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Therapeutic Strategies

Ichthyoses/Disorders of Cornification

Timothy Berger Bruce Wintroub

Wednesday, October 15, 2008


Ichthyosis results from abnormal retention and/or production of the stratum corneum layer of the epidermis. Acquired ichthyosis can be a cutaneous manifestation of an underlying disease (eg, malignant neoplasm, metabolic disorder, malabsorption). The genetic ichthyoses comprise a heterogeneous group of disorders that are either limited to the skin (primary ichthyoses) or part of a systemic or developmental disease complex (eg, Sjögren-Larsson syndrome, Refsum disease). Not only are these disorders diverse in etiology, but the extent of scaling is variable as well, ranging from mild to severe. Regardless of the diagnosis, the therapeutic strategy is similar and related to the extent and severity of the process rather than to the specific diagnosis. Thus, for practical purposes, management is separated here into the therapy of mild and severe disease.

Mild Ichthyosis

H2 First Steps

Emollients with added alpha-hydroxy acids (lactic acid), or hygroscopic agents (urea) are usually tried first. The efficacy of these agents are similar and the clinician may choose ammonium lactate 12% gel, lactic acid 6% lotion, or 40% urea in petrolatum with or without 5-10% lactic acid depending on the degree of emollience needed. Each of these preparations is applied daily immediately after bathing, while skin is still damp.

Alternative Steps

  1. Occlusive therapy: Hydrated petrolatum with 6% lactic acid; or with 10-20% urea; or 40% propylene glycol in water-(any of the above), applied overnight under a space suit or occlusive treatment suit.

Ancillary Steps

Most milder forms of ichthyosis are accompanied by a relative inability of the skin to retain moisture. Therefore, the following general measures should be used in all cases regardless of diagnosis:

  1. Oilated baths one half cup/bath daily: Soak at least 15 minutes in the tub to hydrate the skin. Apply the appropriate topical agent (above) immediately after bathing on still-moist skin.
  2. Cool-water bathing, in general, will result in less delipidization, and hence, better water retention of the stratum corneum.
  3. Milder soaps: Glycerinated or nonglycerinated, and oilated soaps are equally effective. Soap should be applied to the axillae, groin, and scalp only.

Subsequent Steps

  1. The inherited ichthyoses are life-long diseases, and therapy should be adjusted for maximum patient convenience.
  2. The hydroxy acids (ie, lactic acid lotion, ammonium lactate gel, or glycolic acid lotion) are especially efficacious in X-linked ichthyosis, and may be the only specific therapy needed for this disease.
  3. Patients with acquired ichthyosis need to be evaluated for associated systemic diseases.
  4. Exacerbations in winter and remissions in summer are the rule for the milder forms of ichthyosis, and therapy should be adjusted accordingly.

Severe Forms of Ichthyosis

Severe forms of ichthyosis generally require the same topical approaches as milder forms. However, in addition, systemic retinoids may be indicated. Because the doses required for successful control of bullous ichthyosiform erythroderma (epidermolytic hyperkeratosis), lamellar ichthyosis, and nonbullous congenital ichthyosiform erythroderma generally are higher than those used for other applications (eg, acne, cancer chemoprevention, or psoriasis), acute side effects can be more severe. Moreover, the benefits of improvement of the skin must be weighed against long-term risks of systemic retinoid therapy. Finally, in prepubertal children, there is the additional risk of premature closure of the epiphyses.

First Steps

  1. Acitretin 1-2 mg/kg/day.
  2. Isotretinoin 2-4 mg/kg/ day; initial therapy should be at the lower dose levels indicated.

Subsequent Steps

  1. Improvement should be evident within 6 weeks. If no change has occurred, the dose can be increased. If and when dramatic improvement has occurred, attempts should be made to reduce the dosage, and/or to use every-other-day therapy.
  2. Topical therapy should be pursued aggressively throughout to allow reduction in total dosage of systemic retinoids.


  1. As the structural abnormality of the skin is different for different disorders, the percutaneous absorption may be diminished, normal, or enhanced. Topical products that are potentially irritating or absorbed may result in cutaneous or systemic toxicities. Topical salicylic acid may cause salicylism or persistent hypoglycemia if enhanced percutaneous absorption occurs and excretion is reduced. This is particularly likely to occur in neonates or adults with impaired renal function.
  2. Many persons with ichthyosis vulgaris also have atopic dermatitis. High concentrations of lactic acid (>5%) may exacerbate or trigger an inflammatory dermatosis in atopics. Lower concentrations of lactic acid in combination with urea is preferred in atopics.
  3. Patients on long-term systemic retinoid therapy require monitoring of serum lipids, liver function tests, and complete blood count with platelets, as well as sequential radiographic studies (to look for calcification of the ligaments and premature epiphysial closure). Retinoid therapy is best managed by a physician with special expertise in these applications at these high dosages.

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