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Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent self-limiting attacks of joint, chest and abdominal pain associated with fever. The most serious complication in FMF is the development of amyloidosis, which usually leads to death from renal failure within a year. The use of colchicine has dramatically reduced this complication. We describe a 56-yr-old female patient with FMF in whom the arthropathy became the dominant clinical feature, resulting in the development of an erosive large and small joint arthritis during the course of the disease. The patient was treated with colchicine, but despite this, later developed amyloidosis confirmed on rectal biopsy, and chlorambucil was added to her treatment. For 10 yr, she also suffered intermittent abdominal pain and had terminal ileal changes suggestive of Crohn's disease. However, she was found to have ischaemic colitis at post mortem secondary to amyloidosis. Ischaemic bowel disease is an extremely unusual event in FMF. Other factors which may have contributed to the terminal ischaemia in this patient include anaemia secondary to blood loss and a drug-induced myelodysplasia, as well as hypotension during the final septicaemic illness. Clinicians should consider an ischaemic colitis as a possible differential diagnosis of abdominal pain in patients with FMF even in the absence of other clinical evidence of systemic amyloidosis.

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An unequivocal diagnosis of vasculitis typical of polyarteritis was made in a sixty one year old male. At post mortem no vasculitis was found, but there were widespread microabscesses and tumour emboli from an occult adenocarcinoma of the caecum. The importance of considering other pathologies which may mimic vasculitis is emphasised.

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OBJECTIVES: To determine if increasing physical activity is protective of diaphysial (cortical) bone mass METHODS: Fifteen patients attending two rheumatology clinics who had developed seropositive or classical rheumatoid arthritis up to 26 months previously were studied prospectively for two to three years. Rates of loss (or gain) in bone mass in the radial diaphysis and the trabecular bone of the distal radius were measured by quantitative computed tomography, and in the spine by dual photon absorptiometry. Physical activity was assessed by the Framingham physical activity index. Disease activity was followed at three-monthly clinic visits at which the haemoglobin, erythrocyte sedimentation rate, and platelet count were measured. The urinary hydroxyproline to creatinine ratio and plasma osteocalcin were measured at the beginning and end of the observation period. RESULTS: Eleven patients required treatment with disease modifying drugs but none was given corticosteroids. Those whose physical activity did not improve lost radial diaphysial bone at about 4% annually. There was, however, a statistically significant inverse relation, accounting for 48.5% of the variance, between bone loss at this site and improvement in physical activity as assessed by the Framingham index. The other two sites showed much weaker associations. Adjusting for indices of disease activity hardly affected the first relation. Three biochemical indices related to bone turnover showed weak tendencies to decrease with increasing physical activity. CONCLUSIONS: Peripheral cortical bone, distant from inflamed joints, is conserved more successfully in patients who achieve higher levels of physical rehabilitation. This may have implications for avoiding long bone fractures later in the disease.

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The distinction between polymyalgia rheumatica and polymyositis is important for treatment and prognosis. Four elderly patients were diagnosed and treated for polymyalgia: raised creatine kinase led to muscle biopsy and a diagnosis of polymyositis.

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Non-steroidal anti-inflammatory drug induced small intestinal inflammation may have an adverse effect on the joints of patients with rheumatoid arthritis. We therefore assessed small intestinal and joint inflammation in patients with rheumatoid arthritis before and after three to nine months' treatment with sulphasalazine (n = 40) and other second line drugs (n = 20), while keeping the dosage of non-steroidal anti-inflammatory drug at the same level. Sulphasalazine significantly decreased the mean (SD) faecal excretion of 111indium labelled leucocytes from 2.39 (2.22)% to 1.33 (1.13)% (normal less than 1%, p less than 0.01) and improved the joint inflammation as assessed by a variety of parameters. There was no significant correlation between the effects of sulphasalazine treatment on the intestine and the joints. Treatment with other second line drugs had no significant effect on the faecal excretion of 111indium (1.58 (1.04)% and 1.86 (1.51)%, respectively) but improved joint inflammation significantly. The lack of correlation between the intestinal and joint inflammation and their response to treatment suggests that the two are not causally related.

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For approximately 2 years, bone loss was measured in women with early stages of rheumatoid arthritis (RA) and in control subjects, using serial computed tomography and dual photon absorptiometry. Rapid trabecular bone loss from the distal radius was observed in the RA patients but not the controls. The bone loss correlated with initial plasma levels of parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol) concentrations. It has been suggested that these humoral factors may interact with cytokines or other mediators produced in the adjacent wrist joint. Losses of the cortical bone of the radial midshaft and the lumbar spine were modest and were comparable in the 2 groups. Indices relating to both bone formation and bone resorption predicted bone loss at these 2 sites, but changes in the parathyroid hormone and calcitriol concentrations did not.

