What medications can induce lupus?

Drug-Induced Lupus: High-Risk Medications

The medications most strongly associated with drug-induced lupus are hydralazine and procainamide (highest risk), followed by isoniazid, TNF-α inhibitors (etanercept, adalimumab, infliximab), and several other agents including quinidine, methyldopa, chlorpromazine, penicillamine, and sulfasalazine.

Highest Risk Medications

Hydralazine

• Hydralazine carries the highest risk of drug-induced lupus, particularly at higher doses and in slow acetylators 1, 2, 3
• Can produce a lupus-like syndrome that may include glomerulonephritis, which is unusual for traditional drug-induced lupus 1
• Symptoms may persist for years after discontinuation and sometimes require long-term steroid therapy 1
• Requires immediate discontinuation unless the benefit-to-risk ratio necessitates continued therapy 1
• Rarely presents with bullous lupus erythematosus, characterized by hemorrhagic blister-type lesions 4

Procainamide

• Procainamide is associated with the highest risk of developing lupus alongside hydralazine 2, 3
• Considered a high-risk drug for systemic drug-induced lupus 5

Isoniazid

• Approximately 22% of patients treated for a mean of 6 months develop antinuclear antibodies 1
• Classified as a high-risk medication for drug-induced lupus 5
• Monitoring for symptoms such as arthralgia, fever, and pleuritis is recommended during treatment 1

Moderate Risk Medications

TNF-α Inhibitors (Etanercept, Adalimumab, Infliximab)

• TNF-α inhibitor-induced lupus presents differently from traditional drug-induced lupus and may include renal complications 6, 1
• Development of or increase in circulating antinuclear antibodies may occur in patients taking any of the three anti-TNF agents 6
• Several reported cases of patients developed signs and symptoms of systemic lupus erythematosus while receiving anti-TNF therapy, though this condition may be reversible on cessation 6
• Anti-TNF-induced lupus differs from classic drug-induced lupus in several ways: higher incidence of rashes, more frequent renal involvement, low serum complement levels in half of cases, presence of anti-dsDNA antibodies, and decreased incidence of anti-histone antibodies 5, 7
• May represent unmasking of latent idiopathic SLE rather than true drug-induced disease 7

Other Implicated Medications

Moderate-to-Low Risk Individual Agents

• Quinidine: moderate risk 2
• Methyldopa: less frequently associated 3, 4
• Chlorpromazine: less frequently associated 3
• Penicillamine: less frequently associated 3, 4
• Sulfasalazine: less frequently associated 3

Drug Classes Associated with Drug-Induced Lupus

• Anticonvulsants as a class have been implicated 3
• Beta-blockers as a class 3
• Sulfonamides as a class 3
• Calcium channel blockers: associated with drug-induced subacute cutaneous lupus erythematosus (SCLE) 5
• Angiotensin-converting enzyme inhibitors: associated with drug-induced SCLE 5
• Thiazide diuretics: associated with drug-induced SCLE 5
• Terbinafine: associated with drug-induced SCLE 5
• Interferons: associated with drug-induced SCLE and newer biological modulators 2, 5
• Fluorouracil agents: rarely associated with drug-induced chronic cutaneous lupus 5
• NSAIDs: rarely associated with drug-induced chronic cutaneous lupus 5

Clinical Presentation and Key Distinguishing Features

Traditional Drug-Induced Lupus

• Characterized by arthralgia, myalgia, pleurisy, rashes, and fever in association with antinuclear antibodies 3, 5
• Positive antinuclear and anti-histone antibodies are typical 5
• Anti-double strand DNA and anti-extractable nuclear antigens antibodies are rare 5
• More serious features of idiopathic lupus such as nephritis and cerebral disease are rare in traditional drug-induced disease 3
• Resolution of symptoms generally occurs after cessation of the drug 2

Drug-Induced Subacute Cutaneous Lupus (SCLE)

• Very similar to idiopathic SCLE in clinical and serologic characteristics 5
• More common than the systemic form of drug-induced lupus 5

Critical Management Principles

Diagnosis

• Requires identification of a temporal relationship between drug administration and symptom development (months to years of exposure) 2, 5
• In traditional drug-induced lupus, there must be no pre-existing lupus 2
• Recognition can be difficult with anti-TNF agents due to symptoms of the underlying disease being treated 5
• Standardized diagnostic criteria for drug-induced lupus have not been established 5

Treatment Approach

• Discontinue the offending drug immediately 1, 2, 3
• Resolution typically occurs within a few weeks of stopping the drug 3
• For hydralazine-induced lupus with persistent symptoms, long-term steroid therapy may be required 1

Important Caveats

• The mechanism(s) responsible for drug-induced lupus may vary depending on the drug or even on the patient 2
• Vigilance and early diagnosis are critical 2
• Deaths have been reported from hypersensitivity reactions, blood dyscrasias, and organ damage with certain drugs like sulfasalazine 8
• The presence of clinical signs such as sore throat, fever, pallor, purpura, or jaundice may indicate serious complications requiring immediate drug discontinuation 8