Darier-White Disease

Autosomal dominant, slowly progressive disorder of keratinization. Lesions usually coalesce and result in crusted papillomatous lesions.

Keratosis Follicularis; Dyskeratosis Follicularis.

Four new cases per million per 10 years. Gene map locus is 12q23-q24.1

Autosomal dominant.

Results from an abnormal desmosome-keratin filament complex that leads to disruption of cell adhesion.

Diagnosis is made by family history and clinical aspect.

Histological studies of the skin are diagnostic and characterized by hyperkeratosis, dyskeratotic epidermal cells, suprabasal separation of the spinal layer with formation of clefts and lacunae containing acantholytic cells, dermal villi extending in the epidermis, and mild nonspecific perivascular dermal infiltration.

Age of onset is usually between 6 and 20 years, with peak onset around puberty. Keratotic papules appear predominantly on the upper trunk and may involve the face, scalp, neck, hands (palms), feet (soles), and limb flexures (axillae, groins). The papillomatous masses may become malodorous. Nail dystrophy manifests as subungual hyperkeratosis, fragility, longitudinal ridging and splitting, and longitudinal red and white lines. Mucous membranes, such as lips, buccal mucosa, hard palate, alveolar ridges, uvula, pharynx, larynx, and vulva, are rarely involved. However, if involved, papules, fissures, crusts, and ulcers may result. Secondary cutaneous infection (herpes virus, bacterial) is a frequent complication. The disease is exacerbated by sunlight or sunburn. Occasionally, patients suffer from a seizure disorder and mild mental retardation.

Inquire about dermatologic treatment. Adverse effects of oral retinoid derivatives include increased intracranial pressure, pseudotumor cerebri, hypoplastic anemia, leukopenia, optic neuropathy, hypercalcemia, bone demineralization, increased alkaline phosphatase level, hepatomegaly, splenomegaly, dermatotoxicity, carcinogenicity, photosensitization, and teratogenicity. A newer generation of more selective topical retinoids seems almost devoid of toxic side effects. Topical steroids are of little use in Darier disease. In the presence of oral retinoid treatment, obtain a complete blood count, hemoglobin level, liver function tests, and calcium level, and evaluate for the presence of increased intracranial pressure. If necessary, obtain a neurologic consultation.

Involvement of the mucous membranes is extremely rare and does not compromise airway management. In the presence of retinoic acid toxicity, correction of anemia and hypercalcemia may be necessary. In the rare cases of increased intracranial pressure, precautions to prevent further elevation should be taken. In cases with an associated seizure disorder, patients on anticonvulsant treatment should receive their medication perioperatively.

In the presence of a seizure disorder, avoid potentially epileptogenic drugs such as methohexital, ketamine, enflurane, atracurium, cis-atracurium, and meperidine (the last three only if given in large quantities because of their metabolites laudanosine and normeperidine, respectively).