Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study.

OBJECTIVE: To determine whether the HLA-DRB1 shared epitope (SE) is associated with early mortality and specific causes of death in rheumatoid arthritis (RA). METHODS: HLA-DRB1 genotyping was carried out on blood samples from 767 patients recruited for the Early RA Study (ERAS), a multicenter, inception cohort study with followup over 18 years. Dates and causes of death (n = 186) were obtained from the Office of National Statistics. The association of HLA-DRB1 alleles with risk of mortality was assessed using Cox proportional hazards regression analyses. Multivariate stepwise models were used to assess the predictive value of HLA-DRB1 genotypes compared with other potential baseline risk factors. RESULTS: The SE was not significantly associated with overall mortality. However, the presence of 2 SE alleles was associated with risk of mortality from ischemic heart disease (hazard ratio [HR] 2.02 [95% confidence interval 1.04-3.94], P = 0.04), and malignancy (HR 2.18 [95% confidence interval 1.17-4.08], P = 0.01). Analysis of specific SE genotypes (corrected for age and sex) revealed that the HLA-DRB1*0101/*0401 and 0404/*0404 genotypes were the strongest predictors of mortality from ischemic heart disease (HR 5.11 and HR 7.55, respectively), and DRB1*0101/*0401 showed a possible interaction with smoking. Male sex, erythrocyte sedimentation rate, and Carstairs Deprivation Index were also predictive, but the Health Assessment Questionnaire score, rheumatoid factor, nodules, and swollen joint counts were not. Mortality due to malignancy was particularly associated with DRB1*0101 genotypes. CONCLUSION: The risk of mortality due to ischemic heart disease or cancer in RA is increased in patients carrying HLA-DRB1 genotypes with particular homozygous and compound heterozygous SE combinations.

Enteric coated naproxen; a double blind trial comparing the tolerance of enteric coated and standard formulations.

Enteric coated naproxen (Nycopren) was compared with standard naproxen in a double blind comparative trial of 348 patients with either rheumatoid or osteoarthritis. There were slightly fewer gastric side effects and slightly fewer withdrawals because of side effects in the enteric coated naproxen group but the differences did not reach statistical significance. There was no significant difference in the efficacy of the two formulations. A satisfaction index was used to assess the therapeutic ratio with visual analogue scales assigned to both efficacy and side effects. The scale performed as intended and is worthy of further exploration.

Continuing medical education undertaken by general practitioners using the rural registrar scheme.

OBJECTIVE: To evaluate the first full year of operation of the rural registrar scheme by comparing the educational activities undertaken by the participating rural general practitioners with those undertaken in the previous year. DESIGN: Retrospective questionnaire survey mailed to all participants. SETTING: Continuing medical education (CME) for rural general practitioners (GPs) in South Australia. PARTICIPANTS: All 25 GPs who used the scheme from July 1989 to June 1990 were included in the study. All were from solo or two person practices in rural South Australia. One had gone abroad and could not be contacted, and 23 of the remaining 24 responded. INTERVENTIONS: A competent locum was supplied at no cost to the GP, so that the GP could leave the practice to undertake CME. MAIN OUTCOME MEASURES: GPs were asked to outline CME activities for two consecutive years, to rate the educational value of each activity, and to note whether skill or knowledge acquisition was most relevant. RESULTS: The rural registrar scheme increased the amount of time that rural GPs spent on CME. The range of topics studied increased considerably. CONCLUSIONS: The provision of a satisfactory locum service has enabled rural GPs to participate in a wide range of CME activities, which reflect the diversity of general practice. Most participants preferred individual, experiential study programmes to more structured CME programmes.

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'.

Demonstration of antiglobulin activity in the synovial membrane of patients with rheumatoid arthritis and ankylosing spondylitis after pepsin treatment: real or artefact?

The results of immunofluorescence studies in nine cases of rheumatoid arthritis and nine cases of ankylosing spondylitis are presented. Antiglobulin activity was sought with fluorescein labelled, heat aggregated human IgG and rabbit immunoglobulin (indirect immunofluorescence). A similar degree of increased staining for rheumatoid factor activity was seen after pepsin digestion in all cases of rheumatoid arthritis and three of the ankylosing spondylitic cases. This staining for rheumatoid factor could also be shown in control tissue after pepsin digestion, suggesting that the enhanced staining was an artefact.

Palindromic rheumatism and Felty's syndrome.

The coexistence of palindromic rheumatism and Felty's syndrome in a single patient is described. It is likely that these two manifestations are linked with the patient's possession of HLA-DR4 and that they are prodromata of the patient's eventual development of rheumatoid arthritis.

Recurrent rheumatic fever.

Although recurrent rheumatic fever in adults is uncommon and the recurrence rate declines with age and with the interval from the attack, we describe a patient who has had four attacks of rheumatic fever, two in childhood and two in adult life.

The pathergy test and Behçet's syndrome in Britain.

