Darier’s disease

The topical and oral use of retinoids for treatment of hyperkeratotic disorders such as psoriasis and Darier s disease has long been established. Systemic retinoid therapy is often combined with topical diugs such as corticosteroids, dithranol, tar, and also UVA/UVB phototherapies where synergistic effects have been reported. 

Acitretine ch3o x x Oral 0.25-1.0 mg/kg/d Psoriasis (erythrodermic, pustular, and severe recalcitrant) Palmoplantar keratoderma pustulosis palmoplantaris, icthyosis, Darier s disease, pityriasis rubra pilaris, lichen ruber planus... 

Sakuntabhai A, Burge S, Monk S, Hovnanian A 1999 Spectrum of novel ATP2A2 mutations in patients with Darier s disease. Hum Mol Genet 8 1611-1619... 

The establishment of quantitative methods for the determination of vitamins in body fluids and tissues by microbiological assay techniques should stimulate the search for the significance of vitamins in disease, not only in nutritional deficiency, but in the much wider field of all metabolic disturbances. Functional vitamin deficiencies are produced by malabsorption, by inhibitors of the vitamin function through products of the body, and particularly through drugs and other toxic substances. Vitamin deficiencies may be relative deficiencies whenever an individual s metabolism is deranged so as to require enhanced quantities of a given vitamin to cure or to counteract certain symptoms as, e.g., in Darier s disease (keratosis follicularis) (P2a). 

P2a. Peck, S. M., Chargin, L., and Sobotka, H., Keratosis follicularis (Darier s disease). A vitamin A deficiency disease. Arch. Dermatol, and Syphilol. 43, 223-229 (1941). 

There are many retinol containing preparations to treat vitamin deficiency states. Retinoids are also used to treat dermatological diseases like acne, psoriasis, Darier s disease, and ichthyosis. Tretinoin, all-trans-retinoic acid, is a topical preparation while isotretinoin or 13-cis-retinoic acid, and etretinate are available for oral administration. 

Darier s disease (DD)(MIM 124200) or Darier-White s disease (also referred as keratosis follicularis) is a rare autosomal dominant disease, first described by Darier and White in 1889. DD affects both sexes and all ethnic groups, with a prevalence estimated between 1 in 26 300 and 1 in 100,000 in different countries (Godic et at., 2005), (Tavadia et al., 2002), (Wilkinson, 1977) (Cooper and Burge, 2003 Svendsen and Albrecten, 1959). Penetrance of the disease is complete, and expression is highly variable between and within affected families. 

A possible relationship with Darier s disease has long been postulated. Although initially viewed as distinct entities, AKV and DD, especially in its acral form, have been considered as related disorders by several authors, even by Hopf and Darier themselves (Panja, 1977). In support of AKV being part of the DD spectrum is the description of the co-occurrence of AKV and DD in the same patient (Hafner and Vakilzadeh, 1997 Piskin et al., 2004) or in affected members of the same family (Herndon and Wilson, 1966). In addition, it is notable that 50% of DD patients have acral warty papules and that patients with histological changes of AKV have been reported to develop typical histological features of DD (Penrod et al., 1960 Waisman, 1960). 

Craddock, N., Burge, S., Parfitt, L., and Owen, M., 1993, Linkage is excluded between Darier s disease and the Duffy blood group locus in five British families. Ann Genet, 36 211-3. 

Craddock, N., Owen, M., Burge, S., Kurian, B., Thomas, P., and McGuffin, P., 1994, Familial cosegregation of major affective disorder and Darier s disease (keratosis follicularis). Br J Psychiatry, 164 ... 

Dhitavat, J., Cobbold, C., Leslie, N., Burge, S., and Hovnanian, 2003a A. Impaired trafficking of the desmoplakins in cultured Darier s disease keratinocytes. J Invest Dermatol, 121 1349—55. 

Dhitavat, J., Macfarlane, S., Dode, L., Leshe, N., Sakuntabhai, A., MacSween, R., Saihan, E., and Hovnanian, A., 2003c, Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2 evidence that it is allelic to Darier s disease. J Invest Dermatol, 120 229—32. 

Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier s disease. Br J Dermatol, 142 702—11. 

Herndon, J., and Wilson, J., 1966, Acrokeratosis verruciformis (Hopf) and Darier s disease, genetic evidence for a unitary origin. Arch Derm, 93 305-310. 

Hovnanian, A., 2004, Darier s disease from dyskeratosis to endoplasmic reticulum calcium ATPase deficiency. Biochem Biophys Res Commun, 322 1237—44. 

Jones, I., Jacobsen, N., Green, E. K., Elvidge, G. P., Owen, M. J., and Craddock, N., 2002, Evidence for familial cosegregation of major affective disorder and genetic markers flanking the gene for Darier s disease. Mol Psychiatry, 7 424-7. 

Munro, C. S., and Cox, N. H., 1992, An acantholytic dyskeratotic epidermal naevus with other features of Darier s disease on the same side of the body. Br J Dermatol, 127 168-71. 

Racz, E., Csikos, M., Benko, R., Kornsee, Z., and Karpati, S., 2005, Three novel mutations in the ATP2A2 gene in Hungarian families with Darier s disease, including a novel splice site generating intronic nucleotide change. J Dermatol Sci, 38 231—4. 

Rubegni, P., Poggiali, S., Sbano, P., Risulo, M., and Fimiani, M., 2006, A case of Darier s disease successfully treated with topical tacrolimus. J Eur Acad Dermatol Venereol, 20 84—7. 

Ruiz-Perez, V. L., Carter, S. A., Healy, E., Todd, C., Rees, J. L., Steijlen, P. M., Carmichael, A. J., Lewis, H. M., Hohl, D., Itin, P., Vahlquist, A., Gobello, T., Mazzanti, C., Reggazini, R., Nagy, G., Munro, C. S., and Strachan, T., 1999, ATP2A2 mutations in Darier s disease variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class. Hum Mol Genet, 8 1621-30. 

Svendsen, I. B., and Albrecten, B., 1959, The prevalence of dyskeratosis follicularis (Darier s disease) in Danemark. Acta Derm Venereol, 39 256-69. 

Takahashi, H., Atsuta, Y., Sato, K., Ishida-Yamamoto, A., Suzuki, H., and Iizuka, H., 2001, Novel mutations of ATP2A2 gene in Japanese patients of Darier s disease. J Dermatol Sci, 26 169-72. 

Tavadia, S., Authi, K. S., Hodgins, M. B., and Munro, C. S., 2004, Expression of the sarco/endoplasmic reticulum calcium ATPase type 2 and 3 isoforms in normal skin and Darier s disease. Br J Dermatol, 151 440-5. 

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