i54 September 2018 CASE REPORTS

nephritis. The presence of Fabry-like cytoplasmic inclusions was also 82. NOT JUST ANOTHER HYPERMOBILE PATIENT: NOONAN noted on the biopsy, although chloroquine toxicity was considered as a SYNDROME DIAGNOSED IN LATE ADULTHOOD IN THE differential. Fabry disease was confirmed by a low alpha-galactosidase CLINIC level and genetic testing revealed a heterozygote novel missense muta- Fang En Sin1 and Hanadi Kazkaz1 tionintheGLAgene.ShewasdiagnosedwithSLEandmanagedwithpre- 1Rheumatology, University College Hospital, London, UNITED dnisolone, azathioprine and . In 2010 she developed KINGDOM widespread lymphadenopathy, neutropenia, night sweats and fevers, and a fine needle aspirate of the lymph nodes demonstrated a reactive Introduction: We present a case of Noonan syndrome, which was diag- picture. Azathioprine was stopped due to the significant neutropenia. nosed for the first time in a lady at the age of 50. She was referred to rheu- Therewassomeinitialimprovementinneutrophilcountfollowingincreas- matology for assessment of , but was noted to have an ing her steroid dose suggesting an autoimmune aetiology of her neutro- unusual facies which triggered genetic testing. This case highlights the penia, although ANA was negative at this time. She intermittently suffers importance of comprehensive systems review and thorough clinical from , sweats and fevers, weight loss and lymphadenopathy. examinationinpatientswithhypermobility. Subsequent ANA has been positive (up to 1:320 dilution) and further Case description: A 50 year-old lady was referred for assessment of a immunological testing supports the diagnosis of SLE with Anti-Ro, Anti- possible hereditary disease following a colonoscopy C1q and dsDNA being present and C3 and C4 complement levels inter- whichfoundexcessiveloopinginhercolon.Shehasknownhypermobility mittently low. anticoagulant is positive but anticardiolipinantibod- withassociatedbiomechanicalpain,diagnosedinanotherrheumatology ies are negative. In 2012 she developed chest pain on exertion. Resting unit in the past. She worked full time, was single and had no children. She ECG showed T wave inversion in lateral chest leads, I and aVL. A cardiac was very active and held a black belt in kickboxing. However in the past MRI showed extreme myocardial oedema and she underwent a left ven- five years, she had presented with multiple symptoms, culminating in 40 tricular biopsy which did not demonstrate any inflammatory cell infiltra- clinic appointments with eight medical and surgical specialties, physio- tion, complement or immunoglobulin deposition. In view of her SLE therapy and podiatry, as well as several emergency department attend- background she was managed as lupus myocarditis by increasing her ances. Systemic enquiry revealed a multitude of symptoms including prednisolonedose.Furtherimmunosuppressantswerenotadministered widespread musculoskeletal pain, constipation, thickened skin on her due to her persistently low neutrophil count (0.2) However, questions soles and easy bruising. Past medical history include convergent squint, remain regarding whether the Fabry disease may be the underlying narrow angle glaucoma, two corrective surgeries for ptosis aged 5 and cause. A repeat cardiac MRI showed ongoing myocardial oedema with 30, dilated pulmonary artery and pulmonary regurgitation and multiple apical hypertrophic change with T2 enhancement suggesting Fabry dis- trauma-relatedfractures.Onexamination,shewasnotedtohaveunusual ease.Ophthalmologyreviewconfirmedbilateralinferiorepiscleralmicro- facial features including ptosis, low set ears, thin eyebrows, thick curly aneurysms consistent with Fabry disease. In 2013, she had a significant hair and a short neck. She had a normal body mass index and a height of flare of her renal disease and repeat biopsy showed active Class III and 167cm. She was hypermobile with a Beighton score of 6/9 and marked Class V nephritis. Segmental sclerosing lesions were seen within the