SELF ASSESSMENT ANSWERS Postgrad Med J: First Published As 10.1136/Pmj.77.907.347F on 1 May 2001

Postgrad Med J 2001;77:347–357 347

SELF ASSESSMENT ANSWERS Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from

An elderly woman with dyspnoea and bronchorrhoea Learning points x The incidence of bronchioloalveolar Q1: What is your diagnosis? carcinoma and lung adenocarcinoma Histological examination of a transbronchial have markedly increased in the last biopsy specimen revealed bronchioalveolar decade. carcinoma of mucinous type, with extensive x A non-resolving consolidative pneumonia, vascular invasion. despite correct treatment in an adult with normal immunity, must raise Q2: What other disorders may show a the suspicion of bronchioloalveolar diVuse alveolar pattern? carcinoma. DiVuse alveolar radiographic pattern may x Diagnosis of primary bronchioloalveolar develop either acutely or as a chronic process. carcinoma can only be made when other The major causes of both presentations are extrathoracic primary adenocarcinomas listed in box 1. have been excluded.

Q3: What are other causes of bronchorrhoea? Its distinctive pathological feature is growth DiVerent volumes of daily sputum have been along alveolar septae without distortion of pul- used to deﬁne excessive sputum production.1 monary interstitium. Three histopathological Some of its causes are depicted in box 2. Bron- subtypes have been described: mucinous, non- chorrhoea is usually accepted as the produc- mucinous, and sclerotic. tion of >100 ml/day of sputum. Prior pulmonary lesions, some professional exposures, cigarette smoking, and even a viral Discussion agent have been proposed as risk factors for Bronchioloalveolar carcinoma is one of the developing bronchioloalveolar carcinoma.3 four recognised subtypes of lung adenocarci- Males and females are equally aVected. noma. The dramatical increase in the incidence Patients may be asymptomatic in up to half of of lung adenocarcinoma in the last decade, cases. Clinical symptoms include cough, hae- being in some series the most frequent moptysis, chest pain, dyspnoea, and weight histological type among all lung malignancies,2 loss. Two characteristic features, both present seems to be mostly due to the raising incidence in the case under discussion, are large volume of bronchioloalveolar carcinoma. bronchorrhoea and refractory hypoxaemia caused by intrapulmonary shunting. Radiographic patterns include solitary nod- Box 1: Disorders associated with ules or masses, localised or diVuse consolida- diVuse alveolar pattern tion, and diVuse nodules.4 In diVerential diagno- http://pmj.bmj.com/ Acute sis, benign and malignant neoplasms (including x Pulmonary oedema. metastatic disease), lobar pneumonia, conges- x Pneumonia. tive heart failure, alveolar haemorrhage, and x Respiratory distress. alveolar proteinosis must be considered. Prog- x Aspiration. nosis is usually poor,5 and it has been correlated x Pulmonary haemorrhage. with the presence or absence of symptoms,

x Allergic bronchopulmonary aspergillosis. tumour extension, and histological type. on October 2, 2021 by guest. Protected copyright. x Leukaemic infiltrates. The clincal course of this patient was rapidly Chronic fatal, and she died on the 11th hospital day x Sarcoidosis. after two episodes of massive haemoptysis. x Tuberculosis. Necropsy confirmed the diagnosis and ex- x Fungal infections. cluded any other primary neoplasm. This was x Bronchioloalveolar carcinoma. an important finding, as several adenocarcino- x Lymphoma. mas may show pulmonary metastases with his- x Alveolar proteinosis. tological pictures indistinguishable from primary bronchioloalveolar carcinoma.6 Final diagnosis Box 2: Causes of excessive sputum Bronchioloalveolar carcinoma. production Postnasal drip syndrome. 1 Smyrnios NA, Irwin RS, Curley FJ. Chronic cough with a x history of excessive sputum production. Chest x Asthma. 1995;108:991–7. 2 Barsky SH, Cameron R, Osann KE, et al. Rising incidence x Gastroesophageal reflux disease. of bronchioloalveolar lung carcinoma and its unique x Bronchitis. clinicopathologic features. Cancer 1994;73:1163–70. Bronchiectasis. 3 Barkley JE, Green MR. Bronchioloalveolar carcinoma. J x Clin Oncol 1996;14:2377–86. x Left ventricular failure. 4 Hill CA. Bronchioloalveolar carcinoma: a review. Radiology DiVuse panbronchiolitis. 1984;150:15–20. x 5 Regnard JF, Santelmo N, Romdhani N, et al. Bronchioloal- x Bronchioloalveolar carcinoma. veolar lung carcinoma. Results of surgical treatment and prognostic factors. Chest 1998;114:45–50. x Cystic fibrosis. 6 Rosenblatt MB, Lisa JR, Collier F. Primary and metastatic bronchiolo-alveolar carcinoma. Dis Chest 1967;52:147–52.

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Unexplained weight loss and a palpable scarring. Follow up computed tomography abdominal mass in a middle aged woman showed thickened bowel loops in the right iliac Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from fossa with some calcification visible in the Q1: What does the barium enema study mesenteric nodes. She remains well 18 months (figs 1 and 2; p 341) show? after treatment. A small bowel study showed normal stomach and upper small bowel and a somewhat Discussion featureless terminal ileum. The caecum and Abdominal tuberculosis remains rare, and its right hemicolon appeared abnormal and a incidence over the last decade has remained barium enema was suggested. The barium stable despite variation in reported rates of enema (figs 1 and 2) shows classic radiographic pulmonary tuberculosis.2 It is more common in features of ileocaecal and colonic tuberculosis1 patients with AIDS. As with pulmonary tuber- confirming a diVusely abnormal terminal culosis most reported cases in the UK are ileum with a long stricture aVecting the immigrants. Our patient had never travelled caecum, ascending colon, and proximal por- outside the UK but may have been exposed to tion of the transverse colon with shortening of tuberculosis at the same time as her brother. these bowel segments. The left hemicolon Another possible source was her neighbours, appears normal. both recent immigrants, who were found through contact tracing to have active pulmo- Q2: What is the diVerential diagnosis and nary tuberculosis. what test should be performed to confirm Her chest radiograph was normal on two the diagnosis? occasions. Reports suggest that 20% of patients The main diVerential diagnosis is between ileo- with abdominal tuberculosis have coexistent colonic Crohn’s disease or tuberculosis. While pulmonary disease on chest radiography at an intestinal lymphoma or colonic malignancy presentation, but reported rates vary widely could produce similar radiological findings, the (6%–86%). Non-specific symptoms at presen- extent of the colonic involvement in a relatively tation are not unusual and a high index of sus- asymptomatic patient is against these. Other picion is required to make the diagnosis. In infections—for example, gastrointestinal addition to weight loss (66%), abdominal pain amoebiasis, actinomycosis or yersinia, though (85%), diarrhoea (20%), fever (35%–50%), rare, are possible causes. weakness, nausea, vomiting, melaena, or rectal The patient was further investigated with a bleeding may be presenting features. An colonoscopy. This revealed ulceration and nar- abdominal mass, usually in the right lower rowing at the level of the mid-transverse colon quadrant, is palpable in 25%–50% of patients.3 that could not be crossed. Biopsy samples were Investigations typically show a normal white taken both for standard histological assessment cell count. Mild anaemia is common with and for tuberculosis culture. Haematoxylin and inflammatory markers characteristically raised. eosin stains of the biopsy samples showed Abdominal ultrasound or computed tomogra- acutely inflamed granulation tissue but normal phy may confirm an abdominal mass or

