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Journal ArticleDOI

Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy

11 Sep 1993-The Lancet (Elsevier)-Vol. 342, Iss: 8872, pp 651-652
TL;DR: Antineutrophil cytoplasmic antibodies (ANCA) have been described in association with several vasculitic disorders, such as vasculitis associated with propylthiouracil therapy as mentioned in this paper.
About: This article is published in The Lancet.The article was published on 1993-09-11. It has received 311 citations till now. The article focuses on the topics: Vasculitis & Anti-neutrophil cytoplasmic antibody.
Citations
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Journal ArticleDOI
TL;DR: Adverse cutaneous reactions to drugs are frequent, affecting 2 to 3 percent of hospitalized patients, and prompt withdrawal of the offending drug is often the most important action to minimize morbidity.
Abstract: Although the rate of acute severe adverse cutaneous reactions to medications is low, these reactions can affect anyone who takes medications and can result in death or disability1. Even a small number of cases associated with a particular drug may alter the recommendations for its use2–4. Prompt differentiation of severe adverse cutaneous reactions from less serious skin disorders may be difficult. Rapid recognition of severe reactions is essential. Prompt withdrawal of the offending drug is often the most important action to minimize morbidity. Adverse cutaneous reactions to drugs are frequent, affecting 2 to 3 percent of hospitalized . . .

1,425 citations

Journal ArticleDOI
TL;DR: Protean clinical manifestations, combined with the etiologic nonspecificity of the histologic lesions, complicate the diagnosis of specific forms of vasculitis.
Abstract: Vasculitis is inflammation of vessel walls. It has many causes, although they result in only a few histologic patterns of vascular inflammation. Vessels of any type in any organ can be affected, a fact that results in a wide variety of signs and symptoms. These protean clinical manifestations, combined with the etiologic nonspecificity of the histologic lesions, complicate the diagnosis of specific forms of vasculitis. This is problematic because different vasculitides with indistinguishable clinical presentations have very different prognoses and treatments. For example, a patient with purpura, nephritis, and abdominal pain caused by Henoch–Schonlein purpura usually has a good prognosis . . .

1,187 citations

Journal ArticleDOI
TL;DR: Any report of positive neutrophil fluorescence issued before the ELISA results are available should indicate that positive fluorescence alone is not specific for the diagnosis of Wegener granulomatosis or microscopic polyangiitis and that decisions about treatment should not be based solely on the ANCA results.
Abstract: Antineutrophil cytoplasmic antibody (ANCA) tests are used to diagnose and monitor inflammatory activity in the primary systemic small vessel vasculitides. ANCA is best demonstrated in these diseases by using a combination of indirect immunofluorescence (IIF) of normal peripheral blood neutrophils and enzyme-linked immunosorbent assays (ELISAs) that detect ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). For ANCA testing in "new" patients, IIF must be performed on all serum samples. Serum samples containing ANCA, any other cytoplasmic fluorescence, or an antinuclear antibody (ANA) that results in homogeneous or peripheral nuclear fluorescence then should be tested in ELISAs for PR3-ANCA and MPO-ANCA. Optimally, ELISAs for PR3-ANCA and MPO-ANCA should be performed on all serum samples. Inclusion of the most recent positive sample in the IIF or ELISA may help demonstrate a change in antibody level. Reports should use recommended terms. Any report of positive neutrophil fluorescence issued before the ELISA results are available should indicate that positive fluorescence alone is not specific for the diagnosis of Wegener granulomatosis or microscopic polyangiitis and that decisions about treatment should not be based solely on the ANCA results.

561 citations

Journal ArticleDOI
TL;DR: The data have now been confirmed and support the view that ANCA-associated glomerulonephritis and vasculitis is, indeed, a distinct disease category, and a critical reappraisal of the diagnostic significance of AN CA-testing seems justified.

