Darier's Disease

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Keratosis Follicularis

The diagnosis of Darier's disease is dependent on clinical features, family history and a characteristic histopathology. Darier's disease is a genodermatosis of autosomal dominant inheritance causing abnormalities of keratinization. Two clinical variants can be seen: a "seborrheic" form of the disease with crusted plaques on the face, neck, and intertriginous areas; and a cornifying variant, characterized by hypertrophic, vegetative lesions, primarily on the lower extremities. Some patients may have both variants simultaneously. Because the underlying genetic defect cannot be corrected, therapeutic strategies attempt to minimize the clinical consequences of abnormal keratinization and to treat the complications that result from the inherited defect. Because of seasonal exacerbations and partial remissions, therapy should be adjusted accordingly.

First Steps

1. The currently accepted primary treatment of moderate-to-severe Darier's disease is systemic retinoids. Isotretinoin and acitretin are equally effective for most patients. Acitretin may be more effective for the hyperkeratotic lesions. For either medication, the starting dose is 0.2-0.3 mg/kg/day, with gradual escalation of the dose to the therapeutic range of 0.5-1 mg/kg/day. Note: Because of possible long-term musculoskeletal toxicity (see below), do not administer retinoids to growing children.
2. For mild or localized disease, topical retinoic acid 0.025% gel or 0.1% cream before bed may suffice for patients with mild or limited disease. Adapalene or tazarotene are acceptable alternative topical retinoids. Some patients may tolerate or respond better to one agent over another, so do not abandon topical treatment until all three classes of medications have been used.

Subsequent Steps

As soon as a good response to systemic retinoids is observed (ie, usually after about 4-8 weeks), reduce the daily retinoid dose. Maintenance therapy constitutes the lowest dose that suppresses the most severe disease features. Since the disease tends to be relatively quiescent during winter months, if possible discontinue retinoid therapy completely during this period, thereby potentially minimizing long-term side effects.

Ancillary Steps

1. Flares of Darier's disease are often precipitated by secondary bacterial (most common) and candidal infections owing both to a defective skin barrier and to minor immunologic dysfunction in this disease. Hence, therapy often includes an initial 10- to 14-day course of a bacteriocidal antibiotic (e.g., oral cephalexin 500 mg three times daily, dicloxacillin 500 mg three times daily) directed against coagulase-positive S. aureus, the most commonly encountered pathogen. This should be combined with rifampin 600 mg once daily for at least one week.
2. In penicillin-allergic individuals or in patients in whom methicillin resistant S. aureus is possible, in addition to the rifampin treatment , trimethoprim-sulfamethoxazole (Bactrim DS or Septra DS) 1 tablet twice daily, clindamycin 150-300 mg twice daily, doxycycline 100 mg twice daily or ciprofloxacin 500 mg twice daily may be employed. Obtain surveillance cultures and sensitivities routinely, as patients with Darier's disease often develop antibiotic-resistant pathogens due to frequent exposures to antibiotics. If Candida is grown on routine cultures, and trials of topical nystatin and Burow's soaks 1:20 are not effective, administer oral fluconazole 150 mg daily for one week.
3. Because Darier's disease flares after acute exposure to sunlight (UVB is the active wavelength), instruct patients to use maximum photoprotection with sun protective clothing and a high UVB SPF sunblock (SPF 30 or greater) daily.
4. Heat, sweating, and friction can exacerbate Darier's disease, either directly or indirectly via secondary bacterial infections. Weight reduction and even surgical removal of pendulous breasts may be associated with dramatic improvement in macerated areas.
5. Patients with a history of frequent bacterial superinfections may benefit from prophylactic topical antibiotics, such as clindamycin 1% solution to disease-prone areas.

Pitfalls

1. Some patients with the seborrheic variant of keratosis follicularis may be worsened by systemic retinoids owing to the tendency of these agents to cause epidermal fragility. However, failure with one retinoid does not necessarily preclude the use of others. Thus, acitretin-resistant cases may benefit from isotretinoin and vice versa. If both retinoids cause worsening of disease, the patient must be managed with the other conservative measures described above.
2. Frequent courses of oral antibiotics often result in colonization by resistant strains of staphylococci. Oral retinoid therapy also predisposes to staphylococcal nasal carriage, which may exacerbate the Darier's disease. Intranasal mupirocin 5 consecutive days per month may be effective in reducing this complication.
3. As described above, secondary infections owing to heat and excessive friction, as well as to acute exposure to ultraviolet light, can cause disease flares.
4. Systemic retinoids can cause both acute and chronic side effects. Hence, patients must be fully aware of the risks and benefits of this therapy.