describe a case of TP in a native changed, without improvement. Serology for auto-immune Dutch patient. hepatitis was negativeand MRI liver shoewed no abnor- Case: a 42-year-old patient was referred to the outpatient malities. A liver biopsy was consistently refused by the clinic because of weight loss. He had no other complaints patient. Biochemistry improved but did not normalize. In and no medical history. Physical examination, laboratory november 2014 hepatitis E PCR was performed and proved tests, abdominal ultrasound and CT-scan showed no abnor- positive. In contrast to 2014 Ig M antibodies to hepatitis E malities. A watchfull waiting strategy was adopted. were present, suggesting a recent infection. However on Six months later, he was referred again because of clinical grounds is it was assumed that the acute infection progressive weight loss, accompanied by night sweats and was in September 2013. This was proven by a positive myalgia. A submandibular swelling was noted. Cytology Hepatitis E PCR on left over blood from October 2013. was consistent with a lateral or median neck cyst. Conclusion: as increasingly recognized and reported in the Three months later, a CT scan was performed because literature Hepatitis E is a cause of chronic hepatitis in solid of clinical suspicion of pulmonary embolism. Strikingly, organ transplant recipients. Serology is unreliable in these it showed lymphadenopathy in the epigastrium and immunocompromized patients liver hilum. Subsequent abdominal CT-scan revealed ascites, omental lymphadenopathy and a diffusely C192 Rituximab induced Posterior Reversible thickened mesentery. Malignancy and tuberculosis were Encephalopathy Syndrome considered and a diagnostic laparoscopy was performed. Laparoscopic findings were consistent with miliary tuber- K. Blijdorp, J.P.A. Samijn, I.J.A.M. Verberk-Jonkers culosis and culture of a peritoneal biopsy was positive for Maasstad Hospital, Department of Internal Medicine, Mycobacterium tuberculosis. The patient had frequently Rotterdam, the Netherlands travelled to Asia until 3 years before presentation. He was treated with tuberculostatics for 6 months and slowly A 26-year old woman recently treated with rituximab recovered. and corticosteroids for lupus nephritis, was re-admitted Discussion: TP represents a diagnostic challenge (21 days after first dosage of rituximab) with edema and because of the lack of specific symptoms and absence of hypertension due to progressive renal insufficiency. She non-invasive diagnostic tests. Treatment delay is especially was treated with antihypertensive medication, diuretics common in countries with a low prevalence of tuberculosis and pulse methylprednisolone. During admission, blood and leads to high morbidity and mortality. pressure normalized (140/82 mmHg). On day 4 she TP should be considered in patients with weight loss, developed headache without visual loss, followed by abdominal pain and ascites. Laparoscopy with peritoneal tonic clonic insults. Fundoscopic evaluation showed biopsy is the diagnostic tool of choice. no hypertensive retinopathy. MRI of the brain showed extensive subcortical T2 hyperintensities, multifocal but C191 Elevated liver enzymes after kidney transplantation predominantly in the occipital region, related to posterior a long delay in diagnosis reversible encephalopathy syndrome (PRES), likely rituximab-induced. The differential diagnosis of neuro-SLE M.J. Krol-van Straaten was considered and treatment with antiepileptics and HagaZiekenhuis, Department of Internal Medicine, Den intravenous immunoglobulins was started. During Haag, the Netherlands admission she recovered completely from her neurologic symptoms, while due to further kidney function decline Case: In September 2013 a 47 year old woman Surinam hemodialysis was initiated. Repeated MRI 2 weeks later, Hindustan ethnic background was admitted with showed almost complete resolution of the parieto-occipital abdominal pain, diarrhea, elevated liver enzymes (ASAT lesions, compatible with the diagnosis rituximab-induced and ALAT around 200, GGTP 400) and worsening of PRES. renal function. In April 2012 a second kidney transplant PRES, first described in 1996, is a clinical syndrome of had been performed because of end stage renal failure due headache, altered consciousness, visual disturbances and to focal segmental glomerulosclerosis. She was on triple seizures, in combination with characteristic neuroimaging immunosuppression with prednisolon, tacrolimus and findings of posterior white matter edema. It is associated mycophenolate and had new onset diabetes after trans- with several medical conditions, of which hypertensive plantation. After rehydration clinical conditionand kidney crisis and cytotoxic immunosuppressive therapy are the function improved, and stools normalized, however liver most important. So far six cases related to rituximab biochemistry worsened. Viral serology’s for hepatitis A, have been reported, rare compared to the broad usage of B, C, E, CMV and EBV were all negative. An adverse drug rituximab. The pathophysiology is unclear, but related effect was supposed and medications were stopped or to breakthrough of the auto regulation of cerebral blood

89 flow and endothelial dysfunction. Treatment consists of lowering blood pressure and withdrawing the offending Case 1: A 67-year-old kidney transplantation recipient was cytotoxic agent. Most patients recover completely within admitted because of diarrhea and vomiting. Her immuno- weeks. suppressive agents were mycophenolate mofetil 720mg (MMF), prednisolone 10 mg and tacrolimus (TAC) 8 mg C193 Acute kidney failure with Hantavirus infection; not daily. TAC levels were stable (0.007 mg/l; therapeutic a typical interstitial nephritis presentation level 0.005-0.015 mg/l). The patient was afebrile, mildly dehydrated, s-creatinin doubled (351 mmol/l). IV T.D. Rohde, H. Boom rehydration was started, TAC was held. At admission, Reinier de Graaf Gasthuis, Department of Internal Medicine, serum TAC level was toxic: 0.034 mg/l. Four days after Delft, the Netherlands admission TAC was restarted (2 mg iv daily) when serum level was 0.009 mg/l, and increased when diarrhea abated. Case report: A 49-year old man was admitted to our Case 2: A 58-year-old kidney transplantation recipient hospital with acute renal failure, muscle aches, recurrent was admitted because of diarrhea since 2 weeks. His fever and abdominal pains. Until 4 days before admission immunosuppressive agents were MMF 2000mg, predni- patient was in good health, had no significant medical solone 10mg and TAC 8 mg (trough level 0.095). Physical history and used only pravastatin. On admission he examination was unremarkable. Laboratory findings had nausea, but wasn’t vomiting. There was no fever showed normal a toxic TAC level of 0.026mg/l. IV and he appeared not ill. Physical examination was rehydration was started and TAC was discontinued. When unremarkable. Initial laboratory results showed an diarrhea frequency decreased the patient was put back on estimated glomerular filtration (eGFR) rate of 46 ml/ oral TAC. Twelve days after admission his TAC serum level min/1.73m2 and. A peripheral-blood count showed throm- was 0.014 mg/l (dose 4 mg daily). bocytopenia, leukocytosis and high hemoglobin level. Discussion: Tacrolimus toxicity is a relatively unknown CRP, lactate dehydrogenase and liver enzymes were complication of diarrhea. This is somewhat counterintu- slightly elevated. Albumin and protein levels were normal. itive and in contrast to decreased levels of other calcineurin Urine analysis showed blood (3+), and the absence of blockers during diarrhea. Two putative mechanisms are leukocytes. Abdominal ultrasound revealed slight liver involved, both caused by impaired enterocyte function. steatosis, no kidney abnormalities and no urinary tract P-glycoprotein is decreased during diarrhea, resulting in obstruction. During admission, renal function deterio- increased absorption; and C4P3A4 activity is inhibited. As rated. 24-hour urine collection showed proteinuria of this cytochrome metabolizes tacrolimus, decreased activity 5.88 g/24h. Autoimmune serology was negative and there results in higher drug levels. These 2 cases underline that were no signs of complement usage. Renal biopsy showed during diarrhea, early tacrolimus monitoring and dose normal glomeruli and interstitium. Immunofluorescence reduction is recommended in transplant recipients. for IgG/IgM/IgA, kappa or lambda chains and complement was negative. Electron microscopy showed slight podocyt C195 Cohort study outpatient ‘contrast-induced nefropathy fusion compatible with massive proteinuria. During (CIN)’ clinic shows low incidence of CIN but follow-up, renal function recovered and proteinuria substantial mortality disappeared. Virus serology testing showed IgM antibodies against Hantavirus(ns). Repeated virus serology confirmed P.J. Gundlach, J.A.M. van Beek-Peeters, J. Ruissen, a primo Hantavirus infection. I.J.A.M. Verberk-Jonkers Conclusion: We describe an uncommon presentation Maasstad Hospital, Department of Internal Medicine/ of a Hantavirus infection with acute kidney injury and Dialysis, Rotterdam, the Netherlands nephrotic range proteinuria, without interstitial nephritis. Hence, in cases of acute kidney injury with nephrotic Background: In 2011 we initiated an outpatient contrast- range proteinuria with typical findings of fever, abdominal induced nefropathy (CIN) clinic in order to prepare patients tenderness and thrombocytopenia, also Hantavirus with an increased risk for CIN. We aimed to characterise serologic testing should be considered. these patients as well as to assess and follow them for relevant outcomes. C194 The interesting pharmacokinetics of tacrolimus Methods: Between July 2011-May 2013 497 patients with toxicity secondary to diarrhea an increased risk for CIN were seen at the outpatient ‘CIN’ clinic and assessed a.o. for age, renal function, M.G. Dickinson, C. Halma proteinuria and awareness of renal insufficiency. Patients MC Leeuwarden, Department of Internal Medicine, were followed till may 2014 and assessed for referral Leeuwarden, the Netherlands and treatment policy according to the Dutch National

90 Transmural Agreement Chronic Kidney Disease (LTA but is also involved in cyst formation and insulin secretion. CNS), CIN incidence and reversibility and mortality. HNF1B nephropathy is an increasingly recognized entity Results: 49 patients (10%) were unaware of pre-existing that often occurs de novo and may progress to end-stage renal insufficiency. 38% (n = 188) required treatment by renal disease. Hypomagnesemia is one of the more a nephrologist according to the LTA CNS, of which 88 common and discriminating features of this extremely patients were not seeing a nephrologist. Eventually 53 heterogenic disorder. patients were referred to a nephrologist for further care. 4% (n = 20) developed CIN, which was reversible in 19 C197 B-symptoms, cardiac murmur and renal failure patients. One year mortality after contrast investigation was 23% (median survival 203 days). The survival of E.C. de Weerd, K. Farhat patients with contrast investigation because of oncologic Spaarne Hospital, Department of Internal Medicine, disease was significant worse than those with an inves- Hoofddorp, the Netherlands tigation because of non-oncologic disease (20 days, p < 0.001). Case description: a 52 year old woman presented with Conclusion: Characterisation of the outpatient ‘CIN’ clinic renal failure (serum creatinine 1468 mmol/l). The last population showes that a relevant amount of patients is year she experienced fatigue, nausea and weight loss unaware of their renal insufficiency and identifies patients (20 kilograms). Since six weeks these complaints were with insufficient treated kidney disease, who require progressive. She was too weak to get out of bed, had no nefrologic care and follow-up. The incidence of CIN is low fever but had been experiencing night sweats.Her history and almost always reversible, while one year mortality post reported a ventricular-septal defect and 6 months earlier contrast investigation is substantial. an analysis for anemia. Gastro- and colonoscopy had revealed no abnormalities. C196 See the lyte: unexplained hypomagnesemia as clue Physical examination showed a weak woman with normal to HNF1B nephropathy blood pressure and temperature. We heard a systolic murmur over the entire heart. We found no skin lesions, E.J. Hoorn arthritis, lymphadenopathy or edema. Erasmus MC, Department of Internal Medicine, Rotterdam, Laboratory testing showed the earlier mentioned kidney the Netherlands injury, elevated ESR and CRP and normocytic anemia with dysmorphic erytrocyturia. Auto-immune serology was A 33 year-old male was referred by an internist in a negative (ANCA, anti-dsDNA). Three days after admission general hospital because of unexplained hypomagne- blood cultures taken at the ER revealed a streptotoccus semia. His previous medical history included intellectual mitis bacteremia. Hemodialysis and antibiotic treatment disability and epilepsy for which he was using valproic acid were started.Aortic valve endocarditis was confirmed (his only medication). He expressed no complaints and with trans-esophageal echocardiography. An infiltrative had a negative family history. Physical examination was lesion in the lower right pulmonary lobe was seen on unremarkable. His laboratory results revealed hypomagne- PET-scan, without other metastatic abscesses. Two weeks semia (lowest serum magnesium 0.38 mmol/l) with renal after admission she developed apraxia of the right hand, magnesium loss (fractional magnesium excretion 11%) CT-cerebrum showed ischemia in the left frontal lobe, and hypocalciuria (0.04 mmol calcium/mmol creatinine). probably due to septic emboli. No other electrolyte disorders were present, but a reduced Our suspicion of immune complex-mediated glomeru- kidney function was noted (estimated glomerular filtration lonephritis was confirmed by the renal biopsy, showing rate 57 ml/min, proteinuria 0.5 mg/l). Ultrasound showed crescentic glomerulonephritis, likely due to circulating kidneys of 9 cm with 2 cysts in the left kidney and 1 immune complexes. cyst in the right kidney (cyst size 1 to 1.5 cm). Although Conclusion: Immune complex-mediated glomerulone- not present during the first visits, the patient developed phritis is a rare complication of infective endocarditis. diabetes mellitus during follow-up (fasting serum glucose Renal function usually recovers to baseline with antibac- 8.3 mmol/l, HbA1c 51 mmol/mmol). This constellation terial treatment, however irreversible renal damage can of findings suggested HNF1B nephropathy (also known occur when treatment is delayed. as maturity onset of diabetes type 5). Genetic analysis revealed a chromosome 17q12 deletion, which includes C198 Patient with kidney failure and HIV HNF1B as the critical gene, but also explained intellectual disability and epilepsy. HNF1B (hepatocyte nuclear factor R.J. Rodenburg, S. van Esch 1 homeobox B) is a transcription factor that is crucial for Elisabeth-TweeSteden Hospital, Department of Internal magnesium reabsorption in the distal convoluted tubule, Medicine, Tilburg, the Netherlands

91 lenalidomide, kidney function improved. No renal biopsy Case description: a 48-year old male was referred to our was obtained. Four months later patient’s kidney function hospital because of acute kidney failure. On physical had normalized. It is very plausible that lenalidomide examination a decreased consciousness and diffuse caused ARF in our patient, because of immediate renal exanthema were observed. Laboratory results showed insufficiency after starting and the rapid recovery after severe kidney failure (creatinine 1348 mmol/l) and a discontinuation of lenalidomide. thrombopenia (115x10E9/l) without signs of microan- Although kidney dysfunction due to lenalidomide is giopathic hemolytic anemia. The urinesediment showed not infrequent, it does not seem to be a well-known side 500 leukocytes, 200 erythrocytes and 3+ protein. Patient effect. The mechanism of this ARF is unknown. It is was started on dialyses. In the regular work-up we hypothesized that the combination of paraproteins, which performed a HIV test (ELISA) which came back positive. are potentially nephrotoxic, and the immunomodulatory The confirmative Western blot was negative although the and anti-angiogenic effects of lenalidomide could be the viral load was > 10.000.000 copies/mL matching an acute cause. Another case report described an acute interstitial HIV infection. nephritis due to lenalidomide. Kidney failure in HIV patients is often due to an acute With this case report we would like to highlight this side tubules necrosis, HAART medication or HIVAN in longer effect and we would advise adequate follow-up of the existing HIV. Our patient was not yet on HAART and kidney function during lenalidomide therapy. a HIVAN was not plausible because of the very recent infection. We performed a kidney biopsy which showed C200 Progressive kidney failure in chronic myelomono- interstitial inflammation. Hence, we hypothesised about cytic leukemia: don’t forget lysozyme! other causes independently of HIV. Lastly the Hanta IgM became positive. Therefore we J.M. Hillen1, J. Raemaekers1, E. Steenbergen2, J. Wetzels2, concluded the acute kidney failure was due to an infection J.C. Verhave1 with Hanta virus independent of the HIV. Our patient was 1Rijnstate, Department of Internal Medicine, Arnhem, the on dialyses for over 2 months and his kidney function fully Netherlands, 2Radboudumc, Department of Pathology, recovered. Nijmegen, the Netherlands Background: Hantaviruses are part of the family of Bunjaviridae and contain at least 20 different species Introduction: Kidney failure is common in hematologic including the Puumalavirus. In The the Netherlands malignancies. However, the nephrotoxic influence of the Puumala virus is spread by the bank vole (Myodes lysozyme is seldom recognised. Chronic myelomono- glareolus) through contact with its excreta or aerosols. In cytic leukemia (CMMoL) is characterized by increased 2007 27 cases of Hanta virus infection were reported to the production of lysozyme, which is filtrated through the RIVM. Most patients return to baseline GFR. glomeruli and absorbed by the tubuli. Lysozyme causes kidney injury by tubular toxicity. C199 Acute renal failure due to lenalidomide Case description: A 78-year-old man was referred to the outpatient department with progressive kidney failure. In R.S. Dekker, L. van Gils-Verrij 2012, he was diagnosed with CMMoL, which required no Rode Kruis Hospital, Department of Internal Medicine, treatment. Since that time, his kidney function deterio- Beverwijk, the Netherlands rated. At time of presentation, he had no complaints except fatigue, which he attributed to the CMMoL. Physical A 67-year old man with multiple myeloma was admitted examination was unremarkable. Laboratory results showed to the hospital because of acute renal failure (ARF), which kidney dysfunction, with an eGFR of 20 ml/min/1.73m2. was noticed by routine laboratory investigation. Two His urinary sediment contained no dysmorphic eryth- weeks before admission, lenalidomide/dexamethasone rocytes and no erythrocyte or leukocyte casts. The urine was started because of a slowly raising paraprotein. He had albumin/creatinine ratio was 3.6 mg/mmol Cr, or approx no further complaints. His fluid intake and diuresis were 40 mg/24h. Total proteinuria was 700 mg/24h, thus normal. Patient did not use any nephrotoxic drug. Physical indicating the loss of another protein than albumin. examination was unremarkable, including a normal Kidney ultrasound showed no abnormalities. A kidney blood pressure. Laboratory results showed a creatinine of biopsy was performed, showing tubular atrophy, inter- 274 mmol/l. His urine showed hematuria, no leucocytes stitial fibrosis and remarkably abnormal tubuli, charac- and the known proteinuria. Ultrasound of the urinary terized by vacuoles in the cytoplasm compatible with tract showed no post renal obstruction. ANA, ANCA and lysosomal overload. This picture is typical for lysozyme complement were normal. A cystoscopy found no urologic induced kidney injury, which is often seen in patients cause for the hematuria. Three weeks after stopping with CMMoL. The advanced renal failure and the lack of a

92 proven effective therapy, discouraged us to start CMMoL M.H. Kallenberg1, J. de Gelder2, B. de Groot2, treatment. J.A. Lucke2, A.J. Fogteloo2, T.J. Rabelink2, M. van Buren2, Discussion: In CMMoL, toxicity of lysozyme in the tubuli S.P. Mooijaart2 causes kidney failure and kidney replacement therapy may Leiden University Medical Centre, Departments of 1Nephrology be necessary. Early recognition of the lysozyme toxicity is and 2Geriatrics, Leiden, the Netherlands essential to allow treatment directed at preventing further kidney damage. Background: Older patients represent a growing population in the Emergency Department (ED). These patients are C201 Smoldering myeloma of renal significance: C3 especially vulnerable for experiencing negative outcomes glomerulopathy due to activation of the alternative and deterioration in functioning. Furthermore, the pathway of complement by monoclonal light chains prevalence of impaired renal function increases with age, which may be an additional risk factor for poor clinical D. Soonawala, B.W. Florijn outcome. Leiden University Medical Centre, Department of Internal In the present study we aim to study the association Medicine, Leiden, the Netherlands between renal function and cognitive and functional impairment in older patients with acute illness. Case: At a routine yearly check-up, a 68-year old man Methods: We initiated the prospective Acutely Presenting presented with new-onset renal insufficiency (rise in Older Patient (APOP) study, in which we included all serum creatinine from 75 to 250 micromol/l), proteinuria consecutive patients aged 70 and over presenting to the (0.6 g/l) and hematuria, with overactivation of the ED. Data collection included renal function, the Six Item alternative complement pathway (AP 9%, CP 84%, C3 level Cognitive Impairment Test (6CIT) for cognition, and the reduced, C4 level normal). A renal biopsy showed glomeru- Identification Seniors At Risk score (ISAR) and Katz Index litis and transmembranous granular C3 positive deposits. of Independence in Activities of Daily Living (Katz ADL) Based on a differential diagnosis of post-infectious glomer- for functional status. ulonephritis or C3 glomerulopathy he was managed Results: 570 patients with a mean age of 79 years were conservatively. His serum creatinine slowly increased to included. In patients with impaired renal function (MDRD 360 micromol/L, whereafter he was referred to our centre. < 30) cognitive impairment was present more frequently He still had overactivation of the alternative complement than in patients with MDRD > 60 (30.8 vs. 15.4%, p = pathway. The result of a second renal biopsy was consistent 0.017). Association between impaired renal function with the first biopsy. We diagnosed C3 glomerulopathy. In and functional impairment measured by the ISAR and addition he was diagnosed with smouldering myeloma Katz-ADL score seemed to be even stronger (78.6% vs. (serum M-protein IgG-k 19 g/l, serum free k-light chain 55.9% (p = < 0.001) and 42.9% vs. 16.4% (p = < 0.001) 290 mg/l, λ-light chain 15 mg/l, urine M-protein 0.3 respectively). g/24h, bonemarrow 10-15% clonal k-light chain restricted Conclusion: This study shows that impaired renal function plasma cells, Hb 6.0 mmol/l, normocalcemia, no osteolytic in the acute setting is correlated with cognitive and lesions). He was treated with prednisone, high-dose functional impairment in older patients presenting to the melphalan and bortezomib after which his serum ED. In the future, early identification of these vulnerable complement levels quickly normalised. Over the course patients may enable a more tailored trajectory. of six months, serum M-protein disappeared, as did the proteinuria and hematuria. His serum creatinine improved C203 Legionnaires’ disease: a uncommon cause of to 160 mmol/l. Other cases of C3 glomerulopathy secondary rhabdomyolysis to activation of the alternative pathway of complement by monoclonal light chains have been reported. In one case, M.D. Stradmeijer a monoclonal λ-light chain was found to interact with Kennemer Gasthuis, Department of Internal Medicine, factor H and inhibit its regulatory function. Analysis of Haarlem, the Netherlands the complement system is being performed to identify the mechanism in our case. Introduction: Rhabdomyolysis, a well-known cause of acute renal failure is frequently caused by crush injuries, C202 Cognitive and functional decline in older patients immobilization or sepsis. Another, less common cause is with impaired renal function presenting to the Legionnaires’ disease, as described below. emergency department; The APOP study Case: a 79-year old man was admitted with a, on chest X-ray confirmed, community acquired pneumonia of the left lower lobe for which he was started on amoxicillin/ ciprofloxacin. Besides decreased oxygen saturation his

