Vasculitis associated with ANCA

Choi, H.K., Merkel, P.A., and Niles, J.L., ANCA-positive vasculitis associated with al-lopurinol therapy, Clin. Exp. Rheumatol., 16, 743, 1998. 

Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leucocytoclastic vasculitis associated with antithyroid therapy in Graves disease. Australas J Dermatol 1998 39(2) 96-9. 

Choi HK, Merkel PA, Niles JL. ANCA-positive vasculitis associated with allopurinol therapy. Clin Exp Rheumatol 1998 16(6) 743. ... 

Four cases of new or relapsing vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) have been described after influenza immunization [33. Several trials in patients with pre-existing autoimmune diseases failed to show an... 

Uses Alemtuzumab is indicated for the treatment of patients with B-cell chronic lymphocytic leukemia for whom fludarabine combination chemotherapy is not appropriate. Alemtuzumab may also be effective in early multiple sclerosis [138 ], as induction therapy before transplantation [139 140 ], and in vasculitis associated with anti-neutro-phil cytoplasmic antibodies (ANCA) [141 ]. 

Immunologic Vasculitis associated with myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) caused by... 

Antithyroid drugs, especially propylthiouracil, can be associated with the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, often manifesting as renal disease. Atypical presentations, with pulmonary capillaritis (58) and lupus-like syndrome (59), have been described in individual cases. Furthermore, two cases of vasculitis have been associated with carbimazole, one presenting with eosinophilic granulomatous vasculitis localized to the stomach (60) and another with p-ANCA positive vasculitis causing simultaneous acute renal insufficiency and massive pulmonary hemorrhage (61). 

Cutaneous vasculitis is often a feature of such cases, although severe systemic manifestations often also occur. Two patients with propylthiouracil hypersensitivity presented with skin manifestations but also had renal, rheu-matological, and hematological features (66). A review of the literature showed that the symptoms and signs in patients with ANCA-associated thionamide-induced vasculitis are diverse. Acral purpuric skin lesions are typically seen recognition of these classical clinical features may allow early diagnosis and limit associated morbidity and the requirement for other therapies, particularly immunosuppression. Several other reports have described... 

ANCA-positive microscopic polyangiitis has been associated with propylthiouracil, with a fatal outcome despite treatment with glucocorticoids and cyclophosphamide (87). Another patient presented atypically with acute pericarditis 10 months after starting to take propylthiouracil 100 mg tds (88). Another patient developed ANCA-negative leukocytoclastic vasculitis of the skin (89). 

Yu F, Zhao MH, Zhang YK, Zhang Y, Wang HY. Anti-endothelial cell antibodies (AECA) in patients with propylthiouracil (PTU)-induced ANCA positive vasculitis are associated with disease activity. Clin Exp Immunol 2005 139(3) 569-74. 

Long-term outcomes in a series of seven children who developed myeloperoxidase-specific ANCA-positive necrotizing crescentic glomerulonephritis associated with propylthiouracil were studied in Japan (67). Three had nephritis alone and four had extrarenal vasculitis. All had taken glucocorticoids, some with additional drugs, and aU... 

There have also been several cohort and case-control studies of silica exposure and scleroderma (Table 10) and six case-control studies of silica exposure and various forms of systemic small-vessel or ANCA-associated vasculitis. As with rheumatoid arthritis, almost all of these studies have reported a 2- to 3-fold increased risk of these diseases with silica exposure. 

Microscopic polyangiitis (MPA). ANCA-associated necrotizing, pauci immune vasculitis of the small vessels (capillaries, venules, arterioles) frequently associated with rapidly progressive glomerulonephritis and/or haemorrhagic alveolitis as well as autoantibodies against myeloperoxidase. 

Hogan et al. 2001 [76a] 65 cases with ANCA-associated small vessel vasculitis 65 age/sex-matched other renal failure patients Silica dust 4.4 (1.36-13.4)... 

Numerous drugs have been associated with the development of vasculitis (ten Holder et al. 2002 Cuellar 2002). For example propylthiouracil is associated with cutaneous, renal, and pulmonary vascultis aUopurinol is associated with cutaneous, renal, and hepatic vasculitis hydralazine is associated with cutaneous, renal, and pulmonary vascultis and isotretinoin is associated with cutaneous, renal, pulmonary, and gastrointestinal vascultis (Cuellar 2002 ten Holder et al. 2002). Systemic polyarteritis nodosa, a vasculitis with involvement of small- and mediumsized renal arteries, has been described following minocycline use (Cuellar 2002). Patients may present with hematuria, proteinuria, reduced renal function, and hypertension. Hydralazine, propylthiouracil, aUopurinol, and peniciUamine have been implicated in the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (Choi et al. 2000). Patients exposed to these drugs... 

Two patients developed a cocaine-associated ANCA-positive vasculitis, with retiform purpura, which was typically PR3-positive (c-ANCA>p-ANCA) and most closely resembled Wegener granulomatosis [IS ]. The uniqueness of retiform purpura in the setting of cocaine use suggested levamisole as a possible culprit. In two cases of cutaneous necrosis associated with cocaine use levamisole contamination was suspected [16" ]. Complete clinical resolution of skin lesions usually occurs 2-3 weeks after stopping levamisole and abnormal serology normalizes within 2-14 months. 

Skin Cutaneous necrosis associated with levamisole-contaminated cocaine has been described in two patients [199], in whom there were mottled non-infiammatory erythematous and purpuric patches on both legs and buttocks, with scattered, punched-out ulcers with central eschars. Biopsies showed extensive vascular thrombosis with no evidence of vasculitis, making cocaine-induced vasculitis highly unlikely. There were strongly positive perinuclear ANCAs in both patients and weakly positive IgM anticardiohpin antibodies in one. There were no coagulopathies. 

Environmental and genetic factors appear to influence the risk for ANCA-associated vasculitis (1). For example, sihca exposure appears to be a risk factor for ANCA-associated vasculitis (13,14). ANCA and ANCA-associated vasculitis can be induced by exposure to certain drugs, best documented for propylthiouracil and hydralazine (15-19). ANCAs are more frequent in patients treated with propylthiouracil, which is used to treat thyroid disease however, ANCAs are more frequent in patients with thyroid disease irrespective of treatment regimen (20), thus the respective roles of treatment for thyroid disease versus thyroid disease in risk for ANCA disease is difficult to discern. 

Choi HK, Merkel PA, Walker AM, et al. Drug-associated antineutrophil cytoplasmic antihody-positive vasculitis prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum 2000 43(2) 405-413. lionaki S, Hogan SL, Falk RJ, et al. Association of thyroid disease and its treatment with ANCA smaU-vessel vasculitis a case control study. Nephrol Dial Transplant 2007 22(12) 3508 3515. 

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