Keratolytics - Definition and Examples

• Dissolving the intercellular "cement" or cell surface proteins that bind corneocytes together
• Increasing water content of the stratum corneum
• Activating endogenous hydrolytic enzymes
• Reducing pH, which promotes desquamation

Major Examples

1. Salicylic Acid (most widely used)

• Keratolytic at 3-6% concentrations; destructive to tissue at >6%
• Solubilizes cell surface proteins holding the stratum corneum intact, causing desquamation of keratotic debris
• Used in: acne, warts, psoriasis, dandruff, corns, calluses, ichthyosis
• Toxicity: Salicylism (toxicity) can occur with widespread/prolonged use - especially dangerous in children and patients with renal/hepatic impairment. Hemodialysis is treatment of choice for severe intoxication
• (Katzung's Basic and Clinical Pharmacology, 16th Ed.)

2. Urea

• At low concentrations (<40%): increases skin hydration and flexibility (humectant)
• At >40%: denatures and dissolves proteins - used to dissolve calluses or avulse dystrophic nails
• Used in: ichthyosis, dry skin, hyperkeratosis, nail disorders
• (Goodman & Gilman's, 14th Ed.)

3. Alpha-Hydroxy Acids (AHAs)

• Includes: glycolic acid, lactic acid, malic acid, citric acid, mandelic acid
• Mechanism: solubilize desmosome components, activate endogenous hydrolytic enzymes, draw water into stratum corneum
• Also increase glycosaminoglycans, collagen, and elastic fibers in the dermis - used to reverse photoaging
• FDA requires sunburn alert warning on cosmetics containing AHAs
• (Goodman & Gilman's)

4. Lactic Acid (an AHA)

• Available up to 12% concentration
• Dual action: keratolytic + humectant
• Also increases ceramide production by keratinocytes, improving water barrier function
• (Fitzpatrick's Dermatology)

5. Sulfur

• Mechanism: reacts with cysteine in keratinocytes → produces cystine + hydrogen sulfide (H₂S) → H₂S breaks down keratin, dissolving the stratum corneum
• Additional properties: antiseptic, antiparasitic, antiseborrheic
• Used in: acne, seborrheic dermatitis, scabies
• (Goodman & Gilman's)

6. Propylene Glycol

• Used in 40-70% concentrations as a keratolytic (alone or with 6% salicylic acid gel under plastic occlusion)
• Acts as humectant - creates osmotic gradient through the stratum corneum, increasing hydration
• Also used as a vehicle to enhance penetration of other topical agents
• Absorbed propylene glycol is oxidized by the liver to lactic and pyruvic acid
• (Katzung's)

7. Beta-Hydroxy Acids (BHAs)

• Salicylic acid is classically listed here (though chemically not a true BHA)
• Other BHAs: beta-hydroxybutanoic acid, tropic acid, trethocanic acid
• Lipophilic - penetrate sebaceous follicles better than AHAs, hence effective in acne

8. Hydrogen Peroxide 40% (Eskata)

• FDA-approved for raised seborrheic keratoses
• Applied only by healthcare providers due to caustic nature
• Contraindicated near the orbital rim; can cause permanent eye injury

Summary Table