Primary systemic vasculitis: treatment of difficult cases R Foster 2 , E Rosenthal 1 , S Marques 1 , P Vounotrypidis 1 , S Sangle 1 and D D’Cruz 1 * 1 Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London, UK; and 2 Department of Immunology, St Thomas’ Hospital, London, UK The primary systemic necrotizing vasculitides are a severe group of diseases, which untreated have a high mortality. The majority respond to treatment with high dose steroids and cyclophosphamide, however a significant proportion of those treated suffer morbidity due to the side effects of these agents, and a number of patients are refractory to treatment. We review and discuss alternative and emerging treatment options for patients who fail or cannot tolerate conventional therapy. An interesting subgroup of patients with systemic vasculitis and antiphospholipid antibodies provides an additional diagnostic and therapeutic challenge. We review what is known about this subgroup, and suggest screening for antiphospholipid antibodies in all patients with systemic vasculitis. Lupus (2006) 15, 143–147. Key words: antiphospholipid antibodies; anti-TNF alpha therapy; mycophenolate mofetil; rituximab; vasculitis Lupus (2006) 15, 143–147 www.lupus-journal.com REVIEW Introduction The vasculitides are a heterogeneous group of uncommon diseases, characterized by inflammatory cell infiltration and necrosis of blood vessel walls. The primary systemic necrotizing vasculitides are a severe group of diseases, of which the ANCA-associated small-vessel vasculitides, namely Wegener’s Granulomatosis, Churg Strauss Syndrome and Microscopic PolyAngiitis are the best defined and most studied subgroup. Untreated, these diseases have a two-year mortality of up to 90%. 1 Since the introduction of cyclophosphamide and high-dose corticosteroids by Fauci et al. 2 in the 1970s, prognosis has greatly improved and disease is con- trolled in 80–90% of patients. For those patients who respond to treatment, the morbidity associated with long-term steroids and cyclophosphamide ie, diabetes, infection, bladder cancer, haemorrhagic cystitis, bone marrow toxicity and infertility, dictates that exposure to these drugs should be kept to a minimum and other less toxic treatments sought. In those who do not respond, an alternative, effective treatment is urgently needed. A subgroup of patients with systemic vasculitis who are also positive for antiphospholipid antibodies, are being increasingly reported in the literature. These patients present an additional diagnostic and therapeutic challenge in the treatment of systemic vasculitides. Conventional treatment of ANCA-associated vasculitis (AAV) Induction of remission Conventional treatment of AAV comprises both an induction and a maintenance phase. Standard induc- tion therapy consists of high dose corticosteroids and cyclophosphamide (CYC). 3 CYC can be given as a daily oral or as a pulsed IV regime. Pulsed therapy seems to be as effective at inducing remission as oral therapy and is less toxic, but there is a slightly higher risk of disease relapse. 4 Whether pulsed or oral, CYC therapy is associated with significant side effects. An alternative to CYC during the induction phase is methotrexate (MTX), this has been shown to be as effective at inducing remission as oral CYC in early, less severe vasculitis © 2006 Edward Arnold (Publishers) Ltd 10.1191/0961203306lu2277rr *Correspondence: David D’Cruz, Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, Lambeth Palace Road, London, SE1 9LN, UK. E-mail: david.d’cruz@kcl.ac.uk