93 vital parameters were stable. Laboratory results showed it was mainly the history that triggered the suspicion of elevated inflammation values and creatinine-level of Hantavirus infection. Conservative management was 417 mmol/l. Because of acute renal failure, creatine kinase conducted and 3 days after discharge his creatinine started was measured, with a level of 9825 U/l. Renal ultrasound to decline to 97 mmol/l and Hantavirus serology came back showed no abnormalities. The diagnosis of acute renal positive. failure due to rhabdomyolysis was made and volume Hantavirus infections are uncommon in the the resuscitation started. Urine antigen test for Legionella Netherlands. Nevertheless, in patients with classical was positive and confirmed by sputum-PCR for Legionella symptoms and exposure to rodents the diagnosis can Pneumophilia. The diagnosis Legionnaires’ disease was be made without extensive diagnostic procedures such made. Because of progressive dyspnea, persistent oliguria as kidney biopsy, and treatment with supportive care is and increasing CK-levels, hemodialysis on the ICU was sufficient. started. His respiratory condition improved markedly within days and slowly renal function improved as well C205 Intentionele Atripla Intoxicatie – hemodialyse with a serum creatinine of 223 mmol/l on discharge. indicatie? Discussion: Renal involvement is not uncommon in Legionnaires’ disease and is often seen in critically ill A.M.L. Oude Lashof, M. Visschers, E.J.R. Litjens, patients. However, as illustrated above, can also be present J.A. Schippers, T.R.A. Havenith in the non-critically ill. Rhabdomyolysis is an known but Maastricht UMC+, Department of Medical Microbiology and uncommon cause of acute renal failure in Legionella Unfectious Diseases, Maastricht, the Netherlands infection. Currently, the mechanism is incompletely understood, but early recognition is important to prevent Een 50-jarige man presenteerde zich op de spoedeisende mortality and morbidity. Encountering a patient with the hulp elders met een auto-intoxicatie met 86 tabletten clinical picture of pneumonia and acute renal failure, Atripla® (efavirenz 600mg, emtricitabine 200mg, rhabdomyolysis and Legionnaires’ disease should be tenofovir disoproxil 245mg. Hij was sinds 9 maanden considered. bekend HIV-1 positief, en gebruikte sinds 4 maanden Atripla®. C204 Acute kidney injury? Think Hantavirus Bij presentatie elders, 12 uur na inname, had hij behoudens misselijkheid en diarree, geen klachten. Het H. Wessel1, E.M.E. Verbeek2, A. van Tellingen2, kreatinine was 110 mmol/l (MDRD 61 ml/min), voorheen N.C. van der Weerd1 91 mmol/l. Patiënt werd niet direct gedialyseerd aangezien 1AMC, Department of Neprology, Amsterdam, the de nierfunctie nog goed was. Helaas verslechterde deze Netherlands, 2Zaans Meidcal Centre, Department of Internal zeer snel, met als belangrijkste differentiaal diagnose acute Medicine, Zaandam, the Netherlands tubulus necrose op basis van tenofovir-intoxicatie/toxiciteit. Eén dag na opname was de MDRD 21 ml/min, en 48 u na Case report: The first patient is a 19-year old man, who opname was het gedaald tot 10 ml/min. Het urinesediment presented with a fever and abdominal pain. Three weeks was niet afwijkend. Hydronefrose werd uitgesloten. Vier before presentation he had been camping in the Ardennes. dagen na opname werd patiënt overgeplaatst naar ons He had a temperature of 39,5 °C, other vital signs and centrum waar geen acute dialyse indicatie meer bestond. physical examination were normal. His laboratory findings Uiteindelijk werd 9 dagen na auto-intoxicatie gestart met showed an ALAT of 77 U/l, a creatinine of 314 mmol/l and hemodialyse omwille van hyperkaliemie en mogelijk a platelet count of 48 10E9/l. Urinalysis revealed 1+ protein uremische klachten. and microscopy demonstrated 2 red blood cells/ml. The Met de gemeten tenofovir plasmaconcentraties hebben we camping trip, combined with symptoms and laboratory de berekende invloed van acute hemodialyse, bestaande results raised suspicion of an acute kidney injury due to uit 4 dagen 4 uur, gesimuleerd. Daaruit blijkt dat acute Hantavirus infection. He was treated conservatively. 14 hemodialyse de tenofovir-concentratie veel sneller zou Days later his laboratory results returned to normal and hebben verlaagd en dat daardoor de blootstelling (AUC) Hantavirus serology turned out positive. aan tenofovir ook aanzienlijk minder zou zijn geweest, met The second patient is a 42-yr-old man, admitted with mogelijk behoud van normale nierfunctie. a fever, headache and malaise. He recently cleaned his Hemodialyse werd gestaakt na zes weken. Er resteert een barn, populated with rodents. His temperature was chronische nierinsufficiëntie stadium III. 39,55 °C. Laboratory examination disclosed a creatinine Deze casus toont dat acute hemodialyse een te overwegen of 350 mmol/l, a platelet count of 71 10E9/l and an ALAT behandeling is ter mogelijke preventie van nefrotoxiciteit of 88 U/l. Urinalysis revealed proteinuria of 5 gram/l and door langdurig verhoogde tenofovir-concentraties. microscopy demonstrated 77 red blood cells/ml. Likewise,

94 C206 See the Pee: proteinuria as a clue for a haemato- medication. Further improvement was observed when the logical diagnosis hypothyroidism was adequately treated. Case two: A 52-year-old man was referred with recently R.L. Kriekaart, M.P. Kooistra diagnosed hypertension, edema and hypothyroidism. On Rijnstate, Department of Internal Medicine, Arnhem, the admission a creatinine of 268 mmol/l, TSH 3.86mU/L, Netherlands F-T4 14.6 pmol/L were seen. 24-hour urine sampling showed 8.5 gram proteinuria and creatinine clearance of A 72-year old woman, with a history of hypertension, 25 ml/min. Renal biopsy showed focal segmental glomeru- was revered to our clinic because of progressive fatigue losclerosis. Immunosuppressive treatment induced rapid and weight loss. Analysis revealed a nephrotic syndrome improvement. His hypothyroidism improved as well and with mild renal insufficiency, without haematuria. ANA, levothyroxine was discontinued on follow-up. serology for rheumatoid arthritis and complement were Discussion: The main pathophysiologic mechanism in normal. Cryoglobulins and antibodies against hepatitis hypothyroidism induced kidney failure is decreased renal were negative. Microscopy on renal biopsy displayed blood flow due to reduced cardiac output. This needs to be a membranoproliferative glomerulopathy (MPGN). differentiated, using isotope GFR-studies, from pseudo Immunofluorescence (IF) showed positive IgG and IgM. kidney failure which may occur in hypothyroidism due MPGN classification has changed recently since the patho- to increased creatinine generation from muscles and physiology of the disease has been clarified further. The decreased tubular secretion of creatinine. Hypothyroidism old classification (type 1-3), based on EM findings, has been rarely results from nephrotic syndrome and cannot be replaced with a new system, based on IF findings. MPGN attributed to the loss of protein bound thyroid hormones. is now subdevided in immune-complex associated and Urinary loss of FT4 may be the cause, though this remains immune-complexlex negative disease. Immune complex- to be elucidated. associated MPGN is driven by chronic antigenemia or Conclusion: When kidney disease and hypothyroidism circulating immune complexes. Causes include infections, are related they are potentially reversible. Therefore we auto-immune diseases, (haematological) malignancies, suggest measurement of thyroid function in the work up sarcoidosis, certain drugs. Immune complex negative of a patient with kidney disease. MPGN is referred to as C3 glomerulopathy, since it is caused by dysregulation of the alternative complement C208 Lithium nephropathy: a long-term complication of pathway and terminal complement complex.Our patient chronic lithium therapy suffered from immune complex associated MPGN. Infectious causes (e.g. hepatitis C and other chronic A. Hercegovac1, T.M. Bosch1, R. Hoekstra2, infections) and autoimmune diseases (lupus, Sjögren, A.M. van Alphen1 rheumatoid arthritis) were excluded. A bone marrow 1Maasstad Hospital, Department of Internal Medicine, biopsy was performed and a small cell CLL lymphoma Rotterdam, the Netherlands, 2Delta Center for Mental Health was diagnosed, for which she is treated now. At present Care, Department of Psychiatry, Rotterdam, the Netherlands the nephrotic syndrome has improved.Investigation of the urine of patients with general complaints can give us a Background: Lithium is the treatment for bipolar disorder. significant clue to a non-renal diagnosis, and should never Lithium-induced nephropathy is a known complication be forgotten. limiting its use. The aim of this study is to establish the prevalence of renal failure in our population and to relate C207 Kidney disease and hypothyrodism its occurrence to lithium serum concentration, number of intoxications and duration of lithium therapy. S. Bos, W.P. Haanstra, R.R.H. Nap Methods: We selected 1751 patients on lithium therapy Scheper Hospital, Department of Internal Medicine, Emmen, from the laboratory database of the Delta Centre for Mental the Netherlands Health Care, Rotterdam. The database contains measurements of lithium and creatinine concentration over a Introduction: Hypothyroidism has been reported as the period from 2000 to 2011. eGFR was calculated using cause as well as the consequence of kidney disease. the 4-variable MDRD formula. Renal failure was defined Case one: A 62-year-old women with a recent history of as having GFR<60mL/min on at least 2 measurements 6 hypothyroidism and hypertension was admitted with weeks apart. A comparison was made between patients kidney function decline. Her symptoms, i.e. edema, with and without renal insufficiency regarding the number fatigue, lowering of her voice, dysphagia, improved with of lithium intoxications, mean lithium concentration in levothyroxine. A creatinine of 278 mmol/l was revealed serum, duration of therapy, cardiovascular disease, hyper- with slight improvement after alteration in hypertension tension and diabetes mellitus.

95 Results: 305 out of 1751 (17.4%) patients were developed to systemic immune dysregulation and cytokine activation. renal failure. Renal failure was positively correlated with Close and careful monitoring of renal function is therefore duration of lithium therapy (p < 0,0001). Mean lithium warranted in patients with a diagnosis of IBD. serum concentration and a history of lithium intoxication did not prove different between groups. Significant C210 Tinnitus and headaches as presenting symptoms of correlation was observed between renal insufficiency and fibromuscular dysplasia in a middle aged male cardiovascular disease, hypertension and diabetes mellitus. Conclusions: The incidence of renal insufficiency in our M. Brands, C.E.H. Siegert cohort is comparable to other reports. Longer duration Sint Lucas Andreas Hospital, Department of Internal of lithium therapy was found to be associated with an Medicine, Amsterdam, the Netherlands increased risk of renal insufficiency. Contrary to our expectation the frequency of toxic lithium serum concen- Introduction: Fibromuscular dysplasia (FMD) is a tration was not clearly associated with an increased risk of non-inflammatory vascular disease occurring primarily renal failure. in middle aged women (female: male ratio 10:1). Presenting symptoms depend on the arteries involved. C209 Granulomatous interstitial nephritis in Crohn’s A recent large registry study showed that hypertension, Disease: an extraintestinal manifestation? headeaches, pulsatile tinnitus and dizziness are the most common presenting symptoms (Olin et al. Circulation, S.A.M.E.G Timmermans, M.H.L. Christiaans, 2012;125:3182-3190). M.A. Abdul-Hamid, J. Potjewijd, P. van Paassen Case description: A 52-year old Caucasian male presented Maastricht UMC+, Department of Nephrology and Clinical at our emergency department with new onset of hyper- Immunology, Maastricht, the Netherlands tension, severe headache, nausea, and vomiting. Symptoms had been progressive over the last 5 days. The patient had Extraintestinal manifestations of inflammatory bowel suffered from tinnitus without hearing loss for a longer disease (IBD), including Crohn’s disease and ulcerative period. His medical history included agenesis of the left colitis, probably reflect systemic inflammation, kidney. At presentation he had mild photophobia and a autoimmune susceptibility, or drug-related toxicity. blood pressure of 190/116 mmHg. Further physical and Although these manifestations are prevalent, renal disease, neurologic examination were unremarkable. as such, is considered rare. Laboratory results showed a normal blood count, ESR, Here, we present two adolescent patients with either CRP, electrolytes and lipid spectrum. Serum creatinine a recent onset or past history of Crohn’s disease who was elevated (153 mmol/l), with estimated GFR of 48 ml/ present with acute kidney injury (AKI; serum creatinine min (MDRD). MRA and CT showed 3 right renal arteries 165 mmol/L and 233 mmol/L, respectively) and minimal of which the upper two were irregularly narrowed over urinary abnormalities without hypertension. Pre- and prolonged segments and obstruction of the right carotid postrenal causes of AKI were excluded and a renal biopsy artery. Additional conventional angiography demonstrated procedure was performed. Both biopsies revealed a segmental narrowing of arteries in multiple effluents predominant lymphoplasmacellular infiltrate and the compatible with FMD. PTA of the upper 2 renal arteries formation of noncaseating granulomata in the tubulo- was performed. Hereafter, antihypertensive was attenuated interstitial compartment, whereas the glomeruli and the with lower blood pressure and near complete resolution of vasculature were not involved. Routine immunofluores- headaches. cence was negative. Hence, a diagnosis of granulomatous Conclusion: FMD in men is rare and should be suspected interstitial nephritis was made. in acute onset of symptomatic hypertension, especially in Granulomatous interstitial nephritis in IBD is extremely patients with headache and tinnitus. rare, since only six case reports have been published in the English literature to date. Of our patients, one patient was shortly treated with mesalamine for more than a year XIV ONCOLOGY ago. Although drug-induced nephrotoxicity by 5-amino- salicylic acid has been considered an etiological factor in tubulo-interstitial nephritis, there is no clear relationship C211 Chemotherapy in patients aged 75 years or older with between the duration and dose and the development of metastatic breast cancer: a retrospective single-center renal disease. Moreover, the other therapy-naive patient series still developed renal disease. Therefore, both cases raise the possibility of granulomatous interstitial nephritis as a L.M. van der Plas, S.C. Linn, H. van Tinteren, genuine extraintestinal manifestation of IBD, perhaps due C.H. Smorenburg

96 Antoni van Leeuwenhoek, Department of Medical Oncology, rapidly normalized during chemotherapy. Within a month Amsterdam, the Netherlands after his last course of chemotherapy he presented with jaundice (bilirubin 131mmol/l). Further laboratory results Background: Data on feasibility and outcome of chemo- showed elevated transaminases levels (ALAT 1634U/l therapy in elderly patients with metastatic breast cancer and ASAT 1228U/l). Based on serology acute hepatitis (MBC) remain scarce. E infection was diagnosed. Serum tumor markers were Methods: We reviewed the files of patients aged ≥ 75 years also assessed and AFP was increased to 45mg/l. On the who received first-line chemotherapy for MBC between posttreatment CT scan enlarged retroperitoneal lymph January 2000 and January 2014 at our hospital. nodes had normalized. During the next weeks bilirubin Results: Twenty-four patients were treated with palliative and AFP returned to normal levels. We could conclude chemotherapy. The median age was 80 years (range 75-89). that his elevated AFP was the result of his temporal liver The majority of patients (67%) had ER-positive disease, dysfunction due to acute hepatitis E infection. During while triple negative breast cancer and HER2-positive further follow-up the patient remained disease free. breast cancer was diagnosed in 13% and 29%, respectively. Conclusion: Serum of tumor markers are of utmost None of the patients was frail or had a WHO performance importance for the management of patients with testicular score > 2. Most patients received low dose weekly germ cell tumors. Elevations of these markers usually are doxorubicin (n=9, 38%) or capecitabine (n = 7, 29%), while caused by disease progression or relapse. However one 4 patients (17%) received vinorelbine plus trastuzumab should be aware that other conditions such as hepatic (VINOHER). Seven patients (29%) discontinued chemo- dysfunction may also influence serum concentration of therapy due to toxicity. No febrile neutropenia or hospital these tumor markers. admission for toxicity occurred. Best response was partial response (PR) and stable disease (SD) in 13 (54%) and C213 Introduction of radiotherapy in Suriname: impact on 6 (25%), respectively. Nine patients (38%) had clinical the treatment of cervical cancer benefit, defined as SD or PR > 6 months. Patients treated with chemotherapy without trastuzumab had a median E.T.h.M. Dams1, W.B. Hawkins2, M.Y. Lichtveld2 time-to-progression (TTP) of 5.1 months (95% confidence 1Diakonessenhuis, Department of Internal Medicine/Oncology, interval (CI) 4.3-5.9) and a median overall survival (OS) of Paramaribo, Suriname, 2Tulane University, School of Public 11.4 months (95% CI 8.4-14.4). The median TTP and OS Health & Tropical Medicine, New Orleans, United States of in patients treated with VINOHER were 8.1 months (95% America CI 0-15.1) and 20.2 months (95% CI 0-31.9), respectively. Cause of death was MBC in all deceased patients. Background: Cervical cancer is the 2nd most frequent Conclusion: In selected patients aged ≥ 75 years, single cancer and accounts for the leading cause of cancer-related agent chemotherapy for MBC is feasible and moderately death in Surinamese women. Radiotherapy is an essential effective. part of treatment, but until recently was not available in Suriname. Affected women were treated abroad. This study C212 The pitfall of tumor marker determination in a evaluated the effect of the introduction of radiotherapy in patient with testicular cancer 2012 on treatment coverage and quality of care. Methods: A retrospective cohort study was conducted, M.F. Thijs, A. van der Gaast comparing treatment of women diagnosed with cervical Erasmus MC, Department of Oncology, Rotterdam, the cancer in the period 2008-2011, prior to introduction of Netherlands radiotherapy, to treatment of women diagnosed in the period 2012-2013, who received radiotherapy locally. Introduction: The tumor markers chorionic gonadotropin Results: During the study period January 2008 - December (HCG) and alpha-fetoprotein (AFP) are important for 2013, 339 women received a first diagnosis of cervical diagnosis, treatment and follow up We present a case in cancer, corresponding to an average annual incidence with a transient rise of AFP is not due to tumor activity. rate of 21,3 ± 1,7 per 100,000 female population, with Case description: A 34-year-old male underwent no significant changes during the study period. More orchiectomy for a right-sided testicular tumor. Preoperative than 80% of the women presented with late-stage HCG was 30 IU/l and AFP was 8,5 mg/l. Initial CT-scan disease. Creoles and Indigenous women showed much revealed no signs of metastatic disease. Postoperative higher incidence rates than the other ethnic groups. The AFP levels failed to normalize and a second CT scan proportion of women receiving appropriate radiotherapy showed enlarged pathologic retroperitoneal lymph increased from 71,6% in the period 2008-2011 to 82,4% nodes. Treatment consisted of 3 courses chemotherapy in 2012-2013. The waiting time between diagnosis and (cisplatin, etoposide and bleomycin). Tumor markers treatment diminished with 38 days on average. In addition,

97 the percentage women with a delay of > 150 days decreased administrating oxaliplatin he developed acute chest pain, from 29% to 7%. nausea and shortness of breath. On physical examination Conclusion: Cervical cancer continues to pose an there was diaphoresis, low blood pressure and a confused important health problem for women in Suriname. The mental status with a short period of unconsciousness. introduction of radiotherapy has demonstrated improved Oxaliplatin was discontinued immediately and electrocar- treatment of invasive cervical cancer. However, additional diography showed elevations of the ST-segments in leads prevention and early detection strategies are needed to II, III and aVF with reciprocal ST-depression. With volume lower incidence and mortality rates. expansion the complaints disappeared spontaneously and mental status recovered quickly. He was admitted to the C214 Case report: Sunitinib treatment in a patient with cardiac care unit for rhythm observation. Repeated ECG metastatic renal cell carcinoma and bariatric surgery showed normalization and cardiac enzyme levels were normal. He was treated with aspirin, b-blockade and C.M.J. van Kinschot1, V.O. Dezentje1, N.P. van Erp2, statins. The chemotherapeutic regimen was changed to T. Feberwee1 capecitabine monotherapy. 1Reinier de Graaf Gasthuis, Department of Internal Medicine, Conclusion: This case illustrates the probability of coronary Delft, the Netherlands, 2Radboudumc, Paharmacy, Nijmegen, vasospastic angina as a side effect of oxaliplatin treatment. the Netherlands Kounis syndrome should be considered in patients who experience chest pain or shortness of breath during or In the past decade many tyrosine kinase inhibitors (TKI) shortly after administration of oxaliplatin. were added to the arsenal of oral oncolytics used in the treatment of a variety of malignancies. In contrary C216 Burden and distress of caregivers of patients on to intravenous drugs, bioavailability of orally adminis- tyrosine kinase inhibitors (TKI) for gastrointestinal tered drugs depends on gastrointestinal absorption and stromal tumors (GIST): a cross-sectional study first-passmetabolism. Challenges in reaching effective plasma levels may arise in patients with altered gastro- S.M.C.H. Langenberg1, A.N.M. Wymenga2, intestinal anatomy, while pharmacokinetics can differ. A.K.L. Reyners3, C.M.L. van Herpen4, J.B. Prins4, In this case report we demonstrate a patient with a W.T.A. van der Graaf4 history of gastric bypass surgery due to obesity and an 1Radboudumc, Department of Medical Oncology, Nijmegen, indication for treatment with sunitinib for metastatic renal the Netherlands, 2Medisch Spectrum Twente, Department cell carcinoma (mRCC). Since the plasmaconcentration of Medical Oncology, Enschede, the Netherlands, 3UMC of sunitinib and its active metabolite desethylsunitinib Groningen, Department of Medical Oncology, Groningen, the appeared to be inadequate during the standard treatment Netherlands, 4Radboudumc, Department of Medical Oncology, regimen, the sunitinib dose was successfully escalated. Nijmegen, the Netherlands

