Rheumatoid arthritis, pyrexia of unknown origin (PUO) and pancytopenia.

A 61-yr-old previously fit lorry driver was referred by his general practitioner in October 1999 to an orthopaedic clinic with a 6-month history of painful hands, shoulders and feet. His general practitioner had treated him with ibuprofen without much improvement. He admitted to a recent history of loss of appetite with loss of two stones (12.7 kg) in weight. His joint pains had been increasing in severity with visible swelling of his fingers and knees. He had no relevant family history. He was an ex-smoker and drank little alcohol. Physical examination revealed a healthy-looking man with signs of synovitis in the symptomatic joints. The orthopaedic surgeon referred him to the rheumatologist (K.C.). The preliminary blood tests showed haemoglobin of 10.4 g/dl with normal haematocrit, leucocyte and platelet counts and normal serum vitamin B12 and red-cell folate levels. His serum ferritin was 468 g/l (normal range 18–400 g/l). He also had transient random hyperglycaemia, which was followed by a normal glucose tolerance test. His rheumatoid factor was elevated at 1:2560. His chest X-ray was normal except for some thickening of the bronchiolar wall. He was seen in the rheumatology clinic 2 months later, in December 1999, with classical symptoms and signs of a symmetrical inflammatory polyarthritis suggestive of rheumatoid disease. His knees were drained and injected with methyl prednisolone and local anaesthetic. He was also given intramuscular methyl prednisolone (120mg) to induce remission of active disease. Investigations revealed haemoglobin 10.3 g/dl, white cell count 6.4 10/l, platelet count 449 l0/l and ESR of 100mm in the first hour. The biochemical screens were all normal, including liver, renal and bone panels. The rheumatoid factor was 2460 IU (normal range 30 IU) and CRP was elevated at 85.1mg/dl (normal range <10mg/dl). The X-rays of his hands and feet showed no obvious erosions. The option of commencing methotrexate as a second-line drug was discussed but he preferred to wait until he returned from a planned Christmas holiday in Spain. Soon after his return from holiday he developed sudden severe cramp-like pains associated with numbness in his legs. He was virtually unable to walk. An MRI scan of his whole spine was done on the advice of the neurosurgeons, and, as the scans were normal, he was referred to the neurologists, who performed a lumbar puncture to exclude acute infective polyneuritis. The neurologists also noted a skin rash on his legs associated with left foot drop (Fig. 1). An autoimmune disease was suspected and the rheumatologist (K.C.) was consulted. On examination he had a vasculitic rash with peripheral neuropathy. There was no lymphadenopathy or organomegaly. Given the recent diagnosis of seropositive rheumatoid arthritis (RA), systemic rheumatoid vasculitis (SRV) seemed to be the most plausible diagnosis. Investigations at this time revealed haemoglobin 9.0 g/dl, white cell count 12.1 10/l and neutrophils 9.6 10/l with normal platelet and lymphocyte count. The ESR was 110mm in the first hour and CRP was 121mg/dl (normal range <5mg/dl). The biochemical, serological and microbiological screens including hepatitis A, B and C were all normal/negative. His anti nuclear antibodies, anti DNA antibodies, extractable nuclear antigens, anti cardiolipin antibodies, anti neutrophil cytoplasmic antibodies and cryoglobulins were all negative. Echocardiogram was normal. A cerebrospinal fluid study showed a mild increase in cerebrospinal fluid protein but no oligoclonal band or albumino-cytological dissociation. Electromyography showed severe sensorimotor polyneuropathy of the axonal type with some denervation changes in the peroneal muscles. A skin biopsy confirmed active necrotizing vasculitis, consistent with SRV (Fig. 2). He was commenced on pulse intravenous methyl prednisolone (500mg) and cyclophosphamide (500mg) with some symptomatic improvement, and was discharged home on a 2-weekly regime.