Influence of age at onset on the duration of treatment in idiopathic adult polymyositis and dermatomyositis.

Twenty-five patients with adult idiopathic dermatomyositis/polymyositis were followed for 59 +/- 39.3 months from initiation of therapy. Forty-two percent of the patients were able to discontinue prednisone therapy after 56 +/- 33 months of therapy and remained disease free for 34 +/- 35.2 months after discontinuing therapy. The mean dose of prednisone in 14 patients being treated at the end of the follow-up period was 16.0 mg. A positive correlation between age at diagnosis and duration of therapy was noted, but not with the creatine kinase value at diagnosis. Sex and dermal involvement were also not associated with treatment duration. All seven patients who received immunosuppressants continued to receive treatment during the follow-up period.

Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A case-control study of 131 patients.

One hundred thirty-one patients with rheumatoid arthritis treated with either azathioprine sodium (n = 37, 102.7 +/- 32.9 mg/d) or methotrexate sodium (n = 94, 8.4 +/- 3.0 mg/wk) were followed up for 38 +/- 23.3 months to determine the nature, frequency, and potential predictors of "major" toxic reactions. Thirty-one methotrexate-treated patients (33%) and 11 patients (30%) receiving azathioprine experienced a major toxic reaction during the study period. With the case-control method, no predictors of major toxic reactions secondary to azathioprine therapy were found. Sex, drug dosage, response to prior slow-acting antirheumatic drug therapy, concurrent use of salicylates, and age did not predict major toxic reactions secondary to methotrexate treatment, but the methotrexate-treated patients who experienced a major toxic reaction had a significantly greater mean level of blood urea nitrogen at the time of their reaction compared with the control group. Life-table analysis suggested toxic reactions posed a greater risk of treatment termination in methotrexate-treated patients compared with the lack or loss of efficacy. This trend was not apparent in the azathioprine group. The majority of patients in each treatment group (79 for methotrexate and 29 for azathioprine) experienced one or more "minor" toxic reactions during the follow-up period.

International study of ketanserin in Raynaud's phenomenon.

PURPOSE: The effects of ketanserin on primary or secondary Raynaud's phenomenon due to connective tissue disease were studied in a large, international group of patients. PATIENTS AND METHODS: The study population consisted of 222 patients from 10 countries. After a run-in period of one month of placebo therapy, patients were randomly assigned in a double-blind manner to receive ketanserin 40 mg three times daily (n = 113) or placebo (n = 109) for three months. Total finger blood flow was measured in 41 patients in a warm and cool room before and during treatment. Vasospastic episodes were assessed by diaries and global evaluations. RESULTS: A significant reduction of 34% in frequency of episodes occurred with ketanserin, compared to 18% with placebo (p = 0.011). There was a 1% reduction in duration of episodes with ketanserin therapy, compared to a 2% increase with placebo therapy, but this finding was not statistically significant (p = 0.29). No difference was observed in severity of attacks. Global evaluations by investigators (p = 0.03) and patients (p less than 0.01) showed an overall benefit with ketanserin compared to that seen with placebo. Patients with primary or secondary Raynaud's phenomenon responded similarly to treatment. No changes in total finger blood flow were found. CONCLUSION: Ketanserin significantly improves the subjective symptoms of patients with primary or secondary Raynaud's phenomenon and is an appropriate agent to use in this disease when conservative measures fail.

A comparison of the clinical usefulness of eight tests for IgM rheumatoid factor.

The clinical usefulness of seven commercially available tests for IgM rheumatoid factor are compared using sera from 28 patients with classical rheumatoid arthritis with 126 patients from appropriate control groups. The test system which provided the greatest sensitivity and specificity for the diagnosis of rheumatoid arthritis was considered the most desirable. No attempt was made to test reproducibility. The Ortho latex slide screening test demonstrated the best balance of sensitivity and specificity with 24/28 positive in sera from patients with classical rheumatoid arthritis, and 6/127 positive in non-rheumatoid controls. Of the systems tested, the Behring latex test was least useful due to an unacceptable lack of sensitivity, with only 8/28 positive using sera from patients with classical rheumatoid arthritis. Until a more internationally standardized rheumatoid factor assay is available, the comparative results of this study may serve as a guide to clinicians and laboratory directors in selecting a clinical useful, commercially available test system.

The remarkable spectrum of methotrexate toxicities.