underlying colonic mucosa with no evidence of enlarged lymph nodes but are often unhelpful http://pmj.bmj.com/ an underlying inflammatory bowel disease, in distinguishing the underlying cause. Lapar- infection or neoplastic process. Ziehl-Neelsen oscopy and biopsy can be helpful but are safer stains were negative for acid-fast bacilli; if ascites is present, reducing the risk of bowel however, three weeks following the colonos- perforation. copy a positive tuberculosis culture was Our case illustrates the value of colonoscopy, reported. Mycobacterium tuberculosis sensitive to biopsy, and culture in establishing the diagno- isaniazid, rifampicin, and ethambutol was sis. Classical caseating granulomas on routine grown. histology or Ziehl-Neelsen staining may give an on October 2, 2021 by guest. Protected copyright. immediate answer but may be negative. Fine Q3: What treatment would you initiate? needle aspiration cytology at colonoscopy may The treatment of Crohn’s disease and abdomi- improve the diagnostic yield when nodular nal tuberculosis diVer widely. Blind treatment lesions are seen.4 The major disadvantage with with steroids may lead to deterioration in a tuberculosis culture of biopsy samples is the patient with tuberculosis. Fortunately, our time taken to get the result. Because of this new patient had only mild symptoms allowing the “rapid culture” methods have been developed. delay of definitive treatment until the results of Approximately 85% of patients will have a tuberculosis culture were available. A nine positive purified protein derivative or Mantoux month course of standard antituberculous test, but a negative result does not exclude the treatment was started (rifampicin 450 mg diagnosis. Enzyme linked immunosorbent daily, isoniazid 300 mg daily, pyrazinamide 1.5 assay, soluble antigen fluorescent antibody, or g daily, and pyridoxine 10 mg daily) and was polymerase chain reaction based tests have tolerated without any side eVects. Her pyrazi- been developed but reduced specificity limits namide was stopped after two months. their routine use. The inflammatory markers fluctuated over Such extensive colonic involvement is unu- the next nine months but showed a general sual. The ileocaecal region is most commonly downward trend. Her weight increased pro- involved (75%). Involvement of the transverse gressively to 46 kg, parallelling her improved colon is less common.12The abnormality seen exercise tolerance and general clinical condi- on the initial barium meal investigation re- tion. A repeat colonoscopy to the caecum was mains unexplained. Oesophageal tuberculosis normal with no evidence of residual fibrous is very uncommon, but usually aVects the

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upper half of the oesophagus. It may present Low back pain in a child—a diagnostic with disruption of normal peristalsis secondary dilemma Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from to intramural thickening, though thickened mucosa or ulceration is usually visible on Q1: What is the diVerential diagnosis? endoscopic examination. Vertebra plana: diVerential diagnosis1: Pathologically three gross appearances of x Acute lymphoblastic leukaemia. intestinal tuberculosis are described; ulcerative, x Tuberculosis of the spine. hypertrophic, or ulcerohypertrophic, although x Metastasis from neuroblastoma. there is considerable overlap.3 Fibrous strictures x Hodgkin’s lymphoma. may develop. Mesenteric lymph nodes are often x Langerhan’s cell histiocytosis. involved and may calcify. Of the complications, intestinal obstruction is the most frequently Q2: What further investigations should be encountered (20% of cases). Massive gastro- performed? The further investigations that should be intestinal bleeding is less common. Perforation performed are a skeletal survey, bone scan, of the bowel or fistula formation also occur and bone marrow aspiration, and biopsy. are associated with a poorer prognosis. In this patient a skeletal survey showed The use of short course chemotherapy for radiographic features suggestive of diVuse abdominal tuberculosis has not been evaluated marrow or bone infiltration (figs 1A and B and in controlled trials but both six and nine month 2). Diagnosis was confirmed by bone marrow regimens are probably as eVective as they are in aspiration, biopsy of the ileum, periodic acid pulmonary disease. Success rates of 95% have staining by cytochemistry and detection of cell 2 been reported. Occasionally, when investiga- marker CD10. Bone marrow aspiration re- tions have failed to determine the underlying vealed a solidly cellular, hypercellular marrow diagnosis, the decision to treat with antituber- with a high nuclear to cytoplasmic ratio, a scant culous therapy is based on a high index of rim of basophilic cytoplasm without granules clinical suspicion alone. This can pose a and lacy chromatin without conspicuous nu- diYcult clinical dilemma, particularly as the cleoli. A biopsy specimen of the peripheral main diVerential diagnosis is Crohn’s disease, skeletal lesions showed a “streaming artefact” which may require treatment with steroids. in these patients.

Final diagnosis Q3: What is the treatment of this Abdominal tuberculosis. condition? Musculoskeletal pain does not respond to salicylate treatment, but improves rapidly with 1 Reeder MM, Palmer PES. Miscellaneous disorders of the chemotherapy. The chemotherapeutic regimen gastrointestinal tract: infections and infestations. In: Freeny PC, Stevenson GW, eds. Margulis & Burhenne’s alimentary includes induction therapy, consolidation tract radiology. 5th Ed. St Louis: Mosby, 1994: 889–95. therapy, and reinduction therapy using drugs 2 Dawson A. The respiratory system: pulmonary diseases aVecting the gastrointestinal system. In: Haubrich WS, like prednisolone, L-asparginase, vincristine, http://pmj.bmj.com/ SchaVner F and Back JE, eds. Bockus gastroenterology.5th and Adriamycin in combinations. Ed. Philadelphia: W B Saunders, 1995: 3404–6. 3 Marshall JB. Tuberculosis of the gastrointestinal tract and peritoneum. Am J Gastroenterol 1993;88:989–99. Discussion 4 Kochhar R, Rajwanshi A, Goenka MK, et al. Colonoscopic Leukaemia is a haematological disorder that ﬁne needle aspiration cytology in the diagnosis of ileocaecal tuberculosis by colonoscopy. Am J Gastroenterol 1991;86: initially may only cause complaints referable to 102–4. the musculoskeletal system and hence may mimic several orthopaedic conditions when the on October 2, 2021 by guest. Protected copyright.

