Behçet's syndrome--classification criteria.

Behçet's syndrome, classified as a vasculitis, is a multisystem disease of uncertain pathogenesis without any specific diagnostic feature or laboratory investigation. Diagnosis, therefore, depends on the grouping together of sufficient clinical manifestations for the clinician to be convinced of the diagnosis. Over many years various sets of diagnostic criteria have been proposed. In 1989 international criteria were proposed, which are better known as classification criteria, which depend on the presence of recurrent oral ulceration plus two of recurrent genital ulceration, typical eye lesions, typical skin lesions or a positive pathergy (skin hyperreactivity) test. It is emphasized that these are criteria for the classification of groups of patients participating in research programmes to ensure comparability of the groups, and not for the diagnosis of the individual patient in the clinical situation.

Practical treatment recommendations for pharmacotherapy of Behçet's syndrome.

Behçet's syndrome is a disease of unknown aetiology classified among the vasculitides. It runs a course of exacerbations and remissions which gradually abate with time. Eye disease, the most frequent cause of serious morbidity, may lead to blindness in 20% of those affected. The syndrome may occasionally be fatal due to vasculitis leading to arterial occlusion, ruptured arterial aneurysms or pulmonary vasculitis, or involvement of the central nervous system. Immunosuppressive drugs have been shown to be moderately successful in inducing and maintaining remissions. Azathioprine at a dose of 2.5 mg/kg/day has been shown to control the progression of existing, and the development of new, eye disease. Cyclosporin A is also beneficial in controlling active eye disease and although it has a more rapid action than azathioprine, its toxicity limits its long term use. Colchicine, although widely prescribed, has been shown in a controlled trial to be effective only in reducing the development of erythema nodosum and arthralgia. Systemic corticosteroids, once widely used, are now reserved only for the most severe cases of inflammatory eye disease and vasculitis, where they are frequently used as intravenous pulse therapy. Local mydriatics are used to prevent synechiae. Local treatment with corticosteroids, sometimes in conjunction with antibiotics, control oral and genital ulcers which may also be controlled by immunosuppressives, which are reserved for the most severe cases. Thrombophlebitis usually only requires antiplatelet agents, whereas arteritis is treated conventionally with a combination of corticosteroids and immunosuppressive drugs, usually cyclophosphamide.

Response to intradermal injection of monosodium urate crystals in Behçet's syndrome.

The cutaneous response to intradermal injection of monosodium urate crystals was investigated in 97 patients with Behçet's syndrome in Turkey and 14 in the United Kingdom, and in 82 healthy and 88 diseased controls. Urate crystals produced an increased erythematous response in patients compared with controls in both countries. This response was different from that of the pathergy test performed at the same time. The systemic acute phase response, studied only in Turkey, showed no differences between patients and controls.

A controlled trial of azathioprine in Behçet's syndrome.

Cytotoxic agents have long been used in Behçet's syndrome, especially for eye involvement, but their effectiveness has been uncertain. We conducted a two-year randomized, placebo-controlled, double-blind trial of azathioprine (2.5 mg per kilogram of body weight per day) in Turkish men with Behçet's syndrome without eye disease (group 1; n = 25) or with eye disease (group 2; n = 48). Corticosteroid treatment remained available to all the patients. All six patients withdrawn from the study because of severe eye disease were receiving placebo (P less than 0.001). Azathioprine was superior to placebo in the prevention of new eye disease in group 1 (1 vs. 8 patients; P less than 0.01) and in group 2 among the 14 patients who at entry had disease in only one eye (P less than 0.001). There were fewer episodes of hypopyon uveitis (1 vs. 15; P less than 0.001) among the group 2 patients who took azathioprine. The patients taking azathioprine also had less frequent oral ulcers, genital ulcers, and arthritis. There were no serious side effects attributable to azathioprine. We conclude that azathioprine is effective in controlling the progression of Behçet's syndrome, especially its most serious manifestation, eye disease.

Circadian rhythm of serum cytidine deaminase in patients with rheumatoid arthritis during rest and exercise.

Circadian rhythm of serum cytidine deaminase and C reactive protein was assessed in 11 inpatients with rheumatoid arthritis who were crossed between 24 hours of bed rest and 24 hours of normal ward activity. Blood was taken at six hourly intervals and the results analysed by fitting sine waves with an assumed period of 24 hours to the measured concentrations. Cytidine deaminase after activity, but not at rest, showed circadian variation, with a 24 hour mean level of 17.4 units (normal 3-13 units) and an amplitude of 1.1 units. The circadian variation, defined as the curve's peak to trough difference as a percentage of the 24 hour mean, was 12.3% and occurred at 1208 hours. C reactive protein showed no significant circadian rhythm, in keeping with published findings. The timing of the peak in serum cytidine deaminase concentrations after a period of morning physiotherapy, but not during the bedrest morning, suggests that exercise accounts for the circadian rhythm, probably by increasing the lymphatic clearance from inflamed joints.

Spontaneous atlantoaxial subluxation: an unusual presenting manifestation of Reiter's syndrome.

A male Sikh presented with spontaneous neck pain. Plain cervical radiography showed gross atlantoaxial subluxation (AAS). Computed tomography showed soft tissue anterior to a subluxed odontoid peg. A diagnosis of atlantoaxial tuberculosis was considered. Confirmation of this would have required a trans-oral anterior cervical biopsy. Despite the paucity of other rheumatic symptoms a diagnosis of Reiter's syndrome with spondylitis was made, and the only surgical procedure required was posterior fusion of C1 and C2, with resultant spinal stability and pain relief. This is the first report of Reiter's syndrome presenting with AAS.

