Inpatient treatment of rheumatoid arthritis with synacthen depot: a double blind placebo controlled trial with 6 month followup.

OBJECTIVE: To assess the additional benefit of synacthen depot over standard inpatient care for patients hospitalized with active rheumatoid arthritis (RA). METHODS: All patients admitted to our unit with active RA without exclusion criteria were invited to participate and randomized to subcutaneous synacthen depot 0.5 mg on alternate days for 2 injections or 2 injections of saline. Patients, staff, and assessors of response were blinded to the intervention. Assessment [OMERACT set, American College of Rheumatology (ACR) global improvement, dose of intraarticular (IA) or intramuscular (IM) methylprednisolone] was performed at admission to hospital, at discharge, and at 3 and 6 months. Oral prednisone use constituted a protocol violation. RESULTS: Of 137 patients with RA admitted over the period of recruitment, 36 (26%) were enrolled; 31 completed followup. There were no between-group differences in the change from admission of any individual disease activity measure at any time point. However, using a rigorous global response measure (ACR 50%), a difference was detected in favor of synacthen depot at discharge (52.6% of the intervention group improved vs. 17.6% of controls; p = 0.029, number-needed-to-treat 2.86). Patients treated with synacthen depot showed a trend toward more IA or IM corticosteroid between discharge and 3 months (mean dose 56 vs. 31 mg; p = 0.19) and a trend toward more patients requiring a change in slow acting antirheumatic drug after discharge (4 vs. 1; p = 0.27). CONCLUSION: There is some additional benefit of synacthen depot in the hospital treatment of RA, but the effect is lost by 3 months, with a suggestion of rebound worsening in these patients. We postulate that oversuppression of corticotrophin releasing hormone by exogenous adrenocorticotrophic hormone in patients who already have a hypothalamic deficit may contribute to the rebound worsening of disease activity seen in these patients.

Bacterial infections: osteoarticular brucellosis.

Osteoarticular brucellosis has been documented extensively from the Middle East and Spain in the last 5 years, but it has only been reported infrequently from the UK and USA. Brucella melitensis from goat and sheep is the most frequently isolated organism. Peripheral articular pain, particularly of the large joints, is the commonest osteoarticular manifestation, while effusions that seldom yield organisms on culture, also occur frequently. Sacroiliitis which most frequently is unilateral, often presents acutely and dramatically with severe pain that is poorly localized to the lower back and buttock, leading to difficulty in walking and even standing. Tapping the heel and springing the sacrum is probably the best way of localizing the pain to the sacroiliac joint in this acute stage. Lack of awareness of this pattern of presentation could lead to misdiagnosis. Spondylitis is the third major manifestation of osteoarticular brucellosis. It occurs in older patients and is insidious and chronic in onset and course. The lumbar spine is most frequently involved, although cervical involvement is frequently associated with more complications, particularly compressive neurological deficits. Osteomyelitis occurs unusually. Several large series have been reported among children. In them peripheral large joint involvement in association with systemic features predominate while sacroiliitis may occur unusually. Plain X-rays often demonstrate vertebral damage, involving the upper anterior margin most frequently. CT scans define better vertebral damage that is characterized by bony sclerosis and the less frequently encountered extradural extension and para-vertebral abscess formation. Technetium bone scan is the most sensitive technique for detecting acute sacroiliitis and other sites of early osteoarticular involvement. A four-fold rise in Brucella agglutination titre is the most frequently utilized diagnostic aid. A 6 week culture in a CO2-enriched medium is recommended for growing Brucella. Tetracycline or doxycycline 200 mg per day for 6 weeks is the mainstay of most medical treatment schedules. Combination with streptomycin for 3 weeks or rifampicin for 6 weeks is recommended, to reduce significantly the failure and relapse rate. Spinal involvement is associated with an increased failure and relapse rate while they occurred least among those with no osteoarticular involvement. Surgical intervention to stabilize the spine and relieve neurological compression may become necessary. With the use of these various measures, the outlook for complete recovery is good.

Cutaneous polyarteritis nodosa and ulcerative colitis.

Vasculitis in many forms has been reported rarely in association with ulcerative colitis. We report the occurrence of necrotizing vasculitis in a 48-year-old man 19 years after the onset of ulcerative colitis and 5 years after total colectomy with rectal preservation. The disease was limited to small arteries of skin and muscle consistent with the syndrome of cutaneous polyarteritis nodosa that has been reported with regional enteritis but not previously with ulcerative colitis.

A genetic marker for rheumatic heart disease.

The frequency of antigen types (A, B, C, and DR) in an unselected group of 25 patients with chronic rheumatic heart disease and an unselected group of 15 patients with acute rheumatic fever was compared with that in a group of 100 healthy volunteers. All patients and controls were Arabs of Saudi origin. Only the frequency of HLA-DR4 was significantly different in the controls and the patient groups--controls 12%, chronic rheumatic heart disease 72%, acute rheumatic fever 53%, both patient groups together 65% (relative risk 13.6 with 95% confidence interval 10.5-16.7). Eighty three per cent of 12 patients with mitral stenosis and 70% of seven with aortic incompetence had HLA-DR4 antigen. In 17 non-Saudi Arab patients who had acute rheumatic fever or chronic rheumatic heart disease, the frequency of HLA-DR4 was identical (65%) to that in Saudi patients. These findings may have implications for the pathogenesis of rheumatic fever and rheumatic heart disease.

