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Abstract

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. References

The authors have indicated no significant interest with commercial supporters.

Darier's disease, also known as keratosis follicularis or Darier-White disease, is chronic and unremitting. Lesions may be pruritic and painful and, depending on the extent of involvement, cause the patient distress. Current treatment methods include topical retinoids,1,2 topical 5-fluorouracil,3,4 oral retinoids,5,6 topical tacrolimus,7 electrosurgery,8 dermabrasion,9 surgery,10,11 carbon dioxide (CO2) laser ablation,12,13 erbium-doped yttrium aluminum garnet (Er:YAG) laser therapy,14 and photodynamic therapy with 5-aminolevulinic acid.15 Oral retinoids are the most effective treatment option, but their adverse effects can be a deterrent.16 We present a case of Darier's disease treated with a 1,550-nm erbium-doped fiber laser. Owing to the success of non-ablative fractional photothermolysis in treating epidermal and upper dermal skin conditions,17,18 it was hypothesized that this patient's widespread Darier's disease might be improved using this technology.

Case Report

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. References

A 43-year-old white woman with Fitzpatrick skin type I presented with a 13-year history of a papular eruption on the chest, upper arms, back, upper thighs, and lower legs. Initially, the patient noticed a few papules on her back; thereafter, new lesions appeared every 3 to 4 months on the legs, arms, and chest. The new papules were erythematous, tender, and nonpruritic. Over 1 to 2 weeks, the papules turned brown and nontender and became permanent. The patient recalled transient “breakouts” in her axillae at a young age. In the hot summer months, the lesions worsened.

The patient's past medical history included rosacea of the face, which first appeared around the same time as the other skin findings. The patient noted that her sister had similar, less extensive, and less bothersome lesions in the popliteal fossae and on the calves (since age 40), which also did not resolve. A female cousin had similar skin lesions. Previous unsuccessful treatments included topical steroids, a sulfur-based lotion, and cryotherapy. The only regular medications taken by the patient were birth control pills. She reported using daily sunscreen with a sun protection factor (SPF) of 70 on all her sun-exposed areas.

Physical examination revealed multiple, scattered, erythematous to brown, flat-topped papules and macules on the chest, upper arms, upper and lower legs, and back (Figures 1–3A). A shave biopsy taken from the anterior thigh demonstrated acantholytic dyskeratosis and hyperkeratosis, consistent with Darier's disease. The clinical findings were consistent with this diagnosis. In addition to the lesions from the Darier's disease, there was brown lentiginous freckling on the chest. No nail, oral mucosal, or hand findings of Darier's disease were noted.

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Figure 1.  (A) Darier's disease on the chest before treatments. (B) Thirteen weeks after three treatments with fractional photothermolysis. The treating physician and the patient noted almost complete resolution of the lesions.

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Figure 2.  (A) Darier's disease on the shoulder before treatment. (B) Thirteen weeks after two treatments with fractional photothermolysis. The treating physician and the patient noted almost complete resolution of the lesions.

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Figure 3.  (A) Darier's disease on the lower leg before treatment with fractional photothermolysis. (B) Five weeks after four treatments with fractional photothermolysis. The physician and patient noted approximately 50% improvement of the lesions.

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Treatments were conducted using the 1,550-nm erbium-doped fiber laser (Fraxel SR 1,500, Reliant Technologies Inc., Mountain View, CA). The treatment area was cleansed before the procedure using a mild soap (Cetaphil Gentle Skin Cleanser, Galderma Laboratories, L.P., Ft. Worth, TX). A topical triple anesthetic cream consisting of 10% benzocaine, 6% lidocaine, and 4% tetracaine (New England Compounding Center, Framingham, MA) was applied under occlusion to the treatment area for 1 hour before treatment. An ointment (LipoThene Inc., Pacific Grove, CA) was applied over the treatment area so that the laser handpiece could glide smoothly over the treatment area.

The chest was treated with three treatment sessions using the 1,550-nm erbium-doped fiber laser at 6- to 8-week intervals. The upper arms and shoulders were treated with two treatment sessions 11 weeks apart. The lower legs were treated with four treatment sessions at 2- to 5-week intervals. Laser settings for all treatments were an energy fluence of 70 mJ and treatment level of 11, which corresponded to a coverage of 32%. Eight passes were performed at each treatment session. A cold-air cooling system (Cryo 5, Zimmer Medizin Systems, Irvine, CA) was used to cool the skin during treatment to minimize patient discomfort (fan power 3–5, 10–14 cm from the skin). The patient was advised to continue using a daily broad-spectrum sunscreen with ultraviolet A and B protection (minimum SPF 45) on the treated areas and cautioned to avoid sun exposure to the treated areas for 7 days.

Photographic documentation using identical camera settings, lighting, and patient positioning was obtained at baseline, before each treatment, and at follow-up visits (13 weeks after the final chest and upper arm and shoulder treatment and 5 weeks after the final lower leg treatment). During each treatment, the patient experienced mild pain, with moderate post-procedural erythema and edema, which resolved over 24 to 48 hours. At the follow-up visits, a more than 75% improvement of the Darier's lesions was noted on the chest and upper arms and shoulders, and approximately 50% improvement was noted on the lower legs (Figures 1–3B). The evaluating physician did not note any post-procedural complications or recurrence. The patient's degree of satisfaction paralleled the physician's assessment of improvement.

