Drug-Induced Vasculitis

This chapter aims to draw attention to the features that distinguish drug-induced vasculitis from those of idiopathic autoimmune syndromes, first and foremost primary vasculitides. Development of a systemic drug-induced syndrome only develops in a minority of patients treated with a drug over a prolonged period of time, whereas cutaneous vasculitis occurs quite commonly. The most frequent symptoms as onset are arthralgia, myalgia and skin rash. Early withdrawal of the offending drug mostly leads to complete recovery while more advanced disease and late withdrawal of the drug may necessitate use of corticosteroid and/or immunosuppressive therapy. The recent discovery of anti-neutrophil cytoplasm antibodies (ANCA) in a large serological subset of drug-induced vasculitis caused by long-term antithyroid drug treatment has opened new avenues for differential diagnostics. Certain medications such as propylthiouracil can induce ANCA associated vasculitis. This chapter focuses on the data on causal drugs, possible pathogenesis, clinical description, diagnosis, treatment and prognosis of patients with drug-induced vasculitis. ANCA with specificity to more than one lysosomal antigen combined with presence of antibodies to histones and beta-2 glycoprotein 1 constitute a unique serological profile for drug-induced vasculitis. The pathogenesis of drug-induced ANCA associated vasculitis might be multifactorial. The clinical manifestations are similar to those of primary ANCA associated vasculitis, but ANCA with multi-antigenicity may help to differentiate it from primary ANCA associated vasculitis. Rational use of laboratory marker profiles is likely to aid in distinguishing druginduced from idiopathic syndromes. However, the use of ANCA and other autoantibodies as biomarkers of different phenotypes of drug-induced vasculitis is one of the focuses of this chapter. To date, ANCA are important serological markers for certain small-vessel vasculitides, encompassing Wegener granulomatosis (WG), microscopic polyangiitis (MPA) and Churg– Strauss syndrome (CSS). By indirect immunofluorescence (IIF) technique, ANCAs are classified as a perinuclear pattern (P-ANCA) and a cytoplasmic pattern (C-ANCA). C-ANCA is caused almost exclusively by antibodies against proteinase 3 (PR3). In contrast, P-ANCA can be caused by antibodies reacting with a variety of different neutrophil granule constituents, including myeloperoxidase (MPO), lactoferrin, human leucocyte elastase (HLE) and others. Evidence is mounting that these specific antibodies are pathogenic in small-vessel vasculitis. However, the aetiology of ANCA associated vasculitis is largely unknown. The diagnosis of drug-induced ANCA associated vasculitis is based on the temporal relationship between clinically evident vasculitis and administration of the offending drugs,