glo- flexibilityofthesmalljointsofthehands.Therewasamildscoliosisandan meruli which would be in keeping with either previous active lupus but abnormally shaped chest wall. She had low archedfeet with ankle prona- also Anderson-Fabry disease given the presence of Fabry-type inclu- tion on standing and mild lymphoedema. She had high arched palate, sions in swollen protocytes. On two separate occasions in 2017, she extensible skin but no abnormal scars. Large bruises were noted on her developed infected hair follicles alongside significant neutropenia. legs. The initial clinical impression was that ofa possible genetic collagen Following antibiotic therapy with GCSF she then developed a severe disorder, including rare forms of Ehlers Danlos syndrome. Genetic thrombocytopenia andwhichresponded well toIVIg and she wasstarted screening was arranged, which revealed an SOS1 mutation in keeping on mycophenolate mofetil (MMF). She currently remains stable on MMF withNoonansyndrome. from a renal, haematological and cardiac perspective and has not Discussion: Noonan syndrome is an autosomal dominant disorder with requiredanyenzymereplacementtherapy. a prevalence of 1 in 1000 to 1 in 2500. Its clinical presentation changes Discussion:Fabrydiseaseismulti-systemicandsharescommonsymp- with age. The musculoskeletal system can be affected, with features of toms with autoimmune rheumatic diseases, for example fatigue (62%) small joint hypermobility and scoliosis. Our patient has a mild form of andneuropathicpain(77%).Theco-existenceofFabrydiseaseandlupus Noonan syndrome, which was only diagnosed at the age of 50. Yet, she nephritis histology on renal biopsy has previously been reported. It has exhibitedtypicalclinicalfeaturesofNoonansyndrome,includingunusual alsobeenshownthatthereisanincreaseinthrombotictendencyinFabry facial appearance, small joint hypermobility, cardiac malformation, easy patients (12%). Autoantibodies are commonly seen inFabry disease. In a bruising, lymphoedema and ophthalmic manifestations. A number of cohortofArgentinianFabrydiseasepatients,57%patientsshowedreac- these seemingly unrelated conditions, some of which may appear trivial tion to at least one autoantibody (extractable nuclear antigen, double- in isolation, had been managed as single entities by a wide variety of stranded DNA, anticardiolipin or phosphatidylserine) with 45% patients health care professionals. Her unusual facial and musculoskeletal having detectable anti-phospholipid antibodies. However, it is not clear appearance, coupled by the collection of systemic manifestations, led to how often these autoantibodies correlate with clinical sequelae specific genetic testing and a unifying diagnosis. For the patient, this diagnosis to the connective tissue disease, rather than Fabry’s, as they appear to in was extremely important. She had always felt that she looked different, both our described cases. The high rateof prior misdiagnosis as rheuma- andnowsheknewwhy. tological disease, may in reality reflect a high rate of co-morbidity with Key Learning Points: This case highlights the importance of careful and connective tissue disease. The abnormally deposited lipid products may thorough clinical examination in all patients. In this case, the detection of act as an antigen to trigger the development of autoimmunity. subtle but unusual physical appearance led to a suspicion and eventually Autoimmune diseases must therefore always be considered when a diagnosis of a genetic disorder. Non-inflammatory, biomechanical reviewingpatientswithFabrydisease.Bothpatientsalsohighlightthedif- musculoskeletal symptoms form a large proportion of new patient case- ficulty of distinguishing Fabry pathology from on load in the general rheumatology clinic. Hypermobility, with or without biopsy. Myocyte enlargement due to perinuclear vacuolation and sarco- associated musculoskeletal pain, is also increasingly recognised, plasmic myelinoid bodies can be seen in ventricular biopsies of both reflected in increased referrals for its assessment to Rheumatology clin- Fabry