Salicylism and death have occurred following topical application. In an adult, 1 g of a topically applied 6% salicylic acid preparation will raise the serum salicylate level not more than 0.5 mg/ dL of plasma; the threshold for toxicity is 30–50 mg/dL. Higher serum levels are possible in children, who are therefore at a greater risk for salicylism. In cases of severe intoxication, hemodialysis is the treatment of choice (see Chapter 58). It is advisable to limit both the total amount of salicylic acid applied and the frequency of application. Urticarial, anaphylactic, and erythema multiforme reactions may occur in patients who are allergic to salicylates.
Topical use may be associated with local irritation, acute inflammation, and even ulceration with the use of high concentrations of salicylic acid. Particular care must be exercised when using the drug on the extremities of patients with diabetes or peripheral vascular disease.
Propylene glycol is used extensively in topical preparations because it is an excellent vehicle for organic compounds. It has been used alone as a keratolytic agent in 40–70% concentrations, with plastic occlusion, or in gel with 6% salicylic acid.
Only minimal amounts of a topically applied dose are absorbed through normal stratum corneum. Percutaneously absorbed propylene glycol is oxidized by the liver to lactic acid and pyruvic acid, with subsequent utilization in general body metabolism. Approximately 12–45% of the absorbed agent is excreted unchanged in the urine.
Propylene glycol is an effective keratolytic agent for the removal of hyperkeratotic debris. It is also an effective humectant and increases the water content of the stratum corneum. The hygroscopic characteristics of propylene glycol may help it to develop an osmotic gradient through the stratum corneum, thereby increasing hydration of the outermost layers by drawing water out from the inner layers of the skin.
Propylene glycol is used under polyethylene occlusion or with 6% salicylic acid for the treatment of ichthyosis, palmar and plantar keratodermas, psoriasis, pityriasis rubra pilaris, keratosis pilaris, and hypertrophic lichen planus.
In concentrations greater than 10%, propylene glycol may act as an irritant in some patients; those with eczematous dermatitis may be more sensitive. Allergic contact dermatitis occurs with propylene glycol, and a 4% aqueous propylene glycol solution is recommended for the purpose of patch testing.
Urea in a compatible cream vehicle or ointment base has a softening and moisturizing effect on the stratum corneum. It has the ability to make creams and lotions feel less greasy, and this has been utilized in dermatologic preparations to decrease the oily feel of a preparation that otherwise might feel unpleasant. It is a white crystalline powder with a slight ammonia odor when moist.
Urea is absorbed percutaneously, although the amount absorbed is minimal. It is distributed predominantly in the extracellular space and excreted in urine. Urea is a natural product of metabolism, and systemic toxicities with topical application do not occur.
Urea increases the water content of the stratum corneum, presumably as a result of the hygroscopic characteristics of this naturally occurring molecule. Urea is also keratolytic. The mechanism of action appears to involve alterations in prekeratin and keratin, leading to increased solubilization. In addition, urea may break hydrogen bonds that keep the stratum corneum intact.