What medications can cause drug-induced lupus?

Medications That Can Cause Drug-Induced Lupus

Hydralazine is the medication most strongly associated with drug-induced lupus, followed by procainamide, isoniazid, and TNF-α inhibitors. 1

High-Risk Medications

• Hydralazine: Associated with drug-induced lupus-like syndrome, especially at higher doses (100-200 mg daily) 1
• Procainamide: One of the most frequent causes of drug-induced lupus syndrome, with approximately 20% of patients on long-term therapy developing the syndrome 2, 3
• Isoniazid: Can cause drug-induced lupus as a rare adverse effect, with approximately 22% of patients treated for a mean of 6 months developing antinuclear antibodies 1, 4

Moderate-Risk Medications

• Quinidine: Associated with moderate risk of drug-induced lupus 5, 6
• TNF-α inhibitors (biologics):
  • Etanercept: Can cause drug-induced lupus without renal or CNS complications 1
  • Adalimumab: Associated with rare reports of drug-induced, reversible lupus 1
  • Infliximab: Can cause drug-induced lupus without renal or CNS complications 1

Lower-Risk Medications

• Methyldopa: Less frequently associated with drug-induced lupus 6
• Penicillamine: Less frequently associated with drug-induced lupus 6
• Sulfasalazine: Less frequently associated with drug-induced lupus 6, 4
• Chlorpromazine: Less frequently associated with drug-induced lupus 6

Drug Classes Associated with Drug-Induced Lupus

• Anticonvulsants: As a group, have been implicated in drug-induced lupus 6
• Beta-blockers: As a group, have been implicated in drug-induced lupus 6
• Calcium channel blockers: Associated with subacute cutaneous lupus erythematosus 7
• Angiotensin-converting enzyme inhibitors: Associated with subacute cutaneous lupus erythematosus 7
• Interferons: Associated with subacute cutaneous lupus erythematosus 7
• Thiazide diuretics: Associated with subacute cutaneous lupus erythematosus 7
• Terbinafine: Associated with subacute cutaneous lupus erythematosus 7

Clinical Presentation and Diagnosis

• Drug-induced lupus typically presents with:

  • Arthralgia/arthritis
  • Myalgia
  • Pleurisy
  • Rashes
  • Fever
  • Positive antinuclear antibodies (ANA) 5, 6

• Traditional drug-induced lupus rarely involves:

  • Kidneys
  • Central nervous system 5, 3

• Anti-histone antibodies are common in traditional drug-induced lupus, while anti-dsDNA antibodies are rare 5, 7

• TNF-α inhibitor-induced lupus differs from traditional drug-induced lupus:

  • Higher incidence of rashes
  • Possible renal involvement
  • Anti-dsDNA antibodies may be present 7

Management

• Discontinuation of the offending drug is the primary treatment 5, 6
• Symptoms typically resolve within weeks after stopping the medication 6
• Some patients may require corticosteroid treatment if symptoms persist 3

Prevention and Monitoring

• For high-risk medications (hydralazine, procainamide):
  • Monitor for symptoms of drug-induced lupus
  • Consider periodic ANA testing 2
• For patients on isoniazid, monitor for symptoms such as arthralgia, fever, and pleuritis 1
• For patients on TNF-α inhibitors, be vigilant for new-onset lupus-like symptoms 7

Special Considerations

• Acetylation status may be a determining factor in the development of procainamide-induced lupus syndrome 3
• Patients should be counseled to report symptoms such as arthralgia, myalgia, fever, rash, and chest pain while on high-risk medications 2
• Drug-induced lupus can occur months to years after starting the offending medication 7