Figure 1 (A) Plain AP radiograph of the skull and (B) plain lateral radiograph of the skull.

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chronic childhood diseases. Generalised metabolic dysfunction interfering with the Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from proper osteogenesis of the epiphyseal growth plate results in transverse zones of diminished density. (3) Periosteal bone formation—resulting from the lifting of the periosteum from the centre by the leukaemic infiltrate. (4) Osteolytic lesions—producing a “moth eaten” appearance common in the metaphysis of the long bones and flat bones. These lesions are predisposed to pathological fractures. (5) Osteosclerosis—in the metaphysis of long bones is mostly a late manifestation. (6) Mixed lesions—result from both osteoblas- tic and osteoclastic activity. (7) Permeative pattern—indicates an aggressive lesion with rapid growth. (8) Pathological fracture—in association with osteoporosis results in vertebra plana. In India and other Asian countries tubercu- Figure 2 Plain AP radiograph of the wrist. losis of the spine accounts for 50% of skeletal 5 patient is first seen. This association may lead tuberculosis. Lumbar spine involvement is the patient to seek orthopaedic treatment only second in common after lower dorsal initially. The orthopaedist, therefore, must rec- spine. A central type of involvement results in ognise the unusual patterns of presentation vertebral collapse and a vertebra plana-like that characterise leukaemia and maintain a picture. Usually, the disc space is reduced in high index of suspicion if the correct diagnosis association, which is a distinctive feature. is to be made promptly. Spinal tuberculosis is common both in children Radiographic abnormalities of leukaemia and adults and in support with the laboratory that develop at the time of presentation and investigations may precede as the most likely during the course of the disease are not always diagnosis over other local or systemic inflam- pathognomonic as they are seen in wide range matory conditions. of systemic disorders and chronic disease As the initial presentation of leukaemia com- states.2 The peak incidence of acute paediatric monly involves the musculoskeletal system, the clinician therefore must include acute leukaemia leukaemia occurs at approximately 4 years of in the diVerential diagnosis of any child with age with a secondary peak at 15–20 years of unexplained radiographic skeletal pathology. age. Boys are more often aVected than girls (1.44:1). Clinical manifestations that occur http://pmj.bmj.com/ Final diagnosis after a decrease in the production of normal Acute lymphoblastic leukaemia causing osteo- blood components include lethargy, pallor, penia. purpura, fever, hepatosplenomegaly, lymphadenopathy, and bleeding. The features suggestive of acute lympho- We thank the Dean, KEM Hospital and SethGSMedical Col- lege for granting us permission to use hospital data. blastic leukaemia are3: on October 2, 2021 by guest. Protected copyright. x Pain and swelling non-responsive to 1 Tachdjian MO. Paediatric orthopaedics. Vol 2. 2nd Ed. Phila- delphia: WB Saunders, 1990: 1281–4. salicylates. 2 Rogalsky RJ, Black GB, Reed MH. Orthopaedic manifesta- x Hepatosplenomegaly. tions of leukaemia in children. JBoneJointSurgAm 1986;68:494–501. x Severe anaemia. 3 Gallagher DJ, Phillips DJ, Heinrich SD. Orthopaedic mani- x Thrombocytopenia. festations of acute pediatric leukaemia. Orthop Clin North Am 1996;27:635–44. x Characteristic bony changes. 4 Heinrich SD, Gallagher D, Warrior R, et al. The prognostic significance of the skeletal manifestations of acute lympho- Skeletal lesions occur more often in children blastic leukaemia of childhood. J Pediatr Orthop 1994;14: most likely due to the eVect of cytokines. 105–11. 5 Tuli SM. Tuberculosis of the skeletal system. India: Jaypee Pub- Involvement of the skeleton has better progno- lishers, 1993: 136–9. sis but delay in diagnosis has adverse eVect on survival.4 Radiographic skeletal changes include: Atopy, proptosis, and nasal polyposis (1) Osteopenia—resulting from gradual and progressive generalised demineralisation Q1: What is the diagnosis? due to an alteration on protein and mineral The diagnosis is allergic fungal sinusitis. The metabolism or eVect of cytokines. A verte- diagnosis is based on the clinical features of bra plana is associated with severe oste- nasal polyposis and atopy, presence of allergic oporosis and necessitates an immediate mucin, characteristic computed tomography neurological evaluation.4 features of soft tissue masses interspersed with (2) Radiolucent metaphyseal bands—originally hyperdense areas filling the sinuses, typical his- described by Baty and Vogt and is a topathological appearance of allergic mucin, non-specific finding also seen in other and isolation of Aspergillus flavus on culture.

