Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.

OBJECTIVE The triggers that induce antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (APV) are largely unknown. However, there have been reports suggesting that hydralazine, propylthiouracil, and several other drugs may cause some cases of APV, and the majority of these cases have been associated with antimyeloperoxidase (anti-MPO) ANCA. Our experience led us to hypothesize that cases of high titers of anti-MPO antibodies are often drug-associated. METHODS In this study, we determined the prevalence of exposure to hydralazine, propylthiouracil, and other drugs previously implicated in APV among 30 patients with vasculitis and the highest titers of anti-MPO antibodies newly detected in our laboratory between 1994 and 1998. The clinical, histologic, and other serologic features of these 30 patients were also examined. RESULTS The 30 study patients accounted for 12% of the 250 new patients with APV and anti-MPO who were tested during the study period. All 30 study subjects had anti-MPO titers that were more than 12 times the median titer of the 250 patients. Ten (33%) of the 30 patients had been exposed to hydralazine and 3 (10%) had been exposed to propylthiouracil. An additional 5 patients (17%) had been exposed to 1 of the other previously reported candidate drugs: 2 to penicillamine, 2 to allopurinol, and 1 to sulfasalazine. One of the patients exposed to hydralazine had also been exposed to allopurinol. In all cases, the clinical and histologic findings were typical of APV. There was a strong association between the presence of antielastase and/ or antilactoferrin antibodies and exposure to candidate drugs. CONCLUSION These data suggest that a sizable proportion of cases of APV with high titers of anti-MPO antibodies are drug-associated, especially following exposure to hydralazine or propylthiouracil. We recommend that the use of these drugs should be sought in cases of anti-MPO-positive vasculitis, particularly among patients with high titers of these antibodies.

[1]  P. Merkel,et al.  Alternating antineutrophil cytoplasmic antibody specificity: drug-induced vasculitis in a patient with Wegener's granulomatosis. , 1999, Arthritis and rheumatism.

[2]  P. Merkel,et al.  ANCA-positive vasculitis associated with allopurinol therapy. , 1998, Clinical and experimental rheumatology.

[3]  M. Pillinger,et al.  Wegener's granulomatosis in a patient receivingpropylthiouracil for Graves' disease , 1998 .

[4]  P Lesavre,et al.  Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization. , 1998, Kidney international.

[5]  P. Merkel,et al.  Prevalence of Antineutrophil Cytoplasmic Antibodies in a Large Inception Cohort of Patients with Connective Tissue Disease , 1997, Annals of Internal Medicine.

[6]  K. Hiromura,et al.  Case of propylthiouracil-induced vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA); review of literature. , 1997, Clinical nephrology.

[7]  A. Collins,et al.  Comparison of anti-GBM antibodies in sera with or without ANCA. , 1997, Journal of the American Society of Nephrology : JASN.

[8]  R. Falk,et al.  ANCA small-vessel vasculitis. , 1997, Journal of the American Society of Nephrology : JASN.

[9]  J. Uetrecht,et al.  Antibodies to myeloperoxidase in propylthiouracil-induced autoimmune disease in the cat. , 1996, Toxicology.

[10]  M. Yaron,et al.  Minocycline induced arthritis associated with fever, livedo reticularis, and pANCA. , 1996, Annals of the rheumatic diseases.

[11]  C. Meyer,et al.  Sulfasalazine pulmonary toxicity in ulcerative colitis mimicking clinical features of Wegener's granulomatosis. , 1996, Chest.

[12]  P. Mathieson,et al.  Coexistent membranous nephropathy and ANCA-positive crescentic glomerulonephritis in association with penicillamine. , 1996, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[13]  R. Parry,et al.  Phenytoin-associated vasculitis and ANCA positivity: a case report. , 1996, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  X. Bosch,et al.  Occurrence of antineutrophil cytoplasmic and antineutrophil (peri)nuclear antibodies in rheumatoid arthritis. , 1995, The Journal of rheumatology.

[15]  M. J. Hurst,et al.  Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with anti-thyroid drug treatment. , 1995, British journal of rheumatology.

[16]  C. Lockwood,et al.  Antigen specificity in hydralazine associated ANCA positive systemic vasculitis. , 1995, QJM : monthly journal of the Association of Physicians.

