Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Genevieve A. Casey and Susan M. Cooper
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
(Courtesy of Dr Susan M. Burge.)
Darier disease is a dominantly inherited condition, incidence 1 : 25 000–1 : 100 000, that is characterized by persistent greasy, hyperkeratotic papules. The disease is caused by mutations in the ATP2A2 gene that encodes type 2 sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA 2).
The warty, keratotic papules, which usually appear before the age of 20 years, can be malodorous, irritate, and look unsightly. The flexures can be a particular problem, as plaques here are frequently hypertrophic and may smell unpleasant. Initial treatment is aimed at controlling irritation. Simple emollients, soap substitutes, and topical corticosteroid creams are helpful. Keeping the skin cool by wearing comfortable pure cotton clothing helps. Sunblock is recommended for those with a history of photoaggravation.
In the mild form or linear disease reflecting a genetic mosaicism, topical retinoids may be sufficient. These include topical isotretinoin (0.05% and 0.1%), tretinoin cream, adapalene gel, and tazarotene gel. Treatment is applied on alternate days to begin with, increasing to once daily if possible, as irritation is common. The addition of a topical corticosteroid (alternating with the retinoid) may alleviate some of the side effects. Superinfection with viruses and bacteria is frequent, so combined corticosteroid/antibiotic preparations are logical.
In more extensive disease, an oral retinoid is required. Etretinate, acitretin, and isotretinoin are effective. Teratogenicity is a problem, and pregnancy is contraindicated for 2 years after stopping treatment with etretinate or acitretin and 1 month with isotretinoin. For this reason, isotretinoin is the usual choice in women of childbearing age. Treatment may be given either long term or as intermittent short courses. The usual starting dose of acitretin is 10–25 mg daily, but this can be increased gradually. Isotretinoin is usually started at 0.5–1.0 mg/kg daily. In the UK, etretinate is only available on a ‘named patient’ basis but may work where other retinoids have failed.
The rare vesiculobullous form of the disease may respond to prednisolone. Hypertrophic flexural disease, unresponsive to retinoids, may require a surgical approach with laser, electrosurgery, debridement or excision. Recurrence is a problem.
Oral lithium exacerbates the disease and should be avoided if possible.
Skin biopsy. The characteristic finding is focal acantholytic dyskeratosis. The acantholysis is suprabasal
Skin swab for bacterial and viral culture if infection is suspected
Burge SM, Wilkinson JD. J Am Acad Dermatol 1992; 27: 40–50.
Fourteen percent of patients in this series had herpes simplex complicating their disease.
Painful blisters arising in a patient with Darier disease are usually due to secondary infection with Staphylococcus aureus or herpes simplex.
Cooper SM, Burge SM. Am J Clin Dermatol 2003; 4: 97–105.
A detailed review of the management of Darier disease.
Genetic counselling can be helpful and written information is often appreciated.
Brazezelli V, Prestinari F, Barbagallo T, Vassallo C, Agozzino M, Borroni G. Eur J Dermatol 2006; 16: 59–61.
Linear Darier disease affecting the trunk was treated with tazarotene for 15 minutes once daily over 6 weeks, with a good response.
Burge SM, Buxton PK. Br J Dermatol 1995; 133: 924–8.
Six of 11 patients improved with 0.05% isotretinoin applied to a test patch. Erythema, burning, and irritation were common.
Abe M, Inoue C, Yokoyama Y, Ishikawa O. Pediatr Dermatol 2011; 28: 197–8.
Adapalene gel 0.1% applied for 2 months to the abdomen of a 12-year-old boy resulted in dramatic improvement.
Lauharanta J, Kanerva L, Turjanmaa K, Geiger JM. Acta Dermatol Venereol 1988; 68: 492–8.
Thirteen patients treated with acitretin starting at 30 mg daily for 16 weeks showed some improvement, but side effects included itching (five patients) and hair loss (two patients).
Dicken CH, Bauer EA, Hazen PG, Krueger GG, Marks Jr JG, McGuire JS, et al. J Am Acad Dermatol 1982; 6: 721–6.
This multicenter open study assessed the effect of short and longer courses of treatment. The starting dose was 0.5 mg/kg, but longer courses were adjusted according to symptoms. Isotretinoin was effective, but did not give long-term remission. Some patients were maintained on alternate-day or alternate-week regimens.
Bleiker TO, Bourke JF, Graham-Brown RA, Hutchinson PE. Br J Dermatol 1997; 136: 368–70.
Two patients with Darier disease unresponsive to acitretin responded to etretinate.
Barnstedt SE. Hautarzt 2012; 63: 139–41.
A case report of severe disease responding to alitretinoin 30 mg daily, with significant improvement after 4 weeks. Treatment was continued for 52 weeks.
Sbidian E, Maza A, Montaudie H, Gallini A, Aractingi S, Aubin F, et al. J Eur Acad Dermatol Venereol 2011; 25: 28–33.
