Male osteoporosis associated with longterm cyproterone treatment.

A 58-year-old man with previous dorsal vertebral fractures was referred for continuing management of osteoporosis. He was treated in the past with cyproterone acetate for hypersexuality. There were no other risk factors for osteoporosis. A dual energy radiographic absorptiometry scan confirmed osteoporosis. Treatment with alendronate 10 mg/day improved bone density and back pain. Patients receiving longterm treatment with cyproterone might be at risk for developing osteoporosis and would benefit from regular bone density monitoring.

Corticosteroids do not alter the threshold for vertebral fracture.

Corticosteroid use is one of the most important secondary causes of osteoporosis. Generally, it has been believed that in addition to its effect on bone mineral density (BMD), it also causes an alteration in bone quality that means that fractures occur at a lower BMD than might be expected. To establish if this is the case, we have compared the relationship between BMD and vertebral fracture in patients receiving corticosteroids with that in patients who had never received such therapy. Information was gathered on those patients who had been referred to the participating centers and had both BMD measurements and lateral thoracolumbar radiographs. In all, 452 patients (391 female) were identified; of these 82 (63 female) were receiving corticosteroids. There was no significant difference in BMD between the patients on corticosteroids and those with other suspected causes of osteoporosis. Vertebral fractures were present in 53% of patients on steroids compared with 35% of those who had no such treatment (p = 0.0035). The fractures were more likely to be multiple in patients on corticosteroids (p = 0.0042). However, if the relationship between bone density and fracture is investigated by plotting the cumulative prevalence of fracture against the bone density, measured by T score, the median BMD for fractures actually was marginally lower in patients on steroids, -2.74 (95% confidence interval [CI], -2.77 to -2.70) compared with -2.65 (95% CI, -2.66 to -2.65) in those who had not received steroids. Our results fail to support the notion that the fracture threshold is altered in patients on long-term steroids and suggest that the same diagnostic criteria should be used for osteoporosis in patients whether or not they are taking corticosteroid therapy.

Defective antibody production in patients with rheumatoid arthritis and bronchiectasis.

Bronchiectasis (BR) occurs in about 3% of patients with rheumatoid arthritis (RA). Defective antibody production is a rare but well-recognised cause of both BR and inflammatory arthritis. We examined the hypothesis that subtle specific antibody defects might play a role in the pathogenesis of BR associated with RA. Identification of defects in antibody production is important because substantial benefits may be gained from immunoglobulin replacement. Specific antibody production was assessed in 20 patients with RA and BR, 20 with BR alone, 20 with RA alone and 20 healthy controls (all groups matched for age and sex). All had normal total IgG. IgA and IgM and IgG subclass levels. Specific antibody production was assessed by assay of antibodies to representative polysaccharide and protein antigens. Subjects with subprotective titres were challenged with the appropriate vaccine. Defective antibody production was defined as a subprotective level despite immunisation. Three out of 20 patients with RA and BR had a defective IgG2 response to the polysaccharide antigen, but normal responses to the protein antigen. All of the subjects in the BR alone or healthy control group had normal antibody production. Two out of 20 patients with RA alone had defective production of antibodies against both protein and polysaccharide antigens; both were receiving gold therapy, a recognised cause of functional antibody defects. It was concluded that some patients with RA and BR have functional antibody defects and may benefit from antibody replacement. An unexpectedly high proportion of patients with RA alone also have functional antibody defects, possibly secondary to gold therapy.

Treatment of Felty's syndrome with the haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF).