C215 A rare case of ST elevations Background: Informal caregivers of patients facing cancer and its treatment may encounter burden and distress. This M.W.A. Kamermans, M.P. Hendriks may have serious consequences for caregivers’ health and MC Alkmaar, Department of Internal Medicine, Alkmaar, lead to problems in patients’ adjustment to their illness. the Netherlands What effect patients’ long-term TKI treatment for GIST has on their caregivers is unknown. We aimed to explore Introduction: Vasospastic or nonvasospastic angina in informal caregivers’ burden and distress during patients’ combination with an allergic or hypersensivity reaction is long-term treatment. known as Kounis syndrome. During this reaction there Methods: Patients and their caregivers were included is release of histamine, which can cause vasospasmen by when patients were treated with TKI for at least 6 months. activating histamine receptors. Caregivers and patients completed the Hospital Anxiety Case: A 62-year old man was diagnosed with esophageal and Depression scale (HADS) (distress: total score cancer with liver metastases 10 months ago. He received > 12). Caregivers completed the Self-Perceived Pressure six cycles of capecitabine and oxaliplatin (CAPOX). After a from Informal Care questionnaire (burden: 0-3 = low, chemotherapy-free interval the patient showed progressive 4-6 = moderate, 7-9 = high). disease and would be treated with CAPOX again. The Results: 61 couples were included for analysis. Caregivers’ patient was admitted to the oncology unit for the first and patients’ median age was 60 (IQR 51-68) and 66 (ICR infusion of oxaliplatin. At that time he had not taken 55-75) years, 66% and 43% were female, respectively. 78% capecitabine yet. He received dexamethasone, calcium of the caregivers were patients’ partner. The mean score of gluconate and magnesium sulphate. A few minutes after the total sample for burden was normal (M2.4, SD2.3) and

98 caregivers’ distress was below the cut-off score for manifest Structured screening for these clinically relevant DDIs, by distress (M8.1, SD5.7). On individual level, 16% of the (hemato)oncologists in close collaborations with clinical caregivers experienced moderate and 10% severe burden, pharmacologists, should take place before the start and and 23% of the caregivers was distressed. Caregivers’ during anticancer treatment. burden and distress were significantly correlated (r = .58, p = .0001). Additionally, caregivers’ burden and distress C218 Relationship between sunitinib pharmacokinetics were significantly correlated to patients’ distress (r = .44, and administration time: preclinical and clinical p = .0001 and r = .38, p = .003, respectively). evidence Conclusion: A quarter of all informal caregivers suffered from long-term burden and distress. Timely recognition J.S.L. Kloth1, L. Binkhorst2, A.S. de Wit2, P. de Bruijn2, and support of these caregivers is of importance, especially P. Hamberg 3, M.H. Lam2, H. Burger2, I. Chaves2, given the fact that generally TKI treatment of GIST patients E.A.C. Wiemer2, G.T.J. van der Horst2, R.H.J. Mathijssen2 has a long duration. 1Maasstad Hospital, Department of Internal Medicine, Rotterdam, the Netherlands, 2Erasmus MC, Department C217 Drug-drug interactions in patients treated for cancer: of Internal Oncology, Rotterdam, the Netherlands, 3Sint a prospective study on clinical interventions Franciscus Gasthuis, Department of Internal Medicine, Rotterdam, the Netherlands R.W.F. van Leeuwen1, F.G.A. Jansman2, P.M.L.A. van den Bemt1, F. de Man1, F. Piran1, Background: Circadian rhythms may influence the Ì. Vincenten1, A. Jager1, A. Rijneveld1, J.D. Brugma1, pharmacokinetics of drugs. Therefore, efficacy of drugs R.H.J. Mathijssen1, T. van Gelder1 may be dependent on the time of administration. Sunitinib 1Erasmus MC, Pharmacy and Department of Medical is an oral anti-cancer drug taken once daily. This study Oncology, Rotterdam, the Netherlands, 2Deventer Hospital, aimed to elucidate whether sunitinib pharmacokinetics is Department of Clinical Pharmacy, Deventer, the Netherlands subject to circadian variation. Methods: We performed studies in mice, treated with Background: Drug-drug interactions (DDIs) are of major sunitinib at 6 dosing times. Plasma and tissue samples concern in oncology, since cancer patients typically take were obtained for pharmacokinetic analysis and to monitor many concomitant medications. Some retrospective studies mRNA expression of relevant metabolizing enzymes and have been conducted to determine the prevalence of drug transporters. In parallel, a prospective randomized potential DDIs. However, prospective studies on DDIs cross-over study was performed in which patients took needing interventions in cancer patients have not yet sunitinib once daily at 3 courses at 8AM, 1PM and 6PM. been performed. Therefore we investigated DDIs leading Primary endpoint in both studies was the difference in to an intervention proposed by a clinical pharmacol- plasma area under the curve (AUC) between dosing times. ogist in ambulatory cancer patients receiving oral and/or Results: Plasma sunitinib AUC in mice followed a ~12h intravenous anticancer treatment. rhythm as a function of administration time (p ≤ 0.04), Methods: Patients starting with a new I.V. or oral with 14-27% difference in AUC between dosing times. anticancer treatment regimen were asked to participate. Circadian rhythms were seen in the mRNA levels of drug Data on demographic characteristics, use of co-medication, transporters and metabolizing enzymes. In 12 patients, over-the-counter (OTC) drugs and co-morbidities sunitinib trough levels were higher when the drug was were collected by the clinical pharmacologist during a taken at 1PM or 6PM, than when taken at 8AM (p= 0.006), structured interview with the patient. Subsequently, the resulting in better balanced concentrations of sunitinib patients’ medication was checked for DDIs by using drug during the day. The AUC was not significantly different interaction software. An expert team of 3 clinical pharma- between dosing times. cologists evaluated the relevance of these identified DDIs. Conclusions: Our study indicates that sunitinib pharma- If a DDI was qualified as clinically relevant, an inter- cokinetics follows a ~12h rhythm in mice. In humans, vention was proposed to the treating physician. Descriptive dosing in the afternoon or evening resulted in higher statistics were performed. trough levels, most likely resulting from differences in Results: In this study 302 patients were included. The elimination. This could have implications for dosing based drug interaction software identified 603 PDDIs. Next to on therapeutic drug monitoring. the intervention proposed by the (hemato)oncologists, an additional intervention was proposed by the expert team C219 A patient with gynecomastia and hyperthyroidism for 42 patients (14%). Conclusion: Clinical interventions on DDIs are frequently R. van der Pas1, D.G.J. Robbrecht2, J.M.G.H. van Riel1, required among patients starting with anticancer therapy. W.A.C.M. Nieuwlaat1

99 1Elisabeth-TweeSteden Hospital, Department of Internal Caregivers completed the Self-Perceived Pressure from Medicine, Tilburg, the Netherlands, 2Erasmus MC, Informal Care questionnaire. Measurements were Department of Internal Medicine, Rotterdam, the Netherlands conducted prior to CRT (T0), 1 week (T1) and 3 months after completing CRT (T2). A 41-year old patient was referred to our outpatient clinic Results: 60 couples were included. 93% completed T0, with a 4-week history of palpitations, fatigue, 13 kg weight 82% T1 and 75% T2. Caregivers’ and patients’ mean age loss and gynecomastia. His GP diagnosed an anti-TSH- was 54 (SD14) and 56 years (SD10), 75% and 34% were receptor antibody negative primary hyperthyroidism and female, respectively. 70% of the caregivers were patients’ started treatment with metoprolol and thiamazole. On partner. Caregivers’ burden was moderate at T0 and T1 physical examination, he had a normal thyroid gland, (M4.1, SD2.4; M4.6, SD2.4), and decreased significantly at there was clear gynecomastia, he had an enlarged liver and T2 (M3.2, SD2.4; p=.001). For caregivers’ fatigue, normal a soft, enlarged right testis which was without palpable levels were found at T0 (M24.3, SD13), with an increase abnormalities. at T1 (M27.5, SD12.4), and a significant decrease at T2 Laboratory examination was compatible with primary (M22.4, SD11.8; p = .019). Caregivers’ fatigue and burden hyperthyroidism; human chorionic gonadotropin (hCG) were correlated at all time points (r = 0.43-0.54, p = .001). was >1.000.000 U/l, estradiol was 11.946 pmol/l and FSH Comparing caregivers’ fatigue to patients’ fatigue, a was suppressed. Alfa-fetoprotein was 4 mg/l. An ultrasound peak in fatigue at T1 was found for both groups (p=.001). of the testis showed a hydrocele of the right testis, but no Patients were more fatigued over time (p = .025), with malignancy. CT confirmed gynecomastia and revealed lower levels at baseline, but a faster increase than their multiple lesions in both lungs and kidneys, a large hepatic caregivers (p = .003), and higher levels at T2 compared to abnormality and a heterogeneous 4x3x6cm mass ventral T0 (p = .026). of the inferior caval vein. Later on, cerebral lesions were Conclusion: Before and after CRT, caregivers’ burden detected on MRI as well. A biopsy of one of the lesions and fatigue were correlated and followed patients’ from the right kidney showed a hCG positive malignancy course of fatigue over time. When proactive caregiver which most likely represents a choriocarcinoma. support is considered, intervention early during CRT is The patient was therefore diagnosed with a metastasized recommended. hCG-producing germline malignancy with an unknown primary localization. C221 Complete hydatidiform mole along with a co-existing He was started on 3-weekly courses of VIP-chemotherapy live fetus (etoposide, ifosfamide and cisplatinum). After 4 cycli, there was a partial remission with decreased volume of all E.M. Assenberg van Eijsden metastases. hCG dropped to 165 U/l. Isala, Department of Oncology, Zwolle, the Netherlands In summary, hCG-producing tumors can induce hyperthyroidism and gynaecomastia. This effect is explained by the A 34-year-old woman was presented to the out-patient- structural homology of hCG, TSH and FSH. department because of persisted blood loss after 14 weeks of pregnancy.The ultrasound showed an intact pregnancy C220 Informal caregivers’ burden and fatigue during and a spongy structure in fundi. This structure was patients’ treatment with curative, concomitant expansively growing during the following weeks.The chemoradiotherapy (CRT) for locally advanced head diagnosis, hydatidiform mole along with a co-existing live and neck cancer (LAHNC): a prospective, observa- fetus, was further supported by an extremely high plasma tional study level of beta-hCG of 943.000U/l. The patient decided to continue the pregnancy. S.M.C.H. Langenberg1, C.M.L. v a n H e r p e n 1, C.C.M. v a n O p s t a l 1, Amniocentesis at 20 weeks of gestation revealed a normal A.N.M. Wymenga2, W.T.A. van der Graaf1, J.B. Prins1 46XY karyotype, compatible with a complete hydatidiform 1Radboudumc, Department of Medical Oncology, Nijmegen, mole with co-existing live fetus (CMCF).Unlike a partial the Netherlands, 2Medisch Spectrum Twente, Department of hydatidiform mole, which has an abnormal triploid fetus, Medical Oncology, Enschede, the Netherlands CMCF is associated with fetal survival. However, it carries a significant risk of severe complications such as preec- Background: Since patients’ treatment for LAHNC is lampsia or persistent gestational trophoblastic disease. burdensome, this may impact informal caregivers as well. One week later the patient became dyspnoeic.A thoracic- We aimed to explore the course of caregivers’ burden and and abdominal CT-scan showed signs of multiple lung fatigue in relation to patients’ fatigue before and after CRT. metastases and liver metastasis.Because of the suspicion Methods: Caregivers and patients completed the subscale of multiple metastases polychemotherapy was started with ‘fatigue severity’ of the Checklist Individual Strength. BEP (bleomycin, etoposide and cisplatinum).

100 At 23 weeks of gestation the patient developed severe signs of HELLP syndrome.Despite treatment, the clinical C223 Desmoplastic small round cell tumour: large condition of the patient deteriorated and the pregnancy was consequences terminated on maternal indication.Due to deformity and expected bleeding the removal of the uterus and adnexa L. Schilder, C.E.H. Siegert, A.C. Ogilvie was inevitable.The pathology of the uterus showed an Sint Lucas Andreas Hospital, Department of Internal invasive molar carcinoma. Further, no evidence of chorio- Medicine, Amsterdam, the Netherlands carcinoma or trophoblastic proliferations was seen. Post-operatively the chemotherapy continued with Introduction: Desmoplastic small round cell tumour EMA/CO (Etoposide, Methotrexate, Dactinomycin, is an extremely rare and highly aggressive tumour of Cyclofofamide and Vincristin).After eight cycles the mesenchymal origin occurring in relatively young patients beta-hCG level is reduced to 949U/L.There was no Case: A formerly healthy, 37-year old Caucasian man indication for further chemotherapy and post-treatment was referred to our hospital with two week complaints follow-up started. of abdominal discomfort and constipation followed by diarrhoea. He had gained 2kg in weight in this time C222 Adrenocortical carcinoma: a rare cause of hyper- period. At physical examination he was not acutely ill tension, hypokalemia, delusions and hallucinations (WHO = 0), however, his abdomen was distended and there was shifting dullness. CRP (174 mg/l), Leucoytes M. Westerman, W.L.E. Vasmel, C.E.H. Siegert (10.6 E09/l), Thrombocytes (447 E09/l), ASAT (48 U/l), Sint Lucas Andreas Hospital, Department of Internal ALAT (56 U/l), LD (305 U/l) were increased at laboratory Medicine, Amsterdam, the Netherlands evaluation. Abdominal CT scan showed ascites and a diffuse malignant peritonitis with isolated large tumour Introduction: Adrenal cortical carcinomas (ACC) are rare depositions. Tumour markers (CEA, AFP, CA-19.9) were with an incidence of approximately one per million per not elevated. Ultrasound guided biopsy demonstrated a year. 45 percent of the patients present with a clinical overt desmoplastic small round cell tumour (DSRCT). DSRCT Cushing syndrome. We describe a patient diagnosed with has a very low incidence of 0.2 cases/million and is thus ACC after a psychiatric deterioration. an extremely rare cause of sudden abdominal discomfort. Case: A 58 year old male was referred to our hospital Treatment options of DSRCT consist of chemotherapy in for somatic evaluation because of a rapid psychiatric an Ewing’s sarcoma like scheme followed by resection deterioration. He had no relevant medical or psychiatric of the tumours if a decrease in tumour size occurs. history. The patient lately suffered from hallucina- Intraperitoneal hyperthermal chemoperfusion (HIPEC) tions and delusions. Standard physical and neurological is also occasionally performed in tertiary centres. Despite evaluation was unremarkable despite of hypertension treatment options, the prognosis of DSRCT is very poor (186/111 mmHg). Laboratory tests revealed a hypokalaemia with 5-year survival rates of 15-30%. Our patient did (2.9 mmol/l) and elevated hepatocyte enzymes (ASAT 68 not respond to chemotherapy and within months he U/l; ALAT 98 U/l; LDH 1800 U/l). Radiologic imaging, progressed to terminal illness. i.e. abdominal ultrasonography followed by a total body Conclusion: Desmoplastic small round cell tumour is an CT scan, revealed an 18 by 17 cm mass in the left adrenal extremely rare cause of sudden abdominal discomfort and gland with encasement of the renal artery, inhomogeneous carries a poor prognosis. liver parenchyma, and nodular pulmonary lesions, and no intracranial pathology. A liver biopsy demonstrated C224 Prevalence of low muscle mass in patients with metastases of an adrenocortical carcinoma. Subsequent metastatic breast cancer undergoing chemothera- laboratory testing showed an increased level of cortisol (1.33 peutic treatment umol/l), albeit not tested in 24 hour urine collection, and a normal level of aldosterone (0.23 nmol/l). The diagnosis H.N. Rier1, M. Meinardi1, H.H.S. Kharagjitsing1, of adrenocortical carcinoma with pulmonary and liver J. van Vooren1, M. Kock1, J.J.E.M. Kitzen1, A.B. Maier2, metastases was made with psychiatric decompensation S. Sleijfer3, M.D. Levin1 caused by hypercortisolism. Metyrapon treatment was 1Albert Schweitzer Hospital, Department of Internal Medicine, started and the patient was referred to an academic centre Dordrecht, the Netherlands, 2VUmc, Departments of Internal where palliative chemotherapy was initiated. Medicine and Geriatrics, Amsterdam, the Netherlands, Conclusion: In patients presenting with hypertension 3Erasmus MC, Department of Oncology, Rotterdam, the combined with hypokalaemia and novel psychiatric Netherlands deterioration, hypercortisolism should be considered. Adrenocortical carcinoma is a rare cause of this trias.

101 Background: Low skeletal muscle mass (sarcopenia) is a in breast cancer patients treated by the nurse practitioner. promising new prognostic factor for survival and chemo- Information concerning type and duration of endocrine therapeutic toxicity in cancer patients and can be present therapy, as well as the reasons for discontinuation, in patients with normal or even high body weight. We were retrospectively obtained from the medical records. performed a pilot study to explore the prevalence of Adherence was evaluated by self report and pharmacy sarcopenia in patients with metastatic breast cancer. check at the scheduled visits. The follow up of the patients Methods: Women with metastatic breast cancer receiving was done by a nurse practitioner (NP) according to the palliative chemotherapeutic treatment who underwent Dutch guidelines. CT-imaging before start of the first palliative chemo- Results: 221 patients were treated with endocrine therapeutic treatment were retrospectively identified from therapy in the adjuvant setting. After 1 and respectively 01.01.2001 to 01.06.2014. Total muscle cross-sectional 2 years follow up 5,1% and in total 6,9% stopped with the area (cm2) at the L3 level was measured using slice-o- endocrine therapy because of side effects. In the first two matic (Tomovision, Canada) and normalized for height. years 11.6% switched from endocrine therapy because of Sarcopenia was defined as a lumbar skeletal muscle index side effects and 2.8% because of relative contraindications. (SMI) of <38.6 cm2/m2, using a previously published cutoff Conclusion: Patients followed by the NP had an adherence point. We analyzed the results from the first 48 patients. to oral endocrine which is much better than most reports Results: Sarcopenia was demonstrated in 25 patients in literature. The follow up by the NP is probably the most (52.1%). Sarcopenic patients showed a median SMI of 35.4 important reason for this better adherence. Generally they cm2/m2 (range 30.4-38.5) and an average body mass index have more time for explanations, are often more accessible (BMI) of 24.7 kg/m2 (range 19.3-37.6). Non-sarcopenic to ask questions and are in general easier to contact. patients showed a median SMI of 43.9 cm2/m2 (range 39.2-57.9) and an average BMI of 31.2 kg/m2 (range C226 Adjuvant treatment of colon cancer patients, need for 19.3-49.1). Age was similar in both groups, however seven appropriate treatment for elderly patients. of the sarcopenic patients (28%) were below 50 years of age with two being younger than 35 years old. B.J. Laan1, J. Eising1, S.M. Wittenberg2, W.G. Meijer1 Conclusion: This study demonstrates the presence of 1Westfriesgasthuis, Department of Internal Medicine, Hoorn, sarcopenia in more than half of the patients diagnosed the Netherlands, 2MC Alkmaar, Department of Clinical with metastatic breast cancer. Sarcopenia occurs in all age Geriatrics, Alkmaar, the Netherlands groups and across a wide BMI range. Analyses are ongoing in a larger cohort of patients to establish the prognostic Background: Guidelines for the adjuvant chemotherapy significance of sarcopenia. of patients with adenocarcinoma of the colon are based on research in patients aged less than 70 years. These C225 Adherence to adjuvant oral endocrine treatments guidelines are not necessarily applicable to older patients. for breast cancer in clinical practise; can others do it Methods: In this descriptive study we included patients better than the oncologist? who had surgical treatment for adenocarcinoma of the colon. All patients treated within the period from 2005 B.M.J. Scholtes1, S.G.F. Erdkamp2, M. Portz1, to 2012 in a general hospital in The the Netherlands were A.K.M. Claessens3, Y.L.J. Vissers1, F.L.G. Erdkamp1 entered into the study. We compared adjuvant treatment in 1Atrium-Orbis Medical Centre, Department of Internal 2 cohorts of patients, respectively below (≤ 70) or beyond Medicine, Sittard, the Netherlands, 2VU University, Faculty (> 70) the age of 70 years. Rectal carcinoma patients were of Medicine, Amsterdam, the Netherlands, 3University excluded. Maastricht, Faculty of Health, Medicine and Life Science, Results: In the study period 222 patients > 70 years of age Maastricht, the Netherlands and 168 ≤ 70 patients underwent surgery. Based on tumor stage 84 (38%) in the > 70 and 96 (57%) in the ≤ 70 group Background: The effectiveness of adjuvant endocrine were candidates for adjuvant chemotherapy. In the > 70 therapy in reducing recurrence risk and improving group 32 (38%) of candidates received adjuvant chemo- survival in breast cancer patients is well demonstrated. therapy compared to 70 (73%) in the ≤ 70 group. Only 10 Despite these benefits, studies have shown 20%-50% of (31%) of the > 70 patients were treated in accordance to the women discontinue endocrine therapy before completing guidelines. In contrast 55 (79%) patients in the ≤ 70 group the recommended 5 years of treatment. About 10-12% received treatment according to the guidelines. In the > 70 discontinue endocrine therapy within the first year. group chemotherapy was adjusted more frequently but had Methods: We used a retrospective, single centre, case comparable side effects as had the ≤ 70 group. study between January 2010 and December 2012 to Conclusion: In our study population decisions on chemo- determine the adherence to adjuvant endocrine therapy therapy regimen are apparently made on clinical intuition.

