What is the lupus-like syndrome?

Lupus-Like Syndrome (Drug-Induced Lupus)

Definition and Pathophysiology

Lupus-like syndrome, also known as drug-induced lupus, is an autoimmune condition that develops following exposure to certain medications—most notably TNF-alpha antagonists—and resolves after discontinuation of the offending agent. 1, 2

The pathogenic mechanism involves medication-induced apoptosis leading to accumulation of nucleosomal antigens from apoptotic cells, which triggers autoantibody production in susceptible individuals. 2 Treatment with adalimumab and other TNF-blockers may result in formation of autoantibodies and, rarely, development of a lupus-like syndrome. 1

Key Distinguishing Features from Systemic Lupus Erythematosus

Drug-induced lupus differs from true SLE in several critical ways:

• Temporal relationship: Symptoms occur after exposure to the causative medication and disappear after drug discontinuation 1, 2
• Demographics: Predominantly affects women (4:1 ratio) with average age of onset 46-51 years 2
• Reversibility: Complete resolution typically occurs upon stopping the offending agent 1, 2

Clinical Manifestations

Cutaneous Manifestations

The most common skin findings include:

• Maculopapular exanthem 2
• Malar rash 2
• Alopecia 2
• Photosensitivity 2
• Leukocytoclastic vasculitis (rare but documented with adalimumab) 2

Extracutaneous Manifestations

Systemic symptoms may include:

• Fever 2
• Weight loss 2
• Arthritis or arthralgia 2
• Myositis 2
• Hematological abnormalities 2

Laboratory Findings

Antinuclear antibody (ANA) may be positive in 80% of cases, and anti-histone antibody is considered a disease marker for TNF-alpha antagonist-induced lupus-like syndrome. 2

This contrasts with true SLE, where anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies are more characteristic. 3, 4

Common Causative Medications

TNF-alpha antagonists are the most commonly implicated agents in contemporary practice:

• Adalimumab 1, 5, 2
• Infliximab 5
• Other TNF-blockers 1

Sequential treatment with multiple TNF-alpha antagonists (such as infliximab followed by adalimumab) has been documented to precipitate complete SLE conversion in susceptible patients. 5

Management Approach

The definitive treatment is immediate discontinuation of the offending medication. 1, 2

Specific Steps:

• Discontinue the causative drug immediately upon recognition of lupus-like symptoms 1, 2
• Monitor for symptom resolution, which typically occurs after drug withdrawal 2
• Avoid reintroduction of the same medication or related agents in the same class 1
• Consider alternative therapeutic options for the underlying condition that necessitated the original medication 1

Critical Clinical Pitfalls

If a patient develops symptoms suggestive of lupus-like syndrome following treatment with TNF-alpha antagonists, discontinue treatment immediately. 1 The FDA explicitly warns that treatment with adalimumab products may result in development of a lupus-like syndrome. 1

Be vigilant for progression to true SLE: While drug-induced lupus typically resolves with medication discontinuation, rare cases of complete conversion to systemic lupus erythematosus have been documented, particularly with sequential TNF-alpha antagonist exposure. 5 This underscores the need for careful monitoring and consideration of alternative immunobiologic agents when autoimmune phenomena develop. 5