Felty's syndrome (FS) (rheumatoid arthritis with neutropenia and splenomegaly) has a poor prognosis, largely because of the high risk of severe infection. Granulocyte colony-stimulating factor (G-CSF) is an emerging treatment for chronic neutropenia. We prospectively monitored its use in eight patients with recurrent infections or who required joint surgery. Significant side-effects were documented in five, including nausea, malaise, generalized joint pains, and in one patient, a vasculitic skin rash. In two patients treatment had to be stopped, and in these cases G-CSF had been started at full vial dosage (300 micrograms/ml filgrastim or 263 micrograms/ml lenograstim) alternate days or daily. G-CSF treatment was continued in three patients by restarting at reduced dose, and changing the proprietary formulation. G-CSF raised the neutrophil count, reduced severe infection, and allowed surgery to be performed. A combined clinical and laboratory index suggested that long-term treatment (up to 3.5 years) did not exacerbate the arthritis. Once on established treatment, it may be possible to use smaller weekly doses of G-CSF to maintain the same clinical benefit. One of the three patients whose FS was associated with a large granular T-cell lymphocytosis showed a reduction in this subset of lymphocytes during G-CSF treatment.

Decreased survival in patients with co-existent rheumatoid arthritis and bronchiectasis.

The aim was to compare the 5 yr survival in patients with rheumatoid arthritis (RA) alone, bronchiectasis (Br) alone and RA plus Br (RA-Br). A case-control study was carried out in which 32 patients with RA-Br were matched for age (within 5 yr), sex and (where possible) disease duration with 32 patients with RA alone. An additional comparison group of 31 unselected patients with Br was chosen. All patients were followed for 5 yr. Patients with RA-Br were 7.3 times more likely to die than the general population, 5.0 times more likely than the RA group and 2.4 times more likely than the Br group. An increased risk of death within the RA-Br group was associated with a history of smoking, more severe RA and steroid usage. The co-existence of RA and Br is associated with a poor 5 yr survival.

An unusual association of Felty syndrome and TCR gamma delta lymphocytosis.

Felty syndrome, comprised of neutropenia, rheumatoid arthritis and splenomegaly, occurs in approximately 1% of patients with rheumatoid arthritis. Up to one third of these patients have an increased number of large granular lymphocytes. The usual immunophenotype of these cells is CD3+, CD8+, CD57+, T cell receptor (TCR) alpha beta. A patient with Felty syndrome and large granular lymphocytosis, who had an unusual immunophenotype CD3+, CD4-, CD8-, TCR gamma delta, is described. Her neutropenia responded to treatment with granulocyte colony stimulating factor (G-CSF), which was given in order to raise her neutrophil count prior to bilateral knee replacement surgery. Thus, Felty syndrome with large granular lymphocytosis is a heterogeneous condition, one in which TCR gamma delta large granular lymphocytosis may be found, and also shows a response to treatment with G-CSF.

Bronchiectasis and rheumatoid arthritis: a clinical study.

OBJECTIVES: To examine the relation between rheumatoid arthritis (RA) and bronchiectasis (BR). METHODS: Disease activity, outcome, extra-articular manifestations, and laboratory features were compared in 32 patients with BR and RA (RA-BR group), 32 matched patients with RA without BR (RA group), and 31 patients with BR but without arthritis (BR group). RESULTS: In 30 of the 32 (94%) patients with RA-BR, BR preceded RA. There was no functional or radiological difference between the RA-BR and RA groups, and except for xerophthalmia, which was more common in patients with RA-BR than patients with RA, there was no difference in extra-articular or laboratory features. CONCLUSIONS: Bronchiectasis does not lead to a more aggressive disease course in RA and, despite the recognised association, BR is not an extra-articular manifestation of rheumatoid disease.

Large granular T lymphocytes, neutropenia and polyarthropathy: an underdiagnosed syndrome?

Thirteen patients with expansion of an unusual subset of T lymphocytes, defined by large size, cytoplasmic granularity and CD3+ CD8+ Leu 7+ surface phenotype, are reported. Although morphologically and/or phenotypically abnormal lymphocytes were found in all patients, only five had an absolute peripheral blood lymphocytosis. Ten patients had a bone marrow lymphocytosis. As in previous series, there was a strong association with neutropenia (12 patients) and polyarthropathy (seven patients). The latter group displayed a wide range of articular disease: classical or definite rheumatoid arthritis in four patients and milder non-erosive disease in the remainder. All 13 patients showed evidence of abnormal B cell function: IgM rheumatoid factor was present in nine patients, neutrophil-specific antibodies in six and all showed an increased level of at least one immunoglobulin isotype. These patients may be difficult to distinguish from those with idiopathic neutropenia and Felty's syndrome. Such a distinction may not be made on clinical grounds alone: critical assessment of lymphocyte morphology, bone marrow examination and analysis of lymphocyte phenotype should be considered in all patients with unexplained neutropenia, particularly in the context of arthritis. It is suggested that the true prevalence of this syndrome may have been greatly underestimated.

