Annals ofthe Rheumatic Diseases 1990; 49: 547-548 547 Concurrent onset of adult onset Still's disease and Ann Rheum Dis: first published as 10.1136/ard.49.7.547 on 1 July 1990. Downloaded from insulin dependent diabetes mellitus J T Sibley Abstract time, partial thromboplastin time, C3, C4, Clq Within two weeks after symptoms of an upper binding, tri-iodothyronine, thyroxine, serum respiratory tract infection a 32 year old man amylase, serum protein electrophoresis, and developed Still's disease and insulin dependent gallium scan. diabetes mellitus, both ofwhich have persisted Initial and convalescent serum rubella titres for 24 months. Investigations failed to confirm (haemagglutination inhibition) were both 1/640. acute infection but did show isolated persistent Hepatic transaminases were five times normal. increase of serum antibodies to rubelia virus. Abdominal ultrasound confirmed splenomegaly The simultaneous onset of these two diseases and showed decreased echogenicity of the suggests a shared cause, possibly associated pancreas. An abdominal computed tomography with rubella infection. scan was normal except for hepatosplenomegaly. Percutaneous liver biopsy showed only minor focal portal tract inflammation. A two dimen- Adult onset Still's disease is an uncommon sional echocardiogram showed a small peri- entity characterised by a multisystem illness cardial effusion. HLA typing results were with a wide constellation of features, notably A2,-;B44,5 1 ;Cw2,-;DR1,7. fever, rash, and arthritis.' Its cause is unknown, The diagnosis of adult onset Still's disease though there are a few reports of association was based on the typical clinical features, with viral illness.2A Insulin dependent diabetes including the characteristic evanescent rash and mellitus is also thought in some cases to have a daily fever in the absence ofclinical or laboratory viral cause,5 but I am unaware of any reports of confirmation of other diagnostic possibilities.' 6 the simultaneous onset of these two diseases. Despite diclofenac 150 mg/day and paracetamol Such a case is described here and the possible 3250 mg/day he continued to have daily spiking aetiological implications discussed. fever up to 39-2°C. Initially, unexpectedly large amounts of insulin, up to 117 units daily, were Case report necessary, but after two weeks' treatment the http://ard.bmj.com/ A 32 year old man, who had previously been fever subsided and insulin requirements entirely well, presented with malaise and sore declined. He was eventually discharged from throat. In the preceding two weeks his wife and hospital asymptomatic but still requiring 22 2 year old child had had similar symptoms, units of insulin daily to control hyperglycaemia which had resolved spontaneously. Despite oral and ketosis. antibiotics and diclofenac the patient's One month later he developed monoarthritis symptoms persisted and over the next four of a knee, his first joint symptom. Viral and on September 24, 2021 by guest. Protected copyright. weeks he developed fever, chills, nocturnal bacterial cultures of the synovial fluid were sweats, myalgia, evanescent rash, polyuria, and negative. Diclofenac was restarted but within a 12 kg weight loss, prompting referral to a two months he had profound persistent poly- rheumatologist. arthritis unresponsive to non-steroidal anti- Examination showed fever (39°C), faint ery- inflammatory drugs, auranofm and metho- thematous truncal rash, splenomegaly, proxi- trexate. Radiographs were initially normal but mal limb soft tissue tenderness, and marked nine months later showed joint space narrowing muscle wasting and weakness. There was no of wrists, hips, knees, and ankles with sparing evidence of joint disease. Initial investigations of fingers and toes. He now has ankylosis of the showed a normochromic, normocytic anaemia wrists. After 24 months of polyarthritis he (112 g/l), leucocytosis (16 2x109 cells/I), remains rheumatoid factor negative and insulin thrombocytosis (455 x 109 cells/I), an erythrocyte requirements are unchanged at 22 units daily. sedimentation rate of 120 mm/h, hyperglycaemia (22 1 mmol/l), and 4+ ketonuria. He was admitted to hospital and treatment started with Discussion synthetic human insulin, diclofenac, and This patient's illness fulfils recently proposed paracetamol. criteria for establishing the diagnosis of adult The following investigations in hospital were onset Still's disease.6 His illness started with a Rheumatic Disease Unit, University of normal or negative: all cultures (six blood, two constellation of features typical of the disease- Saskatchewan, stool, two urine, one sputum): viral serology notably, evanescent rash and daily fever, and Saskatoon, (including mumps, Coxsackie virus B1-6, cyto- after two years of follow up no other diagnosis Saskatchewan, Canada S7N OXO megalovirus, Epstein-Barr virus, and hepatitis has evolved. Although a diagnosis of sero- J T Sibley A and