disease or chloroquine toxicity. The presence of curvilinear bodies ics.Itisimportantforrheumatologisttobeawareofthefactthathypermo- may help to distinguish cases of chloroquine toxicity. Fabry disease was bility can be a feature of genetic disorders other than the commonly diagnosed quickly in patient B because of the characteristic findings on known Ehlers Danlos syndrome and . Having an open kidneybiopsy,however,patientApresentedwithFabrydiseaseaffecting mind, and taking into account patients’ symptoms which may not imme- the heart which is less easily accessible to biopsy and subsequently her diately appearrelevanttotheproblemathandcan behelpfulinjoiningthe diagnosiswasdelayedbyfiveyears. dots. Having a physician who is able to look at the whole picture, and pro- Key Learning Points: Fabry disease and autoimmune rheumatic dis- vide a unifying explanation for their collection of ill-health, can be an ease can co-exist and auto-antibodies are commonly found. Symptoms extremelypositiveexperienceforthepatient. usually start in adolescence with intermittent acroparasthesiae, angio- Disclosure:F.Sin:None.H.Kazkaz:None. keratomas, corneal opacity, hypohidrosis, heat, cold and exercise intol- erance,proteinuria,andgastrointestinaldisturbance. 83. ASYMPTOMATIC CARDIAC ARRHYTHMIA IN SYSTEMIC End-stage renal failure, severe cardiac or cerebrovascular disease are SCLEROSIS late manifestations of disease. Fabry disease is X-linked meaning females often present later with a milder phenotype. Enzyme replace- Fatemah Baron1, Rajneet Singh1, and Bernadette Lynch1 menttherapyisavailablebutreliesonearlydiagnosis. 1Rheumatology, Galway University Hospital, Galway, IRELAND Disclosure:J.Hannah:None.S.Sangle:None.D.D’Cruz:None. Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by microangiopathy and excessive cutaneous and CASE REPORTS September 2018 i55

visceral fibrosis. Internationally, systemic sclerosis is estimated to occur 84. EOSINOPHILIC in 3 to 10 people per one million. Two main variants which are widely rec- Janardhana Golla1 and Emma J. Robinson2 ognised are limited cutaneous systemic sclerosis (lcSSc) in which skin 1 sclerosis is limited to distal extremities and diffuse cutaneous systemic Rheumatology, NHS Tayside, Dundee, UNITED KINGDOM, and 2Gastroenterology, NHS Tayside, Dundee, UNITED KINGDOM sclerosis (dcSSc) which involves sclerosis of skin proximally. Systemic sclerosis can present with protean manifestations and can cause signifi- Introduction:Eosinophilic fasciitis is a rare disorder ofunknown etiology cant organ dysfunction. Cardiac involvement in SSc can virtually effects and pathogenesis characterised by symmetrical erythema and oedema any structure and when symptomatic, it predicts a poor prognosis. Here, of extremities in early phase, followed by collagenous thickening of the we describe a case of 37 year old male with established diagnosis of dif- subcutaneous in the later stage. It was first described in 1974 by fuse systemic sclerosis who presented with asymptomatic Shulman (known as Shulman syndrome) in two men with a - tachyarrhythmia. like disease of the extremities associated with and hyper- Casedescription:37yearmalewith15packyearhistory ofsmoking and gammaglobulinaemia. It was later named as eosinophilic fasciitis by a background of hypertension, presented to rheumatology clinic with Rodnan et.al based on striking histological features showing inflamma- generalised without any other features of CTD or inflammatory tion of fascia between the subcutis and the muscle. Eosinophilic fasciitis arthritis.Examinationwasunremarkableandlaboratoryworkuprevealed predominantly affects forearms and spare fingers. Absence of mildly positive anti-SCL 70 antibody around 14 (normal <7) by ELISA. On Raynaud’sandvisceralmanifestationsareincontrastwithscleroderma. follow-upreview,clinicalexaminationwasconsistentwithsclerodactyly, Case description: A 57-year-old busdriver was admittedto acute medi- calcinosis and Raynaud’s phenomenon. Repeat antibody screen cal admissions for the