A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group.

The ability of antimalarials to moderate severe disease activity in systemic lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long-term effectiveness of maintaining treatment with hydroxychloroquine sulphate (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as part of a 24-week withdrawal trial were evaluated for an additional 3 years. The primary outcome was time to a major flare of SLE which resulted in either the institution of or an increase in the current dosage of prednisone of 10 mg/day or more, or institution of therapy with immunosuppressive agents. Secondary outcomes included the specific subtype of these major flares (glomerulonephritis, vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to-treat analysis was conducted. Over the 42 months of study, 11 of 22 (50%) patients randomized initially to placebo, and seven of 25 (28%) patients randomized to continue treatment experienced a major flare. The relative risk of major flare for those randomized to continue HCQ compared with controls was 0.43 (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95% CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65 (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative risk of hospitalization for major flare for patients randomized to continue hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not statistically significant, they are compatible with the clinical belief that HCQ has a long-term protective effect against major disease flares in SLE and suggest that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to 12% increase).

Risk factors for adult Still's disease.

OBJECTIVE: To assess risk factors for adult Still's disease (ASD). METHODS: A matched case-control study of 60 patients with ASD and 60 same sex siblings closest in age was conducted. Subjects were recruited from cohorts in Eastern Canada, Pittsburgh, and the Arthritis, Rheumatism, and Aging, Medical Information Systems (ARAMIS). A questionnaire was used to obtain data on demographic characteristics, education, income, occupation, exposure to toxic substances, stress, and medical history. RESULTS: 116 patients with ASD were identified, of which 104 participated. 86 identified same sex siblings, of which 60 replied. When compared to same sex siblings, ASD patients were similar with respect to education and occupation but had a trend to higher median income. There were no significant associations of ASD with smoking, alcohol consumption, individual toxic substances, vaccination, blood transfusion, minor or major surgery, pregnancy, or diet in the year preceding disease onset. There were no significant associations with tonsillectomy or adenoidectomy, appendectomy, asthma, hay fever, allergy shots, or pregnancy at any time preceding the onset of disease. There was a statistically nonsignificant increase in a history of exposure to coal dust [odds ratio (OR) 3.0; 95% confidence interval (CI) 0.30 to 28.84], in allergy preceding the onset of disease (OR 2.67; 95% CI 0.71 to 10.05), and in oral contraceptive use in the year preceding onset (OR 2.00; 95% CI 0.18 to 22.06). Stressful life events (OR 2.56; 95% CI 1.18 to 5.52) in the year preceding onset was significantly associated with increased risk for ASD. This positive association should be treated with caution unless confirmed by a separate study. CONCLUSION: This exploratory study of risk factors for ASD draws attention to stress as a potentially important risk factor, while likely excluding a considerable number of others.

Constrictive bronchiolitis obliterans following gold therapy for psoriatic arthritis.

A 41 year old male with psoriatic arthritis developed progressive dyspnoea and airflow obstruction following 4 months of intramuscular gold therapy. Open lung biopsy revealed bronchiolitis obliterans of the constrictive type. This case suggests a possible aetiological role for gold in the pathogenesis of constrictive bronchiolitis obliterans, or alternatively an association between psoriatic arthritis and this inflammatory airway condition.

A controlled study of the long-term prognosis of adult Still's disease.

PURPOSE: To assess the long-term prognosis of patients with adult Still's disease for physical and psychological disability, pain, social functioning, social support, medication use, formal education, occupation, time lost from work, and family income, and to contrast these results with those of same-sex sibling controls. PATIENTS AND METHODS: Patients were recruited from medical center-based cohorts in Pittsburgh and Eastern Canada and from a national survey of rheumatologists. Patients and same-sex sibling controls completed the Health Assessment Questionnaire for physical disability, the psychological and social function domains of the Arthritis Impact Measurement Scales, and the Interpersonal Skills Evaluation List questionnaire for social support, and replied to questions on medication use, formal education, occupation, time lost from work, and family income. RESULTS: One hundred four of 111 eligible adult Still's patients (94%) provided data. They identified 86 same-sex sibling controls, of whom 60 (70%) participated. The mean duration of adult Still's disease was 10 years. Approximately half of patients continued to require medication even 10 years after diagnosis. Patients had significantly higher levels of pain, physical disability, and psychological disability when compared with the controls. However, the levels of pain and physical disability were low compared to patients with other rheumatic diseases. Educational achievement, occupational prestige, social functioning and support, time lost from work, and family income were similar for both patients and controls. CONCLUSIONS: Despite causing disability, pain, and, in many, the need for long-term medication, patients with adult Still's disease are resilient. The disease did not interfere with educational attainment, occupational prestige, social functioning and support, time lost from work, or family income.

Prognostic factors in systemic necrotizing vasculitis of the polyarteritis nodosa group--a review of 45 cases.