B), antinuclear factor, rheumatoid factor, negative arthritis might be considered, the Accepted for publication lupus erythematosus cells, anti-DNA, Venereal pattern of joint involvement and ankylosing of 15 August 1989 Disease Research Laboratory test, prothrombin wrists is quite characteristic of Still's disease.78 548 Sibley Although it is possible that adult onset Still's tract infection. Acute viral infection could not disease and diabetes mellitus are unrelated in be confirmed, but the titres of rubella antibody this patient, the concurrent onset of both were four- to eightfold higher than those Ann Rheum Dis: first published as 10.1136/ard.49.7.547 on 1 July 1990. Downloaded from diseases is striking and mere coincidence seems normally seen in our laboratory and this increase unlikely. Might one disease cause the other? I seems to be an isolated phenomenon rather than am unaware of any reports or proposed mechan- simply a non-specific response to inflammatory isms of diabetes mellitus causing adult onset disease. In this case possibly the initial sample Still's disease. Conversely, it is possible that the for viral serology, drawn approximately 40 days hypermetabolic state associated with Still's after the onset of symptoms, was obtained too disease might lead to secondary hyperglycaemia. late to detect an initial rise in antibody titres. This mechanism may well account for the Similar non-diagnostic increases of rubella anti- unexpectedly high insulin requirements seen body titres have been reported in Still's disease early in this patient's course but does not by others. "1 account for the diabetes mellitus itself because Thus in this patient with concurrent onset of insulin is now still required to control ketosis Still's disease and insulin dependent diabetes and hyperglycaemia despite resolution of all mellitus the concept of a single agent, possibly symptoms of adult onset Still's disease other viral, possibly rubella, inciting both diseases is than the polyarthritis. tantalising. That specific aetiological agent, if it Thus in this patient adult onset Still's disease exists, remains to be confirmed, however. and insulin dependent diabetes mellitus may share a common cause. If so, then what factor(s) Supported by the Arthritis Society of Canada. may be involved? Although little is known of the cause of either disease, the concept of host 1 Bywaters E G L. Still's disease in the adult. Ann Rheuwn susceptibility genes has been proposed in both. Dhs 1971; 30: 121-33. This patient is HLA-D7 positive and an 2 Huang S H K, DeCoteau W E. Adult onset Still's disease: an unusual presentation of rubella infection: Can Med Assoc increased prevalence of this allele has been 1980; 122: 1275-6. reported in Still's disease9 but not in insulin 3 Grahamne R, Simmons N A, Wilton J M A, Armstrong R, Mims C A, Laurent R. Isolation of rubella virus from dependent diabetes mellitus. It has been sug- synovial fluid in five cases of seronegative arthritis. Lancet gested that the pathogenesis of adult onset 1981; ii: 649-51. 4 Wouters J M G W, van der Veen J, van de Putte L B A, de Still's disease may entail immune complex Rooij D R A M. Adult onset Still's disease and viral vasculitis,'0 but this mechanism would be un- infections. Ann Rhewn Dis 1988; 47: 764-7. 5 Maclaren N K. Viral and immunological bases of beta cell likely to account for diabetes mellitus. Further- failure in insulin dependent diabetes. AmJ Dis Child 1977; more, neither immune complexes nor evidence 131: 1149-54. 6 Reginato A J, Schumacher H R Jr, Baker D G, O'Connor of complement consumption was found. C R, Ferreiros J. Adult onset Still's disease: experience in Viral infection, though, has been associated 23 patients and literature review with emphasis on organ failure. Semin Arthritis Rheum 1987; 17: 39-57. with both adult onset Still's disease and insulin 7 Medsger T A, Christy W C. Carpal arthritis with ankylosis dependent diabetes mellitus and may have in late onset Still's disease. Arthritis Rheum 1976; 19: 232-42. 8 Wouters J M G W, van de Putte L B A. Adult onset Still's http://ard.bmj.com/ played a part in this patient. Preceding rubella disease; clinical and laboratory features, treatment and infection has been reported in a few patients prognosis of 45 cases. QJ Med 1986; 235: 1055-65. 9 Miller M L, Aaron S, Jackson J, et al. HLA gene frequencies with Still's disease,24 and several viruses, in children and adults with systemic onset juvenile rheuma- particularly rubella, mumps, and Coxsackie B, toid arthritis. Arthritis Rheum 1985; 28: 146-50. 10 ELkon K B, Hughes G R V, Bywaters E G L, et al. Adult have been incriminated in some cases of insulin onset Still's disease: twenty-year follow-up and further dependent diabetes mellitus.5 The patient in studies of patients with active disease. Arthritis Rheum 1982; this report, his wife, and 2 year old child all had 25: 647-54. 11 Harth M, Thompson J M, Ralph E D.