Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
American Journal of Clinical Dermatology
Published in: American Journal of Clinical Dermatology 2/2003

01-02-2003 | Review Article

Darier’s Disease

Epidemiology, Pathophysiology, and Management

Authors: Dr Susan M. Cooper, Susan M. Burge

Published in: American Journal of Clinical Dermatology | Issue 2/2003

Login to get access

Abstract

Darier’s disease is a rare cutaneous disease with an autosomal dominant mode of inheritance. Greasy papules and plaques arise on the seborrheic areas and in the flexures and almost all patients have nail abnormalities. Acantholysis and dyskeratosis are the typical histological findings. The underlying defect is a result of mutations in the ATP2A2 gene on chromosome 12q23-24 that encodes for a sarco/endoplasmic reticulum calcium ATPase (SERCA 2). Acantholysis is thought to result from desmosome breakdown. Darier’s disease is an example of a dominantly inherited disease caused by haplo-insufficiency. Oral retinoids are the most effective treatment but their adverse effects are troublesome. Topical retinoids, topical corticosteroids, surgery, and laser surgery have their advocates but evidence for efficacy is sparse.
Literature
1.
Darier J. Psorospermose folliculaire vegetante. Ann Dermatol Syphilol 1889; 10: 597–612
2.
White JC. Acase of keratosis (ichthyosis) follicularis. J Cutan Genito-Urin Dis 1889; 7: 201–209
3.
Sakuntabhai A, Ruiz-Perez V, Carter S, et al. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet 1999; 21: 271–277PubMedCrossRef
4.
Svendson IB, Albrectsen B. The prevalence of dyskeratosis follicularis (Darier’s disease) in Denmark. Acta Derm Venereol 1959; 39: 256–259
5.
Wilkinson JD, Marsden RA, Dawber RPR. Review of Darier’s disease in the Oxford region. Br J Dermatol 1977; 97 Suppl. 15: 15–16CrossRef
6.
Munro CS. The phenotype of Darier’s disease: penetrance and expressivity in adults and children. Br J Dermatol 1992; 127: 126–130PubMedCrossRef
7.
Burge SM, Garrod DR. An immunohistological study of desmosomes in Darier’s disease and Hailey-Hailey disease. Br J Dermatol 1991; 124: 242–251PubMedCrossRef
8.
Burge SM, Cederholm-Williams SA, Garrod DR, et al. Cell adhesion in Hailey-Hailey disease and Darier’s disease:immunocytological and explant-tissue-culture studies. Br J Dermatol 1991; 125: 426–435PubMedCrossRef
9.
Sudbrak R, Brown J, Dobson-Brown C, et al. Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca (2+) pump. Hum Mol Genet 2000; 9: 1131–1140PubMedCrossRef
10.
Zhao XS, Min Shin D, Liu LH, et al. Plasticity and adaption of Ca2+ signaling and Ca2+ dependent exocytosis in SERCA2+/- mice. EMBO J 2001; 20 (11): 2680–2689PubMedCrossRef
11.
Sakuntabhai A, Burge S, Monk S, et al. Spectrum of novel ATP2A2 mutations in patients with Darier’s disease. Hum Mol Genet 1999; 8 (9): 1611–1619PubMedCrossRef
12.
Ruiz-Perez VL, Carter SA, Healey E, et al. ATP2A2 mutations in Darier’s disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of class. Hum Mol Genet 1999; 8 (9): 1621–1630PubMedCrossRef
13.
Jacobsen NJO, Lyons I, Hoogendoorn B, et al. ATP2A2 mutations in Darier’s disease and their relationship to neuropsychiatric phenotypes. Hum Mol Genet 1999; 8 (9): 1631–1636PubMedCrossRef