413 citations

References
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Journal ArticleDOI
TL;DR: It is proposed that, in patients with necrotizing vasculitis, ANCA-induced release of toxic oxygen radicals and noxious granule enzymes from cytokine-primed neutrophils could be mediating vascular inflammation.
Abstract: Anti-neutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of most patients with pauci-immune necrotizing vasculitis and pauci-immune crescentic glomerulonephritis. The current study demonstrates an effect of these autoantibodies on neutrophil function in vitro. ANCA cause normal human neutrophils to undergo an oxidative burst and degranulate. Both ANCA phenotypes (i.e., cytoplasmic-pattern ANCA and myeloperoxidase-specific ANCA) induce neutrophil activation. ANCA sera and purified immunoglobulins significantly increase the release of reactive oxygen species when compared with controls. ANCA, in a dose-dependent manner, induce the release of primary granule contents. These effects are markedly enhanced by priming neutrophils with tumor necrosis factor. Flow cytometry studies demonstrate the presence of myeloperoxidase on the surface of neutrophils after cytokine priming, indicating that primed neutrophils have ANCA antigens at their surfaces to interact with ANCA. These observations suggest an in vivo pathogenetic role for ANCA. We propose that, in patients with necrotizing vasculitis, ANCA-induced release of toxic oxygen radicals and noxious granule enzymes from cytokine-primed neutrophils could be mediating vascular inflammation.

1,208 citations

Journal ArticleDOI
TL;DR: Antibodies against myeloperoxidase (anti‐MPO) and elastase, two granulocyte lysosomal enzymes, were found in patients with SLE but not in those with PSS, except for one patient who had anti‐ MPO.
Abstract: Anti-neutrophil cytoplasm antibody (ANCA) has been shown to be no marker of systemic lupus erythematosus (SLE) including lupus nephritis or of progressive systemic sclerosis (PSS). Antibodies against myeloperoxidase (anti-MPO) and elastase, two granulocyte lysosomal enzymes, were found in patients with SLE but not in those with PSS, except for one patient who had anti-MPO. Anti-MPO was present in 21% of patients with SLE, and at low concentrations in about 80% of these cases. Anti-elastase was found in four patients with SLE. In another group of six patients with a SLE-like syndrome induced by anti-hypertensive treatment with the anti-hypertensive hydralazine, anti-MPO antibodies occurred in all six, and anti-elastase antibodies in five. Monitored during a 2-year follow-up period, anti-MPO antibodies were found to persist, whereas anti-elastase antibodies were rapidly eliminated, after withdrawal of the drug.

165 citations

Journal ArticleDOI
TL;DR: C‐ANCA IgG from eight patients with active WG significantly inhibited PR3 proteolytic activity, particularly towards elastin, which indicates the existence of a hitherto unknown property of C‐ ANCA, which may be of importance in the pathogenesis of WG.
Abstract: Classic anti-neutrophil cytoplasmic autoantibodies (C-ANCA) are disease-specific markers of Wegener's granulomatosis (WG). The possible pathogenetic role of these autoantibodies, which are directed against Proteinase 3 (PR3), is not yet clear. We studied the effect of C-ANCA on PR3 proteolytic activity and on the complexation of PR3 with alpha 1-antitrypsin (alpha 1AT). C-ANCA IgG from eight patients with active WG significantly inhibited PR3 proteolytic activity, particularly towards elastin (median 84.2% inhibition). C-ANCA IgG significantly inhibited the complexation of PR3 with alpha 1AT (median 58.8% inhibition). Moreover, addition of purified PR3 to C-ANCA-positive sera from WG patients yielded less complexes with alpha 1AT (median 44.8%) compared with sera containing perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) or ANCA-negative sera. These findings indicate the existence of a hitherto unknown property of C-ANCA, which may be of importance in the pathogenesis of WG.

91 citations

Journal ArticleDOI
TL;DR: The demonstration of autoantibodies to neutrophil cytoplasmic antigens (ANCA) in systemic vasculitides such as Wegener's granulomatosis, classic polyarteritis nodosa and the Churg Strauss syndrome and idiopathic crescentic glomerulonephritis has placed these disorders within the spectrum of autoimmune diseases.

88 citations

Journal ArticleDOI
01 Feb 1980-JAMA
TL;DR: A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil, and direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition.
Abstract: A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil. Histopathologic changes of acute vasculitis of the superficial and deep dermal blood vessels accompanied by fibrin thrombi formation were found in biopsy specimens of the cutaneous lesions. Direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition. The literature disclosed five cases with similar features associated with propylthiouracil therapy. Characteristic cutaneous findings include a recurrent, self-limited, symmetrical purpuric eruption that can involve the face or earlobes. Clinicians should recognize these changes as a cutaneous sign of a vasculitis associated with propylthiouracil therapy. ( JAMA 243:458-461, 1980)

52 citations