Joint mobility and mitral valve prolapse in an Arab population.

The association of joint laxity and mitral valve prolapse (MVP) has been disputed. In this study of an Arab population, the joint mobility scores of 29 subjects with MVP, 10 of whom were asymptomatic, were compared to 60 normal controls. It was found that the joint mobility score was significantly higher in both the asymptomatic and the symptomatic subjects with MVP when compared to the controls. This suggests that both mitral valve prolapse and joint laxity may be due to the same abnormality of connective tissue structure.

Brucella meningitis.

Infection with Brucella melitensis is endemic in Saudi Arabia but involvement of the central nervous system (CNS) is rare. We report on three patients with acute brucella meningitis, all of whom had a history of exposure to a possible source of infection. Diagnosis was confirmed by isolation of Brucella species from blood cultures. Examination of cerebrospinal fluid revealed lymphocytic pleocytosis with a high concentration of protein and low concentration of glucose. The patients were treated by combinations of co-trimoxazole, doxycycline or rifampicin. All responded well without recurrences. A combination of two of the three drugs was effective in treating brucellosis of the CNS when given for a period of 6-8 weeks.

The spectrum of rheumatic diseases in Saudi Arabia.

The spectrum of rheumatic diseases seen in Saudi Arabia appeared to be broadly similar to that seen in the West although interesting differences were noted. Rheumatoid arthritis was the predominant inflammatory joint disease, but was less severe. Ankylosing spondylitis is probably rare among the Saudis. Brucellosis was an important cause of acute back pain. Osteoarthritis was characterized by frequent involvement of the knee while the hip was rarely involved. Environmental factors may be responsible for this disease pattern. Regional pain syndromes, associated with obesity, bad posture, and poor physical fitness were also frequent problems.

Spinal brucellosis.

The findings in 44 patients with back pain and brucellosis are described. Radiological changes tended to occur in older patients with a longer duration of disease. The younger patients more often experienced an acute arthritis with sacroiliitis resembling a reactive disease. Bone scanning was more sensitive than radiographs, particularly in detecting acute sacroiliitis and hip involvement. The lumbar spine was the most frequently involved site although no part of the spine was spared. Extensive destruction of a vertebral body with little involvement of the adjacent vertebrae, lower lumbar spondylolysis and spondylolisthesis, and discitis with calcification were striking radiological findings hitherto undescribed in brucellosis. Computerized axial tomography (CAT) scanning revealed vertebral-arch destruction in three cases of spondylolisthesis. Circumferential sclerosis of the vertebral bodies was another CAT-scan finding.

Rheumatoid factor production in response to gonococcal polyarthritis and tenosynovitis.

A case of gonococcal polyarthritis in a 19-year old woman was rheumatoid factor positive on presentation. Titres of rheumatoid factor declined to normal as her arthritis resolved with treatment. A positive rheumatoid factor test in a person with possible gonococcal polyarthritis should therefore be disregarded until an infective aetiology has been ruled out.

A comparative trial of a controlled-release formulation of ketoprofen ('Oruvail') and a conventional capsule formulation of ketoprofen ('Orudis') in patients with osteoarthritis of the hip.

An open study was carried out in 46 patients with osteoarthritis of the hip to compare the efficacy and tolerance of treatment with ketoprofen given either as 100 mg capsules twice daily or as 2 capsules of 100 mg ketoprofen in a controlled-release formulation given once daily. The results of subjective and objective assessments before and during 3-months' treatment in the 48 patients who completed the trial showed both treatments produced improvement in all parameters, except for the time taken for inactivity stiffness to develop, and there was no significant difference between treatments in terms of efficacy. The controlled-release preparation, however, was significantly better tolerated than the ordinary capsule form. Minor haematological and biochemical changes during treatment were noted but these were not of clinical importance. Six patients, 2 receiving the controlled-release and 4 receiving the ordinary formulation of ketoprofen, were withdrawn because of lack of efficacy or unacceptable side-effects.

Pharyngo-oesophageal dysphagia in systemic sclerosis.

A patient with systemic sclerosis developed recurrent dysphagia consistently localised to the pharyngo-oesophageal region. This was due to narrowing of the lumen as a result of gross thickening of the pharyngo-oesophageal muscles. Histologically the changes were typical of systemic sclerosis. The lower oesophagus was less involved. Eventually she died of aspiration pneumonia and respiratory arrest.

Patterns of acute renal failure in leptospirosis.

The renal profile was studied in 61 patients having leptospirosis. Leptospira-induced acute renal failure conformed to one of two distinct clinical patterns, either oliguric on non-oliguric renal failure. The prognosis was excellent in the latter variety of renal failure and mortality was confined to patients with oliguric renal failure, where severe glomerular and widespread tubulo-interstitial lesions were invariably present. These patients had unfavourable prognostic features during life, such as prolonged oliguria and anuria, absence of a diruetic phase, persistent elevations in BUN and persistently low urea excretion. The prognostic significance of the age of the patients, hypotension and jaundice in relation to the occurrence and type of acute renal failure have been discussed. Retrospective observations indicate that both a vasculotoxic or haemorrhagic state and oliguric acute renal failure are important causes for mortality in human leptospiral infections.