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The objective was to compare the efficacy and safety of intramuscular methylprednisolone acetate (i.m. MP) with oral prednisolone (OP) in the treatment of polymyalgia rheumatica (PMR), a common steroid-treated illness where prolonged therapy can lead to steroid side-effects. The cumulative dose with i.m. MP injections given every 3-4 weeks is considerably smaller than that with conventional OP, and may therefore be associated with fewer long-term side-effects. A hybrid design was used with an initial 12 week double-blind placebo-controlled phase followed by an open phase on active treatment up to 96 weeks. The study was multicentre hospital out-patient based and included 60 patients with untreated PMR. In the double-blind phase, either 120 mg 3-weekly i.m. MP or gradually tapering daily OP (initial dose 15 mg) were administered. In the open phase, subjects continued their active treatment with gradual tapering of the steroid dosage. The remission rate at 12, 48 and 96 weeks, and other measures of disease activity, i.e. sedimentation rate, pain and morning stiffness, and percentage of adverse reactions and serious complications such as fractures, were the main outcome measures. Sixty patients entered (30 OP:30 i.m. MP) and 49 (25 OP:24 i.m. MP) completed the study. There were similar remission rates after the double-blind phase (60.6% OP and 66.6% i.m. MP, respectively) and similar disease control in the succeeding open phase. With steroid tapering, the mean erythrocyte sedimentation rate for the entire cohort registered a significant increase in the absence of an increase in symptoms. At 96 weeks, the cumulative mean steroid dose in subjects treated with i.m. MP was equivalent to 56% that of subjects treated with OP. There were eight fractures with OP compared to one on i.m. MP. Mean weight gain was significantly greater with OP than i.m. MP (3.42 vs 0.82 kg, P < 0.005). Minor adverse reactions were similar in both groups apart from slightly increased bruising with i.m. MP. Only patients on OP reported moon face, hypertension, cataracts, back pain and depression, but the numbers were small. It is possible to achieve equivalent long-term disease control in PMR with i.m. MP compared to OP. I.m. MP was associated with far fewer fractures and lesser weight gain, presumably related to lower cumulative dose. These findings may have implications in the steroid treatment of PMR, and other rheumatic and non-rheumatic diseases.

Prolactin (PL) is essential for the normal function of the immune system. It is required for the induction of a number of autoimmune conditions in experimental animals. The role of prolactin in the immunopathogenesis of autoimmune human disease has not been established. RA is characterized by a variety of immune and inflammatory processes which determine disease activity. It has a pronounced diurnal periodicity with a peak at 03.15 hours. Since PL has a diurnal rhythm of secretion in man with a peak at about 02.00 hours, it may contribute to the nocturnal worsening of RA. We show that patients with RA secrete an excess of prolactin as evidenced by an upregulated diurnal periodicity and an abnormal increase in plasma prolactin concentration following surgery. By contrast, patients with chronic osteomyelitis, who had chronic inflammation of similar severity to patients with RA, had a normal prolactin diurnal rhythm and response to surgery. Hence, the abnormal changes in prolactin physiology seen in RA appear to be a feature of the disease per se rather than related to chronic inflammation. The elevated levels of prolactin may contribute to disease activity by augmenting immune processes and may be an additional genetic factor, independent of HLA-DR4, in the immunopathogenesis of RA. Furthermore, the effective inhibition of prolactin secretion and/or action may have potential as therapy for RA.

Serum IgA antibodies to Klebsiella pneumoniae were measured in 65 patients with ankylosing spondylitis (AS) during different phases of disease activity and compared with the antibody level in 21 psoriatic arthritis (PsA) patients, 43 rheumatoid arthritis (RA) patients and 57 healthy controls. The mean IgA antibody to Klebsiella in AS patients with an erythrocyte sedimentation rate (ESR) greater than or equal to 15 mm/h was significantly higher than the antibody level in patients with an ESR less than 15 mm/h (p less than 0.02) and tended to increase with rising ESR. There was a significant difference in anti-Klebsiella antibody levels between AS patients with an elevated ESR and antibody levels in PsA patients (p less than 0.001), RA patients (p less than 0.001) and healthy controls (p less than 0.005). There was no difference between healthy controls and patients with PsA, RA or AS patients with a low ESR. The IgA anti-Klebsiella antibody was specifically absorbed out from sera with inactivated klebsiella pneumoniae organisms. Antibody levels to Candida albicans and Escherichia coli did not differ in patients vis-à-vis control subjects. The mean serum anti-Klebsiella IgA level was found to be higher in patients who were either clinically active or had positive faeval cultures, when compared with patients with inactive disease and negative cultures, but these differences were not statistically significant, although when both parameters were examined together a significant additive effect was detected (p less than 0.001). It is concluded that patient with AS exhibit a specific elevation of serum IgA antibody to Klebsiella antigen.

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