This article outlines a general scheme for categorizing medication-related adverse events. This is followed by a review of the less well-recognized adverse events attributed to low-dose methotrexate therapy. Known and suspected risk factors are described and causative mechanisms are suggested. Ultimately, this article aims at increasing the readers awareness of uncommon or underreported methotrexate-associated adverse events so that prescribing and monitoring practices can be tailored to enhance the safe use of this valuable antirheumatic agent.

Benign breast disease in systemic sclerosis (SSc). A case-control study.

We hypothesized that Systemic Sclerosis (SSc) may affect the breast in the form of Benign Breast Disease (BBD). For the purpose of this study BBD was defined as breast symptoms either detected by the patient resulting in physician consultation, or detected by a physician during the course of a routine consultation, or detected by a physician during the course of a routine physical exam. Forty-one of 47 women with SSc were matched to case controls from two disease groups (RA and OA). Case matching was done for age (+/- 5 years), disease duration (+/- 3 years) and gender. A structured telephone interview was administered to all subjects and controls to determine the frequency of BBD and associated risk factors. The SSc group had a higher prevalence of BBD compared to the RA group (12/41 versus 4/41, p less than 0.04). However, a similar proportion of the SSc patients and OA case controls had BBD (7/28 versus 9/28). These differences could not be attributed to any of the evaluated risk factors. The RA group had a higher frequency and longer duration of NSAID use, suggesting that the increased use of NSAIDs in the RA patients may account for the lower prevalence of BBD, although genetic, hormonal or undetermined factors may be operative. Without an age-matched, "healthy" general population control group it is impossible to determine if the observed difference in prevalence of BBD represents a less than normal prevalence in RA or a greater than normal prevalence in SSc and OA.

Azathioprine and methotrexate as combination chemotherapy in rheumatoid arthritis.

Azathioprine or methotrexate (MTX) are each established, and comparably effective, therapies for rheumatoid arthritis (RA). An ongoing, still double blind, 3-arm, 24-week study comparing azathioprine or MTX, or azathioprine and MTX in RA is described. With 146 (of 210 total) patients enrolled, it is apparent that all 3 treatment groups demonstrate clinically significant improvement at Week 24. One treatment arm (Group 1) showed a greater degree of improvement in raw mean scores for most outcome variables. Another treatment arm (Group 2) had an adverse effect dropout rate exceeding the sum of adverse effect dropouts from Group 1 and Group 2. Most adverse effects were due to gastrointestinal intolerance.

Treatment of Sjogren's syndrome with essential fatty acids, pyridoxine and vitamin C.

Sjogren's Syndrome (S.S.) is characterized clinically by oral and ocular dryness and immunologically by its frequent association with autoimmune diseases and the presence of various circulating autoantibodies. Evidence has been presented suggesting that S.S. may be due to a relative deficiency of PGE1 and that elevating PGE1 levels may reduce oral and ocular dryness. In an attempt to increase PGE1 levels, precursors of PGE1 including di-homo-gamma linolenic acid, ascorbic acid and pyridoxine in the form of dietary supplements were administered to 10 patients with S.S. for 10 weeks. There was no significant improvement in any of the patients during the treatment period compared to assessments done pre and post treatment. Measurements of oral and ocular dryness of 6 patients on prostaglandin synthetase inhibiting anti-inflammatory medications were similar to the 4 patients on no medication.

Does the number of trainees in a postgraduate training program influence the pass rates on certifying examinations?

We tested the hypothesis that small training programs (3 or fewer residents) lack the "critical mass" needed for an optimal learning experience, and thus graduates of small programs will have a lower pass rate on the Royal College of Physicians and Surgeons of Canada (RCPSC) certifying exams that graduates of large (10 or more residents) training programs. Pass rates on the RCPSC certifying exams (written and oral) were compared to the training program size for each of 6 years from 1984/85 to 1989/90 within 10 of the 43 RCPSC (sub)specialties selected by meeting predefined program size requirements. These 10 specialties met the size variation requirements needed to test the hypothesis: neurology, cardiology, emergency medicine, community medicine, neurosurgery, urology, plastic surgery, dermatology, anatomical pathology, and respiratory medicine. Of these, 3 specialties had a significantly lower written exam pass rate for candidates trained in small compared to large programs. The same 3 specialties (neurology, neurosurgery, and community medicine) had a higher proportion of International Medical Graduates (IMGs) in small training programs. The significantly lower pass rate of IMGs, compared to Canadian/USA graduates, accounted for a portion of the correlation of small program size with lower pass rates in these 3 specialties. By pooling the results from the 10 specialties evaluated, candidates from small (3 or fewer residents) training programs have slightly lower pass rates (11%) on written certification examinations compared to candidates from large (10 or more residents) training programs. This small but statistically significant effect on the pooled results was due to averaging of a more marked program size effect from 3 of the 10 specialties.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse effects of low dose methotrexate therapy in rheumatoid arthritis.

