Hydralazine is the Most Common Medication Known to Cause Drug-Induced Lupus
The correct answer is C. Hydralazine, which is the most common medication known to cause drug-induced lupus (DIL).
Evidence for Hydralazine as the Leading Cause of DIL
Hydralazine has been consistently identified in medical literature as one of the most common medications associated with drug-induced lupus. According to the FDA drug label, hydralazine can produce "a clinical picture simulating systemic lupus erythematosus including glomerulonephritis" 1. This association is so significant that the drug label specifically warns that hydralazine should be discontinued in patients who develop these symptoms unless the benefit-to-risk determination requires continued antihypertensive therapy.
Multiple guidelines confirm this association:
- The British Journal of Pharmacology states that "hydralazine can rarely cause drug-induced lupus, which can also involve the kidneys leading to renal dysfunction" 2
- The British Thoracic Society guidelines specifically list "drug-induced lupus" as a rare but serious immunological adverse effect of hydralazine 2
Clinical Characteristics of Hydralazine-Induced Lupus
Hydralazine-induced lupus typically presents with:
- Arthralgia and myalgia, particularly in the hands and wrists
- Pleurisy and pericarditis
- Fever and rashes
- Positive antinuclear antibodies (ANA) with homogenous pattern
- Positive anti-histone antibodies (highly specific)
A retrospective study found that the majority of individuals with hydralazine-induced lupus:
- Were exposed to hydralazine for more than 12 months (83%)
- Had positive ANA with homogenous pattern (86%)
- Had positive anti-histone antibody (71%) 3
Risk Factors for Hydralazine-Induced Lupus
Several factors increase the risk of developing hydralazine-induced lupus:
- Higher doses (>200 mg/day)
- Prolonged treatment duration (typically >12 months)
- Slow acetylator status
- Female sex (though less pronounced than in idiopathic SLE)
- Genetic predisposition
Comparison with Other Options
While the other medications listed in the question can cause adverse reactions, they are not commonly associated with drug-induced lupus:
Ceftriaxone (Option A): Not known to cause drug-induced lupus. It's an antibiotic that may cause hypersensitivity reactions but is not associated with DIL.
Vancomycin (Option B): Not associated with drug-induced lupus. It can cause "red man syndrome" and other hypersensitivity reactions, but not DIL.
Paracetamol/Acetaminophen (Option D): While it can cause hepatotoxicity in overdose, it is not associated with drug-induced lupus.
Differences Between Drug-Induced and Idiopathic Lupus
Drug-induced lupus differs from idiopathic SLE in several ways:
- DIL typically resolves within weeks to months after discontinuation of the offending drug
- DIL has less female predominance (approximately 1:1 ratio compared to 9:1 in idiopathic SLE)
- DIL rarely affects major organs like kidneys and central nervous system
- DIL patients are typically older (average age ~60 years vs. 30 years in idiopathic SLE)
Management of Hydralazine-Induced Lupus
The primary management strategy is discontinuation of hydralazine. Most symptoms resolve within weeks to months after stopping the medication. In cases with severe manifestations, additional treatments may include:
- Hydroxychloroquine for persistent symptoms
- Corticosteroids for more severe manifestations
- Immunosuppressants for organ involvement
Prevention
To prevent hydralazine-induced lupus:
- Limit daily dose to ≤200 mg when possible
- Consider baseline ANA testing before initiating therapy
- Monitor patients on long-term therapy for symptoms of DIL
- Consider alternative antihypertensive medications in patients with risk factors
In conclusion, hydralazine stands out as the most common medication associated with drug-induced lupus among the options provided, supported by substantial evidence in medical literature and drug labeling.