title: Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides.
abstract: Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.
authors.affiliation: Institute of Allergy and Clinical Immunology, Clinical Centre of Serbia, Belgrade, Serbia and Montenegro. branka_bonaci@yahoo.com
authors.forename: Branka
authors.initials: B
authors.lastname: Bonaci-Nikolic
authors.forename: Milos M
authors.initials: MM
authors.lastname: Nikolic
authors.forename: Sladjana
authors.initials: S
authors.lastname: Andrejevic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Zoric
authors.forename: Mirjana
authors.initials: M
authors.lastname: Bukilica
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis* / Q000276:immunology; D000918:Antibody Specificity; D013956:Antithyroid Agents / Q000009:adverse effects*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D015267:Churg-Strauss Syndrome / Q000139:chemically induced / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D014890:Granulomatosis with Polyangiitis / Q000139:chemically induced / Q000276:immunology; D006111:Graves Disease / Q000150:complications / Q000188:drug therapy; D050031:Hashimoto Disease / Q000150:complications / Q000188:drug therapy; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy; D047468:Immunoprecipitation; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D008713:Methimazole / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D053146:Myeloblastin; D009391:Nephelometry and Turbidimetry; D009195:Peroxidase / Q000276:immunology; D010488:Polyarteritis Nodosa / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000276:immunology; D011441:Propylthiouracil / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000276:immunology; D012867:Skin / Q000473:pathology; D014657:Vasculitis / Q000145:classification* / Q000188:drug therapy / Q000276:immunology; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D013956:Antithyroid Agents; D001324:Autoantigens; D008713:Methimazole; D011441:Propylthiouracil; D003520:Cyclophosphamide; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin; D011241:Prednisone