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The nature and incidence of haematological side-effects of sulphasalazine was sought in a retrospective study of 130 sulphasalazine-treated patients with chronic inflammatory arthritis. Macrocytosis was seen to occur in 27 patients (20.8%) and four patients (3%) developed a macrocytic anaemia. Only eight of 23 macrocytic patients had low red cell folate levels, three of whom were anaemic. An increased risk of developing macrocytosis was seen with doses of sulphasalazine greater than 2 g per day. In most patients the macrocytosis was noted during the first 6 months but did occur in the second and third 6-month period of treatment. Only one patient (0.8%) developed neutropenia and no cases of thrombocytopenia were observed. Regular blood counts should be performed while patients remain on treatment but haematological side-effects are seldom the reason for withdrawal of sulphasalazine.

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Eosinophilic gastroenteritis (EG) is an uncommon disorder, characterised by cramping abdominal pain, diarrhoea and vomiting and histologically by eosinophilic infiltration of bowel wall. We present a patient who developed EG during the course of a systemic, necrotising vasculitis, who became critically ill after failure of treatment with corticosteroids and cytotoxic drugs and responded only to oral sodium chromoglycate.

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The presence of a Baker's cyst may diminish the therapeutic effect of intra-articular 90Y treatment to the knee joint. SPECT (single photon emission computed tomography) was used in 10 patients with Baker's cysts, treated with intra-articular 90Y for persistent synovitis of the knee, to measure the amount of radioisotope within the cyst. Comparison was made with the arthrographic appearances. The likelihood or extent of uptake into Baker's cysts of 90Y injected into the synovial cavity of the knee was not predictable from arthrograms. Deposition of 90Y in cysts was variable, ranging from little or no measurable uptake to a substantial proportion of the administered activity (40% in one case out of 10). It did not appear to relate to clinical response. The low mean uptake (6.3%) in cysts of nine out of 10 patients was probably insignificant in view of the large uncertainty in the prediction of synovial radiation dose.

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Operative small bowel resection specimens received over a period of 16 years were reviewed to assess whether any intestinal disease could be directly attributed to the use of non-steroidal anti-inflammatory drugs (NSAID). Seven cases of intestinal disease associated with the use of NSAID were identified, all of which occurred in the final six years of the survey, which may reflect the increasing use of these compounds. A spectrum of patterns was found from multiple pathognomonic ileal mucosal diaphragms to broad strictures similar to those seen as a complication of enteric potassium. It seems likely that the formation of diaphragm lesions requires an additional factor, but what is not known as yet is whether the effects of NSAID are local or systemic.

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The clinicopathological features in 4 patients are described where nonsteroidal antiinflammatory drugs appear to have caused small intestinal strictures. Two patients had rheumatoid arthritis and 2 patients had osteoarthritis; all had received nonsteroidal antiinflammatory drugs for 1.5-30 yr. Three patients had an initial illness characterized by diarrhea, profound weight loss, and hypoalbuminemia. Intestinal radiology at this stage ranged from subtle changes to those of Crohn's disease. Three patients underwent surgery. At operation the bland external appearance contrasted with the striking mucosal appearances of multiple concentric, circumferential, diaphragmatic strictures that caused luminal stenosis to a pinhole. These septa were due to submucosal fibrosis and the histopathological picture appears to represent a new nosological entity.

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The use of SPECT with Bremsstrahlung radiation has been investigated in studies on patients undergoing 90Y therapy for persistent synovitis of the knee. In particular, its value in the estimation of 90Y uptake into Baker's cysts was assessed and, to this end, realistic 'knee phantoms' were employed in order to calibrate for cysts of different size. Problems associated with the measurement of the extensive Bremsstrahlung spectrum and the estimation of cyst volume have been discussed. It is shown that, although the apparent volume of a cyst is markedly dependent on the chosen count rate threshold, volumes greater than about 30 ml can be estimated with reasonable accuracy using a threshold of 50%. The uptake of 90Y in cysts, measured on 3 occasions within the first 2 days in 10 patients, showed wide variation (0%-40%) between patients and was poorly related to the size of cysts on arthrograms and to the clinical response to therapy. In these studies, the ability to analyse SPECT slices provided a distinct advantage over planar imaging for discriminating between 90Y uptake in cysts and adjacent sites. Retention of 90Y in the total knee was also widely variable, with losses of 2%-38% observed 2 days after injection which, in general, were not fully accounted for by uptake in liver or lymph nodes. The changing distribution of 90Y colloid in the knee during the first two days, as observed in some patients, might explain part of the discrepancy.

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