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Q2: What is allergic mucin? Allergic mucin is the sine qua non of allergic Learning points Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from fungal sinusitis. It appears as a cheesy or muci- x Allergic fungal sinusitis is a disease nous, brown, black, or dark green clump of caused by a type I and type III amorphous material interspersed with nasal hypersensitivity reaction to certain polyps. It may be seen either on direct nasal fungal antigens. examination or at endoscopy. Histological x There is no histological evidence of tissue examination of allergic mucin (fig 2; see p invasion by fungus; most authors believe 343) reveals eosinophilic or basophilic mucus that it is not an infection. with an infiltrate of cells which are chiefly eosi- x Allergic mucin interspersed with polyps is nophils and many of which are necrotic. The the characteristic clinical finding. cells are arranged in layers. Fungal hyphae, x Diagnosis is based on certain definite which are visualised by haematoxylin and eosin criteria (box 1). or special stains like Gomori-methenamine- x Appearance on computed tomography is silver, may be seen lying loose in the mucus. fairly typical. Charcot-Leyden crystals may also be seen. x Treatment is by surgical excision with adjunctive topical steroid; the use of oral Q3: What is the pathophysiology of the steroid and antifungal drugs is disease? recommended by some. Allergic fungal sinusitis is believed to be the result of Gell and Coombs type I and type III hypersensitivity reaction to a fungal antigen Fungal infections of the sinuses have been resulting in chronic inflammation and nasal classified as mycetoma, non-invasive and inva- polyposis.1 This is evidenced by the fact that sive fungal sinusitis.1 Unlike these conditions, these patients have relatively high eosinophil allergic fungal sinusitis is an entity which has counts, positive skin allergy tests, and raised been classified separately because it is not a total serum IgE levels. Serological evaluation true fungal infection. It is believed to be an by the radioallergosorbent test or enzyme allergic response to a fungal antigen. Histologi- linked immunosorbent assay also reveals raised cally, there is no tissue invasion. This is the case IgE and IgG levels to specific fungal antigens even in patients with clinical and radiological like aspergillus or certain dematiacious fungi in evidence of extensive disease. Patients with a high proportion of these patients.2 Histologi- allergic fungal sinusitis are not immunodefi- cal studies have shown that while there is fun- cient. Fungal culture isolates in these patients gal colonisation, there is no tissue invasion. include aspergillus species like A flavus or A fumigatus or dematiacious fungi like Curvu- Discussion laria, Alternaria,orExserophila species.4 These Allergic fungal sinusitis is a clinical entity fungi are ubiquitous in nature with a predilic- which was first described in 1983 by Katzen- tion for soil, plants, and damp areas. stein et al,3 drawing an analogy from allergic Diagnostic criteria for allergic fungal sinusi-

bronchopulmonary aspergillosis in which thick tis are presented in box 1. Some authors http://pmj.bmj.com/ mucus plugs, similar to those seen in the include the appearance of the computed tomo- sinuses of patients with allergic fungal sinusitis, gram as a diagnostic criterion.5 Soft tissue den- are seen in the bronchi. Patients with allergic sities involving the sinuses with hyperdense fungal sinusitis classically present with recur- areas representing allergic mucin, are the usual rent nasal polyposis, history of having had sev- features. Allergic mucin shows up as hyper- eral nasal surgeries in the past and a strong his- dense areas because of the high content of cal- tory of atopy. Unlike patients with simple nasal cium and magnesium salts within. Occasionally polyposis, these patients have allergic mucin areas of bone erosion or expansion causing on October 2, 2021 by guest. Protected copyright. interspersed with polyps. The presence of eosi- extension of disease to adjacent structures like nophilia, raised IgE levels and positive skin test the orbit and anterior and middle cranial fossa results to fungal antigens suggest an underlying may be present. In such cases, diVerentiation type I or IgE mediated hypersensitivity in these from malignancy is diYcult and correlation patients. Similarly, the presence of raised with clinical and intraoperative ﬁndings is fungal speciﬁc IgG antibody levels is indicative imperative. of an underlying type III hypersensitivity. The mainstay of treatment in allergic fungal sinusitis is surgical excision of polyps and allergic mucin and provision of aeration of the Box 1: Diagnostic features of allergic sinuses. This may be achieved by endoscopic fungal sinusitis sinus surgery or by open procedures like x Recurrent nasal polyposis. Caldwell-Luc or lateral rhinotomy approaches. x Presence of allergic mucin. Adjunctive steroid treatment given topically as x Typical histological features of allergic well as orally is recommended by most mucin including absence of tissue authors.1 3–6 Some authors recommend antifun- invasion by fungus. gal drugs like itraconazole also on the basis that x Positive fungal culture; aspergillus species there may be some element of infection, despite and dematiacious fungi usually isolated. the absence of tissue invasion.5 However, their x Presence of atopy as demonstrated by use is controversial. history, skin tests, or serology. x Immunocompetent patient. Final diagnosis Allergic fungal sinusitis with proptosis.

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1 Waxman JE, Spector JG, Sale SR, et al. Allergic aspergillus sinusitis: concepts in diagnosis and treatment of a new clini- Box 1: Drug associated QT Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from cal entity. Laryngoscope 1987;97:261–6. 2 Manning SC, Mabry RL, Schaefer SD, et al. Evidence of prolongation IgE mediated hypersensitivity in allergic fungal sinusitis. Laryngoscope 1993;103:717–21. Antiarrhythmics 3 Katzenstein AL, Sale S, Greenberger P. Allergic aspergillus • Quinidine sinusitis: a newly recognized form of sinusitis. J Allergy Clin Immunol 1983;72:89–93. • Procainamide 4 De Shazo RD, Swain RE. Diagnostic criteria for allergic • Disopyramide fungal sinusitis. J Allergy Clin Immunol 1995;96:24–35. 5 Corey JP, Delsulphe KG, Fergusson BJ. Allergic fungal • Amiodarone sinusitis: allergic, infectious or both? Otolaryngol Head Neck • Surg 1995;113:110–19. Sotalol 6 Kupferberg SB, Bent JP, Kuhn FA. Prognosis for allergic fungal sinusitis. Otolaryngol Head Neck Surg 1997;117:35– Antihistamines 41. • Astemizole • Terfenidine Antimalarials Recurrent syncope • Chloroquine • Quinine Q1: Describe the abnormal features on his 12 lead electrocardiogram Antibiotics The electrocardiogram (ECG; see p 344) • Erythromycin shows marked QT prolongation, U waves, and • Clarithromycin premature ventricular complexes. • Co-trimoxazole The QT interval is measured from the earli- • Ketoconazole est QRS deﬂection to the end of the T wave Psychiatric drugs and increases with slower heart rates. It should • Amitryptiline therefore be corrected for heart rate (QTc) by • Lithium dividing the measured QT interval by the • Chlorpromazine square root of the RR interval. The maximum • Haloperidol QTc in this case is 0.72 seconds with normal • Thioridazine values for males and females being 0.46 sec and 0.47 sec respectively.1 Miscellaneous U waves distort the terminal aspect of the T • Terodiline wave (ﬁg 1) and are thought to represent early • Cisapride after-depolarisations (see below).

