Saturday, January 01, 2011
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
- 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.
- 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.
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. As 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.
- 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 (eg, 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 1 week.
- 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 used. 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 1
- 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.
- 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.
- Patients with a history of frequent bacterial superinfections
may benefit from prophylactic topical antibiotics, such as
clindamycin 1% solution to disease-prone areas.
- 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.
- 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
- As described above, secondary infections owing to heat and
excessive friction, as well as to acute exposure to ultraviolet
light, can cause disease flares.
- Systemic retinoids can cause both acute and chronic side
effects. Hence, patients must be fully aware of the risks and
benefits of this therapy.