Gao Y, Chen M, Ye H, et al. Long-term outcomes of patients with propylthiouracil-induced anti-neutrophil cytoplasmic auto-antibody-associated vasculitis

Department of Nephrology, Peking University First Hospital, Beijing 100034, PR China.
Rheumatology (Oxford, England) (Impact Factor: 4.48). 08/2008; 47(10):1515-20. DOI: 10.1093/rheumatology/ken321
Source: PubMed


It was well known that propylthiouracil (PTU) could induce ANCA-associated vasculitis (AAV) and clinical evident vasculitis could resolve after cessation of PTU with or without immunosuppressive therapy. However, the treatment strategy for patients with PTU-induced AAV remained inconclusive and their long-term outcomes were lacking. The aim of our study was to summarize these data.
Fifteen patients with PTU-induced AAV, receiving immunosuppressive agents for <12 months and following over 24 months, were selected in the current study. The clinical and pathological data, including treatment protocols and outcomes, were retrospectively investigated.
All the patients were followed for a mean of 55.0 (25-98) months. PTU was discontinued upon diagnosis of PTU-induced AAV. Immunosuppressive therapy was administrated only for patients with vital organ involvements, such as lung and kidney, and lasted only 7.9 +/- 3.3 (0.27-12) months. No relapse of vasculitis occurred during follow-up, even after withdrawal of immunosuppressive therapy. Twelve (80%) patients remained in complete remission and one patient remained in partial remission at the latest follow-up. Two patients were treatment resistant due to late referral and late withdrawal of PTU, both of them progressed to end-stage renal disease. For uncontrolled hyperthyroidism on presentation, six patients switched to methimazole and none of them experienced relapse of vasculitis.
The long-term outcomes of patients with PTU-induced AAV were relatively good. PTU should be discontinued immediately after diagnosis. Immunosuppressive therapy may be only used in patients with vital organ involvements, and a long-term maintenance therapy may not be necessary.

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    • "Xiao et al.[4] found that transfer of anti-MPO IgG from MPO-deficient mice immunized with mouse MPO into wild-type mice led to pauci-immune vasculitis. Our previous studies found that in PTU-induced AAV, the most important target antigen of ANCA is MPO [14], and the immunologic characteristics of MPO-ANCA are associated with the development of PTU-induced ANCA-associated vasculitis [25,26]. "
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    ABSTRACT: Increasing evidence has suggested that linear epitopes of antineutrophil cytoplasmic antibody (ANCA) directed to myeloperoxidase (MPO) might provide clues to the pathogenesis of propylthiouracil (PTU)-induced ANCA-associated vasculitis (AAV). This study mapped epitopes of MPO-ANCA in sera from patients with PTU-induced MPO-ANCA (with or without vasculitis) and primary AAV, aiming to analyze certain epitopes associated with the development of PTU-induced AAV. Six recombinant linear fragments, covering the whole amino acid sequence of a single chain of MPO, were produced from Escherichia coli. Sera from 17 patients with PTU-induced AAV, 17 patients with PTU-induced MPO-ANCA but without clinical evidence of vasculitis and 64 patients with primary AAV were collected at presentation. Of the 17 patients with PTU-induced AAV, 12 also had sera at remission. The epitope specificities were detected by enzyme-linked immunosorbent assay using the recombinant fragments as solid phase ligands. Compared with patients with PTU-induced MPO-ANCA but without clinical vasculitis, sera from PTU-induced AAV patients showed significantly higher reactivity against the H1 fragment of MPO (optical density values: 0.17 (0.10 to 0.35) versus 0.10 (0.04 to 0.21), P = 0.038) and could recognize a significantly higher number of fragments (2 (0 to 4) versus 1 (0--2), P = 0.026). Compared with sera from primary AAV patients, sera from PTU-induced AAV patients had significantly higher reactivity to the P fragment and the H4 fragment (47.1% versus 14.1%, P <0.001; 41.2% versus 14.1%, P = 0.034, respectively), and could recognize a significantly higher number of fragments (2 (0 to 4) versus 1 (0 to 2), P = 0.013]. Among the 12 PTU-induced AAV patients with sequential samples, the number of fragments recognized in remission was significantly less than that in initial onset (2 (0 to 4) versus 0 (0 to 0.75), P <0.001]. Linear epitopes of MPO molecules might be associated closely with PTU-induced AAV. In particular, the P and H4 fragments may be important epitopes in PTU-induced AAV.
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    • "There is also growing evidence for their pathogenicity, per se, in in vitro and in vivo studies [4]. However, paradoxically, elevation of serum ANCA titers has also been observed in diverse conditions such as rheumatic diseases [3, 5], inflammatory bowel diseases [3, 5], infectious disorders [5, 6], and drug-induced syndromes [7], which creates a clinical puzzle. "
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    ABSTRACT: Detection of circulating anti-neutrophil cytoplasmic antibody (ANCA) provides a powerful clue in the diagnosis of vasculitis, but the clinical interpretation of the results is difficult in some cases. Here, we describe the case of a 65-year-old man who underwent hemodialysis due to focal segmental glomerulosclerosis and abruptly developed hemoptysis 14 years after a renal biopsy. At the time of the biopsy, computed tomography (CT) showed interstitial shadows in the lungs and pleural thickening, indicating pneumoconiosis that was accompanied by tuberculosis. Circulating myeloperoxidase-ANCA (10.5-32.5 U/ml) was subsequently noted, but the significance of this observation was unclear due to the preexisting disorders in the lungs and kidneys. Potent immunosuppressive therapies were avoided because of the pulmonary lesions and decreased renal function. There were few changes noted on follow-up CT, but infiltrative shadows emerged in the bilateral lungs, consistent with hemoptysis. The hemorrhagic shadows completely disappeared shortly after initiation of steroid therapy, with normalization of the serum ANCA level. Herein, we report this case, with an emphasis on the clinical dilemma faced in deciding the appropriate treatment. The findings in the case provide deep insights into clinical management of ANCA-positive patients.
    Full-text · Article · Oct 2013
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    • "Patients developing PTU-induced ANCA-associated vasculitis have been shown to have a significant higher titre and affinity of anti-MPO antibodies as compared with ANCApositive patients without developing vasculitis [21]. Gao and coworkers found significantly decreased affinity and/or titre of anti-MPO antibodies after cessation of PTU and initiation of immunosuppressive therapy in patients with PTU-induced ANCA-associated vasculitis [22] [32]. Therefore , the titre and affinity of anti-MPO antibodies might be clinical markers for the development of PTU-induced ANCA-associated vasculitis.Further research is needed to establish this association. "
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    ABSTRACT: Propylthiouracil (PTU) is a frequently prescribed drug in the treatment of hyperthyroidism. The use of PTU is, however, accompanied by numerous potentially serious side effects including vasculitis. PTU-related vasculitides can present as haematuria, pulmonary haemorrhage, or cutaneous lesion together with aspecific symptoms such as fever, myalgia, arthralgia, and fatigue. Cerebral involvement is seldom observed. We present a 49-year-old female with Graves' disease and asthma, who developed paresis of the proximal extremities, eosinophilia, pulmonary, and cutaneous lesions following treatment with PTU. A cerebral vasculitis consistent with Churg-Strauss syndrome (CSS) was suspected. Although cerebral involvement is seldom observed with PTU treatment, cerebral vasculitis should be considered in patients developing CNS symptoms.
    Full-text · Article · Mar 2009 · International Journal of Rheumatology
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