In any ichthyosis, there is impaired epidermal barrier function, and moisturizers should be applied immediately after bathing. Substances that are applied to the skin may have increased absorption. For example, hexachlorophene products should not be used because of increased absorption and toxicity.

An emollient, preferably plain petrolatum, mineral oil, or lotions containing urea or α-hydroxy acids (eg, lactic, glycolic, and pyruvic acids), should be applied twice daily, especially after bathing while the skin is still wet. Blotting with a towel removes excess applied material.

Ichthyosis typically responds well to the topical keratolytic propylene glycol. To remove scale (eg, if ichthyosis is severe), patients can apply a preparation containing 40 to 60% propylene glycol in water under occlusion (eg, a thin plastic film or bag worn overnight) every night after hydrating the skin (eg, by bathing or showering); in children, the preparation should be applied twice daily without occlusion. After scale has decreased, less frequent application is required. Other useful topical agents include ceramide-based creams, 6% salicylic acid gel, hydrophilic petrolatum and water (in equal parts), and the α-hydroxy acids in various bases. Topical calcipotriol cream has been used with success; however, this vitamin D derivative can result in hypercalcemia when used over broad areas, especially in small children.

Retinoids are effective in treating inherited ichthyosis. Oral synthetic retinoids are effective for most ichthyoses. Acitretin (see Systemic treatments) is effective in treating most forms of inherited ichthyosis. In lamellar ichthyosis, 0.1% tretinoin cream or oral isotretinoin may be effective. The lowest effective dose should be used. Long-term (1 yr) treatment with oral isotretinoin has resulted in bony exostoses in some patients, and other long-term adverse effects may arise.

Patients with epidermolytic hyperkeratosis may need long-term treatment with cloxacillin 250 mg po tid or qid or erythromycin 250 mg po tid or qid, as long as thick intertriginous scale is present, to prevent bacterial superinfection from causing painful, foul-smelling pustules. Regularly using soaps containing chlorhexidine may also reduce the bacteria, but these soaps tend to dry the skin.