Q2: What is the diagnosis and what are the causes of this condition? in abnormal ventricular repolarisation.2 Indi- The diagnosis is long QT syndrome. viduals have also been identiﬁed with genetic QT prolongation can be divided into ac- mutations that may be insuYcient to cause QT 2 quired and congenital forms. prolongation on the ECG but increase the

arrhythmogenic susceptibility to drug treat- http://pmj.bmj.com/ (1) ACQUIRED ment. x Bradycardia from any cause including atrioventricular block, hypothyroidism, and Q3: What classical arrhythmia is hypothermia. associated with this condition? x Ischaemic heart disease. Torsade de pointes. x Electrolyte abnormalities including This is a polymorphic ventricular tachycar- hypokalaemia, hypomagnesaemia, and dia, at rates of 200 to 250 beats/min character- hypocalcaemia. ised by a QRS complex that changes in ampli- on October 2, 2021 by guest. Protected copyright. 34 x Drug therapy (see box 1). tude and has an axis that twists around the xStarvation/anorexia nervosa. isoelectric line.1 Onset of the arrhythmia is x Subarachnoid haemorrhage. typically preceded by a pause which may be due to sinus arrhythmia, sinus arrest, or more (2) CONGENITAL commonly after a premature ventricular com- Two familial forms of QT prolongation are the plex.2 The pause may result in early after- Romano-Ward (autosomal dominant with nor- depolarisations (U waves) in the next sinus mal hearing) and Jervell-Lange-Neilsen (auto- beat, which if of suYcient amplitude, can somal recessive with deafness) syndromes. A depolarise the cell and initiate the tachycardia. number of genetic mutations have been identi- Episodes are usually non-sustained and may ﬁed involving the HERG (potassium channel) present with palpitations or syncope but there and SCN50 (sodium channel) genes resulting is a risk of sudden death from degeneration into ventricular ﬁbrillation. The relationship V4 between degree of QT prolongation and risk of serious arrhythmia is unpredictable and at- tempts to assess risk by electrophysiological testing are unrewarding. Women appear to be at increased risk from QT prolongation particularly when caused by drug treatment.3 Poor prognostic risk factors in patients with con- Figure 1 U waves (arrows) resulting in a distorted T genital QT prolongation include symptoms wave. during infancy, deafness, a history of cardiac

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arrest, failure of â-blocker therapy, and a QTc therapeutic option.1 It must be stressed that the longer than 0.5 sec.2 literature advocating conservative interven- Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from tions are small and no randomised controlled Q4: How would you treat this man? trials have been performed. Accepting these The main aim of treatment in long QT caveats and after appropriate counselling a syndrome is to identify and correct any revers- patient may undergo cone biopsy and pelvic ible cause. This includes correction of electro- lymphadenectomy (either performed via the lyte abnormalities and discontinuing any pre- laparoscope or at open surgery) or radical tra- cipitating drugs.5 This man had drug induced chelectomy and pelvic lymphadenectomy.2 QT prolongation having been prescribed chloroquine and astemizole. Both drugs were Q2: What are the guidelines in the discontinued and he underwent temporary investigation of menorrhagia in a women atrial pacing, at rates of 90–100 beats/min, under 40 years? which can be life saving by reducing the QT A history should be taken, abdominal and pel- 2 interval and preventing an arrhythmia. Perma- vic examination performed, and a full blood nent pacing may of course be necessary if there count obtained in all women presenting with a is underlying atrioventricular block. Intra- history suggestive of menorrhagia. Tests for venous magnesium, while having little eVect on thyroid function and bleeding disorders should the QT interval, is highly eVective at suppress- be performed only if clinically indicated.3 If the ing recurrent torsade de pointes, even if the 5 menorrhagia persists despite evidence based plasma level is normal. As episodes of medical therapy then endometrial assessment tachycardia can be induced by physical and is indicated.4 This should be by transvaginal emotional stress sedation should be consid- scan and endometrial biopsy. Hysteroscopy ered. In the acquired forms of this disorder, may also be considered. once the underlying cause has been treated the QT interval returns to normal and long term Q3: What further course of management treatment is usually not required. should be recommended for this patient? In the case of the congenital long QT This patient should be referred to the clinical syndromes, however, long term treatment with geneticists for advice regarding her potential â-blockers is indicated often in conjunction risk of developing breast and colonic cancers.5 with permanent pacing. An implantable car- Furthermore she should be o ered entry into dioverter deﬁbrillator may be necessary when V symptoms recur despite combination therapy any trial where genes for human non-polyposis and following survival from cardiac arrest.2 colorectal cancer are being studied. Breast and Screening of relatives is mandatory. gastrointestinal tract surveillance should be oVered. Final diagnosis Drug induced long QT syndrome. Discussion The occurrence of metachronous cancers in an 6

individual is well recognised. However the http://pmj.bmj.com/ 1 Zipes DP. Speciﬁc arrhythmias: diagnosis and treatment In: Braunwald E, ed. Textbook of cardiovascular medicine. occurrence of three diVerent gynaecological Philadelphia: W B Saunders, 1992: 667–725. primaries in a premenopausal women within 2 Viskin S. Long QT syndromes and torsade de pointes. Lan- cet 1999;354:1625–33. three years is a unique clinical occurrence. 3 Roden DM. A practical approach to torsade de pointes. Clin This case serves as a salutary reminder that Cardiol 1997;20: 285–90. 4 Doig JC. Drug-induced cardiac arrhythmias. Incidence, in patients who develop cervical malignancies prevention and management. Drug Safety 1997;17:265–75. of the genital tract, the possibility of a new pri- 5 Napolitano C, Priori SG, Schwartz PJ. Torsade de pointes. Mechanisms and management. Drugs 1994;47:51–65. mary carcinoma must be considered in addition to possible recurrence of the original on October 2, 2021 by guest. Protected copyright. tumour. These patients are at greater risk than Sequential occurrence within three years the normal population for the development of a 7 in a premenopausal woman of cervical, new primary carcinoma. ovarian, and endometrial cancers The incidence of invasive carcinoma of the cervix in women aged 25–34 has increased8 Q1: What is the management of a 1B and with this the challenge of tailoring surgery squamous cervical carcinoma in a patient to preserving fertility. Burghardt et al,ina who wishes to preserve fertility? series of 16 patients with small volume, stage Standard practice for the management of 1B disease reported no recurrence of disease patients with cervical 1B carcinoma is either after ﬁve years after treatment with cone biopsy radical hysterectomy and bilateral pelvic lym- or simple hysterectomy.1 More recently, Shep- phadenopathy for small volume disease (<4 cm herd et al, described radical trachelectomy with diameter) or radiotherapy for large volume dis- pelvic lymphadenectomy as a surgical option ease. The initial step at laparotomy is to assess for preserving fertility potential in early stage the pelvic lymph nodes and to send for frozen cervical carcinoma.2 section any that are thought to be “suspicious”. Our patient had early, small volume disease If the pelvic lymph nodes are shown to be and although technically had stage 1B disease involved with disease, surgery is abandoned was managed as having stage 1A1 disease. and radiotherapy instituted. In patients who Nevertheless, the subsequent histological re- wish to preserve their fertility and have small ports of her uterus, cervix, para-aortic and pel- volume stage 1B disease then there is increas- vic lymph nodes after her surgery for her ovar- ing evidence that conservative surgery may be a ian and endometrial cancers found this

