From the Guidelines
Hydralazine causes vasculitis through an autoimmune mechanism involving the formation of drug-induced autoantibodies, which is more common in slow acetylators, patients on higher doses, those on long-term therapy, and in women, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.
Mechanism of Action
When hydralazine is metabolized, it can act as a hapten, binding to self-proteins and altering their structure. This modification triggers the immune system to recognize these altered proteins as foreign, leading to the production of autoantibodies, particularly antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA).
Key Factors
Some key factors that increase the risk of hydralazine-induced vasculitis include:
- Higher doses (typically >100 mg daily)
- Long-term therapy (usually >3 years)
- Slow acetylators (a genetic variation affecting drug metabolism)
- Female sex
Clinical Presentation
The vasculitis typically presents as drug-induced lupus-like syndrome with symptoms including:
- Fever
- Arthralgia
- Myalgia
- Skin rashes Though more severe manifestations affecting kidneys and lungs can occur, as mentioned in the guidelines 1.
Management
It is essential to monitor patients on hydralazine for signs of vasculitis and adjust the treatment regimen accordingly, considering the potential risks and benefits, as outlined in the guidelines 1.
From the Research
Mechanism of Hydralazine-Induced Vasculitis
The exact mechanism by which hydralazine causes vasculitis is not fully understood, but several studies have shed light on the possible pathways involved.
- Hydralazine has been associated with the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which is characterized by the presence of autoantibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) 2, 3, 4, 5, 6.
- The drug can also induce a lupus-like syndrome, with features such as positive antinuclear antibodies, antihistone antibodies, and anti-dsDNA antibodies 2, 3, 4, 5.
- The development of vasculitis is thought to be related to the formation of these autoantibodies, which can lead to inflammation and damage to blood vessels 4, 5.
- Hydralazine-induced vasculitis can present with a range of clinical manifestations, including renal vasculitis, pulmonary renal syndrome, and digital gangrene 4.
Clinical Features and Diagnosis
The clinical features of hydralazine-induced vasculitis can be varied and nonspecific, making diagnosis challenging.
- Common symptoms include fatigue, weight loss, and renal impairment 2, 3, 5.
- Laboratory tests may reveal positive ANCA and antinuclear antibodies, as well as elevated creatinine and proteinuria 2, 3, 5, 6.
- Renal biopsy can be helpful in establishing the diagnosis, with characteristic findings including pauci-immune crescentic glomerulonephritis 5, 6.
Treatment and Management
Treatment of hydralazine-induced vasculitis typically involves discontinuation of the offending drug and initiation of immunosuppressive therapy.
- Corticosteroids and rituximab may be used to manage the condition, with the goal of reducing inflammation and preventing further organ damage 3, 6.
- In some cases, plasmapheresis may be necessary to remove autoantibodies and reduce disease activity 6.
- Close monitoring of renal function and other affected organs is essential to prevent long-term damage and improve outcomes 2, 3, 5, 6.