[17]  M. Tanemoto,et al.  Myeloperoxidase-antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis complicating the course of Graves' disease: report of three adult cases. , 1995, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[18]  W. Gross,et al.  Antineutrophil cytoplasmic autoantibody testing in vasculitides. , 1995, Rheumatic diseases clinics of North America.

[19]  C. Pusey,et al.  Goodpaststure-like syndrome associated with anti-myeloperoxidase antibodies following pencillamine treatment , 1995 .

[20]  F. Otsuka,et al.  ANCA‐associated vasculitis and lupus‐like syndrome caused by methimazole , 1995, Clinical and experimental dermatology.

[21]  D. Veale,et al.  Sulphasalazine-induced lupus in psoriatic arthritis. , 1995, British journal of rheumatology.

[22]  G. Khursigara,et al.  Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils. , 1994, Science.

[23]  B. Burke,et al.  Antineutrophil cytoplasmic autoantibody-positive crescentic glomerulonephritis as a complication of treatment with propylthiouracil in children. , 1994, The Journal of pediatrics.

[24]  C. Dromer,et al.  Sulfasalazine induced lupus in rheumatoid arthritis. , 1994, The Journal of rheumatology.

[25]  R. Bernstein,et al.  Autoantibodies to myeloperoxidase in idiopathic and drug-induced systemic lupus erythematosus and vasculitis. , 1994, British journal of rheumatology.

[26]  R. Goldschmeding,et al.  Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy , 1993, The Lancet.

[27]  J. Velosa,et al.  Prospective study of anti-neutrophil cytoplasmic autoantibody tests in the diagnosis of idiopathic necrotizing-crescentic glomerulonephritis and renal vasculitis. , 1993, Mayo Clinic proceedings.

[28]  J. Sacristán,et al.  Allopurinol Hypersensitivity Syndrome: A Review , 1993, The Annals of pharmacotherapy.

[29]  E. Mark,et al.  Correlation of antineutrophil cytoplasmic antibodies with the extrarenal histopathology of Wegener's (pathergic) granulomatosis and related forms of vasculitis. , 1993, Human pathology.

[30]  P. Bygren,et al.  Anti‐neutrophil cytoplasm antibodies, anti‐GBM antibodies and anti‐dsDNA antibodies in glomerulonephritis , 1992, European journal of clinical investigation.

[31]  J. Uetrecht,et al.  Antimyeloperoxidase antibodies and adverse reactions to clozapine , 1992, The Lancet.

[32]  J. Hed,et al.  Autoantibodies to leucocyte antigens in hydralazine‐associated nephritis , 1992, Journal of internal medicine.

[33]  S. Skates,et al.  Antigen-specific radioimmunoassays for anti-neutrophil cytoplasmic antibodies in the diagnosis of rapidly progressive glomerulonephritis. , 1991, Journal of the American Society of Nephrology : JASN.

[34]  A. Sjöholm,et al.  Antibodies to neutrophil granulocyte myeloperoxidase and elastase: autoimmune responses in glomerulonephritis due to hydralazine treatment , 1991, Journal of internal medicine.

[35]  A. Sjöholm,et al.  Autoantibodies against neutrophil cytoplasm components in systemic lupus erythematosus and in hydralazine‐induced lupus , 1990, Clinical and experimental immunology.

[36]  R. Goldschmeding,et al.  Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. , 1990, Kidney international.

[37]  H. A. Cameron,et al.  The lupus syndrome induced by hydralazine: a common complication with low dose treatment. , 1984, British medical journal.

[38]  B. Leaker,et al.  Autoantibodies to myeloperoxidase in systemic sclerosis. , 1997, The Journal of rheumatology.

[39]  T. Yura,et al.  Antineutrophil cytoplasmic antibodies (ANCA)-associated crescentic glomerulonephritis and propylthiouracil therapy. , 1996, Nephron.

[40]  J. Niles.  Antineutrophil cytoplasmic antibodies in the classification of vasculitis. , 1996, Annual review of medicine.

[41]  F. Kenny,et al.  Granulocytopenia, lupus-like syndrome, and other complications of propylthiouracil therapy. , 1970, The Journal of pediatrics.