What medications can cause lupus?

Medications That Cause Drug-Induced Lupus

Hydralazine and procainamide are the highest-risk medications for drug-induced lupus, followed by isoniazid, while TNF-α inhibitors (infliximab, adalimumab, etanercept) cause a distinct lupus-like syndrome with different clinical features. 1

High-Risk Medications

Hydralazine

• Causes lupus-like syndrome especially at higher doses and in slow acetylators 1
• Can produce glomerulonephritis requiring immediate discontinuation unless benefit-to-risk ratio necessitates continued therapy 1
• Symptoms may persist for years after discontinuation and sometimes require long-term steroid therapy 1
• Historically associated with the highest risk of developing lupus 2

Procainamide

• Has become the most frequent cause of drug-induced lupus syndrome 3
• Antinuclear antibodies develop in at least 50% of patients with prolonged therapy, and approximately 20% develop the lupus syndrome 3
• Some patients continue to be symptomatic after drug discontinuation and require corticosteroid treatment 3

Isoniazid

• Approximately 22% of patients treated for a mean of 6 months develop antinuclear antibodies 1, 4
• Monitor for arthralgia, fever, and pleuritis during treatment 1
• Pericarditis occurs in approximately 30% of cases, with rare presentations including cardiac tamponade 4
• IgG antibody to the (H2A-H2B)-DNA complex appears specific for isoniazid-induced lupus 4

Moderate-Risk Medications

TNF-α Inhibitors (Infliximab, Adalimumab, Etanercept)

• Cause a clinically distinct lupus-like syndrome that differs from traditional drug-induced lupus 1, 5
• May involve renal complications, unlike traditional drug-induced lupus which rarely affects the kidneys 1
• Patients develop or have increased circulating antinuclear antibodies 1
• Treatment with infliximab products may result in formation of autoantibodies and development of lupus-like syndrome; discontinue if symptoms develop 5

Other Implicated Medications

• Lower risk agents include chlorpromazine, methyldopa, penicillamine, quinidine, and sulfasalazine 6
• Drug classes associated include anticonvulsants, beta-blockers, sulfonamides, and some biological agents 6
• Antihypertensive drugs and terbinafine are most commonly implicated in drug-induced subacute cutaneous lupus erythematosus (SCLE) 7
• Proton pump inhibitors and chemotherapeutic agents have also been associated with drug-induced SCLE 7

Clinical Presentation Differences

Traditional Drug-Induced Lupus

• Presents with arthralgia/arthritis, pleurisy, rashes, and fever 1
• Rarely involves kidneys or central nervous system 1, 6
• Differs from idiopathic SLE in race and sex distribution 3
• Absence of antibody to native DNA 3

TNF-α Inhibitor-Induced Lupus

• Presents differently from traditional drug-induced lupus 1
• May include renal complications 1
• Does not typically involve CNS complications 1

Management Approach

If lupus-like symptoms develop, discontinue the offending medication immediately 1, 5

• Resolution of symptoms generally occurs after drug cessation in traditional drug-induced lupus 2, 6
• Complete remission occurs in most patients following discontinuation, though some require corticosteroid treatment 3
• Symptoms may revert within a few weeks of stopping the drug 6

Critical Pitfall to Avoid

Do not continue the suspected medication while attempting to treat lupus symptoms—the temporal relationship between drug administration and symptom development is essential for diagnosis, and drug discontinuation is the primary treatment 2