14.
Sakuntabhai A, Dhitavat J, Burge S, et al. Mosaicism for ATP2A2 mutations causes segmental Darier’s disease. J Invest Dermatol 2000; 115: 1144–1147PubMedCrossRef
15.
Burge SM, Wilkinson JD. Darier-White disease: a review of the clinical features in 163 patients. J Am Acad Dermatol 1992; 27 (1): 40–50PubMedCrossRef
16.
Coulson IH, Misch KJ. Haemorrhagic Darier’s disease. J Roy Soc Med 1989; 82: 365–366PubMed
17.
Macleod RI, Munro CS. The incidence and distribution of oral lesions in patients with Darier’s disease. Br Dent J 1991; 171: 133–136PubMedCrossRef
18.
Graham-Brown RAC, Mann BS, Downton D, et al. Darier’s disease with salivary gland obstruction. J Roy Soc Med 1983; 76: 609–611PubMed
19.
Venencie PY, Dusser A, Fabre M, et al. Maladie de Darier et encephalopathie evolutive: une observation familiale. Ann Pediatr 1996; 43: 713–715
20.
Harris A, Burge SM, Dykes PJ, et al. Handicap in Darier’s disease and Hailey-Hailey disease. Br J Dermatol 1996; 135: 959–963PubMedCrossRef
21.
Telfer NR, Burge SM, Ryan TJ. Vesico-bullous Darier’s disease. Br J Dermatol 1990; 122: 831–834PubMedCrossRef
22.
23.
Romano C, Massai L, Alessandrini C, et al. A case of acral Darier’s disease. Dermatology 1999; 199 (4): 365–368PubMedCrossRef
24.
Cianchini G, Colonna L, Camaioni D, et al. Acral Darier’s disease successfully treated with adapalene. Acta Derm Venereol 2001; 81 (1): 57–58PubMedCrossRef
25.
Foresman PL, Goldsmith LA, Gunn L, et al. Haemorrhagic Darier’s disease. Arch Dermatol 1993; 129: 511–512PubMedCrossRef
26.
McKenna KE, Walsh MY, Burrows D. Treatment of unilateral Darier’s disease with topical isotretinoin. Clin Exp Dermatol 1999; 24 (5): 425–427PubMedCrossRef
27.
Berth-Jones J, Hutchinson PE. Darier’s disease with perifollicular depigmentation. Br J Dermatol 1989; 120: 827–830PubMedCrossRef
28.
Peterson CM, Lesher JL, Sangueza OP. A unique variant of Darier’s disease. Int J Dermatol 2001; 40: 278–280PubMedCrossRef
29.
Cornelison RL, Smith EB, Knox JM. Guttate leukoderma in Darier’s disease. Arch Dermatol 1970; 102: 447–450PubMedCrossRef
30.
31.
Milton GP, Peck GL, Fu JJ, et al. Exacerbation of Darier’s disease by lithium carbonate. J Am Acad Dermatol 1990; 23 (5): 926–928PubMedCrossRef
32.
33.
Burge SM, Wilkinson JD, Miller AJ, et al. The efficacy of an aromatic retinoid, Tigason (etretinate), in the treatment of Darier’s disease. Br J Dermatol 1981; 104 (6): 675–679PubMedCrossRef
34.
Fulton JE, Gross PR, Cornelius CE, et al. Darier’s disease: treatment with topical vitamin A acid. Arch Dermatol 1968; 98 (4): 396–399PubMedCrossRef
35.
Burge SM, Buxton PK. Topical isotretinoin in Darier’s disease. Br J Dermatol 1995; 133 (6): 924–928PubMedCrossRef
36.
Steijlen PM, Reifenschweiler DOH, Ramaekers FCS, et al. Topical treatment of ichthyoses and Darier’s disease with 13-cis-retinoic acid: a clinical and immunohistological study. Arch Dermatol Res 1993; 285: 221–226PubMedCrossRef
37.
Steijlen PM, Happle R, van Muijen GNP, et al. Topical treatment with 13-cisretinoic acid improves Darier’s disease and induces the expression of a unique keratin pattern. Dermatologica 1991; 182: 178–183PubMedCrossRef
38.
Hofmann B, Stege H, Bruch-Gerharz D, et al. Ichthyosen: alternative indikation fur den Einsatz von tazaroten (Zorac®). Z Hautkr 1997; 10: 767–769
