What medications can cause medication-associated lupus?

Medications That Cause Drug-Induced Lupus

The most common medications causing drug-induced lupus are hydralazine and procainamide (high-risk), followed by isoniazid, TNF-α inhibitors, and proton pump inhibitors (moderate-risk), with hydralazine requiring immediate discontinuation if lupus develops unless the benefit-to-risk ratio necessitates continued therapy. 1, 2

High-Risk Medications

Hydralazine

• Hydralazine is the most well-established cause of drug-induced lupus, particularly at higher doses and in slow acetylators 1, 2
• Can produce a lupus-like syndrome that includes glomerulonephritis, which is unusual for drug-induced lupus 1, 2
• The FDA label explicitly warns that hydralazine should be discontinued when lupus develops unless the benefit-to-risk determination requires continued therapy 2
• Symptoms may persist for years after discontinuation and sometimes require long-term steroid therapy 1

Procainamide

• Procainamide is associated with the highest risk of developing lupus alongside hydralazine 3, 4
• Considered a high-risk medication in traditional drug-induced lupus 5

Isoniazid

• Approximately 22% of patients treated with isoniazid for a mean of 6 months develop antinuclear antibodies 1, 6
• Can present with arthralgia, fever, and pleuritis 1
• Pericarditis occurs in approximately 30% of cases, with rare presentations including cardiac tamponade 6
• Considered a high-risk medication for drug-induced lupus 7

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, which is atypical 1, 8
• Patients can develop or show increases in circulating antinuclear antibodies and signs of systemic lupus erythematosus while receiving anti-TNF therapy 1
• Anti-TNF-α DILE differs from classic DILE with higher incidence of rashes, more frequent visceral involvement including renal disease, and presence of anti-dsDNA antibodies in approximately half of cases 7
• Anti-histone antibodies are less common with TNF-α inhibitors compared to classic drug-induced lupus 7

Proton Pump Inhibitors

• PPIs can cause drug-induced lupus that typically presents without renal or CNS complications 8
• The mechanism likely differs from traditional drug-induced lupus and may involve interactions with DNA or histones, rendering them immunogenic 8
• Have been increasingly recognized as a cause of drug-induced SCLE in recent years 5

Other Implicated Medications

Lower-Risk Individual Agents

• Chlorpromazine, methyldopa, penicillamine, quinidine, and sulfasalazine are less frequently associated 4

Drug Classes

• Anticonvulsants as a class have been implicated 4
• Beta-blockers as a class 4
• Sulfonamides as a class 4
• Calcium channel blockers (particularly for SCLE) 7
• Angiotensin-converting enzyme inhibitors (particularly for SCLE) 7
• Thiazide diuretics (particularly for SCLE) 7
• Terbinafine (particularly for SCLE) 7, 5
• Interferons (newer biological agents) 4, 7

Clinical Presentation Patterns

Traditional Drug-Induced Lupus

• Typically presents with arthralgia/arthritis, pleurisy, rashes, and fever 1
• Traditional drug-induced lupus rarely involves the kidneys 1
• CNS complications are rare in classic drug-induced lupus 8

Important Caveat

Recognition can be difficult when patients are receiving medications for underlying autoimmune diseases, as symptoms may overlap with the disease being treated 7. A temporal association (months to years) with the offending drug and resolution of symptoms upon drug withdrawal provides the best evidence for diagnosis 7.