Accelerated nodulosis and systemic manifestations during methotrexate therapy for rheumatoid arthritis.

OBJECTIVES: Methotrexate is successfully used in the treatment of arthritis but little is known about its effects on extra-articular manifestations of rheumatoid arthritis. We focused this work on the incidence and clinical course of extra-articular manifestations during long-term treatment with methotrexate. METHODS: The effect of methotrexate on extra-articular manifestations was investigated in 176 patients with rheumatoid arthritis who had obtained, in a prospective study, a good clinical response to methotrexate (10 mg/week) taken for 33 months (range 4-68). RESULTS: Before taking methotrexate, 44 patients (25.1%) had extra-articular manifestations: nodules (n = 40) and vasculitis (n = 9). With methotrexate, nodulosis and vasculitis were stable in 31 cases, improved in 3 and worsened in 10 (23%). Among the 132 patients without extra-articular manifestations before methotrexate therapy, 15 (11%) developed accelerated nodulosis preferentially located on the fingers, 7 had a vasculitis and 3 a pericarditis during methotrexate therapy. Extra-articular manifestations occurred between 1 and 24 months of initiating methotrexate therapy. Rheumatoid factor was positive in 88% of the patients with extra-articular manifestations. No relationship was noted between extra-articular manifestations and HLA type or antinuclear antibodies. In 3 out of 4 patients who developed accelerated nodulosis while taking methotrexate, the addition of hydroxychloroquine (400 mg/day) resulted in a significant reduction in the number and size of the nodules within 3 to 10 months after starting combined therapy. CONCLUSION: These data suggest that methotrexate is not effective in the treatment of extra-articular manifestations in rheumatoid arthritis and that nodulosis may occur in about 11% of patients taking methotrexate therapy for rheumatoid arthritis. The combination of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis that needs to be evaluated.

Arthritis associated with primary agammaglobulinemia: new clues to its immunopathology.

Primary agammaglobulinemia is a rare disorder which is associated with articular symptoms in 11% of patients. Septic arthritis may occur, but often patients complain of chronic oligoarthritis and have a clinical presentation similar to rheumatoid arthritis. We report 2 cases of primary agammaglobulinemia in adults, associated with non-erosive chronic arthritis. Peripheral blood lymphocyte phenotyping showed a predominance of CD8 lymphocytes with a CD4/CD8 ratio < 1. We did not find any abnormalities in cellular immunity. A histological study of the synovium showed chronic synovitis with perivascular CD8 lymphocyte infiltrates. Intravenous infusion of immunoglobulins resulted in a dramatic improvement in the arthritis in both cases. In one patient we noticed a decrease in CD8 lymphocytosis. These results suggest that CD8 lymphocytes are involved in the pathogenesis of the arthritis associated with agammaglobulinemia.

[Rheumatoid aortic insufficiencies: severity of the prognosis]. / Insuffisances aortiques rhumatoïdes: sévérité du pronostic.

Rheumatoid aortic incompetence is infrequent, with only 43 cases published in the literature. Seven additional patients (5 females and 2 males) with rheumatoid arthritis (RA) and aortic incompetence are reported herein. All seven patients had seropositive RA with severe joint disease and extraarticular manifestations (nodules, cutaneous vasculitis, multiple neuritis). Development of aortic incompetence was unrelated to age or duration of RA. The aortic disease was diagnosed upon the development of sudden heart failure (pulmonary edema) in three patients and during a routine evaluation in the other four. The course was extremely severe with a fatal outcome in five patients, of whom the youngest was only 24. Only one patient had valve replacement surgery; however, this patient died 8 days after the procedure. Mean survival in the seven patients was 20 months (range 7-56) from diagnosis and 11 months (range 1-28) from the first manifestation of heart failure. Histologic studies done in the only patient who had surgery demonstrated a rheumatoid granuloma in the pericardium and lymphocytic infiltrates in the pericardium and aortic valve.

The B cell repertoire in rheumatoid arthritis. III. Preferential homing of rheumatoid factor-producing B cell precursors in the synovial fluid.

OBJECTIVE: We sought to compare the frequencies of precursors producing IgM rheumatoid factors (IgM-RFs) in synovial fluid and peripheral blood B cells from patients with rheumatoid arthritis (RA). METHODS: We used limiting-dilution analysis of Epstein-Barr virus-activated B cells from seropositive and seronegative patients. B cell precursors producing IgM against insulin, an irrelevant autoantigen, were also assessed for comparison. RESULTS: On average, IgM-RF-producing precursors were 15-fold higher in the synovial fluid than in the peripheral blood of seropositive RA patients, but not in seronegative RA patients. The frequency of B cell precursors producing IgM against insulin was lower in the synovial fluid than in the peripheral blood of both the seropositive and the seronegative patient groups; moreover, the concentrations were similar in both groups. CONCLUSION: The findings provide evidence against a nonspecific accumulation of IgM-producing cells in the synovial fluid, and suggest that there is an active attraction of the RF-producing B cell precursors toward sites of inflammation in RA.

[Lumbar disk herniation with no surgical treatment. Clinical and x-ray computed tomographic follow-up study]. / Hernies discales lombaires non opérées. Evolution clinique et tomodensitométrique.

The authors have studied the clinical and computed tomographic (CT) follow-up of 50 patients with nerve root symptoms and herniated nucleus pulposus (HNP) who received only a conservative medical treatment. The clinical follow-up showed that after 23 months 38 patients (76 percent) did not require surgery and 63 percent of these had good or very good results. Follow-up CT scans, performed in 20 patients, found spontaneous disappearance of NP in 10 cases and partial regression in 3 cases. Several mechanisms may explain this regression, including fragmentation and sequestration of the disc fragment, dehydration and shrinkage of the HNP and its reintegration into the annulus. On the other hand, HNP persisted in some patients who had become asymptomatic, and it was also found in an asymptomatic control subject. These data demonstrate that clinical and CT findings may be dissociated. Not all CT scan-documented HNPs require interventional therapy. Except in case of emergency, surgical treatment should be considered only after failure of conservative medical treatment and whenever clinical and CT data are concordant. CT and other imaging procedures, such as myelography and nuclear magnetic resonance, should only be used preoperatively in patients with appropriate clinical findings.