Keratinization cutaneous disorders

In 1990, etretinate (Tigason) was replaced by acitretin (Neo-Tigason), an aromatic retinoid, a carboxylic acid metabolite of etretinate (15). It is effective in pustular psoriasis and psoriatic palmoplantar keratoderma and in combination with PUVA or topical therapy (calci-potriol or glucocorticoids) in the treatment of other forms of psoriasis. It has also been used to treat disorders of keratinization (ichthyosis, palmoplantar keratoderma, Darier s disease) and severe cutaneous forms of lichen planus. It prevents new skin carcinomas in patients with xeroderma pigmentosum and those who are immunosuppressed. The main advantage of acitretin is its short half-life of 50 hours, compared with over 80 days for etretinate (16). 

An outbreak of chloracne in 17 workers from a British plant manufacturing dichloro-aniline-derived herbicides was reported in 1993. TCAB and TCAOB were the acnegens. Comedones evolved 6-12 weeks after exposure to these chloracnegenic contaminants. Cutaneous xerosis and folliculitis, on the trunk, limbs, thighs and buttocks, previously uncommonly described, was present in 50% of exposed workers. Affected follicles were surrounded by a collarette of scale and frequently the hair shaft was twisted or broken. The pathogenesis of these lesions is unclear but may involve a disorder of keratinization. A direct toxic effect on epidermal keratinocytes or a secondary effect due to a perifollicular inflammatory reaction has been theorized (McDonough et al. 1993). They suggested that folliculitis and xerosis should be included in the clinical spectrum of chloracne. 

Comprised of several genetically transmitted diseases, these disorders appear to be valid disorders of keratinization. Although categorized into several types according to genetic patterns, clinical presentation and histological features, the ichthyoses are all related by the common denominator of defective cutaneous keratinization, which appears to be an isolated epidermal phenomenon insofar as hyperkeratinization of other epithelia does not occur. 

The results of this study, in which a synthetic retinoid was found to have a profound beneficial effect in the treatment of disorders of keratinization, should be of importance to areas other than dermatology. For instance, preneoplastic squamous metaplasia of tracheo-bronchial and urinary bladder epithelia may be other keratinizing disorders of man that could be successfully treated with the synthetic retinoids, as suggested by Sporn . Finally, patients with these cutaneous diseases, which have responded to 13-cis retinoic acid, may provide useful information in the evaluation of newer and potentially more potent and less toxic synthetic retinoids. 

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