There is no strong evidence for an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids.
X-ray screening is not necessary for asymptomatic patients on long-term treatment, but it is prudent to inquire about musculoskeletal problems in these patients.
Retinoids have many side effects, including mucosal dryness and soreness, skin fragility, and itching. They may cause hepatic dysfunction and hyperlipidemia. Liver function, cholesterol, and triglycerides should be monitored during treatment.
Le Bidre E, Delage M, Celevier P, De Muret A, Lorette G. Ann Dermatol Venereol 2010; 137: 455–9.
Topical 5-fluorouracil initially proved effective in three cases, but response was not sustained.
Rubegni P, Poggiali S, Sbano P, Risulo M, Fimiani M. J Eur Acad Dermatol Venereol 2006; 20: 84–7.
Topical tacrolimus 0.1% ointment to the face and neck resulted in complete remission after 6 weeks, with no relapse 1 year later using maintenance therapy of 0.03%.
Shahidullah H, Humphreys F, Beveridge GW. Br J Dermatol 1994; 131: 713–16.
Cyclosporine may be helpful in widespread eczematized Darier disease, but had no effect on the underlying disease.
Stewart LC, Yell J. J Obstet Gynaecol 2008; 28: 108–9.
A previously therapy-resistant case was treated with cyclosporine (initial dose 5 mg/kg) for 6 months with good response, and was subsequently maintained on acitretin.
Speight EL. Br J Dermatol 1998; 139: 934–5.
A patient with the vesiculobullous form of the disease responded to a short course of oral prednisolone.
Prednisolone may also be useful in the eczematized form.
Brown VL, Kelly SE, Burge SM, Walker NPJ. Br J Dermatol 2010; 162: 227–8.
Treatment to trunk, limbs and scalp at 2-monthly intervals under general anesthetic with CO2 laser. Wounds healed within 33 weeks and patient remained disease-free in some areas for 9 years.
Beier C, Kaufmann R. Arch Dermatol 1999; 135: 423–7.
Disease cleared in two patients, but follow-up was less than 2 years.
Roos S, Karsai S, Ockenfel HM, Raulin C. Arch Dermatol 2008; 144: 1073–5.
Submammary disease improved at 8 weeks post treatment, with no progression at 15 months.
Exadaktylou D, Kurwa HA, Calonje E, Barlow RJ. Br J Dermatol 2003; 149: 606–10.
Six patients received photodynamic therapy with topical 5-aminolaevulinic acid as a photosensitizer. One patient could not tolerate the treatment, but five experienced sustained improvement, with initial inflammatory response lasting 2 to 3 weeks.
Kontochristopoulos G, Katsavou AN, Kalogirou O, Agelidis S, Zakopoulou N. Dermatol Surg 2007; 33: 882–3.
Submammary disease was treated with botulinum toxin as adjuvant therapy: 100 U were injected, with improvement sustained for 4 months. Reduced sweating may alleviate maceration and reduce bacterial colonization.
Kittridge A, Wahlgren C, Fuhrer R, Zirwas M, Patton T. Dermatol Ther 2010; 23: 302–4.
Electron beam radiation therapy to the inframammary folds resulted in initial severe local dermatitis, followed by complete resolution sustained for 18 months.
Toombs EL, Peck GL. J Dermatol Surg Oncol 1989; 15: 1277–80.
Electrosurgery was effective in two cases unresponsive to etretinate.
Zachariae H. Acta Dermatol Venereol 1979; 59: 184–5.
Five patients with severe disease were treated by dermabrasion down to and including the papillary dermis. Three-quarters of the treated skin remained disease free 6 months later. Facial treatment was less successful than treatment to the trunk area.
Wheeland RG, Gilmore WA. J Dermatol Surg Oncol 1985; 11: 420–3.
Recalcitrant, hypertrophic lesions were debrided under local anesthesia. Symptomatic and cosmetic improvement was maintained for 2 years
Ahcan U, Dolenc-Voljc M, Zivec K, Zorman P, Jurcic V. J Plast Reconstr Aesthet Surg 2009; 62: e442–6.
Hypertrophic disease of the intergluteal area was successfully treated using tissue expanders inserted 20 days prior to wide excision of diseased skin with primary closure.
Baran R. J Eur Acad Dermatol Venereol 2005; 19: 689–91.
One-third of the distal nail matrix was removed, with wound healing by secondary intention. The nail re-grew with excellent cosmesis.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Cool cotton clothing
Emollients
Topical retinoids
Oral retinoids
Topical 5-fluorouracil
Topical tacrolimus
Cyclosporine
Oral prednisolone (vesiculobullous)
Laser (CO2, erbium : YAG, pulse-dye)
Photodynamic therapy
Botulinum toxin
Electron beam radiation
Dermabrasion
Debridement
Excision
