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 (α1 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 α1 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.
Highlights
Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to Antineutrophil cytoplasmic antibodies (ANCA)-positive antithyroid drug (ATD)-treated patients with symptoms of systemic disease
Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) belong to the idiopathic systemic vasculitides (ISV) group, they can be triggered by some chemicals, viral and bacterial infections and certain drugs, among which antithyroid drugs (ATDs) are very common [5]
In the PTUtreated group, 25% of the patients had MPO-ANCA, while in the MM group only 3.4% had MPO-ANCA [15]. These findings suggest that the altered immune environment associated with Graves' disease (GD) and Hashimoto thyroiditis (HT) is not sufficient to develop ANCA, but treatment with ATD induces ANCA production
Summary
Antineutrophil cytoplasmic antibodies (ANCA) specific for ated with necrotizing vasculitides, especially Wegener's α1 AT = alpha-1 antitrypsin; aCL = anticardiolipin antibodies; AHA = antihistone antibodies; ANA = antinuclear antibodies; ANCA = antineutrophil cytoplasmic antibodies; Anti-β2 GP I = anti-beta 2 glycoprotein I; APS = antiphospholipid syndrome; ARF = acute renal failure; ATD = antithyroid drug; BVAS = Birmingham Vasculitis Activity Score; CR-P = C reactive protein; DID = drug-induced diseases; DIV = drug-induced vasculitis; ELISA = enzyme-linked immunosorbent assay; GD = Graves' disease; HT = Hashimoto thyroiditis; IIF = indirect immunofluorescence; ISV = idiopathic systemic vasculitis; LLD = lupus-like disease; MM = methimazole; MPA = microscopic polyangiitis; MPO = myeloperoxidase; PR3 = proteinase 3; PTU = propylthiouracil; SLE = systemic lupus erythematosus; SNGN = segmental necrotizing glomerulonephritis; WG = Wegener's granulomatosis. Perinuclear MPOANCA is a good serological marker for MPA, but it can be found in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, drug-induced vasculitides (DIV), etc [4]. We compared data from idiopathic and ATD-induced ANCA-positive patients
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