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management to have been successful in treat- ing her cervical disease. The question arises Learning points Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from therefore—is it absolutely necessary to add x Incidence of invasive carcinoma of the pelvic lymphadenectomy after cone biopsy for cervix in women of childbearing potential stage 1B small volume disease? is increasing. In view of the increased predisposition to x After conservative surgery for cancer, new developing a new malignancy, the initial symptoms must be regarded with a high laparotomy for the ovarian cyst should have index of suspicion as occurring from been a staging laparotomy despite a normal CA another possible primary. 125 and reassuring scan. Furthermore because x Guidelines are only guidelines and a low of this increased predisposition to a further threshold for implementing them must be malignancy, the preferred option would have employed in patients with a previous his- been referral to a gynaecological oncological tory of carcinoma. centre, following the recommendations of the x In patients with a previous history of NHS Executive.9 gynaecological malignancy and present- This patient’s personal and family history is ing with a new symptom referable to the strongly suggestive of hereditary non-polyposis genital tract early referral to the regional colorectal cancer (HNPCC). People from gynaecological centre should be em- families fulﬁlling criteria for HNPCC have a ployed. 50% risk of being a gene carrier and a 30% sex x Referral to clinical geneticists is prudent average life time risk of developing colorectal so that risk regarding other systems can cancer. In addition they have an excess risk of be calculated and appropriate manage- developing other cancers, namely endometrial ment employed. (40%), ovarian (10%), and gastric (20%) and other tumours where the risk is lower.5 There is class B evidence for implementing biannual colonoscopy as a screening tool to recognises a previous history of genital tract improve survival in these HNPCC families. In neoplasm as a risk factor. We argue therefore addition it would be prudent to perform that this is an oversight and that in a woman endoscopy at the same time. Unfortunately, with a history of a previous gynaecological there are morbidity and mortality risks associ- malignancy, an endometrial biopsy should be ated with colonoscopy and therefore in an ideal performed as part of the initial investigation of world, gene testing should be employed to menorrhagia regardless of age. identify those carriers of the gene in whom tar- geting of colonoscopy could be implemented. 1 Burghardt E, Girardi F, Lahousen M, et al. Microinvasive Although the gene has been mapped, this carcinoma of the uterine cervix (International Federation of test is only available in some centres on the Gynecology and Obstetrics stage 1A). Cancer 1991;67:1037–45. NHS. Families of HNPCC patients must 2 Shepherd JH, Crawford RAF, Oram DH. Radical therefore be counselled accordingly regarding trachelectomy: a way to preserve fertility in the treatment of

the probabilities of being a carrier of the early cervical cancer. Br J Obstet Gynaecol 1998;105:912–16. http://pmj.bmj.com/ 3 Royal College of Obstetricians and Gynaecologists. The ini- HNPCC gene and the risks and beneﬁts of tial management of menorrhagia—evidence-based clinical guide- gastrointestinal tract surveillance. lines No 1. Guideline summary. London: RCOC, 1998. 4 Royal College of Obstetricians and Gynaecologists. The In this patient’s case ulcerative colitis also management of menorrhagia in secondary care—evidence-based predisposes to colorectal cancer. If there had clinical guidelines No 5. Guideline summary. London: RCOC, been no personal or family history of bowel 1999. 5 Dunlop M, Campbell H. Screening for people with a family pathology the patient would have been at risk history of colorectal cancer: Target invasive screening to of a gastrointestinal tract primary on the basis younger people with truly high risk. BMJ 1997;314:1779–80.

6 Swaroop VS, Winawer SJ, Lightdale CJ, et al. Six primary on October 2, 2021 by guest. Protected copyright. of her endometrial and ovarian cancer and cancers in individuals. Report of four cases. Cancer 1988;61: would have been oVered gastrointestinal tract 1253–4. surveillance, although she would have been at 7 Kleinerman RA, Boice JD Jr, Storm HH, et al. Second primary cancer after treatment for cervical cancer. An less risk than if she had the HNPCC mutation. international cancer registries study. Cancer 1995;76:442–52. In addition to gastrointestinal tract surveil- 8 Cancer Research Campaign. Cervical cancer screening. Factsheet 13.1. London: CRC, 1994. lance the patient should also be oVered entry 9 NHS Executive. Guidance on commissioning cancer services into the breast screening programme. Again improving outcomes in gynaecological cancers. The manual. the exact risk is not known. Wetherby: NHS Executive, Department of Health, July 1999. 10 Gynaecology Audit Project in Scotland II. Endometrial sam- Finally, this case highlights the fact that pling and D&C feedback report. June 1996. (Project initiated guidelines are precisely that—guidelines. The by the Scottish Executive Committee of the RCOG and funded by CRAG. Copies are available from Dr Gillian Royal College of Obstetricians and Gynaecolo- Penny, Scottish Programme for Clinical EVectiveness in gists in their evidence based clinical guidelines Reproductive Health, Room 64, Aberdeen Maternity suggest that an endometrial biopsy is not nec- Hospital, Foresterhill, Aberdeen.) essary in the initial management of menorrhagia.34 The Gynaecology Audit Project in Scotland II are more stringent in their An 80 year old woman with intermittent recommendations by suggesting an age cut oV severe vomiting of 40 years before endometrial sampling should be routinely employed.10 Although both bodies Q1: What does the chest radiograph acknowledge that endometrial evaluation is show? warranted in a subgroup of women for whom The chest radiograph (see p 345) shows a the risk of endometrial cancer is greater than large hiatus hernia extending behind the heart that of the general population, neither body and into both lung ﬁelds.