39.
Micali G, Nasca MR. Tazarotene gel in childhood Darier disease. Pediatr Dermatol 1999; 16 (3): 243–244PubMed
40.
Burkhart CG, Burkhart CN. Tazarotene gel for Darier’s disease. J Am Acad Dermatol 1998; 38 (6): 1001–1002PubMedCrossRef
41.
Oster-Schmidt C. The treatment of Darier’s disease with topical tazarotene. Br J Dermatol 1999; 141 (3): 603–604PubMedCrossRef
42.
English JC, Browne J, Halbach DP. Effective treatment of localised Darier’s disease with adapelene 0.1 % gel. Cutis 1999; 63 (4): 227–230PubMed
43.
Clucas A, Verschoore M, Sorba V, et al. Adapalene 0.1 % gel is better tolerated than isotretinoin 0.0 25% gel in acne patients. J Am Acad Dermatol 1997; 36: S116–S118PubMedCrossRef
44.
Knulst AC, Baart de la Faille H, Van Vloten WA. Topical 5-fluorouracil in the treatment of Darier’s disease. Br J Dermatol 1995; 133 (3): 463–466PubMedCrossRef
45.
Bamshad J, Hilton PE. Darier’s disease: treatment with 5-fluorouracil. Cutis 1971; 8: 555–556
46.
Kragballe K, Steijlen PM, Ibsen HH, et al. Efficacy, tolerability, and safety of calcipotriol ointment in disorders of keratinization: results of a randomised, double-blind, vehicle-controlled, right/left comparative study. Arch Dermatol 1995; 131 (5): 556–560PubMedCrossRef
47.
Peck SM, Chargrin L, Sobotka H. Keratosis follicularis (Darier’s disease): a vitamin A deficiency disease. Arch Dermatol Syph 1941; 43: 223–229CrossRef
48.
Peck SM, Glick AW, Sobotka H. Vitamin A studies in keratosis follicularis (Darier’s disease). Arch Dermatol Syph 1943; 48: 17–31CrossRef
49.
Wilson D, Kay V, Charig M, et al. Skeletal hyperostosis and extraosseous calcification in patients receiving long-term etretinate. Br J Dermatol 1988; 119: 597–607PubMedCrossRef
50.
Burge SM, Wilkinson JD. The use of Tigason (etretinate) in Darier’s disease. In: Cunliffe WJ, Miller AJ, editors. Retinoid therapy. Lancaster: MTP Press Ltd, 1984: 61–62CrossRef
51.
Van Dooren-Greebe RJ, van der Kerkhof PCM, Happle R. Acitretin monotherapy in Darier’s disease. Br J Dermatol 1989; 121: 375–379PubMedCrossRef
52.
Lauharanta J, Kanerva L, Turjanmaa K, et al. Clinical and ultrastructural effects of acitretin in Darier’s disease. Acta Derm Venereol 1988; 68 (6): 492–498PubMed
53.
Christopherson J, Geiger JM, Danneskiold-Samsoe P. A double-blind comparison of acitretin and etretinate in the treatment of Darier’s disease. Acta Derm Venereol 1992; 72: 150–152
54.
Bleiker TO, Bourke JF, Graham-Brown RA, et al. Etretinate may work where acitretin fails. Br J Dermatol 1997; 136: 368–370
55.
Gilgor RS, Chiaramonti A, Goldsmith LA, et al. Evaluation of 13-cis-retinoic acid in lamellar ichthyosis, pityriasis rubra pilaris and Darier’s disease. Cutis 1980; 25: 380–385PubMed
56.
Peck GL, Yoder FW, Olsen TG. Treatment of Darier’s disease, lamellar ichthyosis, pityriasis rubra pilaris, cystic acne and basal cell carcinoma with oral 13-cis retinoic acid. Dermatologica 1978; 157: 1211–1214CrossRef
57.
Dicken CH, Bauer EA, Hazen PG, et al. Isotretinoin treatment of Darier’s disease. J Am Acad Dermatol 1982; 6 (4): 721–726PubMedCrossRef
58.
Speight EL. Vesicobullous Darier’s disease responsive to oral prednisolone steroids. Br J Dermatol 1998; 139 (5): 934–935PubMedCrossRef
