Propylthiouracil-Induced Vasculitis With Alveolar Hemorrhage Confirmed by Clinical, Laboratory, Computed Tomography, and Bronchoscopy Findings: A Case Report and Literature Review

Introduction Propylthiouracil (PTU) is commonly used to treat hyperthyroidism and can induce antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although this is a rare side effect, ANCA-associated vasculitis can progress to severe disease if its diagnosis and treatment are delayed, leading to a poor prognosis. Case Presentation A 43-year-old woman with Graves’ disease developed pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) associated with ANCA against myeloperoxidase and proteinase-3 that was confirmed by computed tomography (CT) and bronchoscopy and treated with PTU. The symptoms and signs of alveolar hemorrhage were rapidly resolved after PTU withdrawal and treatment with corticosteroids. After 6 months of follow-up, the patient maintained complete ANCA-negative clinical remission status, as confirmed by normal CT and bronchoscopy findings. To our knowledge, this is the first documented case of bronchoscopic comparison of PTU-induced DAH before and after steroid treatment. Conclusions Patients treated with PTU should be closely monitored and followed up, even if the drug has been used for several years. When patients develop progressive dyspnea with alveolar opacities on chest imaging that cannot be explained otherwise, alveolar hemorrhage should be an important differential diagnosis while investigating the case. Early diagnosis and prompt discontinuation of the PTU treatment are essential for improving patient outcomes.

[1]  R. Wu,et al.  Propylthiouracil-induced autoimmune syndromes: 11 case report , 2012, Rheumatology International.

[2]  O. Dónal,et al.  SPONTANEOUS REMISSION OF ENCEPHALOPATHY ASSOCIATED WITH AUTOIMMUNE THYROID DISEASE IN A PATIENT WITH GRAVES' DISEASE: A RARE OCCURRENCE IN A RARE CLINICAL PICTURE , 2011 .

[3]  V. Cottin,et al.  Alveolar hemorrhage in vasculitis: primary and secondary. , 2011, Seminars in respiratory and critical care medicine.

[4]  P. Sá-Couto,et al.  Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leukocytoclastic vasculitis induced by propylthiouracil confirmed by positive patch test: a case report and review of the literature , 2011, Cutaneous and ocular toxicology.

[5]  Jae Ho Lee,et al.  Propylthiouracil-induced nonspecific interstitial pneumonia. , 2011, Chest.

[6]  T. Yao,et al.  Occult Pulmonary Hemorrhage as a Rare Presentation of Propylthiouracil-Induced Vasculitis , 2011, Pediatrics.

[7]  G. Choi,et al.  Propylthiouracil‐induced DRESS syndrome confirmed by a positive patch test , 2010, Allergy.

[8]  Joon-Hee Choi,et al.  A Case of p-ANCA-Positive Propylthiouracil-Induced Pyoderma Gangrenosum. , 2010, Annals of dermatology.

[9]  B. Anić,et al.  Propylthiouracil-induced anti-neutrophil cytoplasmic antibodies (ANCA) skin vasculitis: the first case reported in Croatia. , 2010, Acta dermatovenerologica Croatica : ADC.

[10]  F. Irani,et al.  Propylthiouracil-induced leucocytoclastic vasculitis with pulmonary hemorrhage treated with plasmapheresis. , 2009, The American journal of the medical sciences.

[11]  Min Chen,et al.  Long-term outcomes of patients with propylthiouracil-induced anti-neutrophil cytoplasmic auto-antibody-associated vasculitis. , 2008, Rheumatology.

[12]  H-y Wang,et al.  Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. , 2006, Kidney international.

[13]  S. Zorić,et al.  Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides , 2005, Arthritis research & therapy.

[14]  M. Samuels,et al.  Central nervous system vasculitis caused by propylthiouracil therapy: a case report and literature review. , 2005, Thyroid : official journal of the American Thyroid Association.

[15]  S. Matsumoto,et al.  Thoracic Manifestation of Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (MPO-ANCA)-Related Disease: CT Findings in 51 Patients , 2004, Journal of computer assisted tomography.

[16]  N. Ishikawa,et al.  Frequency of appearance of myeloperoxidase‐antineutrophil cytoplasmic antibody (MPO‐ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO‐ANCA and clinical manifestations , 2001, Clinical endocrinology.

[17]  N. Sera,et al.  Treatment with propylthiouracil is associated with appearance of antineutrophil cytoplasmic antibodies in some patients with Graves' disease. , 2000, Thyroid : official journal of the American Thyroid Association.

[18]  P. Cockwell,et al.  Case of propylthiouracil-induced ANCA associated small vessel vasculitis. , 1998, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

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

[20]  C. Goebel,et al.  Neutrophils and drug metabolism. , 1995, Science.

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

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

[23]  S. Stankus,et al.  Propylthiouracil-induced hypersensitivity vasculitis presenting as respiratory failure. , 1992, Chest.

[24]  S. Piantadosi The adverse effect of blood transfusion in lung cancer. , 1992, Chest.

[25]  J. Uetrecht,et al.  Oxidation of propylthiouracil to reactive metabolites by activated neutrophils. Implications for agranulocytosis. , 1991, Drug metabolism and disposition: the biological fate of chemicals.

[26]  E. Lee,et al.  Mechanism of inactivation of myeloperoxidase by propylthiouracil. , 1990, Biochemical pharmacology.

[27]  J. Ramírez,et al.  When to suspect pulmonary vasculitis: radiologic and clinical clues. , 2010, Radiographics : a review publication of the Radiological Society of North America, Inc.

[28]  F. Schaefer,et al.  Distinct roles of Mac-1 and its counter-receptors in neonatal obstructive nephropathy. , 2006, Kidney international.

[29]  B. Goichot,et al.  Antithyroid drugs , 2005, The New England journal of medicine.

[30]  M. Ikeda-Saito,et al.  Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions, are evolutionarily related members of the same gene family , 1988, Proteins.