Pulsed methylprednisolone in active early rheumatoid disease: a dose-ranging study.

A dose-ranging, double-blind study of pulsed methylprednisolone in 71 patients with active classical or definite RA is reported. Single pulses of 40 mg, 500 mg or 1 g were administered during a 24-h admission. All patients benefited transiently, but only in those who received 1 g was this prolonged beyond 3 weeks. Laboratory measurements showed no significant change in any group. Significantly more patients in the 1 g group felt the treatment worthwhile than in the other groups. The drop-out rates in the 40 mg and 500 mg groups differed significantly from that seen in the 1 g group and were such that statistical analysis beyond 3 weeks was difficult to interpret. Side-effects were mild. Three patients subsequently developed avascular necrosis, one in the 1 g and two in the 40 mg groups. The study suggests that single doses of MP below 1 g are not helpful in the management of acute RA.

Study of sulphamethoxazole in rheumatoid arthritis.

Twenty-three patients with rheumatoid arthritis (RA) entered a single-blind cross-over study of sulphamethoxazole 2 g daily compared to placebo. Sulphamethoxazole was administered for 3 months during the 6-month study. Sulphamethoxazole exhibited properties commensurate with a second-line effect with a significant acute-phase reactant response and a parallel change in the clinical state. Adverse effects were common and resulted in nine drug-related withdrawals, mainly due to nausea and vomiting. There were also reversible abnormalities in liver function tests on the active drug. The role of sulphonamides in treatment of RA requires further exploration.

Rehabilitation of the disabled adolescent: experience with a local authority assessment centre.

School leavers and young adults who are severely physically disabled pose particular problems for habilitation and rehabilitation. A local authority unit, the Fourways Assessment Centre, has been providing a comprehensive service to this group of people for the past 10 years. Rather than operating as an independent self contained unit it has been closely integrated with the local authority social services and educational services.

Immunopathology of penicillamine-induced glomerular disease.

Four patients with rheumatoid arthritis developed heavy proteinuria after 5 to 12 months of treatment with D-penicillamine. Light microscopy of renal biopsy samples showed minimal glomerular capillary wall thickening and mesangial matrix increase, or no departure from normal. Electron microscopy, however, revealed subepithelial electron-dense deposits, fusion of epithelial cell foot processes, and evidence of mesangial cell hyperactivity. Immunofluorescence microscopy demonstrated granular capillary wall deposits of IgG and C3. The findings were similar to those in early membranous glomerulonephritis, differences being observed however in the results of staining for the early-acting complement components Clq and C4. It is tentatively concluded that complement was activated by the classical pathway.

Diffuse alveolitis on a small dose of penicillamine.

A 60-year-old man with seropositive rheumatoid arthritis developed rapidly progressive dyspnoea and bilateral pulmonary infiltrates on short exposure to 50 mg penicillamine daily. He made a satisfactory recovery following cessation of penicillamine therapy and the addition of prednisolone. This case has been reported to the Committee on Safety of Medicines and we would like to emphasize that the possibility of penicillamine-induced lung disease should be recognized, even on a small dose of short duration.

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.

Acetylator phenotype and the effect of dapsone in rheumatoid arthritis.

Acetylator phenotype was determined in 54 patients with rheumatoid arthritis (RA) taking dapsone in the course of 2 comparative clinical studies. No significant differences were demonstrated in the assessments, either of efficacy or adverse effects. There appears to be no clinical advantage in assessing acetylator phenotype in patients with RA being treated with dapsone.