Skin hypersensitivity to needle puncture (pathergy test) together with a positive HLA B5 antigen has been reported as a diagnostic test for Behçet's syndrome (BS) in Turkish patients. We have studied the pathergy test by 2 methods in 7 healthy volunteers who have the HLA B5(Bw 51 split) antigen and 19 patients with BS. The test was negative in all the normal volunteers and only one of the 19 patients with BS had a positive test by one of the 2 methods. Cluster analysis of our patients and those reported from Turkey showed no difference in their clinical features. The positivity of the pathergy test, and hence its diagnostic usefulness, seem to differ between Britain and Turkey, and we conclude that this difference is not related to the possession of the HLA B5 (Bw 51 split) antigen.

Patterns of glomerulonephritis in Zimbabwe: survey of disease characterised by nephrotic proteinuria.

Ninety-eight Zimbabweans with glomerulonephritis characterised by nephrotic proteinuria were studied. There was no evidence to implicate Schistosoma mansoni or S. haemotobium in the aetiology, although schistosomiasis was diagnosed in 54 patients in the series. Similarly, Plasmodium malariae proved unimportant as a cause of the nephrotic syndrome, only one patient showing focal segmental glomerulosclerosis which was associated with subclinical quartan malarial infection. Nevertheless, infections were shown to play a major role in the genesis of glomerulonephritis which was associated with beta-haemolytic streptococcal, hepatitis B and syphilitic infection in 45 patients in the series. The major patterns of disease in childhood proved to be membranous glomerulopathy associated with hepatitis B antigenaemia. In young adults post-streptococcal proliferative glomerulonephritis constituted the commonest disease pattern. In older adult patients a miscellany of primary and secondary glomerulonephritides was encountered but proliferative glomerulonephritis, which was both idiopathic and streptococcus-related, predominated.

Fibronectin in the synovium of chronic inflammatory joint disease.

The localisation of fibronectin in the synovial membrane of rheumatoid arthritis (RA) and other chronic inflammatory joint diseases has been studied using a peroxidase-antiperoxidase immunohistochemical method. Synovia were studied from seven cases of seropositive RA three cases of seronegative RA, six cases of ankylosing spondylitis, four cases of Reiter's syndrome and five of psoriatic arthritis. Six were small biopsies and the remaining tissues were obtained at open surgery for orthopaedic procedures or biopsies. Fibronectin was demonstrated in all of the synovia examined and was present in intimal cells, synovial giant cells, the walls of small blood vessels, basement membrane of larger vessels and deposits of fibrin. No difference in this distribution of fibronectin was found in seropositive and seronegative RA, ankylosing spondylitis, Reiter's syndrome or psoriatic arthritis, neither was there any difference in the amount of fibronectin at various sites.

Association of hepatitis B (HBs) antigenaemia and membranous glomerulonephritis in Zimbabwean children.

8 Zimbabwean children are discussed in whom the nephrotic syndrome (NS) was a manifestation of membranous glomerulonephritis (GN) which was associated in every case with hepatitis B antigenaemia. This marks the first occasion that such an association has been reported in African children, although it has been thoroughly documented in children in Europe, the Far East and America. Microhaematuria, hypertension and mild to moderate renal insufficiency were frequent early associated findings, and every child exhibited hypocomplementaemia and a markedly diminished immunoglobulin G (IgG) level. The disease followed a benign course in the majority, and only 1 child died in renal failure.

Arthritis and angioimmunoblastic lymphadenopathy.

We report 2 contrasting cases of a seronegative polyarthritis associated with angioimmunoblastic lymphadenopathy (AILD). Both cases were nonerosive, with symmetrical involvement of the elbows, wrists, knees, and ankles. In one the arthritis appeared concurrently with the main systemic manifestations of AILD. The second presented with polyarthritis 18 months before the onset of AILD. This patient received azathioprine for 11 months before developing AILD, which raises the possibility of this drug being the causative agent.

Measurement of polymorphonuclear leucocyte motility under agarose by computer-linked image analysis.

We have applied computer-linked image analysis to the measurement of polymorphonuclear leucocyte motility under agarose. A high degree of correlation was found between manual and machine values of cell numbers migrating and leading front measurements. This method permits a more complete analysis of cell motility than current methods. It is quick and reliable and allows cell distribution profiles to be studied.

Polymorphonuclear function in Behçet's syndrome.

Three aspects of polymorphonuclear leucocyte (PMN) function were studied in 19 patients with Behçet's syndrome (BS). By 2 different techniques directed motility was found to be increased. This increase was largely due to the subgroup of patients with ocular involvement. Counts of absolute numbers of cells migrating highlighted this finding. No difference was found in the phagocytic or adherent properties of PMN in Behçet's syndrome. Increased PMN motility in Behçet's syndrome may contribute to the expression of the syndrome. It remains to be tested whether altered PMN motility in this syndrome is genetically linked.