102 Older patients who received adjuvant chemotherapy prednisone, while participating in a double blind, placebo- tolerated treatment relatively well. Selection tools, for controlled trial. During treatment, he had an impressive example a comprehensive geriatric assessment, need biochemical response with PSA levels decreasing from further research to avoid the risk of under treatment of 300 mg/l at the start of the study towards below 1.0 mg/l older patients. after 9 months of treatment. Furthermore, the number of bone metastases declined during treatment from C227 A tumour with a twist 6 to 2 after two months of treatment. However, after 18 months, orteronel was discontinued due to side-effects. T.M. Boertien, M.E.M. Rentinck Interestingly, the patient showed a prolonged biochemical Tergooi, Department of Internal Medicine, Hilversum, the response after discontinuation of orteronel, with the first Netherlands rise in PSA levels to 0.3 mg/l 14 months after discontinuation of orteronel, and with no clinical evidence of disease Case: A 75-year-old male was admitted to the oncology ward progression. with suspicion of a malignancy of the liver, as suggested Orteronel is a nonsteroidal, selective, reversible inhibitor on abdominal ultrasound. He presented with abdominal of 17,20-lyase, which is a key enzyme in the production pain, weight loss and fatigue, with no history of fever. of androgenic hormones. Orteronel is hypothesized to Medical history included a laparoscopic cholecystectomy 8 further diminish testosterone synthesis by the adrenal years before. Laboratory tests showed slightly raised CRP glands and possible metastases, resulting in increased and ESR. A CT-scan showed a mass containing a dense survival in patients with metastasized CRPC. However, structure, with unclear relation to the liver. A diagnostic the phase III study showed no benefit in overall survival biopsy unexpectedly revealed pus, with a positive culture for the orteronel group, and therefore, the development of Klebsiella oxytoca. Examination of the operative notes program for orteronel was stopped. Interestingly, our of 2006 revealed spillage of gallstones. The suspicion of patient had an impressive biochemical and radiological malignancy was rejected and the diagnosis of retained response to orteronel, which remained after discontinu- abdominal gallstones with abscess formation was made. ation of orteronel. A possible anti-androgen withdrawal Further drainage was performed after which the stones effect has not been previously described as result of discon- were removed percutaneously. tinuing orteronel. It might be worthwhile to evaluate this Discussion: In the majority of patients with a suspicious phenomenon in the whole trial population as well as in mass on diagnostic imaging, the diagnosis of cancer abiraterone treated patients. is made. However, as presented in this case, further analysis can lead to an unexpected and more favorable C229 Radiation recall mucositis six years after primary outcome. Intraperitoneal gallstone spillage during laparo- treatment?! scopic cholecystectomy is common, occurring in 5-40% of procedures. An important part of these are not retrieved. J.C. Ham, G.O.R.J. Janssens, F.J.A. van den Hoogen, Complications, including abscess formation, are rare C.M.L. van Herpen (0.08-1.4%) and have been reported as late as 20 years after Radboudumc, Department of Medical Oncology, Nijmegen, the procedure. Diagnosis can be challenging since most the Netherlands patients remain afebrile with little sign of inflammation. In these times of ongoing specialization and differentiation Introduction: Radiation recall phenomenon (RRP) is a rare within medicine, doctors must maintain the ability to look tissue reaction of previously irradiated areas and is caused beyond their own field in order to form a correct diagnosis. by certain drugs. A complete medical history, including past events, remains Case: A 74-year old man was admitted because of fever, paramount. severe dysphagia and neutropenia, seven days after the first administration of docetaxel because of prostate cancer. C228 Prolonged biochemical response after discontinu- Six years before he was treated with 60Gy radiotherapy ation of orteronel (TAK-700) in a patient with metas- for a cTisN0M0 laryngeal cancer resulting in a complete tasized castration-resistant prostate cancer response. Antibiotics were started with the diagnosis of an upper respiratory tract infection. However, the fever L. Manenschijn, P. Hamberg persisted and the dysphagia worsened. A laryngoscopy Sint Franciscus Gasthuis, Department of Internal Medicine, showed severe redness, patchy mucositis and edematous Rotterdam, the Netherlands arytenoids. The diagnosis acute laryngitis was made, and treatment with prednison was started. After 3 days A 73-year old man with metastasized castration-resistant the fever was gone and he improved greatly. Because prostate cancer (CRPC), received orteronel together with the laryngitis was localized exactly within the previous

103 radiation field, a radiation recall mucositis was suspected, treatment of EAS would include chemotherapy against the however we could not definitely exclude an infectious underlying cancer. laryngitis, with negative bloodcultures but without direct cultures. C231 Acute superior mesenteric vein thrombosis: a severe Discussion: RRP can be caused by chemotherapy, but complication of epirubicine, oxaliplatin and capecit- antibiotics or statins as well. The time interval between abine combination chemotherapy radiation therapy and the occurrence of RRP can range from 2 days to 15 years. RRP can be treated using steroids I.M.G. Hageman, M.M. Geenen and anti-inflammatory drugs, and also by discontinuation Sint Lucas Andreas Hospital, Department of Internal of the causative drug. The overall incidence of radiation Medicine, Amsterdam, the Netherlands recall dermatitis is 8.8%; radiation recall mucositis is even more rare. Introduction: The combination of epirubicine, oxaliplatin Conclusion: Radiation recall mucositis is a rare and capecitabine (EOX) chemotherapy is being used in phenomenon, which can occur a couple of years after the the (neo-) adjuvant treatment of stomach cancer. Our radiotherapy. It is important to recognize RRP because of case reports a patient with subacute epigastric pain based the need to discontinue the causative agent. on a massive acute superior mesenteric vein thrombosis with small intestinal necrosis. Except for the active C230 Cushing’s syndrome in a patient with a metastasized malignancy, we considered the combination chemotherapy salivary gland tumor an important predisposing factor. Case: A 72-year old Surinamese male was diagnosed with E. Boon, C.M.L. Driessen, I.J.A. de Bruin, C.M.L. van Herpen stomach cancer with locally advanced lymphadenopathy for Radboudumc, Department of Medical Oncology, Nijmegen, which neo-adjuvant EOX-chemotherapy was started every the Netherlands 3 weeks. After 7 days of the second chemotherapy course, the patient presented at the emergency department with Introduction: Ectopic ACTH syndrome (EAS) is progressive epigastric pain, nausea and vomiting in the hallmarked by production of ACTH outside the pituitary. last 4 days. Physical examination showed a very painful Case: A 60-year old male presented with dyspnea and patient, however, no other specific abnormalities were progressive fatigue. Fifteen months before he presented observed. The laboratory results revealed a mild leukocy- with a pT2N0M0 Acinic Cell Carcinoma (AcinicCC) of tosis and elevated lactate. An abdominal CT-scan showed the right parotid gland, for which he underwent a partial a massive acute superior mesenteric vein thrombosis with parotidectomy with right neck dissection followed by small intestinal necrosis. A total of 92cm small intestine postoperative radiotherapy. Recently multiple pulmonary was removed and heparine therapy was started. After his and mediastinal lymph node metastases were diagnosed. recovery, the planned third chemotherapy was cancelled On examination, he had a moon face, severe edema of and patient underwent a partial stomach resection. This the lower extremities and muscle weakness. His blood second operation was complicated by an abdominal sepsis pressure was 185/125 mmHg. Laboratory findings showed: and patient died one week after surgery. potassium 2.4 (normal range 3.5-4.7 mmol/l) and ACTH Conclusion: This case presents a patient with massive acute 28.2 pmol/L (normal range 2.2 - 13.2 pmol/l). Serum superior mesenteric vein thrombosis with small intestinal cortisol was not suppressed by 1 mg dexamethasone: necrosis. Reviewing the literature, each cytostatic drug of 0.96 mmol/l (normal < 0.05 mmol/l). This confirmed the EOX combination gives an increased risk of developing the diagnosis of hypercortisolism, probably due to EAS. this thrombosis. Possibly, the combination of these drugs A pituitary source of ACTH hypersecretion was not further increases this risk. Therefore, doctors should be excluded. Treatment was started with metyrapon, an aware of this rare cause of epigastric pain. inhibitor of cortisol production, after which he rapidly recovered clinically. He declined palliative chemotherapy, C232 Improving the quality of palliative care: an evaluation i.e. oxaliplatin and capecitabin. He died four months later. of the consultation process Discussion and conclusion: EAS is a rare paraneoplastic syndrome, which can occur in several cancers. Only 3 case S. Kemme reports in patients with metastatic AcinicCC are described UMC Groningen, Department of Medical Oncology, before. Although the median overall survival in metastatic Groningen, the Netherlands AcinicCC is not exactly known, the survival of metastatic AcinicCC with EAS is very short (2 to 4 months). Inhibitors Background: The purpose of advices on palliative care of cortisol secretion are important for the immediate is alleviation of symptoms. In some cases no adequate control of the consequences of hypercortisolism. Ideally, palliation is reached and repeated consultation is required.

104 Because of the palliative setting, this is not desirable. By deteriorated he decided to repatriate for further analysis evaluating the reasons for reconsultation, factors can and treatment. be identified which can improve the quality of palliative Obviously a broad differential diagnostic work up was advices. initiated including (myco)bacterial, fungal and parasitic Methods: All palliative consultations from 1-2014 to 11-2014 infection. Non-infectious conditions such as granulo- in a large university medical center were identified. All matosis with polyangiitis, sarcoidosis or a metastatic consultation questions, given advices and reasons for disease e.g. soft tissue tumors were considered. In The reconsultation were discussed in a multidisciplinary the Netherlands, an open lung biopsy by means of palliative care team. The end point was the reconsultation video assisted thoracic surgery (VATS) was performed. rate between one week and one month after the first Pathological examination revealed an extraosseous small consultation. cell osteosarcoma of the lung. Results: 156 patients with 337 consultation questions have Osteosarcoma is a rare disease with an incidence of been identified. The majority (89%) were oncological 1:100.000, while extraosseous types account for 2-4 % of patients, 49% died within one month. The main consul- all cases. tation questions were related to somatic issues, mainly Our patient was initially treated with radiotherapy for pain, dyspneu and nausea (in 69% of all patients), organi- bone metastasis followed by palliative chemotherapy with zation of care (53%) and coping problems (22%). Advices doxorubicin and cisplatin. Unfortunately, he past away were mostly given on symptom management, care arrange- 6 months after initial presentation. ments and referral to specialized care workers. In only ten patients (6%) reconsultation was required. C234 Acute respiratory failure as first clinical presentation Reasons were inadequate palliation of symptoms (6 of gemcitabine-associated thrombotic thrombocyto- patients), clinical implementation of given advices (2), penic purpura-hemolytic uremic syndrome inadequate care arrangements (1) and evaluation of treatment (1). Evaluation showed 6 out of 10 reconsulta- S. Jainandunsing, O.J.L. Loosveld, T.T. Cnossen, tions could possibly have been avoided. They were related K.E.S. Duthoi, J.W.J. van Esser to symptom management and care arrangements. Amphia Hospital, Department of Internal Medicine, Breda, Conclusions: The rate of palliative reconsultation appears the Netherlands to be low. The quality of palliative care can be improved by better implementation and evaluation of symptom Introduction: Gemcitabine is a nucleoside analog currently management and clarity regarding organization of out-of- used for several solid tumors. Although generally well hospital care. tolerated, increased awareness of its toxicity is important as its use is expanding. C233 The unlikely comes true, TB or not TB Case report: A 48-year old male, underwent a Whipple resection because of T2N1M0 pancreatic carcinoma E.M.T. Bots, P.J. Wismans, L. Slobbe followed by adjuvant gemcitabine. He was admitted into Harbour Hospital and Institute for Tropical Diseases, intensive care one month following his last gemcitabine Department of Internal Medicine, Rotterdam, the Netherlands infusion because of respiratory insufficiency and hypertension. As cardiac decompensation seemed to be the A 63-year old Caucasian male presented with lower back most likely diagnosis he was treated with supplemental pain, dyspnea and 5 kg weight loss over the past 5 months. oxygen and diuretics. However, additional testing revealed He works for an international company and lives in a normal echocardiogram, furthermore acute renal failure, The Philippines. He has travelled extensively in tropical high lactate dehydrogenase, anemia, low haptoglobin, regions and is a long term smoker. Physical examination negative direct antiglobulin test (DAT), elevated indirect and additionally performed blood tests revealed no abnor- bilirubin, schistocytes, thrombocytopenia, hematuria and malities. A chest CT showed multiple bilateral pulmonary proteinuria were found. Renal biopsy confirmed presence cavitating lesions, consolidations, ground glass lesions of thrombotic microangiopathy. As ADAMTS13 was 100%, and atypical sclerosing osseous dysplasia, mainly of the this favored gemcitabine-associated TTP-HUS. Patient thoracic vertebrae 5 and 10. successfully received methylprednisolone subsequently Following a CT-guided lung biopsy showing chronic followed by prednisone, and antihypertensive treatment. inflammation and caseating granulomas in The After eighteen months of follow-up his renal function had Philippines – performed prior to presentation in our been normalized. hospital – he was treated with tuberculostatics without Discussion: We report a case of gemcitabine-induced any improvement. Therefore, empirical treatment with TTP-HUS. Overall mortality is 15%. As TTP-HUS is a voriconazol was started. However, as his clinical condition cumulative dose-dependent complication, it may occur

105 long time following the last infusion of gemcitabine. Our rimidine chemotherapy could be cost-effective end a new case presented with hypertension de novo, which in case standard of care. series was an early identifier of TTP-HUS. Preventive measures may consist of periodical assessment of blood C236 Effect of adjuvant chemotherapy on survival of stage pressure, pulmonary and neurological symptoms and renal 2 and 3 colon cancer patients seen in daily practice function. When there is clinical suspicion, haptoglobin, DAT, ADAMTS13 and schistocytes should be included in E.E. van Eeghen, S.D. Bakker, A. van Bochove, the work-up. R.J.L.F. Loffeld Conclusion: Gemcitabine-induced TTP-HUS is a rare but Zaans Medical Centre, Department of Internal Medicine, serious complication, and should be taken into account Amsterdam, the Netherlands even after cessation of gemcitabine treatment. Patients with stage 2 and 3 colon cancer often are treated C235 Case report: Fluoropyrimidine toxicity due to with adjuvant chemotherapy. However, patients seen in c.1236G>A homozygote DPD-deficiency; less known daily practice have more comorbidity than those enrolled but important enough to test on a regular basis? in clinical trials. Therefore, clinicians base treatment decisions on guidelines representing only part of their A.S. Vellinga1, H. de Graaf2 patient population. This study aims to ascertain the 1Isala, Department of Internal Medicine, Zwolle, the benefit of adjuvant chemotherapy on recurrence free Netherlands, 2MC Leeuwarden, Department of Internal survival (RFS) of patients in a normal daily population. Medicine, Leeuwarden, the Netherlands Furthermore, the impact of relative dose intensity of adjuvant therapy on RFS is examined. Background: fluoropyrimidines (FP) are frequently used Chart review was performed for 243 consecutive patients chemotherapy agents. Association between intolerance diagnosed and treated at a single center for stage 2 and 3 for FP and deficiency of the enzyme dihydropy- colon cancer from 2002 to 2008. Adjuvant chemotherapy rimidine-dehydrogenase (DPD) is known. In patients was administered to 66 patients. Data for RFS were with DPD-deficiency chemotherapy clearance will be censored when death occurred before recurrence. delayed, which leads to increased toxicity. The incidence of Median overall survival was 5.84 years, median RFS was DPD-mutations in western population is 4%. 5.37 years. For stage 2 disease, patients treated with or Case: a 68 year old man diagnosed in November 2013 without adjuvant therapy had a median RFS of 5.49 and with a metastatic cT3N1M1 distal esophagus carcinoma 5.73 respectively (p = ns). For stage 3 disease, median RFS was treated with bevacizumab-docetaxel, oxaliplatin and rates were 5.08 and 1.19 respectively (p = 0.084). Overall capecitabine 850mg/m2 twice daily during 14 days. relative dose intensity of oxaliplatin based chemotherapy DPD-status testing of the most common DPD-mutation higher than median, was associated with increased RFS *2A showed wildtype. The patient presented with severe (p = 0.045) fatigue after 6 days of treatment and capecitabine was In conclusion, Adjuvant therapy did not significantly stopped. At day 10 he was admitted to the hospital due to increase recurrence free survival, possibly due to a fever without neutropenia and treated with antibiotics. In combination of insufficient power and a reduced effect july 2014, because of a strong treatment wish, a second size in the normal daily population compared to that of course of capecitabine monochemotherapy, adjusted to randomized controlled trials. This reduced effect size is 75% of planned dose, was started. Again our patient caused by increased co-morbidity in patients. Relative dose experienced severe malaise and fatigue. Additional intensity of oxaliplatin based therapy is associated with DPD-deficiency testing showed a rare homozygote recurrence free survival. DPD-deficiency: c.1236G>A, which can explain our patients toxicity. C237 Impact of age and comorbidity on survival and cause Discussion: As this case presents, we should be aware of death in colorectal cancer of rare DPD-mutations. The diagnosed homozygote c.1236G>A DPD-mutation in our case is found at E.E. van Eeghen, R.J.L.F. Loffeld 0.1 percent of western population. Testing of known Zaans Medical Centre, Department of Internal Medicine, DPD-mutations nowadays is easier, fast and less costly Amsterdam, the Netherlands compared to the past and can be done in general labs in Dutch hospitals. Results of these DPD-tests can be Colorectal cancer patients are often excluded from clinical given in 1 or 2 days. Although its rare incidence, standard trials based on age or a poor performance score. However, DPD-testing on c.1236G>A before starting fluoropy- 70% of colorectal cancers are diagnosed in patients over 65. This study evaluates the influence of age and comorbidity

106 on survival and cause of death in a non-selected decreased compared to non-recipients (3-year OS 91% vs. population, and aims to determine whether elderly patients 73%, HR 0.43, 95%CI 0.28-0.66), and in patients with ≥ 2 are being under- or overtreated for colorectal cancer. risk factors (including pT4-stage) receiving CT compared 621 consecutive patients with colorectal cancer diagnosed to non-recipients (3-year OS 83% vs. 64%, HR 0.58, 95%CI and treated in a single center between 2002 and 2008 were 0.43-0.80). Relative excess risk of dying decreased for included. Chart review was performed for 392 patients patients receiving CT, compared to non-recipients in both with colon cancer and 143 patients with rectal cancer. pT4-stage (3-year RS 94% vs. 85%, RER 0.36, 95%CI 86 patients were excluded for various reasons. Analyses 0.17-0.74) and ≥ 2 risk factors (including pT4-stage) (3-year were performed separately for both groups. Patients RS 86% vs. 75%, RER 0.52, 95%CI 0.34-0.81). For patients were followed for at least five years depending on date of with only poor/undifferentiated grade, emergency surgery inclusion, or until death. or < 10 LNs, no association with RS/OS was observed. Median survival of colon cancer patients was 5.13 years. Conclusions: In high risk stage II CC, CT in pT4-stage Age and comorbidity were significant predictors for overall was associated with improved OS/RS. Due to observa- survival (p < 0.001). Age was a significant predictor of tional data, interpretation should be cautious. However, cause of death (p = 0.001). In rectal cancer patients median refinement of subgroups which could benefit from CT survival was 4.67 years. Neither age or comorbidity were seems indicated. significant predictors of survival. Age was a significant predictor of cause of death (p < 0.001). In conclusion, colon cancer patient age and comorbidity XV RHEUMATOLOGY predict survival and cause of death. This indicates that colon cancer is not the prognosis defining illness in a majority of patients, and represents possible treatment C239 Diagnosing adult-onset Still’s disease (AOSD) bias or a reduced survival benefit of treatment. In rectal remains a clinical challenge cancer patients neither age or comorbidity significantly impacted survival. This does not correspond with results W.R. Cnossen, R. Koot, L.G. Schipper, C. Richter from previous studies. Rijnstate, Department of Internal Medicine, Arnhem, the Netherlands C238 Adjuvant chemotherapy in pT4 stage II colon cancer is associated with improved survival Case: A 67-year-old male presented at the emergency department with since 7 days progressive myalgia, pain of S.R. Verhoeff1, F.N. van Erning2, V.E.P.P. Lemmens2, his right ellebow and low grade fever. Since 2 weeks he had H. de Wilt3, J.F.M. Pruijt1 an itching and painful skin lesion on his back. Recently 1Jeroen Bosch Hospital, Department of Internal Medicine, he had been treated for pneumonia with amoxycilline/ ’S-Hertogenbosch, the Netherlands, 2IKNL, Eindhoven, the clavulanic acid. Netherlands, 3Radboudumc, Surgery Department, Nijmegen, At presentation the patient was afebrile. On physical the Netherlands examination we found a painful erythema of 20cm-diameter on his back and arthritis of his right Background: Adjuvant chemotherapy (CT) should elbow. Laboratory tests showed a high ESR (135 mm/hr) be considered in high risk stage II colon cancer(CC) and CRP (277 mg/l), Hb 7.0 mmol/l, leukocytes 14.3x109/l comprising a pathological T4 tumour (pT4), poor/undif- (neutrophils 12.83x109/l), platelets 685x109/l, and elevated ferentiated tumour grade, vascular invasion, emergency AST and ALT. surgery and/or < 10 lymph nodes (LNs) evaluated. We Clinical course and diagnosis: The patient was treated with evaluated CT-administration to these subgroups, and inves- flucloxaciline for suspicion of cellulitis and tetracycline tigated the effect on overall and relative survival (OS/RS). for possible atypical presentation of borreliosis with no Methods: All patients with high risk stage II CC who result. He developed daily high spiking fever. Blood and underwent resection and were diagnosed in the the joint cultures and extensive serology remained negative. Netherlands between 2008-2012 were included. After Skin biopsy revealed an aspecific inflammation. Total stratification by risk factor(s) (vascular invasion not body FDG-PET scan was not helpful, only showed some included), Cox-regression was used to discriminate the weak FDG positive small lymfnodes. Finally, 2 weeks after independent effect of CT on mortality risk. RS was used to admission and exclusion of other diseases we made the estimate disease-specific survival. diagnosis of Adult-onset Still’s disease (AOSD) although Results: 790/4940 (16%) patients received CT. Patients the ferritine level was not extremely high (1780 IU/l). We more often received CT in case of pT4 (30%) or ≥2 risk started empiric treatment with indomethacine, followed by factors (23%). Mortality risk in pT4 patients receiving CT