OBJECTIVE: To determine (1) the risk of treatment termination for low dose, weekly methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA), and (2) the prevalence, nature and predictors of adverse effects due to longterm low dose MTX therapy. METHODS: A 13-year, retrospective survey of all patients with RA receiving low dose MTX therapy was conducted using life table, logistic regression and case control methods of analyses. Major and minor adverse effects were defined. RESULTS: Consecutive patients with RA (144) starting MTX (mean dose 8.2 mg/week) were observed to have a 75% risk of treatment termination at 60 months. Reasons for 81 patients stopping MTX were adverse effects (43), loss/lack of effect (18), other medical and nonmedical reasons (13), and lost to followup (7). Sixty-two patients experienced 83 major adverse events, including gastrointestinal symptoms (29), hepatic enzyme test abnormalities (23), pneumonitis (5) and severe leukopenia (8). Aging was the only predictor of treatment discontinuation associated with a major toxicity. Five patients developed a malignancy during the observation period. CONCLUSIONS: In our survey the risk of treatment termination was 75% in patients with RA taking MTX after 60 months. An adverse drug effect is a more common reason for treatment termination (53%), compared to loss/lack of beneficial effect (22%) or other reasons (16%) or lost to followup (9%). Increasing age is associated with an increased risk of treatment termination associated with a major toxicity.

Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature.

Methotrexate pneumonitis is emerging as one of the most unpredictable and potentially serious adverse effects associated with the use of low dose, pulse methotrexate in treating rheumatoid arthritis (RA). We report 4 new cases of methotrexate pneumonitis in patients with RA and review 6 published cases. A greater than expected proportion of patients had a smoking history, preexisting pulmonary disease and were male. Prognosis was better in those patients treated with corticosteroids.

Controlled trial of nifedipine in the treatment of Raynaud's phenomenon.

17 patients with moderate to severe Raynaud's phenomenon were entered into a 6 week randomised double-blind crossover study to compare the efficacy of nifedipine with that of placebo. Nifedipine significantly reduced the frequency of attacks and also the severity of attacks, which was assessed by the patients on a linear analogue scale. Patients gave nifedipine a significantly higher drug-effectiveness score than placebo. Skin temperature recovery times were not affected by treatment with nifedipine. 12 of the patients regarded nifedipine as effective in reducing the frequency and severity of Raynaud's phenomenon.

Superior margin rib defects in rheumatoid arthritis.

Twenty patients with severe rheumatoid arthritis and 96 controls were examined for prevalence and type of superior margin rib defects. In both groups a high prevalence of minor degrees of defects were found (40% and 38.5%). Solely in the rheumatoid group, additional erosive-appearing rib defects were found in 3 of the 20 patients. Radionucleotide scanning of these 3 patients did not show increased activity over the involved rib areas. In the rheumatoid group, the presence of severe shoulder disease correlated with the occurrence of rib defect (both types). We suggest that rib defects, particularly the erosive type, are related to scapulothoracic joint disease.

Pancytopenia associated with low dose methotrexate therapy. A regional survey.

OBJECTIVE: To determine which risk factors are associated with serious pancytopenia associated with low dose methotrexate (MTX) therapy. METHODS: All Ottawa area rheumatologists, hematologists and dermatologists were surveyed to obtain cases of pancytopenia associated with low dose MTX therapy between 1981 and 1991. Pancytopenia was defined as white blood cells < 3.5 x 10(9)/l and platelets < 140 x 10(9)/l and hemoglobin < 100 g/l. A case control method was used to evaluate risk factors. RESULTS: Fifteen cases of pancytopenia were identified from returned questionnaires (93% response rate) and from reviewing the medical records of 2 major teaching hospitals. All patients were hospitalized, had MTX therapy discontinued and were treated: 12 patients received transfusions, 8 leucovorin therapy, and 4 folic acid. Two patients died, only 1 directly due to MTX therapy. Identified risk factors were (1) elevated BUN or creatinine levels, (2) increasing mean corpuscular volume values, (3) increased age and (4) concomitant trimethoprim-sulfamethoxazole therapy. CONCLUSIONS: Pancytopenia associated with low dose MTX therapy is a life threatening adverse effect often associated with known risk factors. A change in monitoring guidelines and patient education are suggested as means of risk reduction.