Discussion

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. References

Darier's disease is a genetic disease with an autosomal dominant inheritance characterized by the loss of intercellular adhesion (acantholysis) and disordered keratinization leading to hyperkeratotic papules and/or plaques.16,19 Mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2+ ATPase isoform 2 protein cause the condition.20 This is the calcium pump that plays a role in intracellular calcium signaling and has been found to influence cellular adhesion between keratinocytes and cellular differentiation in the epidermis.20 Prevalence of the disease has been reported to be from 1 in 30,000 to up to 1 in 100,000.16,19 Men and women are affected equally, and the disease usually presents between the ages of 10 and 30.19

Clinically, the lesions of Darier's disease are described as skin-colored to brown, hyperkeratotic, greasy papules that may coalesce into warty plaques. Lesions may be associated with a foul odor, due to secondary bacterial infection. There is often a follicular pattern of distribution, within the seborrheic areas of the chest, mid-back, hair margins, and flexures. Involvement of the hands is seen in the majority of patients. Nail changes associated with Darier's disease include red and white streaks and a V-shaped notch in the nail edge. Oral mucosal involvement may be present that is usually asymptomatic. The most common complaint associated with the disease is itching, with exacerbations attributed to heat, sweating, sunlight, lithium, steroid therapy, stress, and menstruation.16,19,21

Histologic changes seen in Darier's disease include dyskeratosis resulting in the formation of corps ronds and grains, suprabasal acantholysis leading to the formation of suprabasal clefts or lacunae, and proliferation into the lacunae of papillae lined with a single layer of basal cells.22 Acantholytic dyskeratosis in association with corps ronds is seen in several other conditions, including warty dyskeratoma, transient acantholytic dermatosis (Grover's disease), focal acantholytic dyskeratoma, and familial benign pemphigus (Hailey-Hailey disease).21,22

Treatment for Darier's disease has consisted of topical retinoids, steroids, tacrolimus, topical 5-fluorouracil, and oral retinoids.1–7 There are reports of the surgical treatment of Darier's disease, using electro- and cryosurgery.8–11 Er:YAG and CO2 laser ablation have shown clinical efficacy,12–15 although this treatment is associated with greater risks and a longer down-time. Treatment with the flashlamp-pumped pulsed-dye laser has been shown to improve Darier's disease.23 Studies investigating photodynamic therapy with aminolevulinic acid have had variable results.15,24

Fractional photothermolysis is a new technology whereby thermal columns of injury in the dermis and epidermis, known as microscopic treatment zones, are created, surrounded by zones of undisturbed tissue.25 This allows for rapid healing of the treated area through epidermal migration through the viable epidermis. The intact stratum corneum aids in rapid healing. The stimulatory effects of fractional photothermolysis on dermal collagen remodeling and epidermal regeneration are mechanisms that may explain the successful treatment of Darier's disease. Additionally, the extrusion and transepidermal vacuolar elimination of dermal and epidermal content through a compromised dermal–epidermal junction may have played a role. Fractional photothermolysis activates this transport system whereby microscopic epidermal necrotic debris is shuttled up the epidermis to be eliminated through the stratum corneum by epidermal vacuoles.26

The fractionated 1,550-nm erbium-doped fiber laser is able to penetrate to a depth of 382 to 1,400 μm when using energy levels of 4 to 70 mJ. Although Darier's disease affects the epidermis, in some cases, there may be a downward proliferation of epidermal cells into the dermis;22 thus the ideal depth of thermal injury is unclear. The highest energy-level settings (70 mJ) and treatment level (11) were chosen for this patient in an attempt to achieve the deepest and widest treatment coverage possible.

Fractional photothermolysis is associated with a low complication rate. Graber and colleagues.27 investigated 961 treatment sessions with fractional photothermolysis in 422 patients (skin types I–V). Seventy-three (7.6%) complications were noted, including acneiform eruptions (n=18, 1.87%), herpes simplex virus outbreaks (n=17, 1.77%), and erosions (n=13, 1.35%). Postinflammatory hyperpigmentation was noted in only 0.73% of cases. Additionally, the patients who developed postinflammatory hyperpigmentation had significantly darker skin types. The treatment of Darier's disease with ablative lasers including Er:YAG and CO2 may induce complete remission after one treatment session, although some recurrences were noted.12–14 Although ablative laser treatment may require fewer treatment sessions than fractional photothermolysis, the overall complication rate is significantly lower, and there is less down-time with fractional photothermolysis.28,29 Additionally, when using non-ablative fractional photothermolysis off of the face, there is no increased risk of complications.27

Although Darier's disease usually has a chronic course with remissions and frequent recurrences, it is unclear whether this patient's disease will recur. Additional treatments may be necessary in the future, and longer follow-up periods will help determine the longevity of the patient's results. Fractional photothermolysis may represent an exciting new treatment option for patients with Darier's disease and may have a role as a maintenance therapy with adjuvant topical treatment modalities. Controlled studies are warranted to investigate the efficacy, longevity, and optimal laser settings of fractional photothermolysis for the treatment of Darier's disease.

References

  1. Top of page
  2. Abstract
  3. Case Report
  4. Discussion
  5. References