107 prednisolon. The patient responded well, fever subsided, S.W. Tas1, L.F.A. Huitema1, B. Helder1, M.C. Lebre1, CRP and BSE decreased. L. Boon2 Background: AOSD is a rare, multisystemic inflammatory 1AMC/University of Amsterdam, Department of Clinical disorder characterized by fever, arthralgia or artritis, Immunology & Rheumatology, Amsterdam, the Netherlands, typical skin rash, pharyngitis, leukocytosis and myalgia 2Bioceros BV, Department of Immunology, Utrecht, the (major criteria). The initial presentation of the combination Netherlands of fever with only one erythema-like skin lesion, and involvement of a single joint was atypical. Background: AIRE is a transcription factor that is involved in thymic negative selection of autoreactive T cells C240 John P: ‘No anti-TNF for me!’ and therefore is pivotal in the establishment of central tolerance. Non-canonical nuclear factor (NF)-kB signalling P. Veldt-Kok that can be mediated via CD40 is crucially important for HagaZiekenhuis, Department of Rheumatology, Den Haag, Autoimmune Regulator (AIRE) expression in the thymus. the Netherlands We have recently found extrathymic AIRE-expressing cells (eTACs) that may play a role in peripheral tolerance in Introduction: Autoimmune overlap-syndromes are rheumatoid arthritis synovial tissue and glandular tissue frequently found in Rheumatoid Arthritis (RA). The from Sjogren’s syndrome patients. eTACs are mainly prevalence of anti Jo-1 is 0.4% in RA. antigen presenting cells, including dendritic cells (DC), Case description: Two days after starting adalimumab, that can suppress peripheral T cell responses. However, a fifty years old female RA patient visits the emergency until now the stimuli that can induce extrathymic AIRE department because of progressive dyspnea, arthralgia expression in DC are largely unknown. and myalgia. She’s intubated and admitted to the intensive Objective: To study whether activation of the non-canonical care. Laboratory results show elevated LDH, CK and CRP NF-kB pathway stimulates AIRE expression in human levels. The X-ray shows interstitial changes. Broncho monocyte-derived DC. alveolar lavage shows diffuse alveolar hemorrhages. PCR Methods: Human monocyte-derived DC were generated on rhinovirus was positive. with IL-4 and GM-CSF. On day 6, maturation was induced In 2008 she presented with a symmetrical polyarthritis by addition of LPS or the non-canonical NF-kB stimuli of small joints, which was rheumatoid factor and ACPA lymphotoxin, LIGHT, RANKL or anti-CD40 for 48 hours. positive, diagnosed as RA. At that time serology for ANA, Results: Anti-CD40 stimulation ofDC resulted in activation dsDNA, ENA, and SSA was positive. Four months before of the non-canonical NF-kB pathway and upregulation admission she failed MTX treatment, therefore start of AIRE RNA and AIRE protein. Confocal microscopy of anti-TNF was considered. By this time anti-Jo-1 was revealed that AIRE protein was localised in the nucleus. positive. Routine x-ray showed a pulmonary lesion. Further Interestingly, this was accompanied by increased analysis by PET CT did not show pulmonary uptake. expression of the immunoregulatory enzyme indoleamine- However, uptake of gluteal and quadriceps muscles of 2,3-dioxygenase (IDO). radio-labeled glucose was present, suspicious for myositis. Conclusion: CD40 stimulation in DC activates the During admission confirmed by EMG and muscle biopsy. non-canonical NF-kB pathway and simultaneously Based on interstitial pneumonitis, myositis, polyar- upregulates AIRE and IDO expression, suggesting these thritis and raised anti-Jo-1, the diagnosis anti-synthetase cells may have immunoregulatory properties. Eventually, syndrome (ASS) was made. After multiple pulses of this knowledge may be exploited to develop new treatment intravenous methylprednisone, immunoglobulins, and i.v. modalities for patients with autoimmune diseases, cyclofosphamide she recovered. including DC-based therapies. New onset or aggravation of poly-/dermatomyositis after start of anti-TNF has been described, implicating a causal C242 NF-kB-inducing kinase (nik) is a key regulator of relationship. Therefore, one should be cautious with angiogenesis in early arthritis patients and correlates anti-TNF in RA patients with antisynthetase antibodies with markers of inflammation and consider ASS in case of unexpected respiratory insufficiency after anti TNF initiation. S.W. Tas1, K.I. Maijer1, A.R. Noort1, M.J.H. de Hair2, C. van der Leij1, K.P.M. van Zoest1, I.Y. Choi1, D.M. Gerlag1, C241 Activation of the non-canonical NF-kB pathway in M. Maas1, P.P. Tak1 dendritic cells upregulates extrathymic autoimmune 1AMC/University of Amsterdam, Department of Clinical regulator (aire) expression Immunology & Rheumatology, Amsterdam, the Netherlands, 2UMC Utrecht, Department of Rheumatology, Amsterdam, the Netherlands

108 to rheumatoid arthritis, inflammatory bowel disease Objectives: The NF-kB family of transcription factors or lymphoproliferative malignancies. Unfortunately we is strongly involved in synovial inflammation. We have could not explain a strong positive p-ANCA with negative previously shown that NF-kB-inducing kinase (NIK) is a PR-3 and MPO-ANCA.For a second opinion our patient key regulator of inflammation-induced angiogenesis in was admitted twice in the Academic Medical Centre rheumatoid arthritis (RA) synovial tissue (ST). Here, we of Amsterdam, whereby her complaints improved, but investigated synovial NIK expression in early arthritis shortly after discharge they relapsed quickly. Despite patients and in autoantibody-positive individuals at risk thoroughly testing we were still looking at a casus pro for developing RA. diagnosi until a toxicology urine test was done at the Methods: ST biopsies were obtained via arthroscopy emergency department when patient returned because of from 154 early arthritis patients (arthritis duration < 1 unsustainable pain.The urine test was positive for cocaine. year) with various diagnoses and from 54 IgM-RF and/ All of the above can be explained by a levamisol induced or ACPA-positive at risk individuals without any evidence arthritis with skin problems. The strong positive p-ANCA of arthritis. ST was stained for NIK and the endothelial was based on an elastase positive ANCA often seen with cell (EC) marker vWF. Additionally, measures of disease cocaine abuse. Levamisol is used as a filler of cocaine, since activity were collected and contrast-enhanced MRI was it increases the stimulating effect of cocaine. performed in a subset of these patients. Results: In early arthritis patients, NIK was predominantly C244 Acute low back pain and increased acute phase expressed in EC of small blood vessels. Furthermore, NIK reactants: spondylodiscitis vs. atypical presentation expression correlated with ESR and CRP, synovial cellular of spondyloarthritis? markers (CD68+ lining r = 0.585; p < 0.001, sublining macrophages r = 0.728; p < 0.001, CD3+ T cells r = 0.733; S. Ramiro, S. Anten p < 0.001 and CD22+ B cells r = 0.264; p = 0.040), MRI Alrijne Hospital, Department of Internal Medicine, effusion (r = 0.665; p < 0.001), MRI synovitis (r = 0.632; Leiderdorp, the Netherlands p < 0.001) and MRI total score (r = 0.569; p < 0.001). In 18.5% of autoantibody-positive individuals ST NIK+EC were Introduction: Acute low back pain is a rare presentation of present, but this was not predictive of the development of spondyloarthritis (which includes ankylosing spondylitis). arthritis. When it happens, it is usually difficult to establish the Conclusions: NIK+EC are present in the earliest phase diagnosis, as it usually requires time for the development of synovial inflammation and may be indicative of high of other associated manifestations to complete the clinical angiogenic activity in the inflamed ST. Therefore, NIK+EC picture. may play an important role in the persistence of synovitis. Case: A 61-year-old female, with a history of COPD, Collectively, our data underscore the importance of angio- presented to our emergency room with an acute onset of genesis in synovial inflammation and identify NIK as a intense low back pain (10 days). On physical examination potential therapeutic target in arthritis. she had no fever and no pain on percussion of the spine. Lab results revealed an ESR > 100 mm/h, CRP 7 g/l and C243 How to deal with undifferentiated arthritis? leukocytosis of 13.2. MRI from the lumbar spine, though not typical for, was compatible with spondylodiscitis. No N.S. Reyn-Gibson, C.M. Verhoef, M. Kortekaas, K. Vos microorganism was isolated from an intravertebral biopsy Flevo Hospital, Department of Rheumatology, Almere, the or blood cultures. Treatment with flucloxacilline 6 g/day Netherlands was initiated for 6 weeks. Symptoms improved and ESR decreased. One month later she developed dactylitis of A 32-year old woman presented in the Flevohospital with several fingers and three months later arthritis of the knee a recurrent symmetrical polyarthritis. A few months later and ankle. Initially responding well to NSAIDs, later this skin problems developed with nodular pupura and bullous response became poor as well as to steroids. Low back pain, lesions that ruptured with blood and pus. Also she had oral dactylitis, arthritis and persistently increased acute phase ulcers, weight loss and a changed stool pattern with blood. reactants made us suspect the diagnosis of spondyloar- Laboratory tests showed an elevated CRP (31mg/l) and ESR thritis. HLA-B27 positivity reinforced it. (32mm/hr), with negative anti-CCP and IgMreumafactor. Discussion: Acute low back pain associated with elevated During hospital admittance to facilitate the diagnostic acute phase reactants and MRI abnormalities usually lead process our patient got skin lesions at the injection place to suspicion of spondylodyscitis. But as this case shows of the morphine, resembling a positive pathergy test.A spondyloarthritis may mimic spondylodiscitis, especially histological sample of the nodular bullous skin lesions when other symptoms are absent. When microorganisms fitted a neutrophilic dermatoses, often seen secondary cannot be cultured in suspected spondylodiscitis, spondy-

109 loartritis should be considered and awareness should be Amphia Hospital, Department of Internal Medicine, Breda, paid to other manifestations of rheumatic disease. the Netherlands

Introduction: Temporal artery biopsy (TAB) is XVI VASCULAR MEDICINE recommended when giant cell arteritis is suspected. To optimize its sensitivity, a minimum length of 1 cm taken from the affected side and description of mononuclear C245 Hypertension at young age: beware of the infiltration/granulomatous inflammation and corticos- unexpected teroid pretreatment is required. The purposes of this study were to determine (1) to which D.J.L. van Twist, A.W.J.H. Dielis, A.A. Kroon extent temporal artery biopsies met these surgical and Maastricht UMC+, Department of Internal Medicine, pathological criteria, (2) whether surgeons performed Maastricht, the Netherlands better than residents and (3) whether biopsy results influenced treatment. A 25-year-old man with a clear medical record was referred Methods: A retrospective, descriptive analysis of biopsies because of accidently discovered hypertension. He had performed between 2013-2014. Percentages were compared a normal life style and body mass index (20.4 kg/m2) using chi-square test. and used no medication or other substances. Physical Results: 56 samples were analysed (25 men, 31 women). examination was normal, except for high blood pressure Mean age was 71 years, mean BSE 50 mm/hr, Hb (220/95 mmHg). Although 24-hour ambulatory blood 7.1 mmol/l and CRP 59 mg/l. pressure measurement showed a white-coat effect, blood Average length of biopsies was 0.88 cm; 25 biopsies (45%) pressure was nevertheless elevated: 151/101 mmHg. were ≥ 1 cm. Surgeons conducted 11 and residents 40 Routine laboratory tests, including serum potassium biopsies, with a minimum length of 1 cm in 7 (64%) and level, were normal and estimated glomerular filtration 16 (40%) of the cases respectively (p > 0.1). 53 biopsies rate was 85 ml/min/1.73m2. As echocardiography revealed (95%) were taken on the (most) affected side. left ventricular hypertrophy, treatment with valsartan Pathological description was appropriate in 55 cases (98%). 80 mg daily was initiated, resulting in a decrease in blood 15 cases (26.8%) were positive for giant cell arteritis. pressure to 130/75 mmHg. Given his young age and the Despite a negative biopsy, prednisolone was started or strong response to low-dose angiotensin-type-1-receptor- continued in 7 (17%) cases. blockade we suspected renovascular hypertension (e.g. Conclusion: Temporal artery biopsies were often of insuf- due to fibromuscular dysplasia) and performed an ficient length. Pathological criteria were met in almost all invasive renal angiography. At first sight this showed no cases. In 17% of cases, treatment with prednisolone was renovascular abnormalities. However, on second look, the started/continued despite a negative biopsy. right kidney appeared hypoplastic and displaced with a somewhat curved renal artery. Because of this uncommon C247 A simple decision rule including the D-dimer result deformity, we performed an MRI-scan, which showed a to reduce the need for CT-scanning in patients with 9 by 10 cm large retroperitoneal tumor compressing and suspected pulmonary embolism displacing the kidney. Fine-needle-biopsy demonstrated benign neural cells, corresponding to a schwannoma. J. van Es1, L.F.M. Beenen2, R.A. Douma2, Distant metastases were excluded and blood pressure P.L. den Exter3, I.C.M. Mos3, K. Kaasjager4, M.V. Huisman3, continued to be well-controlled. As the patient had no P.W. Kamphuisen5, S. Middeldorp2, P.M.M. Bossuyt2 complaints, a wait-and-see policy was followed. 1Onze Lieve Vrouwe Gasthuis, Department of Internal Discussion: We describe a very uncommon secondary- Medicine, Amsterdam, the Netherlands, 2AMC, Department cause of hypertension, where the renal artery and the of Radiology, Amsterdam, the Netherlands, 3Leiden University kidney were compressed by a benign, probably congenital Medical Centre, Department of Thrombosis and Haemostasis, schwannoma. This case illustrates that physicians should Leiden, the Netherlands, 4UMC Utrecht, Department of be aware of congenital abnormalities in patients with Internal Medicine, Utrecht, the Netherlands, 5UMCG, young-onset hypertension. Department of Vascular Medicine, Groningen, the Netherlands

C246 Giant cell arteritis: the quality of temporal artery Introduction: An unlikely clinical decision rule with a biopsies negative D-dimer test result safely excludes pulmonary embolism (PE) in 30% of presenting patients. We aimed E.C.F. Wagenaar, C. van Guldener to simplify this diagnostic approach and to increase its efficiency.

110 Methods: Data of 723 consecutive patients with suspected Institute of Oncology, Leeds Institute of Cancer and Pathology, PE were analysed. After constructing a logistic regression Leeds, United Kingdom, 11Castle Hill Hospital, Queen’s model with the D-dimer test result and items from Wells’ Centre for Oncology and Haematology, Cottingham, United rule, we identified the most prevalent combinations of Kingdom, 12Brigham and Women’s Hospital and Dana-Farber influential items and selected new D-dimer positivity Cancer Institute, Department of Radiology, Boston, United thresholds. The performance was validated in a dataset States of America including 2,785 consecutive patients. Results: Three Wells items significantly added incremental Introduction: Incidental pulmonary embolism (IPE) is value to the D-dimer test (22% PE prevalence): defined as a pulmonary embolism (PE) diagnosed on haemoptysis, signs of deep vein thrombosis and ‘PE most a CT-scan performed for reasons other than a clinical likely’. Based on the most frequent combinations of these suspicion of PE. IPE has been estimated to occur in 3.1% of three items, we identified two groups: (1) none of these all cancer patients and is a growing challenge for clinicians three items positive (41%), (2) one or more of these items and patients. Nevertheless, knowledge about the treatment positive (59%). When applying a 1000 mg/L D-dimer and prognosis of cancer-associated IPE is scarce. We aimed threshold in group 1 and 500 mg/l in group 2, PE could be to provide the best available evidence on IPE management. excluded without CT-scanning in 36%, at a false-negative Methods: Incidence rates of symptomatic recurrent rate of 1.2% (95%: 0.04-3.3%). In the validation set, these venous thromboembolism (VTE), major haemorrhage proportions were 46% and 1.9% (95% CI 1.2-2.7%), respec- and mortality during 6-month follow-up were pooled tively. Using the conventional Wells rule with a normal using individual patient data from studies identified by a D-dimer result, these rates were respectively 22% and systematic literature search. Subgroup analyses based on 0.6% (95% CI 0.10-2.4%). cancer stage, thrombus localization and management were Conclusion: Combining Wells items with the D-dimer performed. test resulted in a simplified decision rule, which reduced Results: In 926 cancer patients with IPE from 11 cohorts, the need for CT-scanning in patients with suspected weighted pooled 6-month risks of recurrent VTE, major PE. A prospective evaluation is required before it can be haemorrhage and mortality were 5.8% (95%CI 3.7-8.3), implemented in clinical practice. 4.7% (95%CI 3.0-6.8) and 37% (95%CI 28-47). VTE recurrence risk was comparable under low molecular C248 Risk of recurrent venous thromboembolism and weight heparins (LMWH) and vitamin-K antagonists major bleeding in cancer-associated incidental (VKA) (6.2% vs. 6.4%; hazard ratio (HR) 0.9; 95%CI pulmonary embolism amongst treated and untreated 0.3-3.1), while 12% in untreated patients (HR 2.6; 95%CI patients: a pooled analysis of 926 patients 0.91-7.3). Risk of major haemorrhage was higher under VKA than LMWH (13% vs 3.9%; HR 3.9; 95%CI 1.6-10). T. van der Hulle1, P.L. den Exter1, G. Meyer2, VTE recurrence risk was comparable in patients with B. Planquette2, S. Soler3, M. Monreal4, D. Jiménez5, an isolated subsegmental IPE and those with a more A.K. Portillo5, C. O’Connell6, H. Liebman6, M. Shteinberg7, proximally localized IPE (HR 1.1; 95%CI 0.50-2.4). Y. Adir 7, M. Tiseo8, M. Bersanelli8, H.N. Abdel-Razeq9, Conclusions: These results support the current recommen- A.H. Mansour9, O.G. Donnelly10, G. Radhakrishna10, dation to anticoagulate cancer-associated IPE with LMWH S. Ramasamy10, G. Bozas11, A. Maraveyas11, over VKA and argue against different management of A.B. Shinagare12, H. Hatabu12, M. Nishino12, subsegmental IPE. M.V. Huisman1, F.A. Klok1 1Leiden University Medical Centre, Department of Thrombosis C249 Systemic leukocyte-bound apolipoprotein B is and Haemostasis, Leiden, the Netherlands, 2Hôpital inversely associated with the presence of clinical Européen Georges-Pompidou, Department of Respiratory and subclinical atherosclerosis and Intensive Care, Paris, France, 3Hospital Sant Jaume, Department of Internal Medicine, Olot (Gerona), Spain, M.A. de Vries, B. Klop, N. van der Meulen, E. Birnie, 4Hospital Universitari Germans Trias i Pujol, Department of G.J.M. van de Geijn, A.H. Liem, M. Castro Cabezas Internal Medicine, Badalona,Spain, 5Ramon y Cajal Hospital, Sint Franciscus Gasthuis, Department of Internal Medicine, Respiratory Department, Madrid, 6Jane Anne Nohl Division of Rotterdam, the Netherlands Haematology, Los Angeles, United States of America, 7Carmel Medical Centre, Pulmonology Institute and CF Centre, Haifa, Background: A high level of erythrocyte-bound apoli- Israel, 8University Hospital of Parma, Medical Oncology Unit, poprotein (apo) B in humans has been associated with Parma, Italy, 9King Hussein Cancer Centre, Department a decreased prevalence of clinical and subclinical ather- of Internal Medicine and Depa [hier ontbreekt tekst. Graag osclerosis. We aimed to determine the relationship checken], Amman, Jordan, 10University of Leeds and St James’