The effects of Arthritis Society fellowships on career choice.

OBJECTIVE: To find out if The Arthritis Society (TAS) fellowship grants influenced career choice or career development. METHODS: Two hundred former TAS training fellowship recipients (1975-1990 inclusive) were sent a questionnaire to evaluate the effects of TAS clinical or research fellowship support on their subsequent career development. RESULTS: One hundred and forty (70%) completed questionnaires were returned by 88 clinical and 37 research fellowship recipients--a further 17 had received both a clinical and a research fellowship. Fifty-one percent of the respondents are now academic rheumatologists, 40% in community practice and 9% still in training. Seventy-three percent of the research fellowship recipients currently receive research grant support, compared to 16% of the former clinical fellowship recipients. Seventy-one percent agreed that their TAS fellowship support had "directly or indirectly influenced or facilitated their chosen career path"--this included 100% of the research fellowship recipients, compared to 55% of the clinical fellowship recipients. The majority decided on an academic or a community based career path during their postgraduate training. Fourteen percent who trained for an academic career are now in community practice and 9% who planned on a community based career later became academic rheumatologists. Eighty-nine respondents (64%) enclosed a CV. This subset was further analyzed using career markers such as academic rank, number and size of research grants and number of publications. In this subset those who had received both a clinical and a research fellowship had the most advanced academic rank (22% full professor), largest number of publications (n = 39) and largest number of grants (5.3/year; average $40,446), compared to former research fellowship recipients: 4.0% full professor, 22 publications, 3.2 grants/year; average $25,164. Recipients of clinical fellowships in this subset had lower levels of all the academic career markers. CONCLUSION: Of 200 consecutive TAS fellowship recipients 71% of those responding (n = 140) to a career tracking study agreed that the fellowship support "directly or indirectly" influenced or facilitated their career choice. An apparent synergistic effect of providing both clinical and research fellowships on subsequent development of an academic career deserves further study.

Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13-year followup.

The progression of rheumatoid arthritis (RA) is documented in a patient receiving a sex-mismatched, allogeneic bone marrow transplant (BMT) for gold-induced marrow aplasia. DNA typing confirmed a high probability of a full donor engraftment (complete chimerism). Although the RA was in complete remission 2 years post-BMT, clinical, laboratory, histologic, and radiologic evidence of the recurrence of synovitis from 3-13 years post-BMT is presented. Implications of these observations for theories of the pathogenesis of RA and the future of immunotherapies are discussed.

Giant cell arteritis (temporal arteritis) affecting the breast: report of two cases and review of published reports.

The breast is an infrequently recognised site of primary giant cell arteritis. Two cases of giant cell arteritis affecting the breast are described and 11 previously described cases are reviewed. All cases presented with single or multiple breast masses, leading to a diagnosis before biopsy of suspected breast carcinoma. Symptoms similar to those of polymyalgia rheumatica occurred in about half of these patients, though the significance of these symptoms was only appreciated in retrospect. Clinical or pathological evidence of giant cell arteritis outside the breast (temporal artery, thyroid artery) was noted in a minority of cases. Seven patients received corticosteroid treatment, and all patients recovered without complications. Two patients had an adenocarcinoma of the breast contiguous with the giant cell arteritis. Giant cell arteritis affecting the breast may be underrecognised and should be considered in older women with polymyalgia rheumatica-like symptoms and tender breast mass(es).

Diagnostic and predictive value of the lupus band test in undifferentiated connective tissue disease. A followup study.

The value of the lupus band test (LBT) in predicting outcome of patients with undifferentiated connective tissue disease (CTD) was studied. Thirty-three patients with undifferentiated CTD who had LBT between 1977 and 1982 underwent repeat clinical and serological assessments and LBT at 13 to 59 months followup. Six patients (18%) developed SLE, and 2 (6%) developed rheumatoid arthritis during the followup period. No single, combination, number, or intensity of proteins at the dermal-epidermal junction (DEJ) or epidermal nuclear staining (ENS) could be used to predict which undifferentiated CTD patients would develop SLE at followup. Findings on LBT were not significantly different in patients with undifferentiated CTD versus SLE.