Medication Summary
Enhanced survival and decreased morbidity is reported with the use of systemic retinoids; however, infants have survived without systemic retinoid therapy. [21] Retinoids bind to specific retinoic acid receptors and regulate gene transcription. They influence keratinocyte differentiation, normalize abnormal keratinocyte proliferation, and mediate desquamation of hyperkeratotic scale. Rajpopat et al recommend frequent application of emollients to ease this shedding of thick plates when retinoids are given. [13]
Etretinate was first used for the treatment of this disorder in 1985. An effective dose of 1 mg/kg/d was established. Etretinate is no longer available and has been replaced by other retinoids with improved safety profiles.
Acitretin, a carboxylic acid derivative of etretinate, is the retinoid most commonly prescribed in neonates with harlequin ichthyosis. [7, 28] Initial doses of 0.5 mg/kg/d are recommended. [13] Improvement in hyperkeratosis, ectropion, and eclabium is reported. The duration of therapy is variable, and continuous, long-term, daily therapy may be required. The daily dose can be titrated to the degree of ichthyosis. In infants, the oral acitretin can be dissolved (10-mg capsules) in Ora-Plus solution for precise weight-based dosing. [29]
Rajpopat et al reported that of 24 babies given oral retinoids, 20 received acitretin, 2 received etretinate, and 2 received isotretinoin. Twenty of the 24 treated patients survived (83%). [13]
A topical retinoid (tazarotene) has been used to treat local and mechanical circulatory problems caused by hyperkeratosis. [24, 25]
Isotretinoin has also been used in harlequin ichthyosis. The reported dose is 0.5 mg/kg/d. Treatment is usually initiated within the first few days of life and given orally. Case reports have documented improvement in pliability of the skin, limb movements, sucking, and eyelid closing within a week of starting therapy. Treatment has been continued for several years in some patients.
Liver function and serum lipid levels should be monitored during retinoid therapy. Clinical monitoring for skeletal adverse effects should be done periodically. Before retinoid therapy is considered, discuss the expected outcome and the potential adverse effects with the parents.
Retinoid-like Agents
Class Summary
These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes. They modulate keratinocyte differentiation.
Isotretinoin (Amnesteem, Claravis, Sotret)
Synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). Both agents structurally related to vitamin A.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Acitretin (Soriatane)
Metabolite of etretinate and related to retinoic acid and retinol (vitamin A). Mechanism of action unknown but thought to exert therapeutic effect by modulating keratinocyte differentiation, keratinocyte hyperproliferation, and tissue infiltration by inflammatory cells.
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Harlequin ichthyosis. Courtesy of Dr Bernice Krafchik.
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Harlequin ichthyosis. Courtesy of Jason K Rivers, MD, FRCPC, and Dr Lawler.
