A man with intermittent fever and arthralgia.

Case report A 44 year old, previously healthy, white man, who was a milk depot manager, was referred to a general physician in November 1991 with a 16 month history of febrile episodes, lasting for three or four days, which recurred approximately every six weeks. During the episodes his temperature rose to 40°C, he felt flu-like and had aching limbs and profuse night sweats. He had no other symptoms of note and in particular no rash, no weight loss, no joint swelling, and no gastrointestinal or genitourinary symptoms. There was a family history of thyroid disease. He smoked 15–20 cigarettes a day. He had been on holiday to Tunisia in 1987, the Greek islands in 1990 and Portugal in 1991. He weighed 81.2 kg. No abnormalities were found on examination. Initial investigations focused on screening for infection. Full blood count, erythrocyte sedimentation rate, renal function, liver function, thyroid function, chest radiography, and computed tomography of the abdomen were normal. Blood cultures were negative, as were a Mantoux test and early morning urine analysis for tuberculosis. He also had negative serology for syphilis, brucella, toxoplasma, and leptospirosis. In May 1992 the febrile episodes became more frequent and he was referred for a second opinion to an infectious diseases unit. The differential diagnosis included an occult infection and a connective disease. An infection screen was again negative. Rheumatoid factor, antinucleur antibodies, and ds-DNA antibodies were negative and immunoglobulin concentrations were normal. It was suggested that he might have adult onset Still’s disease. In November 1992 he was referred and admitted to a teaching hospital rheumatology unit for further investigation of his intermittent fevers and arthralgia. The arthralgia aVected predominantly the left knee and shoulder. Examination was again normal with no rash, no lymphadenopathy and no synovitis. The differential diagnosis included occult infection, a malignancy (in particular a lymphoproliferative malignancy), inflammatory bowel disease, and a connective disease. Table 1 shows the indications and the results of his investigations. The working diagnosis remained adult onset Still’s disease and he was treated with indomethacin. In April 1993 he was given prednisolone 10 mg daily because his joint symptoms were becoming more prominent, and he had some pleuritic chest pain although he still had no documented synovitis. Three months later his symptoms were no better and methotrexate was added. By September 1993 his fevers had largely settled but he began to complain of back pain. His modified Schober’s index was 6 cm. By July 1994 he had begun to experience joint swelling as well as pain. He had documented synovitis of a number of small joints including the right wrist. There were no other new symptoms. He was taking prednisolone 5 mg daily (which he increased to 15 mg when he experienced fevers) and methotrexate 12.5 mg weekly. His erythrocyte sedimentation rate was 56 mm 1st h. In October 1994 he lost his job and subsequently became depressed, requiring treatment with dothiepin. During 1995 he was referred to another rheumatologist in a nearby town for a further opinion but the diagnosis was not changed. He was then referred back to the original hospital for follow up in the newly established rheumatology department. He had synovitis of several