111 between leukocyte-bound apo B in the circulation and incidence of adverse reactions with emphasis on liver and atherosclerosis. kidney injury and myopathy. Methods: The level of apo B on circulating leukocytes was Results: Twenty studies were analyzed. Quality safety measured by flow cytometry in subjects with and without assessment was low in the majority of studies. RYR coronary artery disease (CAD) in a cross-sectional design, lowered LDL cholesterol with 1.02 mmol/l [-1.20; -0.83] and expressed as mean fluorescent intensity in arbitrary compared to placebo. Effect of RYR on LDL was not units (au). Carotid intima media thickness (cIMT) was different from statin therapy (0.03 mmol/l [-0.36; 0.41]). measured using B-mode ultrasound. Data are given as The incidence of liver and kidney injury was 0-5% and mean ± SD. the risk was not different between treatment and control Results: 442 subjects were included, of whom 185 had groups (risk difference -0.01 [-0.01; 0.0] and 0.0 [-0.01; a history of CAD. Compared to subjects without CAD, 0.02]). patients with CAD had lower levels of apo B bound to Conclusion: RYR exerts a clinically and statistically neutrophils (12.9 ± 4.8 and 14.3 ± 5.8 au, respectively, significant reduction of 1.02 mmol/l LDL cholesterol. p = 0.006) and to monocytes (2.6 ± 1.1 and 2.8 ± 1.3 Only when the mild profile of adverse reactions can be au, respectively, p = 0.02). No differences existed for affirmed in studies with adequate methodology for safety lymphocyte-bound apo B. Neutrophil-bound apo B was assessment, RYR might be a safe and effective treatment inversely correlated with cIMT (Spearman rho: -0.102, option for dyslipidemia and cardiovascular risk reduction p = 0.035). Furthermore, both monocyte- and neutrophil- in statin intolerant patients. bound apo B were significantly and positively associated to different components of the metabolic syndrome, C251 Hypertriglyceridemia-induced pancreatitis in a such as BMI, triglycerides and C3. There was also a patient with a history of normal triglyceride levels positive association between leukocyte-bound apo B and erythrocyte-bound apo B (rho: 0.502, p < 0.001; rho: R. Loeffen, A. Iglesias del Sol 0.304, p < 0.001; rho 0.190, p < 0.001 for lymphocyte-, Alrijne Hospital, Department of Internal Medicine, monocyte- and neutrophil-bound apo B, respectively), Leiderdorp, the Netherlands possibly reflecting a similar binding mechanism. Conclusion: Unexpectedly, binding of apo B-containing Introduction: Hypertriglyceridemia is a rare cause of lipoproteins to circulating leukocytes may represent a pancreatitis. We describe a case of acute hypertriglyc- protective mechanism against atherosclerosis. eridemic pancreatitis in a patient with no history of dyslipidemia. C250 Safety and effectiveness of red yeast rice extract to Case description: A 40-year old male with no medical reduce LDL cholesterol – a systematic review and history presented at the emergency department with meta-analysis progressive epigastric pain, vomitus and weight loss. He did not use medication nor alcohol. Palpation of M.C. Gerards1, T. Ruben2, H. Yu1, K. Koks3, V. Gerdes1 the epigastric area was painful. Abdominal computed 1Slotervaart Hospital, Department of Internal Medicine, tomography revealed evidence of peripancreatic fat Amsterdam, the Netherlands, 2AMC, Department of stranding and fluid collections consistent with acute Haematology/ Experimental Immunology, Amsterdam, pancreatitis. Abdominal ultrasound ruled out gallstones. the Netherlands, 3Antoni van Leeuwenhoek, Pharmacy, Laboratory results showed a normal amylase level, however Amsterdam, the Netherlands liver biochemical tests were elevated. Additional tests revealed markedly increased serum triglyceride and Background: Red yeast rice-extract (RYR) is claimed to be a cholesterol levels of 125 mmol/l and 34 mmol/l, respec- safer alternative to regular statins but case reports suggest tively. Fasting glucose level was normal. Remarkably, that RYR may cause adverse reactions similar to that in normal lipid levels were obtained two years prior to statin therapy. We verified safety and effectiveness of RYR admission and family history was negative for hyper- to reduce LDL cholesterol. triglyceridemia. The diagnosis of acute hypertriglyceri- Methods: Systematic literature review and meta-analysis. demic pancreatitis was made and in addition to standard We searched Medline and EMBASE until November 2014 management, treatment was started with heparin without language restriction. We included randomized and a fibrate. Within a week triglycerides decreased to studies in which RYR was tested against placebo or an 4.6 mmol/l. The symptoms of pancreatitis resolved with active control group for at least 4 weeks. Data was extracted treatment, and the patient was discharged. using standardized data extraction forms. Main outcomes Discussion: Pancreatitis secondary to hypertriglyceridemia measures were the effect of RYR on LDL cholesterol and is typically seen in the presence of one or more secondary factors, such as uncontrolled diabetes, alcoholism,

112 medications, and in patients with a genetic abnormality M.W.J. de Ronde1, M.G.M. Kok1, E.E. Creemers1, of lipoprotein metabolism. However, in this case the exact P.D. Moerland1, J.C.M. Meijers2, S.J. Pinto-Sietsma1 cause of the hypertriglyceridemia remains unclear. No 1AMC, Department of Vascular Medicine, Amsterdam, the secondary factors were present and since there was no Netherlands, 2Sanquin, Department of Plasma Proteins, history of hypertriglyceridemia and treatment resulted Amsterdam, the Netherlands in normalization of triglycerides, no evidence of a genetic cause was found. Background: Worldwide, tobacco use is the most important avoidable cause of cardiovascular disease C252 Skin autofluorescence as a measure of advanced (CVD), redoubling the risk of developing a myocardial glycation end products deposition predicts 5-year infarction. However, numerous smokers never develop amputation in patients with Peripheral Artery cardiovascular complaints. MicroRNAs (miRNAs) are Disease small non-coding RNAs that control gene expression and are involved in CVD. In this study, we aimed to find L.C. de Vos, J. Boersema, D.J. Mulder, A.J. Smit, monocyte miRNAs that can identify smoking individuals C.J. Zeebregts, J.D. Lefrandt that will develop CVD. Methods/Results: We performed a UMC Groningen, Department of Internal Medicine, miRNA microarray on isolated monocytes in 40 subjects Groningen, the Netherlands with premature atherosclerosis and 40 healthy controls. MicroRNA expression levels revealed that miRNA-X had Background: Patients with peripheral artery disease (PAD) a low expression among non-smokers, whereas smokers are at risk for critical limb ischemia (CLI) and amputation. varied strongly: some smokers showed equal levels as in Accumulation of advanced glycation end products (AGEs) non-smokers and others showed high miRNA-X levels. To is increased and predictive for coronary and cerebrovas- validate these findings, we performed the same analysis cular events in several high cardiovascular risk groups. We in an independent cohort of 40 CVD patients and 27 hypothesized that accumulation of tissue AGEs, measured healthy family members and found similar results. This by skin autofluorescence (SAF), predicts amputation in finding led to the hypothesis that monocytes of certain patients with PAD. smokers, handle smoking differently, possibly leading to Methods and results: Between October 2007 and June high miRNA-X levels and more atherosclerosis. To test 2008, 252 with PAD were included at the outpatient this hypothesis, we compared miRNA-X levels in a cohort clinic Vascular Surgery. During a 5-year follow-up, 22 of 38 smokers with subclinical atherosclerosis, as assessed (9%) had an amputation because of CLI. Competing risk by coronary CT scan (coronary calcium score > 80th analysis showed a subproportional hazard ratio (sHR) of percentile) and 32 healthy smoking subjects (coronary 3.05; 95% confidence interval (CI), 1.87-4.96; p < 0.0001 calcium score 0), using RT-qPCR. MiRNA-X expression for amputation per unit of SAF. After correction for levels were significantly higher in subclinical athero- diabetes mellitus and Fontaine stage, sHR was 2.72; 95% sclerosis subjects compared to controls (OR 2.4, 95% CI CI, 1.38-5.39; p = 0.004. In patients with Fontaine stage 1.8-4.6, p = 0.007). Conclusion: This study showed that I and II only (n = 215), SAF was the only predictor for high miRNA-X expression levels can identify subclinical amputation, sHR: 4.05; 95% CI, 2.09-7.83; p < 0.0001. atherosclerosis in smokers. Therefore, miRNA-X may be a Fontaine stage multiplied by SAF resulted in a significant useful biomarker to identify smoking individuals at high increase of the area under the curve (AUC) for prediction risk of developing CVD. of amputation as compared to Fontaine stage only: AUC increased from 0.74; 95% CI, 0.63-0.86 to 0.83; 95% CI. C254 A patient with haemophilia A and arterial 0.74-0.92; p = 0.003. thrombosis caused by large vessel vasculitis: a case Conclusions: SAF, a measure of tissue AGEs deposition, report predicts amputation in patients with PAD during a 5-year follow-up, independent from the presence of diabetes R.H.H. Bemelmans1, L.M. Vos2, H.W. de Valk2, mellitus and Fontaine stage. Even at lower Fontaine stage W. Spiering2, R.E.G. Schutgens2 (I or II), SAF is a strong predictor of amputation. The 1Gelderse Vallei, Department of Internal Medicine, Ede, multiplication of Fontaine stage by SAF results in a good the Netherlands, 2UMC Utrecht, Department of Internal prediction model of amputation. Medicine, Utrecht, the Netherlands

C253 MicroRNA-X can identify smokers at risk for Presenting symptoms and clinical findings: We saw a atherosclerosis 57-year old Caucasian male with acute abdominal pain on the left side radiating to the scrotal area. His medical history included haemophilia A with multiple bleeding

113 episodes. He used factor VIII replacement therapy on lopathy states such as the antiphopholipid syndrome and demand. Physical examination was unremarkable; particu- severe homocysteinemia. Tests however failed to confirm larly there was no peritonitis or fever. Laboratory findings these, although heterozygosity for factor V Leiden was included high inflammatory parameters and impaired noted. Prior to presentation he never suffered from a renal function. An abdominal CT-scan revealed thrombus thrombo-embolic event. formation in both renal arteries and in the superior Recent literature data have shed light on the hypothesis mesenteric artery, and bilateral renal infarction. A PET/ that both thrombophilic episodes could have been CT-scan showed high glucose uptake in the thoracic and secondary to the myxoma. Systemic hypercoagulability abdominal aortic wall. occurring as a paraneoplastic (and mechanic) effect, has Diagnosis: Intra-arterial thrombosis due to large vessel been described. vasculitis. The post-surgery pathology report confirmed the diagnosis Interventions: Treatment with high-dose prednisone, myxoma. The patient recovered well and any constitutional heparin, oral anticoagulation and prophylactic clotting symptoms resolved, which supports the hypothesis of a factor VIII replacement therapy was started. paraneoplastic syndrome. Clinical course: Symptoms and inflammatory parameters In conclusion, we report a case with arterial and decreased with this therapy, and renal function improved. paradoxical pulmonary embolism, in a patient under After three months, oral anticoagulation was replaced by anti-coagulation therapy as first presentation of a cardiac platelet inhibition. Eight months later the disease was still myxoma. This presentation is quite possible given the in remission. systemic and paraneoplastic manifestations of the Discussion: In vasculitis there is an inflammatory reaction myxoma, in combination with pre-existent atrial fibrillation in the blood vessel wall with release of cytokines. These and Factor V Leiden heterozygosity. pro-inflammatory cytokines such as TNF a, IL-1, IL-6 and IFN-g, directly stimulate the clotting cascade. Furthermore, C256 Increased tissue accumulation of advanced glycation platelets are activated by increased expression of P-selectin end products is associated with glycemic stress but and platelet surface aggregates. Together, these changes not with LDL in patients with familial hypercholes- lead to a pro-thrombotic state, which may clinically result terolemia without Diabetes Mellitus in thrombo-embolic complications. Apparently this reaction is so strong, that even in a patient with a high S.A. Kochen, D.J. Mulder, A.J. Smit, M. Zwiers, bleeding tendency due to haemophilia A, intra-arterial R.P.F. Dullaart, J.D. Lefrandt thrombosis can occur. UMC Groningen, Department of Internal Medicine, Groningen, the Netherlands C255 Left atrial cardiac myxoma presenting as arterial and paradoxical venous embolism. Objective: Advanced Glycation End Products (AGEs) are formed by non-enzymatic glycation and oxidative E.W. de Roos, A. Dees, A.A. Zandbergen reactions. Tissue accumulation of AGEs is accelerated Ikazia Hospital, Department of Internal Medicine, and associated with cardiovascular (CV) events and Rotterdam, the Netherlands mortality in patients at increased CV risk, such as diabetes mellitus (DM) and chronic kidney disease (CKD). Familial We report a 58-year-old male who presented with acute Hypercholesterolemia (FH) is associated with increased dyspnea, recurrent abdominal pain and thrombophlebitis oxidative stress and associated with premature CV events. since two months. Furthermore he suffered several consti- Whether AGEs are increased in FH is unknown. The aims tutional symptoms, e.g. weight loss, fever, itch and cutanic of the present study were to study tissue accumulation of rash. Relevant medical history entailed therapeutic antico- AGEs and the association with LDL and glycemic stress in agulation therapy for over seven years due to permanent FH patients. atrial fibrillation. Methods and results: 136 FH patients without DM (mean CT-scan showed, next to multiple pulmonary embolism age 41 ± 12) were included, matched (sex and age) with and renal infarction, a tumorous mass in the left atrium. 136 non-FH patients with hypercholesterolemia (Tot Chol Transesophageal echocardiography supported the > 5.0 or LDL > 2.5 mmol/l) and classified according to diagnosis of a myxoma, but could not explain the marked tertiles of HbA1c and LDL. Tissue AGEs were noninva- coincidence of venous and arterial emboli (so called sively measured with the AGE-reader[TRADEMARK]. paradoxical emboli) since an intracardiac shunt was LDL was higher in FH patients (4.2 ± 1.5 versus 3.8 ± excluded. 1.0 mmol/l, p = 0.01) and HbA1c similar (5.5 ± 0.4 in The further differential diagnosis of arterial thrombosis both groups). AGEs were only slightly increased in both combined with deep vein thrombosis will include coagu- FH patients (Z-score 0.29, p = 0.03 one-sample t-test)

114 and non-FH patients (Z-score 0.21, p = 0.02), while no M.M.E. Krekels1, H.W.M.P. Bergmans2, L.C. Crasborn2, difference existed between the groups (1.91 ± 0.53 versus P.W. de Leeuw1 1.93 ± 0.47 a.u., p = 0.71, t-test). AGEs were associated with 1Orbis Medical Centre, Department of Internal Medicine, HbA1c tertiles (1st:1.78 ± 0.46, 2nd:1.93 ± 0.47, 3rd:2.12 ± Sittard-Geleen, the Netherlands, 2MCC Omnes, Department 0.54 a.u., p < 0.0001, ANOVA) in FH patients but not in of Family Medicine, Sittard-Geleen, the Netherlands non-FH patients. AGEs were not associated with tertiles of LDL in both groups. Multivariate analysis showed the Background: In comparison with other areas in the the same results. Netherlands, FH is underdiagnosed in Limburg. Whereas Conclusion: Tissue accumulation of AGEs is slightly Zeeland and Friesland have identified 100 and 93% respec- increased and positively associated with glycemic stress in tively of all expected FH patients, this is true for only 38% FH patients without DM, but not with LDL. of patients in Limburg. Methods: First, we performed a retrospective search of C257 Low low-density-lipoprotein cholesterol levels in laboratory results to identify patients in whom a LDL patients with systemic mastocytosis > 6.5 mmol/l (representing five points on the LEEFH-scale) was found during the last 15 years. Their family doctors S. Indhirajanti, J.E. Roeters van Lennep, P.L.A. van Daele were asked whether a diagnosis of FH had been considered Erasmus MC, Department of Internal Medicine – Vascular and whether the patients had been referred for further diseases, Rotterdam, the Netherlands workup. In case of a probable FH diagnosis they were asked to send the patient for further DNA investigation if Background: Inflammation and lipid accumulation are this had not been done before. This strategy is now applied key processes in atherosclerosis. The influence of mast prospectively. cells, a prominent inflammatory cell, on atherosclerosis Results: In total, the laboratory identified 632 patients is extensively studied in animals. Murine activated mast from the retrospective cohort and 176 of these were sent cells can bind low-density-lipoprotein cholesterol (LDL-c) for further investigation. In these 176 patients, FH was and enhance atherosclerosis. In mast cell-deficient mice diagnosed in 22 (13%). Since the introduction of the lower serum cholesterol levels were found. However, it new strategy, 22 patients have been referred of whom 6 is unknown if this mechanism also applies in humans. (27%) proved to have FH. So, despite similar criteria for Our objective was to study whether patients with systemic diagnosing FH our present prospective approach identifies mastocytosis (SM) have higher LDL-c levels than a more patients than in the past. reference group. Conclusion: The low percentage of FH in the retrospective Methods: We measured LDL-c levels in patients with group suggests a less strict application of the FH criteria by SM treated at the Immunology outpatient clinic of the family doctors in the past. A proactive approach, therefore, Erasmus Medical Centre. Clinical data including LDL-c seems to be worthwhile for identifying FH patients. levels and statin use were analyzed. As reference we used the age and sex matched lipid data of the Lipid Research C259 Tissue accumulation of advanced glycation Clinics Prevalence Study. If untreated LDL-c levels were endproducts is accelerated both in peripheral arterial not available we calculated these by estimating effect of dilating and occlusive disease statin treatments. Results: A total of 43 SM patients (21 men and 22 women) J. Boersema, L.C. de Vos, D.J. Mulder, A.J. Smit, were included. 8 of the 43 patients (18.6%) used statins. R.P.F. Dullaart, C.J. Zeebregts, J.D. Lefrandt Untreated LDL-c levels were known in 39 patients. In UMC Groningen, Department of Vascular Internal Medicine, 4 patients these were calculated. The mean LDL-c in Groningen, the Netherlands patients with SM was 3.30 mmol/l, vs. 3.69 mmol/l for the reference group (p 0.042). Background: Advanced glycation endproducts (AGEs) play Conclusion: Contrary to expected we found that patients a pivotal role in accelerated vascular aging in atheroscle- with SM had statistically significant and clinically relevant rosis. Although dilating and occlusive peripheral arterial lower LDL levels as compared with the reference group. disease share a number of cardiovascular risk factors, the The pathophysiologic mechanisms and the effect on pathophysiology differs. Abdominal Aortic Aneurysms cardiovascular disease has to be determined. (AAA) are characterized by tunica media weakening and Peripheral Artery Occlusive Disease (PAOD) by intima C258 Pro-active approach of family-doctors in identifying thickening. Whether tissue accumulation of AGES is FH (familial hypercholesterolemia) patients in the accelerated in AAA is unknown. The aim of the present Westelijke Mijnstreek area study was to explore tissue accumulation of AGEs in patients with AAA, PAOD and healthy controls.

115 Methods: 800 patients were studied: 400 with PAOD, Methods: By size-exclusion chromatography, we inves- 150 with AAA, 50 with both (PAOD and AAA) and 200 tigated complex formation by adding different naturally controls, matched 8:3:1:4 for age (mean 69±9 years). Tissue occurring isoforms of pro-IGF-II to pooled normal adult accumulation of AGEs was measured noninvasively with serum. Results were compared with the analysis of the the AGE-reader™, using Skin AutoFluorescence (SAF). serum from the patient with NICTH. Results: SAF differed among the groups: geometric Results: Gel filtration experiments with the serum of the mean 2.78 a.u. (95%CI: 2.71-2.84) in PAOD patients, patient with NICTH demonstrated that ternary complex 2.73 (95%CI: 2.64-2.83) in AAA patients, 3.05 (95%CI: formation was severely compromised. 2.88-3.22) in patients with (AAA and PAOD) and 2.51 The various forms of pro-IGF-II did not induce a shift (95%CI: 2.43-2.59) in controls, p < 0.1x10-8, ANOVA. of IGF-binding protein 3 (IGFBP-3) from 150 kD towards Post-hoc analysis showed that all patient groups had a smaller binary complexes in the normal adult serum, higher SAF than controls and patients with both (AAA suggesting that they did not interfere with the interaction and PAOD) had a higher SAF as compared to patients with between the acid labile subunite and IGFBP-3. AAA or PAOD only. These differences remained after Conclusion: We postulate that, alongside the presence of correction for age, gender, smoking, diabetes mellitus and big IGF-II in the circulation, additional steps are required eGFR (MDRD formula). to stimulate the release of IGF-II and pro-IGF-II isoforms Conclusion: Accumulation of tissue AGEs is accelerated in from IGFBPs in vivo. patients with AAA, PAOD and particularly in patients with both (AAA and PAOD), independent from age, diabetes C261 Sense and nonsense of treatment of comorbid mellitus and renal function. diseases in terminally ill patients * An extended version will be published in JAMA internal medicine (March 2015) XVII OTHER E.C.T. Geijteman, T. van Gelder, L. van Zuylen Erasmus MC, Department of Internal Oncology, Rotterdam, C260 Column chromatographic characterization of the Netherlands complex formation of pro-IGF-II isoforms with acid labile subunit and IGF-binding proteins associated Background: Pharmacotherapy is the appropriate use of with non-islet cell tumour induced hypoglycaemia drug to prevent and treat diseases and to relieve symptoms. In the final phase of life, treatment goals change, and K.M. van Veggel1, R.M.H.G. Huits2, G.H. Donker3, drugs should be reconsidered. E.G.W.M. Lentjes3, J. van Doorn3 Case: A 69-year-old woman was diagnosed with metastatic 1Alrijne Hospital, Department of Internal Medicine, pancreatic cancer. She had a history of type 2 diabetes Leiderdorp, the Netherlands, 2Center for Infectious Diseases, mellitus, diagnosed 7 years earlier. Initially, her diabetes ID4C, Military Hospital Queen Astrid, Department remained under control by metformin and by strictly of Internal Medicine, Brussels, Belgium, 3UMC Utrecht, adhering to a healthy lifestyle. For example, she had Department of Clinical Chemistry and Haematology, Utrecht, stopped eating her beloved ice cream. She was treated the Netherlands with palliative chemotherapy, including dexamethasone to reduce associated nausea. During the first cycles Background/Case: A 37-year old man presented at the blood glucose levels rose to 16 mmol/l, for which she emergency department with epileptic seizures due to received short-acting insulin. At home, glucose levels recurrent hypoglycaemia. The patient had recently been were occasionally slightly above target values. Under diagnosed with hepatocellular carcinoma. Laboratory inves- these circumstances she stopped eating. The physician tigations supported the diagnosis of non-islet cell tumour told her that higher glucose levels were not a problem hypoglycaemia (NICTH). when they gave her no symptoms. This information was Treatment with glucocorticoids was initiated. Effective very disconcerting to her because she had always been control of glucose levels was achieved. However, the patient told that it was extremely importance that glucose levels died due to progressive malignant disease. would not exceed target values. The physician repeated NICTH is a paraneoplastic phenomenon that is associated that higher levels were unlikely to be harmful, especially with the formation of several isoforms of pro-insulin in the absence of symptoms. He emphasized that she was like growth factor 2 (pro-IGF-II), so called ‘big’ IGF-II. not being abandoned. In contrast, her caregivers were Disturbance of ternary complex formation by big IGF-II is applying tailored therapy. The patient appreciated this assumed to be a crucial event in the pathogenic cascade of explanation, and despite her nausea, she was keen to eat hypoglycaemia. ice cream again.