third time over a three-month period with gradually showed positive antinuclear antibodies (ANA) > 1280, anti- extracted progressive painful, swollen extremities. His legs were painful and heavy nuclear antibodies (ENA) >34.0 and anti- SCL 70 was significantly raised when hewasonholidayinFranceandhaddone alotofcycling. Heinitially with level of 240 byELISA. He was started on hydroxychloroquine 400mg noticed pain and swelling of his legs (calves) and ankles. The pain and daily andnifidipine20mgTDS.Overasix monthperiod,the patient devel- tightness progressed tothe extent thathe had difficulty in climbing stairs. oped diffuse skin thickening with modified Rodnan skin score (MRSS) of He also had intermittent wrist and bilateral hip pain with sparing of other 21/51. He also described history of intermittent , dyspnoea joints. He developed painful, tight forearms two months after his leg andworseningofRaynaud’sphenomenonassociatedwithdigitalulcera- symptoms.Hehadanitchy, nodularrash withplaques onhis backfortwo tion. Pulmonary function tests showed restrictive pattern with FVC of years. His other symptoms included night sweats, weight loss, fatigue 66%, FEV1 of 66% and FEV1/FVC- 82% with reduced DLCO of 56 per- and dry cough. His past medical history included endoscopic nasal poly- cent. Barium swallow showed severe oesophageal reflux to mid thorax pectomy four months prior to his symptoms and recent onset testicular and dilated oesophagus. Oesophageal gastroscopy (OGD) was consis- pain with ultrasound showing bilateral varicoceles. He stopped smoking tent with lower oesophageal ulcer and gastritis. His medications were 25 years prior to his presentation and drank 24 units of alcohol a week. optimisedandhewascommencedonprotonpumpinhibitorandazathio- Therewasfamilyhistoryofcoloniccancer(father),throatcancer(mother), prine.Patientwasfurtheradmittedforilioprostinfusiontotreatactivedigi- lung cancer and Charcot Marie tooth disease (sister). His bowel cancer tal ulcers and worsening Raynaud’s phenomenon. During routine screening colonoscopy has shown haemorrhoids and diverticular dis- observations, he was found to have tachycardia, electrocardiogram ease. On examination he had swollen, erythematous forearms and legs (ECG) showed atrial flutter at a rate of 150 bpm with troponin T and with indurated skin. His proximal leg muscle power was slightly reduced proBNP measurements of - 137ng/L (0- 14ng/L) and 3019 ng/L (0 - 86 ng/ secondary to pain. Systemic examination was normal. His blood counts L) respectively. Patient denied any chest pain, palpitations or orthop- showed eosinophilia (1.9 x 10^9 /L) with an elevated CRP (42) and a low noea.Subsequently,hedevelopedsupraventricular tachycardia (SVT)at albumin of 26. His eosinophils and CRP were mildly elevated in the nine rate of 200 bpm, he was normotensive and asymptomatic. months prior to his reported symptom onset. His liver function tests, uri- Pharmacological cardioversion failed and patient continued to have nalysisandechocardiogramwerenormal.CTchest,abdomenandpelvis intermittent atrial flutters with SVT and underwent two unsuccessful DC was unremarkable. His ANCA, ANA, ENA and rheumatoid factor were cardioversions. Echocardiogram was consistent with severe ventricular negative with normal complements and negative Borrelia antibody impairment, EF of 40%, and extensive posterior, basal and mid inferior screen.AtotalIgEwaswithinnormalrangewithnegativeAspergillusanti- wall akinesia with no evidence of valvular heart disease. Estimated PASP body. Viral hepatitis and HIV tests were negative. Immunoglobulins was 25mmhg. Coronary angiogram and right heart catheterisationsh- showed normal IgGand IgAwith alow IgM witha normal electrophoresis. owednormalcoronarystructureandnoevidenceofpulmonaryhyperten- MRI forearms showed extensive subcutaneous oedema with contrast sion. Cardiac MRI with gadolinium contrast showed multiple pattern enhancement of intermuscular and compartmental fascia consistent