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Multiple eruptive keratoacanthomas associated with leflunomide.

Laura Frances, Jaime Guijarro, Irene Marin

Dermatology Online Journal

|September 10, 2013

Summary

Leflunomide, a rheumatoid arthritis drug, may trigger multiple keratoacanthomas and squamous-cell carcinomas. This case report suggests a potential link between leflunomide and these skin tumors, warranting further investigation.

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Area of Science:

Dermatology
Rheumatology
Oncology

Background:

Rheumatoid arthritis (RA) is a chronic autoimmune disease.
Leflunomide is an immunosuppressive disease-modifying antirheumatic drug (DMARD) used to treat RA.
Skin tumors, including keratoacanthomas and squamous-cell carcinomas, can arise in patients with autoimmune conditions or those on immunosuppressive therapy.

Observation:

A 78-year-old woman with RA, not previously treated with immunosuppressants or with a history of skin tumors, was initiated on leflunomide.
Within one month of starting leflunomide, she developed multiple, recurring crateriform nodules and papules on her lower extremities over two years.
Biopsies confirmed the lesions as keratoacanthomas and squamous-cell carcinomas.

Findings:

The patient's skin lesions ceased appearing after discontinuing leflunomide, with no new lesions observed over 17 months of follow-up.
While multiple keratoacanthomas are documented with other immunosuppressants (e.g., sorafenib, imiquimod), this is the first reported case associated with leflunomide in an RA patient.
The temporal association suggests leflunomide as a potential causative agent for the observed skin tumors.

Implications:

This case highlights a potential, previously unreported adverse effect of leflunomide, specifically the induction of multiple keratoacanthomas and squamous-cell carcinomas.
Further research and case reports are necessary to establish a definitive causal relationship between leflunomide and these dermatological malignancies.
Clinicians should consider monitoring for skin lesions in rheumatoid arthritis patients treated with leflunomide, especially those with risk factors.