Medications Known to Cause Drug-Induced Lupus
High-Risk Medications
Hydralazine and procainamide are the most common causes of drug-induced lupus, with hydralazine producing a lupus-like syndrome that can include glomerulonephritis and requires immediate discontinuation unless the benefit-to-risk ratio necessitates continued therapy. 1, 2, 3
Traditional High-Risk Agents
- Hydralazine causes lupus-like syndrome particularly in slow acetylators at higher doses, and symptoms may persist for years after discontinuation, sometimes requiring long-term steroid therapy 1, 3, 4
- Procainamide is now the most frequent cause of drug-induced lupus syndrome, with antinuclear antibodies developing in at least 50% of patients and clinical lupus syndrome in approximately 20% with prolonged therapy 5, 4
- Isoniazid causes drug-induced lupus as a rare adverse effect, with approximately 22% of patients developing antinuclear antibodies after a mean of 6 months of treatment 2, 4
Moderate-Risk Traditional Agents
- Quinidine carries moderate risk for drug-induced lupus 6, 7
- Chlorpromazine is less frequently associated with the disease 4
- Methyldopa has been implicated in drug-induced lupus 4
- Penicillamine can cause the syndrome 4
- Sulfasalazine is associated with drug-induced lupus 4
Drug Classes Associated with Drug-Induced Lupus
- Anticonvulsants as a class have been implicated 4
- Beta-blockers have been associated with the syndrome 4
- Sulfonamides can cause drug-induced lupus 4
Newer Biological Agents
TNF-α inhibitors (etanercept, adalimumab, infliximab) represent a distinct form of drug-induced lupus that differs significantly from traditional drug-induced lupus, with higher rates of cutaneous involvement and potential for renal complications. 2, 8, 7
Key Differences in TNF-α Inhibitor-Induced Lupus
- TNF-α inhibitor-induced lupus presents with higher incidence of rashes compared to classic systemic drug-induced lupus 8
- Renal involvement can occur with TNF-α inhibitors, unlike traditional drug-induced lupus where kidney disease is rare 2, 8
- Anti-dsDNA antibodies and low complement levels are present in approximately half of anti-TNFα drug-induced lupus cases, whereas they are rare in classic drug-induced lupus 8
- Anti-histone antibodies are less common with TNF-α inhibitors compared to traditional drug-induced lupus 8
Other Biological Agents
- Interferons have been associated with drug-induced lupus, possibly through disruption of the cytokine network 4, 7
Drugs Associated with Subacute Cutaneous Lupus (SCLE)
Drug-induced SCLE is the most common form of drug-induced lupus and closely resembles idiopathic SCLE 8, 7:
- Calcium channel blockers are commonly implicated 8, 7
- Angiotensin-converting enzyme inhibitors can cause drug-induced SCLE 8
- Thiazide diuretics are associated with SCLE 8
- Terbinafine is a common cause 8, 7
- Proton pump inhibitors have been increasingly recognized as causative agents 7
- Chemotherapeutic agents can induce SCLE 7
Clinical Presentation and Key Distinguishing Features
Traditional drug-induced lupus typically presents with arthralgia/arthritis, pleurisy, rashes, and fever, with positive antinuclear and anti-histone antibodies, but rarely involves the kidneys or central nervous system—distinguishing it from idiopathic SLE. 2, 4, 8
Laboratory Profile
- Positive antinuclear antibodies are characteristic 8
- Anti-histone antibodies are typical in traditional drug-induced lupus 8
- Anti-dsDNA antibodies are rare in classic drug-induced lupus but may be present with TNF-α inhibitors 8
- Absence of antibody to native DNA helps distinguish from idiopathic SLE 5
Important Clinical Pitfalls
- Recognition can be difficult in patients receiving anti-TNFα therapy due to overlapping symptoms with their underlying autoimmune disease 8
- Complete remission usually occurs within weeks of stopping the drug, though some patients require corticosteroid treatment 5, 4
- Residual symptoms may persist for years after discontinuation, particularly with hydralazine 3
- No standardized diagnostic criteria exist for drug-induced lupus, making diagnosis dependent on temporal relationship and symptom resolution after drug cessation 8, 7