59.
Gordon PM, Shahidullah H, Humphreys F, et al. Systemic steroids and eczematised Darier’s disease [letter]. Br J Dermatol 1995; 133: 492PubMedCrossRef
60.
Shahidullah. H, Humphreys F, Beveridge GW. Darier’s disease: severe eczematization successfully treated with cyclosporin. Br J Dermatol 1994; 131 (5): 713–716PubMedCrossRef
61.
Larbre B, Nicolas JF, Frappaz A, et al. Cyclosporine et maladie de Darier. Ann Dermatol Venereol 1993; 120 (4): 310–311PubMed
62.
Oostenbrink JH, Cohen EB, Steijlen PM, et al. Oral contraceptives in the treatment of Darier-White disease: a case report and review of the literature. Clin Exp Dermatol 1996; 21 (6): 442–444PubMedCrossRef
63.
Epsy PD, Stone S, Jolly HW. Hormonal dependency in Darier’s disease. Cutis 1976; 17: 315–320
64.
du Plessis PJ, Jacyk WK. Essential fatty acids in the treatment of Darier’s disease. J Dermatol Treat 1998; 9: 97–101CrossRef
65.
Toombs EL, Peck GL. Electrosurgical treatment of etretinate-resistant Darier’s disease. J Dermatol Surg Oncol 1989; 15 (12): 1277–1280PubMed
66.
Zachariae H. Dermabrasion in Darier’s disease. Acta Derm Venereol 1979; 59 (2): 184–185PubMed
67.
Zachariae H. Dermabrasion of Hailey-Hailey disease and Darier’s disease [letter]. J Am Acad Dermatol 1992; 27: 136PubMedCrossRef
68.
Cohen KI, Kraemen KH, Peck GL. Cornifying Darier’s disease — a unique variant II: surgical treatment. Arch Dermatol 1976; 112 (4): 504–506PubMedCrossRef
69.
Wheeland RG, Gilmore WA. The surgical treatment of hypertrophic Darier’s disease. J Dermatol Surg Oncol 1985; 11 (4): 420–423PubMed
70.
Dellon AL, Chretien PB, Peck GL. Successful treatment of Darier’s disease by partial-thickness removal of skin. Plast Reconstr Surg 1977; 59 (6): 823–830PubMedCrossRef
71.
McFadden JP, Mayou BJ, Griffiths WAD. Darier’s disease of the groin treated by surgery [letter]. Br J Dermatol 1991; 125: 52CrossRef
72.
Beier C, Kaufmann R. Efficacy of erbium: YAG:laser ablation in Darier disease and Hailey-Hailey disease. Arch Dermatol 1999; 135 (4): 423–427PubMedCrossRef
73.
McElroy JA, Mehregan DA, Roenigk RK. Carbon dioxide laser vaporization of recalcitrant symptomatic plaques of Hailey-Hailey disease and Darier’s disease. J Am Acad Dermatol 1990; 23 (5): 893–897PubMedCrossRef
74.
Calderon MJ, Landa N, Gardeazabal J, et al. Combined retinoid plus surgical treatment of hypertrophic Darier’s disease. J Eur Acad Dermatol Venereol 1993; 2: 242–244CrossRef
Metadata
Title
Darier’s Disease
Epidemiology, Pathophysiology, and Management
Authors
Dr Susan M. Cooper
Susan M. Burge
Publication date
01-02-2003
Publisher
Springer International Publishing
Published in
American Journal of Clinical Dermatology / Issue 2/2003
Print ISSN: 1175-0561
Electronic ISSN: 1179-1888
DOI
https://doi.org/10.2165/00128071-200304020-00003

Other articles of this Issue 2/2003

American Journal of Clinical Dermatology 2/2003 Go to the issue

Pharmacovigilance

Cutaneous Drug Reaction Case Reports

Original Research Article

Effects of Alefacept on Health-Related Quality of Life in Patients with Psoriasis

Review Article

Ceramides and Skin Function

Review Article

Ichthyosis

Leading Article

The Rationale for Using a Topical Retinoid for Inflammatory Acne