CD4 and CD8 cell responses to herpes simplex virus in Behçet's disease.

The finding of part of the Herpes simplex virus type 1 (HSV1) genome in peripheral blood leucocytes of some patients with Behcet's disease (BD) led to investigations of T cell responses to HSV1 in this disease. A significantly impaired uptake of 3H-thymidine by CD4 cells was found in BD, as compared with healthy HSV1 sero-positive subjects. The impaired cellular response appeared to be specific to HSV1, as neither cytomegalovirus nor varicella-zoster virus showed depressed CD4 cell responses in BD. A similar impairment of CD4 cell responses to HSV1 was found in patients with recurrent herpetic infections, known to be caused by latent HSV1 infections. However, in rheumatoid arthritis which was selected as an unrelated autoimmune disease. 3H-thymidine uptake by CD4 cells stimulated with HSV1 was enhanced. CD8 cells showed generally rather a low uptake of 3H-thymidine, nevertheless, the values in BD and recurrent herpetic infection were again lower than those in sero-positive controls or rheumatoid arthritis. The results are consistent with the hypothesis that HSV1 might be involved in the immunopathogenesis of BD.

Analysis of clinical judgment helps to improve agreement in the assessment of rheumatoid arthritis.

Experienced rheumatologists differ widely in their assessments of rheumatoid arthritis even after extensive efforts to improve agreement by discussion and consensus. The use of computer feedback to provide an analysis of clinicians' judgment policies in a highly structured investigation has been shown to improve agreement, but this may not apply in normal clinical practice. Here the successful convergence of clinical agreements by three rheumatologists using computer assisted feedback over several months in a National Health Service outpatient department is reported. In the three months without feedback their pooled agreement for assessing the severity of rheumatoid arthritis was r2 = 0.62. During the three months in which feedback was provided agreement rose to r2 = 0.92. The principal component of all three judgment policies at the end of the feedback period was 'articular index'.

Coexisting rheumatoid arthritis and ankylosing spondylitis.

Since the second publication by some of the present authors in which 10 patients with coexisting rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were described, 7 new cases have been found. For accuracy, all cases of the original study still available were reexamined. Of the total of 17 cases, 13 were male and 4 female. All had positive tests for rheumatoid factor and 6 had subcutaneous nodules. The male predominance and the frequency of nodules are consistent with other publications. In addition, our study demonstrates the strong association of each of these 2 diseases with its genetic marker: the antigen HLA-DR4 was present in 8 of 12 cases tested and the antigen HLA-B27 was present in 16 of the 17 cases. The coexistence of these 2 classical rheumatological entities in the same patient appears to occur by chance and is probably often overlooked.

Observer variation in grading sacroiliac radiographs might be a cause of 'sacroiliitis' reported in certain disease states.

Radiological sacroiliitis in Behçet's syndrome (BS) has been a subject of controversy. We have examined pelvic radiographs of 38 patients with BS and 28 age and sex matched controls which we reported previously, and also 17 with ankylosing spondylitis (AS), 27 with non-renal familial Mediterranean fever (FMF), and 33 with primary osteoarthrosis (OA). Initially, five observers assessed radiographs on two different occasions according to the New York criteria for sacroiliitis in a blind protocol. Later, three of them examined the various possible abnormalities of the sacroiliac (SI) joints after training sessions. Although the inter- and intraobserver variation was quite high, all observers found the expected changes in patients with AS. The abnormalities detected in the other diseases were either mild, inconsistent, or both. Erosions were confined to patients with AS, and osteophytes and glenoid sulci to patients with OA. We conclude that high observer variation in interpreting a film of the anteroposterior (AP) view of the pelvis for sacroiliitis may be a major cause of reported 'sacroiliitis' in BS and FMF.

Progressive proliferative glomerulonephritis in a patient with rheumatoid arthritis treated with D-penicillamine.

A 49 year old man with rheumatoid arthritis developed a proliferative glomerulonephritis with progressive renal impairment during treatment with D-penicillamine. His renal function continued to deteriorate after the drug was stopped but improved after treatment with corticosteroids and azathioprine.

Practical results of treatment with disease-modifying antirheumatoid drugs.

Reappraisal of disease-modifying antirheumatoid drug (DMARD) therapy in rheumatoid arthritis (RA) has raised the possibility that the risks of treatment outweigh the benefits. To provide more information a retrospective survey of the case-notes of 325 patients with RA was performed. The case-notes were randomly selected from the 2320 RA patients indexed in one department. Improvement was defined by the contemporary written notes of the managing physician. Analysis employed the life-table technique. A total of 247 case-notes could be adequately analysed: 154 patients had received one or more DMARDs constituting 251 drug-patient exposures. Improvement followed drug-patient exposure in 57% of cases after a delay of between one and seven months. Nine per cent occurred within one month and 22% within two months. Of those patients withdrawn from treatment after less than two months, the 'early withdrawal' group, 25% subsequently improved without further DMARD therapy. The probability of still receiving a specific DMARD 8 months, 24 months and 36 months after the start of treatment was 50%, 25% and 10%, respectively. The majority of withdrawals resulted from adverse reactions. There was no evidence for a relationship between patient responses to sequential DMARDs.