[Internal medicine: Which missions? And which future?].
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Biomedical subjects
Publications and source records attributed to L Guillevin.
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OBJECTIVES: The knowledge of systemic necrotizing vasculitides improved since new classifications have been established along with a better understanding of pathogenesis of the diseases. The major vasculitides are described herein. CURRENT KNOWLEDGE AND KEY POINTS: Pathogenesis plays now a major role for classifying diseases and influences the diagnostic strategies. The prospective therapeutic trials established by French and European groups are largely based on our better knowledge of the diseases. FUTURE PROSPECTS AND PROJECTS: Despite the good results obtained with and demonstrated in prospective trials, the vasculitides remain severe and deserve new studies testing new drugs but also strategies based on prognostic factors and scores which should play a major role in treatments decision.
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OBJECTIVES: To examine the potential association of human B19 or V9 erythrovirus infection and onset of ANCA-positive vasculitides. METHODS: We tested the sera of 13 adults with newly diagnosed ANCA-positive vasculitides. Each was age- and sex-matched to three sera obtained from healthy controls. All samples were tested for B19- and V9-specific immunoglobulin (Ig) G and IgM antibodies (Ab) (third-generation ELISA), and B19 or V9 DNA was sought with the polymerase chain reaction. Statistical analysis was performed by conditional logistic regression. RESULTS: Patient diagnoses comprised six cases of Wegener's granulomatosis, six of microscopic polyangiitis and one of Churg-Strauss syndrome. IgG Ab to B19 were detected equally in patient and control sera (77 and 79% respectively) (odds ratio=0.84, P=0.84). All 13 cases and 39 controls were negative for IgM Ab and viral DNA. CONCLUSION: These results suggest that neither acute nor chronic B19 or V9 infection is an aetiological factor in ANCA-associated vasculitides.
Primary low grade marginal zone B cell lymphoma (MZL) of the breast and localised mammary amyloidosis are exceedingly rare entities. This report describes the case of a woman with long standing Sjögren's syndrome presenting with asymptomatic MZL of the breast showing plasmacytic differentiation, associated with local ductular amyloidosis. The lesion was discovered incidentally in breast tissue resected for microcalcifications. Immunohistochemistry revealed kappa light chain restriction, supporting the neoplastic nature of the infiltrate. A retrospective molecular study of the salivary gland biopsy showed a B cell clone. This is the first report of the association of human mammary ductular amyloidosis with cartwheel shaped material identical to corpora amylacea, usually seen in brain, lung, and prostate, but unknown in the human breast. The excellent outcome without treatment seen in this patient further emphasises the need to distinguish between MZL with plasmacytic differentiation and extramedullary plasmacytoma.
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OBJECTIVE: Evidence indicates that tumour necrosis factor (TNF) is a major agent in the pathogenesis of vasculitis. We studied the short-term effect of anti-TNF-alpha antibody in systemic vasculitis patients refractory to steroids and immunosuppressive agents. METHODS: Ten patients refractory to corticosteroids and at least one immunosuppressant and who had persistently active disease or a new flare were included. Seven had Wegener's granulomatosis, two had rheumatoid arthritis-associated vasculitis and one had cryoglobulinaemia with mean duration of 9.1, 21.5 and 17 yr. They received infliximab (5 mg/kg) on days 1, 14, 42 and then every 8 weeks. Immunosuppressants were stopped between days 0 and 42 for eight patients, while the steroid dose was maintained or lowered. The treatment response was evaluated clinically with the Birmingham Vasculitis Activity Score 2000 (BVAS). RESULTS: Complete or partial remission was observed in all patients. The mean BVAS at entry was 9.1 (range 4-15) and had declined to 1.9 (range 0-4) by day 42 and 1.3 (range 0-4) at 6 months; BVAS of 0 was recorded for four patients on day 42 and for five at 6 months. The only adverse effect was cutaneous eruption in two patients. CONCLUSION: Anti-TNF-alpha successfully induced prompt symptomatic responses in patients with systemic vasculitis not responding to conventional treatment. Infliximab was well tolerated during the short-term follow-up.