Drug-Induced Autoimmunity: A Case of Hydralazine-Induced ANCA Vasculitis with Overlapping Autoimmune Markers

Summary: Drug-Induced Autoimmunity: A Case of Hydralazine-Induced ANCA Vasculitis with Overlapping Autoimmune Markers Victor H. Guillen, MD (1); Fernando. Poli, MD (1); Matthew. Ghermezi, MD (1); Ahmed. Elghawy, DO (2). (1) Department of Internal Medicine, Mount Sinai Medical Center, Miami Beach, USA. (2) Division Chief Department of Rheumatology, Mount Sinai Medical Center, Miami Beach, USA. Background: Hydralazine, a common antihypertensive, is associated with drug-induced lupus (DIL) and ANCA-associated vasculitis (AAV), leading to overlapping autoimmune syndromes. Hydralazine-induced AAV targets small vessels and presents as ANCA-associated glomerulonephritis (ANCA-GN) with multi-organ involvement. In a cohort of 1,858 ANCA-GN cases, hydralazine was linked to 4.3%, with most patients having >1 year of exposure at 250 mg daily. Serological testing revealed MPO-ANCA in 98%, ANA in 89%, and anti-histone antibodies in 98%, indicating a strong association with drug-induced lupus (DIL). In DIL cases, there was a greater deposition of immune complexes, increased mesangial hypercellularity, and the presence of endothelial tubule-reticular inclusions, suggesting a lupus-like pathology. In contrast, cases of AAV exhibited pauci-immune features. Hydralazine-induced lupus occurs in 7–13% of users, while vasculitis is less common but more severe, often leading to complications such as pulmonary-renal syndrome. Early recognition, hydralazine discontinuation, and immunosuppressive therapy are key to improving outcomes. This case emphasizes the importance of clinical awareness in managing drug-induced vasculitis, especially with overlapping autoimmune markers. Case Presentation: A 76-year-old woman with hypertension, type 2 diabetes, and hypothyroidism presented with fatigue and nausea. She had been taking hydralazine (25 mg daily) for hypertension for approximately one year. Examination revealed mild dehydration, and labs showed acute kidney injury (Cr 2.34 mg/dL, rapidly progressing to 4.29 mg/dL), normocytic anemia, leukopenia, and hyponatremia. Urinalysis revealed moderate hematuria and mild proteinuria, suggesting intrinsic renal injury. Kidney biopsy confirmed pauci-immune focal crescentic glomerulonephritis with mesangial hypercellularity, consistent with ANCA-associated vasculitis (AAV). Immunofluorescence showed no immune-type electron-dense deposits or endothelial tubulo-reticular inclusions, reinforcing the pauci-immune nature of the GN and supporting a diagnosis of hydralazine-induced AAV. Following hydralazine discontinuation, the patient received pulse steroids and rituximab, resulting in renal stabilization and eventual discharge with close follow-up. Discussion: Hydralazine-induced ANCA-associated vasculitis (AAV) is a rare but serious complication, often overlapping with drug-induced lupus (DIL). ANCA and ANA positivity, along with anti-histone antibodies and hypocomplementemia, suggest complex autoimmune activation. Despite hydralazine’s long history of use, its association with vasculitis and glomerulonephritis remains underrecognized, often leading to delays in diagnosis and treatment. Histopathology in hydralazine-induced AAV resembles primary ANCA-associated glomerulonephritis with paucii immune features. The pathophysiology involves neutrophil activation and ANCA production (MPO and PR3), leading to endothelial damage. Management requires a high index of suspicion, particularly in RPGN. While no specific guidelines exist, early hydralazine discontinuation and immunosuppressive therapy (glucocorticoids and rituximab) are key to improving outcomes and preserving kidney function. Conclusion: This case underscores the need for clinical awareness of hydralazine-induced AAV, particularly in patients with overlapping autoimmune markers. Given its potential for severe renal involvement, timely recognition, drug discontinuation, and appropriate immunosuppressive therapy are critical for optimizing patient outcomes. Further research is needed to better understand the mechanisms underlying drug-induced vasculitis and to establish optimal treatment strategies. References: 1. Dominick Santoriello, et al. Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis complicating treatment with hydralazine. Kidney International.100. 2021.400-446. 2. Lakshmi Kannan, et al. Overlapping Syndromes: Drug-induced Vasculitis from Hydralazine with Positive Antinuclear Antibodies. SAGE Journals.16.2020. 3. V. Mulkareddy, et al. Hydralazine-induced ANCA-associated vasculitis: A rare cause of diffuse alveolar hemorrhage. CHEST.05.2020.408 4. William J. Scheuing, et al. Case Report: Hydralazine-induced ANCA-associated vasculitis. The Rheumatologist. 2021