One study reported 68 instances of hydralazine-induced ANCA vasculitis

One study reported 68 instances of hydralazine-induced ANCA vasculitis. medical demonstration, serological features, and treatment options (4C6). One study reported 68 cases of hydralazine-induced ANCA vasculitis. The disease was found to be prevalent in older females. The mean drug exposure was 4.7 years. The kidney was the primary organ affected followed by lungs, skin, and nerves (4). Patients with pauci-immune GN usually present with rapidly progressive glomerulonephritis with features of brown colored urine suggesting hematuria. Other features include proteinuria and renal insufficiency (7). The extra-renal manifestation of systemic vasculitis syndrome includes non-specific symptoms of fever, malaise, arthralgia, myalgia, and weight loss. Other organ-specific complications such as pulmonary hemorrhage, purpuric rash, livido reticularis, neuropathy, and retinitis can be seen with severe systemic disease (4). The pathogenesis of hydralazine-induced pauci-immune glomerulonephritis is usually unclear. One hypothesis is usually that hydrazine accumulates in neutrophils, binds to myeloperoxidase granules (MPO), and induces cytotoxic products formation that lead to neutrophil apoptosis. The cellular apoptosis in the absence of priming, leads to the expression of ACNA antigen on cellular surface, and hence ANCA formation (8). The presence of multi-antigenicity in drug-induced vasculitis is usually explained by the alteration in molecular configuration of MPO granules by hydralazine, consequently inducing the autoimmune response to other neutrophilic proteins (including lactoferrin, elastase, and nuclear antigen), thereby rendering them immunogenic (9). Jiang et al. suggested the role of T cells in stimulating the immune response. It is proposed that cytotoxic products formed as a result of neutrophilic activation by MPO granules and conversion of drugs into LDS 751 cytotoxic brokers are immunogenic for T cells. Activated T cells then induce B cells to produce ANCA (10). The rarity of drug-induced ANCA vasculitis and overlapping features with idiopathic vasculitis is the greater challenge in early diagnosis. The diagnosis mainly relies on constitutional symptoms, including organ-specific symptoms, detailed medication history, the total duration of drug therapy, the presence of various antibodies, and the resolution of symptoms after discontinuation of the offending agent. Since multi-antigenicity is usually a key feature, various serological markers aid in diagnosing drug-induced pauci-immune GN (Table 1). Another distinct characteristic of drug-induced pauci-immune GN is the presence of very high myeloperoxidase (MPO) antibody titers (11). Table 1 Serological marker difference between idiopathic AAV and drug-induced ANCA vasculitis thead th align=”left” rowspan=”1″ colspan=”1″ /th th align=”center” LDS 751 rowspan=”1″ colspan=”1″ Drug-induced AAV /th th align=”center” rowspan=”1″ colspan=”1″ Idiopathic AAV /th /thead ANCACommona Commonb Antilactoferrin abCommonRareAntihistone abCommonAbsentAntielastase abCommonRareAntiphospholipid abCommonRareImmune complexRareAbsent Open in a separate windows Ab=antibodies, AAV=ANCA-associated vasculitis. aMultispecific, particularly myeloperoxidase antibodies bsingle ANCA LDS 751 specificity. A kidney biopsy is usually strongly motivated for definitive diagnosis of acute kidney injury and to ascertain the severity of disease. Common biopsy in patients with drug-induced ANCA-associated vasculitis (AAV) shows necrotizing and crescentic inflammation (Fig. 1). Interstitial nephritis and significant tubular damage is seen Rabbit Polyclonal to UBE3B on some occasions. A small subset of patients also had subacute disease characterized by glomerular fibrosis, either alone or accompanied by an active focal disease with necrosis and crescent formation (4). No randomized trial looked at the ideal treatment for drug-induced pauci-immune GN. Treatment must be individualized based on the severity of the disease, age, co-morbid conditions, and entry time serum creatinine. Treatment options vary from discontinuing the offending agent alone, to the use of immunosuppressive therapies including steroids (Fig. 2, Table 2). Open in a separate windows Fig. 2 Light microscopy: (a) glomeruli shows cellular crescents; (b) IF: glomeruli with trace IgM mesagnial deposits; (c) glomeruli with trace IgG mesangial deposits; (d) EM: GBM thickening, FPE effacement, and absent.