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Leflunomide: dermatologic perspective.

Virendra N Sehgal1, Prashant Verma

  • 1Dermato-Venereology (Skin/VD) Center, Sehgal Nursing Home, Panchwati, Delhi, India. drsehgal@ndf.vsnl.net.in

The Journal of Dermatological Treatment
|August 2, 2011
PubMed
Summary
This summary is machine-generated.

Leflunomide, a disease-modifying antirheumatic drug, shows promise in treating certain skin conditions by inhibiting pyrimidine synthesis. Its use is currently recommended for psoriasis and psoriatic arthritis, with further research needed for other dermatologic diseases.

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Area of Science:

  • Immunology
  • Dermatology
  • Pharmacology

Background:

  • Leflunomide is an isoxazole derivative and a disease-modifying antirheumatic drug (DMARD).
  • It is an established treatment for rheumatoid arthritis, offering an alternative to methotrexate.
  • Recent interest has emerged regarding its application in various dermatologic conditions.

Purpose of the Study:

  • To review the current evidence and strength of recommendation for leflunomide in dermatologic conditions.
  • To identify the primary mechanism of action of leflunomide in the context of immune-mediated diseases.
  • To evaluate the potential and limitations of leflunomide for specific skin diseases.

Main Methods:

  • A Medline/PubMed search was conducted to identify articles on leflunomide's dermatologic applications.
  • A systematic review and inclusion criteria were applied to select relevant studies (21 out of 201 articles).
  • The primary mechanism of action, inhibition of dihydroorotate dehydrogenase, was analyzed.

Main Results:

  • Leflunomide inhibits dihydroorotate dehydrogenase, a crucial enzyme in the de novo pyrimidine synthesis pathway essential for lymphocyte proliferation.
  • Current evidence supports the use of leflunomide in psoriasis and psoriatic arthritis.
  • Limited evidence exists for its efficacy in severe atopic dermatitis, systemic lupus erythematosus, Wegener's granulomatosis, primary Sjögren's syndrome, bullous pemphigoid, dermatomyositis, sarcoidosis, and systemic sclerosis.

Conclusions:

  • Leflunomide's mechanism of action involves the inhibition of pyrimidine synthesis, impacting lymphocyte clonal expansion.
  • The drug is recommended for psoriasis and psoriatic arthritis based on existing evidence.
  • Further clinical evaluation is necessary to establish the role of leflunomide in other complex dermatologic and autoimmune conditions.