116 Conclusion: In terminally ill patients, physicians must Meander Medical Centre, Department of Internal Medicine, adapt drug treatments to new objectives. This case Amersfoort, the Netherlands illustrates that such management may improve quality of life and potentially reduce unnecessary and costly A 67-year-old male with a history of non-specific interstitial pharmacotherapy. pneumonia presented with progressive dyspnea. He was transported to ICU for mechanical ventilation. An exacer- C262 Effective electroconvulsive therapy for malignant bation of NSIP seemed most likely so he was treated with catatonia in pharmacotherapy-resistant neuroleptic prednisone. A week after initial improvement his clinical malignant syndrome or serotonin syndrome condition worsened and high dose Methylprednisolon was given. Suddenly the patient developed generalized seizures H. Westdorp, C. van der Meer, B.J.J.W. Schouwenberg, with signs of autonomic dysregulation. Cranial-CT M. Pop-Purceleanu, C. Kramers showed no pathology, neither was there any indication Radboudumc, Department of Clinical Farmacolgy and of meningitis or electrolyte disturbances. Phenytoin, Toxicology, Nijmegen, the Netherlands valproate an sedation were started, nonetheless the seizures increased in frequency and intensity. A second CT Introduction: malignant catatonia, neuroleptic malignant 12hrs later showed cerebral edema and signs of herniation. syndrome (NMS) and serotonin syndrome (SS) are Ultimately the patient became brain death. potentially life-threatening conditions with overlapping Laboratory results revealed a strikingly high ammonia level clinical syndromes. The conditions can contain signs of 2700 mmol/l[7-42 mmol/l], with normal liver enzymes. of hypertension, tachypnea, hyperthermia, rigidity, Post-mortem blood/urine analysis was suggestive of a dysautomia and changes in mental status. NMS is urea cycle defect. His two daughters were tested and associated with dopamine antagonists or dopamine agonist found to be carriers of an OTC gene mutation (c.622G>A, withdrawal. SS with increased release of serotonin or p.Arg2o8Thr). Family history revealed this mutation was impaired reuptake from the synaptic cleft. found earlier in two distant cousins, genetically linked Case: a 41-year-old intubated male is admitted at the through the patients grandmother. intensive care unit (ICU) with rhabdomyolysis, persistent OTCD is an X-linked disorder (Xp21.1). Residual activity hyperthermia of 40°C and motoric agitation for which of the enzyme varies, incidentally symptoms only occur the continues use of heavy sedation is required. Initially when environmental factors luxate hyperammonemia. meningitis and (auto-immune) encephalitis were ruled In this case the his catabolic state, glucocorticoids and out. The patient uses valproate 2500 mg/day chronically protein enriched enteral feeding may have contributed. because of epilepsy. First 12 days of admission he was In retrospect, other indications of OTCD were present. treated with metoclopramide 30 mg/day. Discontinuation His brother developed a fatal coma after ‘the flu’ at age of precipitating drugs and therapy with benzodiazepines 15. Also, the patient had a tendency to avoid eating meat, and bromocriptine did not improve the situation. At day he felt uneasy after consumption. This voluntary protein 31 the patient developed an aggravation of autonomic avoidance is characteristic for UCD patients. dysfunction and a persistent stupor after cessation of sedatives. We expected a malignant catatonia upon a NMS C264 The role of empowerment in effectively informing or SS. After consultation of the psychiatrist electrocon- patients about prescribed medication vulsive therapy (ECT) was started every two days. After 25 days since the start of ECT there was a significant E.N. Klarenbeek-de Jonge, F. van Stiphout, S.C.J. Vervoort, improvement of the clinical condition without autonomic E.W.M.T. ter Braak dysfunction, hyperthermia and with a normalised mental UMC Utrecht, Department of Internal Medicine and status. The patient could be extubated and has thereafter Dermatology, Utrecht, the Netherlands been referred to a revalidation centre. Conclusion: we presented a case of malignant catatonia Background: As shown previously, 5.6% of unplanned caused by an underlying NMS or SS. One should keep hospital admissions relate to adverse drug events (ADE’s). in mind that ECT can benefit patients with these clinical Tailoring information to patients’ needs and empowerment syndromes after failed pharmacotherapy. regarding their medication management has been demonstrated to enhance drug adherence and may reduce ADE’s. C263 Fatal hyperammonemia secondary to ornithine Yet, studies show that type and amount of information and transcarbamylase (OTC) deficiency in a patient with its delivery often fail to match with patients’ needs and non-specific interstitial pneumonia preferences. This study aims to identify factors involved and how these relate to empowerment. G.P. Bijvoet

117 Methods: Participants visited the outpatient clinics of consuming. Studentsappreciated their (new) responsibility Internal Medicine and related medical specialties in two for patient care and considered the LC-SRC a very valuable academic hospitals in the Netherlands. In-depth semi- extracurricular activity. structured interviews were performed at their homes. Conclusion: The LC-SRC is feasible and could be a valuable Akin to the principles of grounded theory, interviews were addition to the medical curriculum. The benefits and coded and analysed using constant comparative analysis, to learner effects need to be investigated in a larger study identify factors and to investigate their relations. with a longer follow-up. Results: Interviews with nineteen participants (10F:9M, mean age 56 (28-88), mean no. of medications 9 (5-27) C266 Abdominal mass: not necessarily malignant showed relations of information needs and empowerment with several factors, including: the need for autonomy, J. Stoffers, F.W.P.J. van den Berkmortel the need for relatedness, feeling involved in medication Atrium-Orbis Medical Centre, Department of Internal management, decision-making and trust. The nature Medicine, Heerlen, the Netherlands of the relations between these factors are described and illustrated by verbatim quotations. Case description: A 51-year old male patient was referred by Conclusion: Tailoring the provision of information to the general practitioner, where he presented with headache patients’ needs appears to enhance patient empowerment and an abdominal swelling. A cystic abdominal mass (16 regarding medication management. Knowledge and cm in diameter) was diagnosed by ultrasound. insights about involved factors described here, support His medical history reported hypertension and depression. clinicians to inform their patients in effective ways aiming Valsartan and citalopram were started (< 1 week) recently. to foster drug adherence and reducing ADE’s. The patient reported deliberate weight loss, where upon he noticed an abdominal swelling. He reported no pain, C265 A novel approach to teaching pharmacotherapeutics: only occasional tightness, night sweats and hesitation of learning by doing in a student-run clinic urinating. On physical examination, blood pressure was T. Schutte, R.S. Dekker, J. Tichelaar, A. Thijs, 220/110 mm Hg. Abdominal examination disclosed mild T.h.P.G.M de Vries, M.C. Richir, M.A. van Agtmael diffuse tenderness and a palpable mass in mid abdominal VUmc, Department of Internal Medicine, Section region, which was not well demarcated. Farmacotherapy, Amsterdam, the Netherlands Laboratory studies were normal, including kidney function. In addition a CT scan was performed to locate Background: Medical students should be better prepared the origin of the mass and showed a retroperitoneal mass for their future role as prescribers. A new educational of unknown primary origin (26.5x21.3x14.4 cm) with concept to achieve this is learning by doing. This trabeculae in the cranial part . encompasses legitimate, context-based training and gives Patient was discussed in the multidisciplinary oncology students responsibility as early as possible in their medical meeting on suspicion of malignancy. Because of the cystic education. Student-run clinics (SRCs) are an example of nature and location of the tumour urine retention was this concept. We describe the development of a new SRC considered. primarily focused on medical pharmacotherapy education, A urinary catheter was placed and 3.7L urine was retracted. the learner-centered student-run clinic (LC-SRC), and its Thereafter the palpable mass disappeared. Further feasibility. urological examination to explain the cause of urine Method: A feasibility study was performed in which a team retention is ongoing. The recent start of citalopram may of (1st, 3rd and 5th-year) students treated patients under the have exaggerated already present chronic urine retention. supervision of an internist. Patients were selected from Conclusion: In a patient who presents with an abdominal the internal medicine outpatient clinic for follow-up in the mass, urine retention should always be considered even LC-SRC. Feasibility was evaluated using a set of question- in case of mild to absent symptoms and normal kidney naires for patients, supervisors and students. function. Drugs may exaggerate already present chronic Results: In total 31 consultations were conducted; 31 urine retention. students and 4 clinical specialists participated. A pharmacotherapeutic treatment plan was drawn up in 33% of the C267 To treat or not to treat that is the question. consultations. Patients were content with the care provided Limitations of treatment in clinical practice. and rated the consultation with a 7.9 (SD 1.21) (1(min)- 10(max)). Supervisors regarded LC-SRC safe for patients S.J. Bakker, F.H. Bosch with guaranteed quality of care. They found the LC-SRC Rijnstate, Department of Internal Medicine, Arnhem, the a valuable tool in medical education although it was time- Netherlands

118 for a real patient in three situations of increasing realism: Medical professionals are trusted with the care of their a minimal level (studying a patient record), medium level patients. In case of a medical emergency their first reaction (preparing for a therapeutic consultation), and optimal is to act on the life-threatening situation. Nevertheless it is level (preparing and performing a therapeutic consultation important to take notice of the autonomy of the patients with the patient). and to deliver care in line with the wishes of the patient. Results: In comparison to studying a patient record The next two cases clearly demonstrate how poor commu- (minimal context level), preparing a therapeutic consul- nication and poor documentation can lead to over tation (medium context) improved four of the six steps treatment. of the WHO 6-step plan. Preparing and performing An 87-year-old woman presented to the emergency a therapeutic consultation with a real patient (optimal department and was treated for pneumonia. Initially context) further improved three essential prescribing she recovered, however on the fourth day she presented competencies, namely, checking for contraindications and in respiratory distress, this was followed by circulatory interactions, prescription writing, and instructions to the arrest. There were no treatment limitations registered in patient. her electronic medical records. Resuscitation was started, Conclusion: The results of this first explorative study unsuccessfully. Her husband mentioned after the arrest suggest that enrichment of the learning context (respon- that she had not wished to be resuscitated. This subject had sibility for patientcare) might be an important factor not been discussed during her hospital stay. to improve the training of rational prescribing skills of A 96-year-old woman presented to the emergency medical students during their clinical clerkship. Seemingly department in respiratory distress. Full treatment was small adaptations in the learning context of prescribing administered. The patient had documented her wish to training during clinical clerkships (i.e. with or without withhold curative treatment. The family had assumed she involvement with and responsibility for patient care) was hospitalized for palliative care. Insufficient communi- may have relatively large impact on the development of cation between patient, family and general practitioner had prescribing competencies of our future doctors. lead to 5 days of treatment before the wishes of the patients were acknowledged. Poor communication and documentation can lead to impersonalized medical practice. Even though the conversation about treatment limitations can be difficult it should not be neglected and should always take place. There should be a structural electronic registry of treatment limitations and this should be accessible to every healthcare professional.

C268 The effect of different levels of realism of context learning on prescribing competencies of medical students during the clinical clerkship internal medicine: an exploratory study

J. Tichelaar, C. van Kan, R.J. van Unen, A.J. Schneider, M.A. van Agtmael, T.h.P.G.M de Vries, M.C. Richir VUmc, Department of Internal Medicine section Farmacotherapy, Amsterdam, the Netherlands

Background: This abstract describes the findings from an exploratory study on the effect of different levels of realism of the learning context on the prescribing competencies of medical students during their clinical clerkship internal medicine. Methods: Between 2001 and 2007, 164 medical students took part in the prospective explorative study during their clinical clerkship Internal Medicine at the VU University Medical Centre, Amsterdam, the the Netherlands. In a fixed order, each student had to formulate a treatment plan

119 INDEX

AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Aalbers A.M. O11 Berk G.E.L. van den C167 Aarts E.O. C041 Berkmortel F.W.P.J. van den O02, C266 Aarts M.F. O11 Berrevoets M.A.H. C054, C135 Abdel-Razeq H.N. C248 Bersanelli M. C248 Abdul-Hamid M.A. C209 Betzel B. C041 Adir Y. C248 Beuers U.H. C161 Aerts R.M.M. van C098 Beutler J.J. C166 Agterhuis D.E. C013 Bhansing K.J. C028 Agterof M.J. O04 Bierman W.F.W. C167 Agtmael M.A. van O26, C082, C265, Biesheuvel T. C003 C268 Bieze H. C162 Akanmu S. C138 Biezen P. van C121, C175 Akkerman E.M. C060 Bijvoet G.P. C263 Alam N. C003 Bilo H.J.G. C022 Alipour A. O15 Binkhorst L. C218 Alkemade M. C024 Birnie E. C249 Alphen A.M. van C208 Bisschop P.H. C060 Alsma J. O13, C001, C099 Biter L.U. C067 Ammerlaan H.S.M. C157 Blans M.J. C042, C180, C182 Anten S. C059, C244 Blauw G.J. O24, O29 Anten M.P.G.F. C068 Bleeker-Rovers C.P. C173 Apeldoorn M.J. van C085, C152, C173, C177 Bleumink G.S. C057 Apers J. C034 Blijdorp K. C192 Appelman-Dijkstra N.M. C043, C051 Blockmans D. C171 Arends J.E. C136, C167 Bochove A. van C236 Arends P. C143 Bodelier A.G.L. O17 Arnqvist H.J. C022 Boeckxstaens G.E.E. C062 Asselt S.J. van C016 Boekhorst P.A.W. te C105 Assenberg van Eijsden E.M. C221 Boender T.S. C138 Assink J.H. C089 Boer H. de C021, C041, C053 Baake B.D.C. C106 Boer J.M.M. de C042 Bac D.J. C069 Boer M.G.J. de C071 Bakker S.D. C236 Boerekamps A. C065 Bakker S.J. C267 Boersema J. C252, C259 Balen P. van C071 Boersma R.S. O05, C110 Baltissen-van der Eijck A.A. C169 Boerstra T. C029 Barneveld P.C. C166 Boertien T.M. C227, C104 Bartelet K. C050 Boertien W.E. C177 Bartol S.J. C124 Bokhorst J. van C003 Beek-Peeters J.A.M. van C195 Bommel F. C143 Beenen L.F.M. C247 Bons E. O12 Beijers A.J.M. O07 Bont L.W. de C113 Belle-van Meerkerk G. C098 Boogaard F.E. van den O08, C147 Beltz A.M. C053 Boom H. C193 Bemelman W. C062 Boon E. C230 Bemelmans R.H.H. C254 Boon L. C241 Bemmel T. van C079 Bootsma H.P.R. C190 Bemt P.M.L.A. van den C217 Borggreve H.F. C007 Benner B.J.M. C068 Borren M.M.G.J. van C042 Bennink R. C062 Bos E.H. C053 Berends F.J. C041 Bos J.M. C181 Berg C.H.S.B. van den C153 Bos S. C207 Berg T. C143 Bos W. O20 Bergmans H.W.M.P. C038, C258 Bosch F.H. C267

120 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Bosch T.M. C208 Coenen V. van C189 Bosselaar M. C079 Cornelissen J.J. C115 Bossuyt P.M.M. C247 Cox K.E.M. C114 Botes M. C138 Craen A.J.M. de O29 Bots E.M.T. C233 Craen A.J.M. de O24 Bottieau E. C171 Crasborn L.C. C258 Boulaksil M. C173 Creemers E.E. C253 Bourgeois S. C065 Cremers A.J.H. C178 Bouter K.P. C173 Crevel R. van O25 Boven I.A. C012 Custers I.W. C093 Bozas G. C248 Daalen F.V. van C128 Braak E.W.M.T. ter C264 Daele P.L.A. van C120, C257 Brands M. C210 Daemen C.R.G.M. C037 Brands X. O08, C147 Dalm V.A.S.H. C175 Braunstahl G.J. C017 Dam- Kastelein J. van O28 Bree L.C.J. de C170 Damanik F. O22 Bree S.H.W. van C062 Dammers R. C121 Breedijk A. C094 Dams E.T.h.M. C213 Brink H.S. C024, C089 Dawson L. O27, C187 Brinkman K. C144 Deelen F.H.F. C048 Brkic Z. C001 Deenik W. C104 Broeren L.T.H. C125 Dees A. C066, C123, C255 Broijl A. C099 Dekker R.S. C199, C265 Brok M. C032 Delsing C.E. C142 Brouns S.H.A. C014 Deterding K. C143 Brouwer T. C035 Dezentje V.O. C214 Brouwers A.J.B.W. C017, C067 Diavatopoulos D. O25 Brown A. C143 Dickinson M.G. C194 Bruggeman C.Y. O04 Dielis A.W.J.H. C245 Brugma J.D. C217 Diepeveen S.H.A. C011 Bruijn P. de C218 Dijk P.R. van C022 Bruin I.J.A. de C230 Dijkstra G. C101 Buijs J. C023 Dijkstra I. C151 Buikema J.W. C061 Dinmohamed A.G. C115 Buiter C.W. C019 Dits J. C185 Buren M. van C186, C202 Doesschate T. ten C158 Burg L.M. van der C095, C011 Dofferhoff A.S.M. O12 Burger H. C218 Dogan K. C041 Buti M. C143 Donders R. C181 Buunk G. C002, C010 Donker A.E. C084 Carels R.A. C018 Donker G.H. C260 Carey I. C143 Donnelly O.G. C248 Cartuyvels R. C171 Doorenbos C.L. C146 Castro Cabezas M. O15, C035, C249 Doorn J. van C260 Celis I.M. C134 Dorny P. C171 Chaves I. C218 Douma R.A. C247 Chi H. C143 Drenth J.P.H. C131 Chisalita S.I. C022 Driessen C.M.L. C230 Choi I.Y. C242 Droogendijk J. C169 Christiaans M.H.L. C209 Duijst J. C007 Claassen M.A.A. C167 Duitman J.W. C147 Claessens A.K.M. C225 Duizer M.L. C028 Cloïn A.J.J.M. C141 Dullaart R.P.F. C049, C256, C259 Cloos-van Balen M. C044 Durian M. C169 Cnossen T.T. C234 Dussen L. van C060 Cnossen W.R. C239 Duthoi K.E.S. C234, O05 Cobussen M. C137, C005 Eeden A. van C167 Coenen J.L.L.M. C103 Eeghen E.E. van C236, C237

121 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Eekeren R. van O26 Geffen M.W.L. van C092 Eekhoff E.M.W. C047 Geijn G.J.M. van de C249, O15 Eersel M.E.A. van C050 Geijteman E.C.T. C261 Eising J. C226 Gelder J. de O24, O29, C202 Ekhart R. C057 Gelder M. van C084 Elbers L.P.B. O18 Gelder T. van C217, C261 Eling Y. C160 Gelderblom H. O30 Elizabeth M. C045 Gerards M.C. C250 Endert E. C060 Gerdes V. C250 Engelen L. C023 Gerdes V.E.A. O18 Engwerda E.E. O14 Gerlag D.M. C242 Erdkamp F.L.G. C225 Gerretsen J. O25 Erdkamp S.G.F. C225 Gerrits E.G. C093 Ermens A.A.M. C110 Gerritse S.L. O19 Erning F.N. van C238 Gertje E.C. C049 Erp N.P. van C214 Gevers T.J.G. C131 Es J. van C144, C247 Ghanes K. C003 Esbroeck M. van C171 Gils L. van C080, C199 Esch S. van C198 Gisolf E.H. C163 Esser J.W.J. van O05, O10, O17, Glas H.K. C059 C110, C234 Glaudemans W.J.M. C049 Etten R.W. van C139 Go P. C003 Evers D. C097 Goeijenbier M. C126 Exter P.L. den C247, C248 Göker E. O23 Farhat K. C197 Goos-Peek N. C091 Fasano M. C143 Goossens K. C099 Feberwee T. C214 Gorp E.C.M. van C126 Fehér J. C183 Gosselt A.N.C. C030 Feith G.W. C113, C190 Graaf F. van der C108 Ferwerda G.F. C178 Graaf H. de C235 Fiets R.B. C181 Graaf I. de O23 Fijnheer R. C012, C106 Graaf W.T.A. van der C216, C220 Filius P.M.G. C163 Graaff L.C.G. de C045 Flierman I. C080 Green D.J. C075 Fliers E. C060 Griend R. van der C098 Florence E. C065 Groeneveld A.B.J. C164 Florijn B.W. C201 Groenier K.H. C022 Fogteloo A.J. O24, O29, C202 Groot B. de O29, C202 Fokke C. C052 Grootjans H. C008 Forier A. C171 Grosfeld S. O23 Franca C. C006 Guchelaar H.J. O30 Francque S. C065 Guldener C. van C119, C246 Franken A.A.M. C050 Gulpen A.J.W. C015, C111, C112 Freling H. C013 Gundlach P.J. C195 Frerichs F.C.P. C156 Gyssens I. C171 Frissen P.H.J. C144 Haak H.R. C014, C025, C026 Furth W.R. van C153 Haan Y.C.L. C070 Gaast A. van der C212 Haanstra W.P. C207 Gajadin S.A. C170 Haerkens-Arends H.E. C166 Galan B.E. de O14 Haeseker M.B. C005 Gammeren A. van O10 Hageman I.M.G. C231 Gans R.O.B. C022, C053 Hagen P.M. van C120, C121, C124 Gant C.M. C078 Hair M.J.H. de C242 Geenen M.M. C231 Halkes C.J. C097 Geerlings S.E. C128, C161 Halma C. C194 Geerts J.W.H.J. C107 Ham J.C. C229 Geerts P.A.F. C108 Hamberg P. C218, C228 Geest P. van der C164 Hamdy N.A.T. C051