OBJECTIVE: To evaluate the prognostic importance for mortality of age, fever, hypertension, and involvement of renal, cardiac, neural, pulmonary, gastrointestinal and cutaneous systems as well as elevated transaminases, thrombocytosis, leukocytosis, anemia, smoking status, comorbid diseases and disease severity, in 45 patients with systemic necrotizing vasculitis (SNV) identified by histological, radiological, and clinical criteria. METHODS: Kaplan-Meier nonparametric survival functions and Cox proportional hazards regression models were used. RESULTS: Twenty-four deaths were observed during the 5 year mean followup period. Five year survival was 58%. Comorbidity and severity of involvement were not predictive of mortality. Multivariable survival analysis showed that cardiac or renal involvement was associated with a relative risk of dying of 2.91 (95% CI: 1.25, 6.77). Elevated serum transaminase demonstrated a trend to having a protective effect [relative risk of 0.14 (95% CI: 0.02, 1.07)]. No other variable was an independent predictor of fatality. No cohort effect could be documented following the introduction of cytotoxic drugs in the treatment of SNV. CONCLUSION: SNV remains associated with a high mortality due largely to renal or cardiac involvement.

Arthritis impact measurement scales: reliability of a French version and validity in adult Still's disease.

The Arthritis Impact Measurement Scales (AIMS) questionnaire was administered to 57 patients with adult Still's disease (ASD) and 104 controls. Six of the 9 scales were consistent for both groups (Cronbach's alpha greater than or equal to 0.70). Two scales, Mobility and Dexterity, were consistent for ASD only (alpha greater than or equal to 0.70). The reliability of a French version of the AIMS was similar to the standard AIMS. Of the 13 associations evaluating criterion related validity of the AIMS in ASD, 11 were statistically significant. We conclude that the French and standard AIMS are comparable and that this questionnaire is reliable and valid for assessing outcome in ASD.

Comparison of the efficacy and safety of loratadine, terfenadine, and placebo in the treatment of seasonal allergic rhinitis.

The efficacy and safety of loratadine, 40 mg once daily, were compared with terfenadine, 60 mg twice daily, and placebo in controlling symptoms of ragweed hay fever. The study was a randomized, multicentric, parallel-group, double-blind design involving 280 patients divided into three groups receiving either loratadine, terfenadine, or placebo for a period of 14 days in the autumn of 1984. Both loratadine and terfenadine demonstrated a statistically greater reduction in symptom score compared to placebo. They were not statistically different from each other, and there was no statistical difference in the incidence of side effects between the two drugs.

Rheumatic fever-associated B cell alloantigens as identified by monoclonal antibodies.

Mice immunized with B lymphocytes obtained from patients who had had well-documented rheumatic fever in the past yielded 2 monoclonal antibodies, termed 83S19.23 and 256S10, which identified certain alloantigens present on the B cells of these patients. The frequency of the B cell marker detected by clone 83S19.23 in rheumatic fever patients was found to be 59%, 77%, and 74% in India, New Mexico, and New York, respectively. Monoclonal antibody 256S10 identified 75% of those rheumatic fever patients who were nonreactive to clone 83S19.23. Thus, the 2 antibodies identify approximately 92% of all rheumatic fever patients and suggest the presence of a diallelic genetic marker for susceptibility to rheumatic fever.

T-cell subsets in multiple sclerosis: lack of correlation between helper and suppressor T cells and the clinical state.

Peripheral blood T-lymphocyte subsets were investigated in a group of 26 multiple sclerosis (MS) patients of different clinical categories and compared to those of 15 normal controls and 7 other patients with known immunoregulatory disorders. In addition 17 well-documented acute relapses in 11 MS patients were also studied, some of whom were tested serially prior to, during, and after the acute attack. Using three different commercial preparations of monoclonal antibodies directed against human T3, T4, and T8 lymphocyte markers, none of the MS patients irrespective of disease category exhibited any changes in the absolute numbers of T-cell subsets or ratios thereof; this was true during either quiescent or active stages of the disease. In contrast, several patients with known immunoregulatory disorders exhibited clear changes in T4/T8 ratios. Factors such as type of patient studied, sampling error, and methods of isolation of mononuclear cells, as well as source of monoclonal antibody, failed to explain the lack of change in T-cell subsets in these patients. Thus, our data fail to confirm the previous reports of a decrease in the absolute numbers of T8 cells or the increase in the T4/T8 ratios in active or quiescent MS patients. These negative findings underscore the need for further studies relating these markers to meaningful functional properties of these cells and their interaction with the relevant target organs.

Lymphapheresis in rheumatoid arthritis. The clinical and laboratory effects of a limited course of cell depletion.

Five patients with active rheumatoid arthritis refractory to conventional therapy were treated with a limited course of lymphapheresis--6 procedures during a two week in-hospital stay. Statistically significant improvements in assessments of rheumatoid activity were apparent by 2 weeks following lymphapheresis and persisted for 10-12 weeks. An average of 2.08 X 10(10) lymphocytes were removed from the patients and lymphopenia appeared in the 4 in whom the average daily rate of removal exceeded 1 X 10(9). However, the results of laboratory testing indicate that immuno-suppression, as based on evaluations of skin test reactivity to delayed hypersensitivity antigens and on the proportion of T cells following lymphapheresis, was not required for therapy to be deemed effective.