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Q2: What investigation is shown in fig 2 diaphragm resulting in weakness, which ulti- and what does it demonstrate? How does mately allows the stomach to pass into the tho- Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from this relate to the presenting complaint? rax alongside the original sliding hernia, thus Figure 2 (see p 345) is a single film from a forming a mixed hernia. barium meal series. The film demonstrates a Giant hiatal hernias occur almost exclusively partial rolling volvulus of the stomach. This is in the elderly and are associated with a number typically an intermittent phenomenon and of presentations including postprandial chest when present results in profuse vomiting espe- pain, symptomatic reflux, dysphagia, vomiting, cially after eating. haematemesis, iron deficient anaemia, dyspnoea caused by lung displacement, and Q3: How else can this condition present? aspiration pneumonia.14 Strangulation may Small hiatus hernia rarely cause symptoms occur following gastric volvulus and is sug- other than reflux which can usually be control- gested by severe chest and epigastric pain asso- led medically, but giant hiatal hernias, where ciated with persistent vomiting. The rate of the majority of the stomach is intrathoracic as occurrence of strangulation is controversial but shown here, can present in a number of ways,1 an early series showed six cases in 21 patients including: with giant hiatal hernias treated conserva- 5 x Severe reflux, retching, postprandial pain, tively. Physical signs are rarely helpful in mak- bloating, and dysphagia due to mechanical ing the diagnosis, although bowel sounds may pressure from the herniated stomach. be heard high in the chest and basal breath sounds can be reduced due to upward x Haematemesis and iron deficiency anaemia 1 from a “riding ulcer” formed by mechanical displacement of the lungs. A chest radiograph ulceration and mucosal ischaemia as the may show the stomach as an extramediastinal stomach passes through the diaphragm.2 shadow or there may be an air fluid level behind the heart. Diagnosis is usually con- x Dyspnoea and aspiration pneumonia due to firmed by barium swallow or with fibreoptic the loss of lung volume and high frequency endoscopy. of reflux with aspiration. Surgery is thought to be the best management x Severe epigastric or retrosternal pain with option, as medical therapy does not alter the risk vomiting and fever are features of hernia of strangulation or resolve the mechanical strangulation. displacement of the stomach that accounts for many of the symptoms.14Despite these benefits Q4: How should this woman be managed? surgery had been controversial as many patients Management of this condition is predomi- were elderly, but the introduction of laparoscopy nantly surgical. Until recently the decision to has revolutionised the treatment of giant hiatal operate has been controversial, as patients are hernias and has resulted in an increased number usually elderly and therefore the operative risks of procedures being performed.3 are high. However the condition responds poorly to conservative medical therapy and Final diagnosis

recent improvements in laparoscopic surgery Giant intrathoracic hiatus hernia. http://pmj.bmj.com/ techniques have led to an increase in the number of surgical procedures performed.3 This woman underwent laparoscopic repair of 1 Hashemi M, Sillin L, Peters J. Current concepts in the management of paraoesophageal hiatal hernias. J Clin Gastroen- her hernia with a successful outcome. terol 1999;29:8–13. 2 Cameron AJ. Linear gastric erosion: a lesion associated with large diaphragmatic hernia and chronic blood loss anaemia. Discussion Gastroenterology 1986;91:338–42. Hiatal hernias occur commonly with some 3 Watson DI, Devitt PG, Jamieson GG. The changing face of treatment for hiatus hernia and gastro-oesophageal reflux. prevalence estimates suggesting that 15% of Gut 1999;45:791–2. on October 2, 2021 by guest. Protected copyright. the population may be aVected.1 Most hernias 4 Maziak DE, Todd TR, Pearson FG. Massive hiatus hernia: evaluation and surgical management. J Thorac Cardiovasc are small and are either asymptomatic or asso- Surg 1998;115:53–60. ciated solely with reflux. However, in a small 5 Skinner DB, Belsey RH. Surgical management of esopha- geal reflux and hiatus hernia. Long term results with 1030 proportion of hernias the diaphragmatic defect patients. J Thorac Cardiovasc Surg 1967;53:33–54. is large enough to allow the majority of the stomach to enter the thoracic cavity forming a “giant hiatus hernia” or intrathoracic stom- Pleuropericardial eVusion in a 50 year old ach.1 Hiatal hernias are classified according to woman their mechanism of development into sliding, paraoesophageal, and mixed. Approximately Q1: What are the common causes of 85% of hiatal hernias are of the sliding type pleuropericardial eVusion? with simple upward migration of the gastro- The combination of fever and pleuropericar- oesophageal junction into the mediastinum. dial eVusion is an unusual presenting feature Giant hiatal hernias have traditionally been and raises the possibility of infectious, neoplas- thought to be of the paraoesophageal type, tic and connective tissue disorders. The most where part of the stomach passes through a frequent causes are listed in table 1. defect in the diaphragm adjacent to the oesophagus. However recent evidence suggests Q2: What further investigations are that most hernias, regardless of size, originate necessary in this patient’s case? as the sliding type.4 It is postulated that a “giant Investigations should be directed at determin- hiatus hernia” forms when an existing sliding ing the cause and will initially involve haemato- hernia exerts pressure on tissue around the logical tests including: full blood count, urea

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and electrolytes, liver and thyroid function, Table 2 Criteria for the diagnosis of adult onset Still’s inflammatory markers (ESR or C reactive pro- disease Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from tein), antinuclear antibody (with DNA and The diagnosis requires the presence all of the following: extractable nuclear antigen screen if positive), Fever >39°C antineutrophil cytoplasmic antibody (ANCA), Arthralgia or arthritis Rheumatoid factor <1:80 rheumatoid factor, and serology for viruses and Antinuclear antibody <1:100 other infective causes. Analysis of the pericar- In addition to any two of the following: dial and/or pleural fluid will nearly always be White cell count >15 000 cells/ml Still’s rash necessary and should include culture for Pleuritis or pericarditis bacteria and mycobacteria, protein and glucose Hepatomegaly or splenomegaly or generalised concentrations, diVerential cell count, and lymphadenopathy cytology. Pleural or pericardial biopsy might be indicated if malignancy or tuberculosis is experienced aching and swelling of both wrists suspected. Specific tumour markers might be despite continued aspirin and was started on helpful in detecting occult malignancy. In this hydroxychloroquine 200 mg twice daily. Reas- patient’s case thyroid function and other liver sessment one year after diagnosis showed no function tests were normal, rheumatoid factor, serological or clinical evidence of an evolving antinuclear factor, and ANCA were negative connective tissue disease, supporting the diag- and serology did not suggest recent bacterial or nosis of AOSD. viral infection by any of the common respiratory pathogens. Cytological and microbiologi- Discussion cal analysis of the pericardial and pleural fluid AOSD is a rare disorder typically aVecting did not show any evidence of infection or young adults between the ages of 16 and 35 malignancy. The pleural fluid contained small with equal sex distribution. The diagnosis rests on the combination of typical clinical and lymphocytes and neutrophils with total protein laboratory findings and diagnostic criteria have 41 g/l. Abdominal ultrasound was used to been developed by Cush (table 2).1 Three fea- exclude ovarian carcinoma and other malig- tures (fever, rash, and arthralgia) are common nancies. at presentation.2 A daily spiking fever of 39°C or more is seen in 97% of cases. Eighty eight Q3: The patient’s symptoms and per cent of cases have a characteristic rash, the radiology returned to normal after so-called “Still’s” rash, which is pink, macular treatment with aspirin 3.6 g daily. What is or maculopapular, and evanescent. It usually the likely diagnosis? occurs on the trunk and proximal extremities Pleuropericardial eVusion in the context of a and may coincide with a fever spike. Arthralgia history of joint symptoms together with fever is universal and most develop a predominantly and negative investigations for connective distal polyarthritis. Pharyngitis, splenomegaly, tissue disorders, malignancy, and infection lymphadenopathy, cardiopulmonary involve- suggested a diagnosis of adult onset Still’s dis- ment, and hepatomegaly are sometimes seen.

