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.

Upward subluxation of the axis in ankylosing spondylitis. A clinical pathologic report.

Upward subluxation of the axis associated with cord compression and death was noted in a patient with a long history of idiopathic ankylosing spondylitis. Upward subluxation of the axis has been recognized in up to 8 per cent of patients with rheumatoid arthritis but it is an exceedingly rare complication of ankylosing spondylitis. In this patient psoriasis and then psoriatic dactylitis developed 26 years after the onset of his ankylosing spondylitis. It is tempting to speculate that the unusual destruction of the joints around the atlas might be due to an added effect of psoriasis on idiopathic ankylosing spondylitis.

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.

The response of bone apposition rate to some nonphysiologic conditions.

The response of bone apposition to some nonphysiologic conditions was investigated. In rabbits, the normal osteogenic rhythm was totally abolished shortly following treatment of hydrocortisone at a dose of 2 mg/kg body weight daily. A new rhythm developed after the treatment was continued for 20 1/2--34 days. The rate of bone apposition was significantly depressed compared to normal data reported previously. In rats receiving one U.S.P. unit of parathyroid extract daily for 14 days, the rate of bone apposition was significantly higher than that in control rats. In both sepcies, the response to an exogenous hormone was identified for all skeletal locations. It was concluded that new bone apposition was a function of activated osteoblasts, and that this function responded only to general body control mechanisms.

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.

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.

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.

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.

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.

Proteinuria with gold therapy: when should gold be permanently stopped?

The treatment records of patients on gold therapy have been studied with particular respect to the development of proteinuria. This was classified as mild (up to 0.3 g/l), moderate (0.4-2 g/l), or heavy (more than 2.0 g/l). Particular attention was paid to the mode of onset and prognosis of the proteinuria and to subsequent gold administration. Twenty-seven patients with moderate or heavy proteinuria were identified. Two were suffering from psoriatic arthropathy, the rest were diagnosed as having rheumatoid arthritis, although three were persistently sero-negative. There was a direct correlation between the degree of proteinuria and its duration. Heavy proteinuria persisted for at least three months, whereas moderate proteinuria cleared within this period. No patient developed permanent renal impairment. Nine of 10 patients with heavy proteinuria had preceding mild or moderate proteinuria during which period gold administration had been continued. Fourteen of 17 patients with moderate proteinuria had their gold injections continued or re-started and none of these subsequently developed heavy proteinuria. It is suggested that moderate proteinuria should lead to cessation of gold therapy until the urine is clear but that subsequently treatment may be safely re-started.

Dermatomyositis complicating penicillamine treatment.

A case of dermatomyositis developing during the course of treatment with D-penicillamine in a patient with rheumatoid arthritis is described. Complete remission occurred on withdrawal of the drug. Possible alternative diagnoses are discussed.

Giant cell arteritis presenting as subclavian artery occlusion. A report of two cases.

Two patients with the aortic arch syndrome and biopsy-proved but asymptomatic temporal giant cell arteritis are described. Corticosteroid treatment was followed by the return of peripheral pulsation in these two patients after an interval of a few months. A review of the literature suggests that of patients where giant cell arteritis causes subclavin obstruction there is an undue predominance of women, compared to the sex ratio found in giant cell arteritis overall.

Double-blind trial of dapsone against placebo in the treatment of rheumatoid arthritis.

Dapsone given over 14 weeks in a dose of 50 mg a day for 1 week and thereafter 100 mg a day was found to have a beneficial effect in rheumatoid arthritis when compared with placebo administration to a matched group of patients. Significant improvement in 5 out of 7 clinical measurements and in erythrocyte sedimentation rate, viscosity, C-reactive protein was found in those patients taking dapsone. There was significant improvement compared to the placebo group in 2 out of the 7 clinical measurements and again in all 3 acute-phase reactants. The drug was quite well tolerated over the 14-week duration of the trial. The tendency to cause haemolysis will be its main limiting factor as a practical alternative to other suppressive agents currently in use.

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.

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.

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.

Naproxen sodium, diflunisal, and placebo in the treatment of chronic back pain.

Thirty-seven patients with chronic back pain were entered into a randomised, 3-way, double-blind, cross-over comparison of naproxen sodium 550 mg twice daily, diflunisal 500 mg twice daily, and placebo. Each treatment was given for 14 days after a preadmission wash-out week during which only paracetamol was allowed. Patients were assessed on admission and at the end of each treatment with respect to global pain, night pain, pain on movement, and pain on standing. Both visual analogue scales and simple descriptive scales were used to measure pain. Side effects were elicited by a nonleading question. Both methods of pain measurement gave similar results and were highly correlated. Naproxen sodium was superior to placebo in relieving global pain and depending on the method of measurement, in relieving night pain and pain on movement. Diflunisal showed no significant differences from placebo. Side effects were similar on all 3 treatments. The final preference of the patients was significantly in favour of the active treatments.

Influence of previous gold toxicity on subsequent development of penicillamine toxicity.

The incidence of penicillamine toxicity was determined in 250 patients who had never previously received gold, 76 patients who had received gold without toxic reaction, and 79 patients with a previous history of gold toxicity. The results suggest that there may be a higher incidence of penicillamine toxicity in patients who have previously shown toxic reactions. The interval between stopping the gold and starting the penicillamine did not influence incidence of toxicity. The development of a rash during gold treatment does not seem to influence the development of a rash during penicillamine treatment, but patients who have had proteinuria or bone-marrow depression during gold treatment may have an increased likelihood of developing a similar side effect with penicillamine.

Immunopathology of penicillamine-induced glomerular disease.

Four patients with rheumatoid arthritis developed heavy proteinuria after five 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 C1q and C4. It is tentatively concluded that complement was activated by the classical pathway.