fibrosiswithsignificantbi-ventricularimpairmentduetomyocardialfibro- withafloridfasciitis.Afullthicknessforearmbiopsyshowedthickeningof sis and global myocardial oedema with LVEF of 33% and RVEF of 24%. subcutaneousfasciawithintenseperivascularinfiltrationoflymphocytes MRI findings were suggestive of cardiac scleroderma. The patient was with a very occasional eosinophil. He was initially treated with NSAIDs commenced on anti-arrhythmic, sotalol, and life-long anticoagulation, andnoticedverylimitedimprovementinhissymptoms.Hewaslatercom- apixiban.Patientwasdischargedhomeinviewtohaveimplantablecardi- menced on prednisolone 40mg daily after the forearm biopsy was taken. overter defibrillator (ICD) for primary prevention of ventricular arrhythmia There was significant improvement in his symptoms with steroids. He and sudden death in setting of severe cardiomyopathy and he is plan fur- was commenced on methotrexate and prednisolone dose was tapered. therforintravenouscyclophosphamide. He had recurrence of pain and swelling when the prednisolone dose was Discussion: Cardiac involvement in systemic sclerosis can be mani- less than 20mg. We increased the methotrexate dose to 25mg weekly fested as a direct myocardial, pericardial or conduction system abnor- and theprednisolone wastapered moreslowly. Wemanaged towean his malities and majority of these patients may remain subclinical. The prednisolonegraduallyto10mgdailyoverninemonthswithoutanyrecur- estimated clinical prevalence is about 15-35% . Furthermore, sudden renceofsymptoms.HislasteosinophilcountandCRPwerewithinnormal cardiac death (SCD) is reported in 5-21% of patients with SSc. The litera- limits. ture specific to cardiac scleroderma and strategies on screening and Discussion: This previously fit and healthy gentleman had presented on diagnosing,unlikepulmonaryhypertensionandinterstitiallungdiseaseis three occasions with worsening painful swelling of his limbs. His initial sparse. We present this case to contribute to the experience of diagnos- investigations including urinalysis, liver function tests and echocardio- ingandmanagingcardiaccomplicationsinSSc.Tosuccessfullymanage gram were aimed at looking for a cause of peripheral oedema and low cardiacscleroderma,itrequiresacarefulscreening,ahighindexofsuspi- albumin. Due to uncertainty of diagnosis a number of immunology and cion and a multidisciplinary approach. Anti-arrhythmic therapy is the other blood tests were performed. He was referred after his third admis- mainstay of management with the use of pacemaker and ICD in more sionwhentheaboveinvestigationsfailedtoyieldadiagnosis.Evenaftera severe life threatening arrhythmias. To the best of our knowledge, no careful history and clinical examination in the rheumatology outpatient randomized controlled trials have compared efficacy of anti-arrhythmic clinic Eosinophilic fasciitis was not on our initial list of differentials. We ini- drugs to treat conduction abnormalities in SSc cohort. Thus, medication tiallyalsopursuedapossibleparaneoplasticmyositis.Itwasonlyafterhis selectionistailoredtotheindividualpatientandthetypeofarrhythmia. forearm MRI was reported as showing fasciitis that we began to consider Key Learning Points: Sudden death could happen in up to 20% of SSc Eosinophilic fasciitis. Unlike other reported cases in the literature he did patients, therefore it is important to screen SSc population for cardiac not have a hypergammaglobulinaemia. His initial marked improvement involvement. Greater awareness of SSc manifestations and complica- with high dose steroids was encouraging, but unfortunately this was not tions should necessitate risk stratification. Further research is required sustained once the steroid dose was tapered. It has been challenging to whichmayallowfocusedguidanceforearlydiagnosingandmonitoringof manage his disease given the relapsing symptoms with the initial steroid thesepatientswithcardiacinvolvement. wean. Subsequent changes to his steroid sparing DMARDs have been Disclosure:F.Baron:None. successful and we are now nearly at a point that we can stop steroids