ease (AOSD). This is a diagnosis of exclusion Not all the eventual symptoms and signs may http://pmj.bmj.com/ and in clinical practice care should be taken to be apparent at presentation and the condition continue to look for signs of the more common can evolve over a period of weeks or months. causes such as rheumatoid arthritis or systemic The consistent laboratory findings are anae- lupus erythematosus. mia, high ESR, leucocytosis, and deranged liver function tests. A negative rheumatoid factor Outcome and antinuclear antibody are required for the Once AOSD was suspected the patient was diagnosis to be made. Infection, malignancy, started on 3.6 g of aspirin daily in divided and other connective tissue diseases may give a on October 2, 2021 by guest. Protected copyright. doses. Within three days systemic symptoms similar clinical picture and investigations and pyrexia were beginning to settle and she should be directed at excluding these as possi- was discharged. At review three weeks later her ble causes. Additionally when there are any cough had disappeared, joint pains had settled, atypical features, such as the age of this patient, and chest radiography showed partial resolu- it is essential to review the diagnosis after some tion of the eVusions. Eight weeks later the eVu- months to rule out evolving connective tissue sions were no longer seen, ESR was 13 disorders. mm/hour, and haemoglobin 133 g/l. She Pulmonary involvement in AOSD is re- remained well for five months when she ported in the largest series to occur in 20%–30% of cases.2–6 Pleuritis leading to pleu- V Table 1 Causes of pleuropericardial e usion risy and/or pleural eVusions is the commonest Infection Viruses (influenza, cytomegalovirus, coxsackie), bacteria pulmonary manifestation. EVusions are usually (klebsiella, legionella, listeria) mycobacteria, fungi bilateral and the pleural fluid is an exudate with (actinomycosis) increased numbers of inflammatory cells par- Malignancy Carcinoma, lymphoma, leukaemia, Kaposi’s sarcoma ticularly neutrophils. Pneumonitis occurs in Connective tissue disorders (CTD) Rheumatoid arthritis, systemic lupus erythematosus, about 10% of cases giving rise to chest mixed CTD and other systemic vasculitides, adult onset Still’s disease radiograph opacities. Pulmonary function tests Cardiac causes Post-cardiac injury syndrome, constrictive pericarditis generally show a mild restrictive picture and Drugs Methotrexate, mesalazine, tretinoin, tryptophan gas transfer may be reduced. The commonest Metabolic and endocrine Uraemia, hypothyroidism, hypoparathyroidism cardiac manifestation of AOSD is pericarditis and pericardial e usion, seen in 26%–28% of Sarcoidosis V cases7 and usually occurs with pleural eVusion.

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Tamponade occurs in 1%–2% of cases. Rarer responded completely to NSAIDs we feel this cardiac findings are myocarditis (5%) and is the likely diagnosis. She was unusual in her Postgrad Med J: first published as 10.1136/pmj.77.907.347f on 1 May 2001. Downloaded from endocarditis. late age of presentation and this increased the The treatment of choice is a salicylate, importance of excluding malignancy. The usually aspirin, in high dose and this may be absence of a Still’s rash and the relatively minor combined with another non-steroidal anti- articular involvement are associated with a bet- inflammatory drug (NSAID) if there is no ter prognosis.3 Response to NSAID treatment response to a single agent. Altogether 20%– is also associated with a favourable outcome. 25% of patients respond to NSAIDs alone. Awareness of the condition is important when Systemic corticosteroids can be used if symp- investigating patients with pleural and pericar- toms fail to improve with these measures and dial eVusions particularly when these occur prompt remission is typical. Disease modifying together. antirheumatic drugs may be required particularly if joint symptoms persist as was the case in Final diagnosis this instance and intramuscular gold, penicilla- Pleuropericardial eVusion caused by adult mine, sulfasalazine, and hydroxychloroquine onset Still’s disease. have been used. Methotrexate may be useful if systemic features are present.7 The majority of patients can expect prolonged or permanent 1 Cush JJ, Medsger TA, Christy WC, et al. Adult-onset Still’s remission, however, intermittent relapses or disease. Clinical course and outcome. Arthritis Rheum 1987;30:186–94. chronic disease course does occur in 30%–50% 2 Esdaile JM, Tannenbaum H, Hawkins D. Adult Still’s of cases. During follow up it is necessary to disease. Am J Med 1980;68:825–30. 3 Pouchot J, Sampalis JS, Beaudet F, et al. Adult Still’s check rheumatoid factor and antinuclear anti- disease: manifestations, disease course, and outcome in 62 bodies regularly to ensure that the presenting patients. Medicine (Baltimore) 1991;70:118–36. illness is not an early presentation of another 4 Ohta A, Yamaguchi M, Kaneoka H, et al. Adult Still’s disease: review of 228 cases from the literature. J Rheumatol connective tissue disorder. 1987;14:1139–46. This case fulfils the diagnostic criteria for 5 Liote H, Liote F, Lenique F, et al. Adult-onset Still’s disease revealed by pleuropericarditis. Eur Respir J 1990;3:1064–6. AOSD except for the finding that the leucocy- 6 Yamaguchi M, Ohta A, Tsunematsu T, et al. Preliminary tosis was slightly below that stipulated by criteria for classification of adult Still’s disease. J Rheumatol 1992;19:424–30. Cush. As alternative diagnoses were sought 7 Esdaile JM. Adult Still’s disease. In: Klippel JH, Dieppe PA, thoroughly but not found and the patient eds. Rheumatology. 2nd Ed. Mosby, 1998: 5.21.1–8. http://pmj.bmj.com/ on October 2, 2021 by guest. Protected copyright.