122 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Hamers R.L. C138 Hoogendoorn M. C090 Hamid M.A. C125 Hoogeveen E.K. C166 Hamming J.F. O22 Hoogstins H.A. C090 Hansen B.E. C143 Hooning M. O03 Hanssen N.M.J. C048, C093 Hoorn E.J. C196 Harris V.C. C161 Hopman M.T.E. C075 Hatabu H. C248 Horst G.T.J. van der C218 Hauten P.M.M. van C057 Houwen T.B. van der C124, C126 Havekes B. C048 Hovens M.M.C. C094 Havenith T.R.A. C205 Hovingh G.K. O18 Hawkins W.B. C213 Hubens L.P.A.M. C014 Hazebroek M. C127 Huijssen-Huisman E.J. C105 Hedman C.A. C022 Huisman A. O09 Heek J. van C152 Huisman M.V. C247, C248 Heide L.J.M. de C034, C058 Huitema L.F.A. C241 Heiden P.L.J. van der C186 Huits R.M.H.G. C260 Heijboer A.C. C060 Hulle T. van der C248 Heijden O.W.H. van der C097 Hullegie S.J. C167 Heim N. O24, O29 Huls G. C101 Helder B. C241 Hulscher M.E.J.L. C128 Hellemond J.J. van C175 Huurnink A. C153 Hendriks M.P. C215 Iglesias del Sol A. C251 Hengel A.B. van den C101 Ijtsma A.J.C. C049 Henstra M. C013 Imholz B.P.M. C030, C145 Herbers A.H.E. C086, C152 Indhirajanti S. C257 Hercegovac A. C208 Ingen J. van C163 Heringhaus C. O29 Jacobs E. C108, C118, C149 Herings R.M.C. C025, C026 Jager A. O03, C217 Herk-Sukel M.P.P. van C025, C026 Jager J. C035 Herk H.A.D.M. van C118 Jager S. de C188 Hermans M.M.H. C168 Jainandunsing S. C234, O05 Hermans P.W.M. C178 Jallah B.P. C076 Hermsen B. C032 Jansen T.C. C067 Hermus A.R.M.M. C075 Jansen W.P.J. C070 Herpen C.M.L. van C216, C220, Jansman F.G.A. C217 C229, C230 Janssen A.W.M. C054 Hettema M. C034 Janssen E.H.C.C. C175 Heuvel M.C.E. van den C157 Janssen H.L.A. C143 Heyligers J.J. C007 Janssen I.C.M. C041 Heymans S.R.B. C127 Janssen J.W. O15 Hillen J.M. C200 Janssen L. C168 Hilst J. van der C171 Janssen M. C088 Hira V. C005 Janssens G.O.R.J. C229 Hoeboer S. C164 Jazet I.M. C040 Hoefer I.E. O22 Jie C. C172 Hoeksema M. C188 Jiménez D. C248 Hoekstra R. C208 Johnson J.A. C025 Hoenderboom B.M. C138 Jong B. de C190 Hofman S.E. O29 Jonge P. de C053 Hokken-Koelega A.C.S. C045 Jonge V. de C066, C123 Hollak C.E. C060 Jongen-Lavrencic M. C115 Holle N. C042 Jongmans M.J. C055 Hollenberg M.J. C147 Jorsal A. C023 Hollmann M. C062 Jouini O. C003 Homan J. C041 Kaasjager K. C247 Hoog J. de C121 Kallenberg M.H. C072, C202 Hoogen F.J.A. van den C229 Kamermans M.W.A. C156, C215 Hoogenberg K. C049 Kampen R.J.W. van C114

123 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Kamphuis D.J. C187 Kort J.M.L. de C005 Kamphuis L.S.J. C124 Kortekaas M. C243 Kamphuisen P.W. C247 Koster A. C074 Kan C. van C268 Kox M. O25 Kanter J.L.M. de C163 Kramers C. C181, C262 Kastelein J.J.P. O18 Krekels M.M.E. C258, C038 Keltjens E.B.M. C182 Kreuk A.M. de C174 Kema I.P. C053 Krieckaert C.L.M. C083 Kemme S. C232 Kriekaart R.L. C206 Keulen E. C064 Krol-van Straaten M.J. C072, C073, C191 Keur M.B. C165 Krol S.D. O11 Keuter M. C135 Kroon A.A. C245 Kharagjitsing H.H.S. C224 Kroon J.W. C179 Kiewiet-Kemper R.M. C031 Kruijff I.E. de O10 Kinschot C.M.J. van C214 Kruithof M.K. C047 Kityo C. C138 Kubbenga I.E. C184 Kitzen J.J.E.M. C224, O03 Kuenen j. C079 Klarenbeek-de Jonge E.N. C264 Kuijper P.H.M. C112 Klaver M.N. C070, C104 Kuindersma M. C046 Kleef M.E.A.M. van C186 Kuiper S.G. O21 Kleefstra N. C022 Kusumanto Y. O11 Kleij - Corssmit E.P.M. van der C040, C044 Laan B.J. C226 Kleijn L. de C056 Laar J.A.M. van C120, C121, C124, Kleijnen B. C052 C126 Klein Hesselink M.S. C055 Laguno M. C130 Klein Nagelvoort S.C.E. C001 Lam K.H. C124 - Schuit Lam M.H. C218 Kleinherenbrink W. C185 Lamfers E.J. C181 Klerk B. de C160, C012 Landman G.W.D. C079, C159 Klift M. van der C110 Langenberg S.M.C.H. C216, C220 Klok F.A. C248 Lauw F. C167 Klop B. C249, O15 Leavis H.L. C122, C154 Kloth J.S.L. C218 Lebre M.C. C241 Knapen D.G. C148 Leendert R.J.M. van C031 Knegt R.J. C143 Leenen C.H.M. C172, C174 Knoester M. C165 Leentjens J. O25 Koch B.C.P. C001 Leeuw D.M. de C038 Kochen S.A. C256 Leeuw P.W. de C038, C258 Kock M. C224 Leeuwen-Segarceanu E.M. van O09 Koeijvoets K.C.M.C. C177 Leeuwen R.W.F. van C217 Koek G.H. C087 Lefrandt J.D. C035, C252, Koeleman J.G.M. C129 C256, C259 Koene H.R. C098 Leij C. van der C242 Kok M.G.M. C253 Lemmens V.E.P.P. C238 Koks K. C250 Lemmers J.M.J. C077 Koning M. C132 Lentjes E.G.W.M. C260 Konings C.J.A.M. C125 Levin M.D. O03, C096, C224 Kooistra M.P. C206 Libourel E.J. C017 Koole G. C003 Lichtveld M.Y. C213 Koolen D. C055 Liebman H. C248 Koop S.M.W. O01 Liem A.H. C249 Koopen A.M. C102 Limonard E.J. C060 Koopmans P.P. C167 Linden J. van der C024 Koorstra J.M. C172 Lindert A.S.R. van C122 Koot A.W.A. C021, C133 Lindert E.J. van C039 Koot R. C239 Links T.h.P. C055 Kootstra G.J. C142 Linn S.C. C211 Kort E.A. de C055 Linthorst C. C159

124 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Litjens E.J.R. C205 Modak A.S. O30 Loeffen R. C251 Moeniralam H.S. O28, C158 Loffeld R.J.L.F. C236, C237 Moerland P.D. C253 Logt A. van de C088 Molenaar P.C.M. C053 Logtenberg S.J.J. C022 Mols F. O07 Looij B.J. C038 Monreal M. C248 Loosveld O.J.L. C234 Mooi E.A.N.M. C090 Louter L. C063 Mooij C.E.M. de C085 Louwerens M. O30 Mooijaart S.P. O24, O29, O30, Lowe S.H. C137 C202 Lubbe N. van der C187 Morand P.C. C136 Lucke J.A. O24, O29, C202 Moris W. C087 Luiken G.P.M. O13 Moroni L. O22 Lunshof M.S. O16 Mos I.C.M. C247 Lutgens S.P.M. C166 Mudde A.H. C028, C046, C069 Lynen L. C065 Mulder A.A.W. C020 Maas M. C242 Mulder B. C148 Maat J. C173 Mulder D.J. C035, C252, Maat M.M.R. de C180 C256, C259 Maaten J.C. ter C016 Mulder F. C003 Maessen M.F.H. C075 Mulder L. C142 Magdelijns F.J.H. C004 Mutimer D. C143 Magro A. C116 Muus P. C097 Maier A.B. C224 Nanayakkara P. C003, C047 Maijer K.I. C242 Nap R.R.H. C207 Maijers I. C109 Nefs G. C036 Mairuhu A.T.A. C043 Netea M. O25 Mallolas J. C130 Nieboer D. C164 Man F. de C217 Nieuwenhuizen L. C117, C145 Manders I.G. C142 Nieuwlaat W.A.C.M. C219 Manenschijn L. C228 Nijhof A. C114 Mansour A.H. C248 Nijhoff M.F. C040 Maraveyas A. C248 Nijs J. C171 Marijnen C.A.M. O11 Nijziel M.R. C108 Mark M. van der C115 Nishino M. C248 Martinez-Rebollar M. C130 Noordzij M.J. C035 Masquiller H. C074 Noort A.R. C242 Mathijssen R.H.J. C217, C218 Norel A. van C146 Meer A.J. van der C063 O'Connell C. C248 Meer C. van der C262 Ockenburg S.L. van C053 Meer J.T.M. van der C167 Oerlemans S. O07 Meesters M. C114 Oever D. ten C083 Meeuwes F.O. C103 Ogilvie A.C. C223 Meijer W.G. C226 Oijen M. van C034 Meijers J.C.M. C253 Olgers T.J. C016 Meinardi M. C224 Olie R. C084 Meinders A.J. C151, C158 Olijhoek J.K. C109 Meis J.F. C178 Oo Y. C143 Melsen G.C. van C183 Oomen P.H.N. C035 Merken J.J. C127 Opdam F.L. O30 Messiaen P.E.A. C171 Opstal C.C.M. van C220 Meulen C.G. ter C020 Otten R. C121 Meulen N. van der C249 Oude Lashof A.M.L. C007, C137, C205 Meyer G. C248 Ouwehand A.J. C078 Michielsen P. C065 Ouwendijk R.J.T.h. C066, C124 Middeldorp S. C247 Overgaauw A.J.C. C156 Minderhoud I.M. C070 Paassen P. C125, C127, C209 Minnema M.C. O07, C117 Parving H.H. C023

125 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Pas R. van der C219 Richir M.C. O26, C082, C265, Peerbooms P.G.H. C174 C268 Peeters A. C007 Richter C. C133, C134, C167, C239 Peeters E.F.H.I. C122 Riedl J.A. C096 Peeters R.P. C045 Riel J.M.G.H. van C219 Peeters S.A. C023 Rier H.N. C224, O03 Pereira A.M. C040, C071 Rijke Y.B. de C105 Peters F. C064 Rijnders B.J.A. C167 Peters van Ton A.M. C131 Rijneveld A.W. C115, C217 Petersen J. C143 Rijnsburger E.R. C188 Pickkers P. O25 Rimmelzwaan G. O25 Piersma D. O06 Rinke de Wit T.F. C138 Pijl H. C044 Ritmeijer I. C036 Pijpers E. C004 Robbrecht D.G.J. C219 Pinto-Sietsma S.J. C253 Rodenburg R.J. C198 Piran F. C217 Roelandse-Koop E. C047 Planquette B. C248 Roelofs J.J.T.H. O08, C147 Plas L.M. van der C211 Roerdink H.T.J. C109 Platvoet-Sijtsma S.M. C006 Roerig B. C101 Pluim H.J. C012 Roerink S.H.P.P. C039 Pol L.M. van der C043, C132 Roest A.A. C007 Poll-Franse L.V. van de O07, C025, C026 Roeters van Lennep J.E. C257 Poll T. van der O08, C147 Rohde T.D. C193 Pop-Purceleanu M. C262 Rolfes L. O26 Popal S. C009 Rombach S.M. C188 Popma S.M. O12 Ronde M.W.J. de C253 Portillo A.K. C248 Rood I.M. C180 Portz M. C225 Roon E. van C034 Posthouwer D. C005, C141, C167 Roos E.W. de C255 Posthuma E.F.M. O11 Rooyen G.J. van C027 Postma N. C184 Rosmalen J.G.M. C053 Potjewijd J. C209 Rossing P. C023 Potter van Loon B.J. C032 Rothuizen T.C. O22 Pouwels M.J. C055 Rotmans J.I. O22 Pouwer F. C036 Roukens A.H.E. C071 Pradat P. C143 Rozendaal F.W. C189 Prins G. C089 Ruben T. C250 Prins J.B. C216, C220 Ruissen J. C195 Prins J.M. C128, C153, C161 Runge J.H. C060 Pruijt J.F.M. C238 Russcher H. C105 Puijenbroek E. van O26 Rustemeyer T. C019 Rabelink T.J. O22, C202 Rutgers J. O06 Radhakrishna G. C248 Salmon D. C136 Raemaekers J. C200 Samijn J.P.A. C192 Ramakers B.P. C009, C184 Sanders C. C122 Ramasamy S. C248 Santbergen B. C120 Ramdhani-Joosten A.A.J. C155 Schaar C.G. C159 Ramírez Bollero J. O15 Schalkwijk C.G. C023 Ramiro S. C244 Schepers L. C004 Raymakers R.A.P. O09 Schijns W. C041 Regelink J.C. C160 Schilder L. C223 Regt M.J.A. de C154 Schipper L.G. C239 Reijnders J.G.P. C143 Schipper M.E.I. C129 Rentenaar R.J. C154 Schippers E.F. C132 Rentinck M.E.M. C227, C104 Schippers J.A. C205 Reumerman M.O. O26 Schneider A.J. C268 Reyn-Gibson N.S. C243 Scholtes B.M.J. C225 Reyners A.K.L. C216

126 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Schop R.F.J. C063 Stehouwer C.D.A. C004, C007, Schot B.W. C100 C023 Schouten J.A. C178, C181 Stel H.V. C070 Schouten M. O08 Stienstra R. C058 Schouwenberg B.J.J.W. C262 Stiphout F. van C264 Schrama Y.C. C068 Stoekenbroek R.M. O18 Schrander - V.d. Meer A.M. C107 Stoffers J. C266 Schrijver K. de C171 Stokman R. O25 Schuit S.C.E. O13 Stolk R.F. C163 Schultz M.J. O08, C147 Stoppelaar S.F. de O08, C147 Schutgens R.E.G. O09, C254 Stouten K. C096 Schutte T. O26, C082, C265 Stradmeijer M.D. C203 Seijger C.G.W. C180 Susanto C.R. C118 Shamelian S. C056 Swinkels D.W. C084 Shinagare A.B. C248 Szabó A. C115 Shteinberg M. C248 Szymanski M.K. C017 Siegert C.E.H. C172, C210, C222, Tack C.J. O14 C223 Tak P.P. C242 Sigaloff K.C.E. C138 Tan Y. O19 Simsek S. C102 Tanck M.W. C060 Sint Nicolaas J. C067 Tarnow L. C023 Siwale M. C138 Tas S.W. C241, C242 Sjouke B. O18 Tazelaar C.E. C149 Slavenburg S. C174 Tegtmeier J. C007 Sleijfer S. C224, O03 Tellingen A. van C204 Slieker W.A.T. C102 The F.O. C062 Slobbe L. C233 Theunissen C. C171 Slot S. C083 Thiel S.W. van O16, C140, C176 Smets Y.F.C. C144 Thijs A. C006, C265 Smissaert van de Haere T. C083 Thijs M.F. C212 Smit A.J. C035, C252, Thijssen D.H.T. C075 C256, C259 Tichelaar J. O26, C082, C265, Smit J.W.A. C054 C268 Smits M. C027 Tick L.W. C111, C112 Smorenburg C.H. C211 Tiel F. van C137 Snackey C. C150 Tielgroenestege W.M. C029 Snel M. C043 Tilburg A.J.P. van C067 Soest E.M. van C129 Timmer-Bonte J.N.H. O23 Soethoudt Y.E.P. C149 Timmermans S.A.M.E.G C209 Soler S. C248 Timmermans W.M.C. C124 Sonnaville J.J.J. de C091 Tinteren H. van C211 Sonnborn C.M.Y. C168 Tiseo M. C248 Sonneveld P. C096, C115 Trienekens T. C168 Soomers V.L.M.N. C081 Tukker A.C. C188 Soonawala D. C165, C201 Tusscher B.L. ten C019 Sousa F. C148 Twist D.J.L. van C074, C245 Span L.F.R. C101 Ubels F.L. C058, C090 Spiering W. C254 Unen R.J. van C082, C268 Spil W.E. van C133 Valckx W.J.A.R.M C166 Spooren P.F.M.J. C027, C036 Valdivielso P. O15 Sprengers D. O13 Valk E.S. van der O16 Sprong T. C178 Valk H. van der C050 Stads S. C185 Valk H.W. de C033, C254 Stam F. C083, C102 Vanderschueren S. C171 Stassen P.M. C004, C005, Vanwolleghem T. C065 C007, C093 Vasmel W.L.E. C222 Steenbergen E. C200 Vastbinder M.B. C046 Steendam C.M.J. C122 Veeger N. C034

127 AUTHOR ABSTRACT NR AUTHOR ABSTRACT NR Veen M. van der C190 Vries T.h.P.G.M de C082, C265, C268 Veenstra J. C172 Vuren A.J. van C159, C190 Veer C. van ’t O08, C147 Vuuren A.S.J. van O02 Veggel K.M. van C260, C047 Waal M.W.M. de O30 Vegting I.L. C003 Wachelder J.J.H. C014 Velders G.A. C113 Wagenaar E.C.F. C139, C246, C140 Veldhuis-Vlug A.G. C060 Waizy E. C077, C081 Veldman B.A.J. C020 Wakelkamp I.M.M.J. O04 Veldt-Kok P. C240 Walenkamp A.M.E. C049 Vellenga E. C101 Walraven G. C178 Vellinga A.S. C235 Walter D. C106 Velsen E.F.S. van C031 Wedemeyer H. C143 Ven A.C. van de C039 Weerd E.C. de C197 Veneman T.h.F. C013, C148 Weerd N.C. van der C204 Verbaan B.W. C009 Weg C.A.M. van de C169 Verbeek E.M.E. C204 Weggheleire A. de C065 Verberk-Jonkers I.J.A.M. C089, C192, C195 Weijde E.M. van der C018 Verberne W.R. O20 Weijer B.A.M. de C037 Verhaegh P.L.M. C087 Wellington M. C138 Verhave J.C. C180, C200 Wessel H. C204 Verheggen R.J.H.M. C075 Westdorp H. C262 Verheijden N.A.F. C001, C119 Westerman M. C102, C222 Verhoef C.M. C243 Wetzels J. C200 Verhoeff S.R. C086, C238 Wezel T. C143 Versluis J. C110 Wiel H.E. van der C029 Vervoort S.C.J. C264 Wiel S.E. van der O17 Verwer P.E.B. C010 Wiemer E.A.C. C218 Villodres J.R. O15 Wijer L. van de C176 Vincenten Ì. C217 Wijngaarden P. van C119, C140 Vincken M. O12 Wijting I.E.A. C002 Vink E.E. C079, C159, C052 Willems H.P.J. C092 Visschers M. C205 Willems J.M.W.E. C118 Visser H. C130 Wilt H. de C238 Visser M.J.T. O22 Winter E.M. C051 Visser O. C115 Wintermans B.B. C177 Visser T.J. C045 Wismans P.J. C233 Vissers Y.L.J. C225 Wit A.S. de C218 Vloedbeld M. C078, C155 Wit H.M. de O14 Vlot E.A. O28 Wittenberg S.M. C226 Vogels S.C.M. C036 Woittiez A.J.J. C078 Vogtlander N. C052 Woudstra F.H. C162 Vonderen M.G.A. van C162 Wymenga A.N.M. C216, C220 Vooght K.M.K. de O09 Yozgatli K. C035 Vooren J. van C224 Yska J.P. C034 Vos K. C243 Ytredal H. C122, C154 Vos L.C. de C252, C259 Yu H. C250 Vos L.M. C136, C254 Zaane B. van O18 Vos L.P. C174 Zandbergen A.A. C255 Vossen M.H.E. O27 Zanders M.M.J. C025, C026 Vreeburg G.C.M. C009 Zeben D. van C129 Vreeburg M. C003 Zeebregts C.J. C252, C259 Vreugdenhil G. O07, C015 Zelm M.C. van C124 Vries H. de C100 Zoest K.P.M. van C242 Vries M. de C069 Zoulim F. C143 Vries M.A. de C249, O15 Zuidema M. C032 Vries P.J. de C070 Zuylen L. van C261 Vries T.B. de C155 Zwiers M. C256 Vries T.E.M.S. de C175 Zwietering N.A. C064

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