TSx-Cover

Darier’s Disease

Treatment

First-line therapy: The first-line therapy for Darier’s disease is systemic retinoids.

First steps

  • 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. Successful use of alitretinoin in Darier’s disease has recently been reported.
  •  Topical tretinoin 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 in mild clinical disease. Some patients may tolerate or respond better to one agent over another, so do not abandon topical treatment until all three topical retinoid medications have been tried.
  • Flares of Darier’s disease are often precipitated by secondary bacterial (most common), herpetic superinfection, 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.
  •  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. Viral superinfection with herpes simplex virus requires a course of acyclovir (400 mg t.i.d.) or valacyclovir (500-1000 mg b.i.d.) for 7-10 days.
  • 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 skin folds or breasts may be associated with dramatic improvement in macerated areas.
  • Patients with a history of frequent bacterial superinfections may benefit from prophylactic bleach baths (1/4 cup in a full household bathtub, soak for 10-15 minutes once or twice weekly) to disease-prone areas.

Subsequent steps

As soon as a good response to systemic retinoids is observed (i.e., 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.

Pitfalls

  • Some patients with the seborrheic variant of Darier’s disease may be worsened by systemic retinoids owing to the tendency of these agents to cause epidermal fragility.
  •  Frequent courses of oral antibiotics often result in colonization by resistant strains of staphylococci.
  • 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. It is imperative that female patients utilize consistent contraception to avoid pregnancy during retinoid treatment.

When to refer to a dermatologist

  • When the diagnosis is not clear.
  • To start systemic retinoids, or when systemic retinoids are not effective.
  • For treatment-resistant disease, additional treatment modalities may be considered.
  • For screening for cutaneous malignancy that may arise in association with the disease.