Darier disease

Published on 18/03/2015 by admin

Filed under Dermatology

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 1 (1 votes)

This article have been viewed 2353 times

[level-membership-for-dermatology-category]

Darier disease

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

image

(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).

Management strategy

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.

First-line therapies

image Cool cotton clothing E
image Emollients D
image Topical retinoids D

Second-line therapies

image Oral retinoids B
image Topical 5-fluorouracil E
image Topical tacrolimus E

Third-line therapies

image Cyclosporine E
image Oral prednisolone (vesiculobullous) E
image Laser (CO2, erbium : YAG, pulse-dye) E
image Photodynamic therapy D
image Botulinum toxin E
image Electron beam radiation E
image Dermabrasion E
image Debridement E
image Excision E

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Darier disease

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

image

(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).

Management strategy

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.

First-line therapies

image Cool cotton clothing E
image Emollients D
image Topical retinoids D