Drugs Associated With the Development of Palmoplantar Keratoderma: A Systematic Review

Area of Science:

• Dermatology
• Pharmacology
• Oncology

Background:

• Palmoplantar keratoderma (PPK) encompasses diverse hereditary and acquired conditions causing excessive epidermal thickening on palms and soles.
• PPK is a recognized, albeit rare, adverse event associated with specific pharmaceutical agents.
• Understanding drug-induced PPK is crucial for managing patients and guiding dermatologists and healthcare providers.

Purpose of the Study:

• To systematically review and summarize outcomes of PPK associated with various medications.
• To identify the primary drug classes implicated in causing PPK.
• To provide data assisting clinicians in managing drug-induced PPK.

Main Methods:

• A systematic literature search was conducted using EMBASE and MEDLINE databases.
• The search employed the keyword "palmoplantar keratoderma" adhering to PRISMA guidelines.
• Forty studies met the predefined inclusion criteria for the review.

Main Results:

• The analysis included 247 patients, with a mean age of 57.0 years; 60.3% of those with reported sex were male.
• PPK most commonly occurred following treatment with BRAF inhibitors (73.7%), BRAF/MEK1/2 inhibitors (15.4%), tyrosine kinase inhibitors (TKIs) (3.2%), and chemotherapy (2.4%).
• The mean latency to PPK onset was 7.6 months. Of 24 cases with reported outcomes, 12 resolved completely (after drug cessation) and 12 partially resolved. Keratolytic treatments and topical corticosteroids were common interventions.

Conclusions:

• Targeted kinase inhibitors, particularly BRAF, MEK1/2, and tyrosine kinase inhibitors, are most frequently associated with PPK.
• Drug cessation is effective for complete resolution of PPK.
• Further research into the mechanisms and management of drug-induced PPK is warranted.