Darier disease

Acne and psoriasis Dermatologic problems such as acne and psoriasis are effectively treated with retinoic acid or its derivatives (see Figure 28.21). Mild cases of acne, Darier disease, and skri aging are treated with topical application of tretinoin (all trans retinoic acid), as well as benzoyl peroxide and antibiotics. [Note Tretinoin is too toxic for systemic administration and is confined to topical application.] In patients with severe recalcitrant cystic acre... 

ATP2A3, SERCA1, SERCA2, SERCA3, Brody disease, Darier disease (Darier -White disease), Segmental Darier, Acantholytic dyskeratotic epidermal nevi, Acrokeratosis verruciformis of Hopf (Hopf disease), muscle, heart, skin, Ca2+ pump... 

ATP2A2 12q23-q24.1 SERCA2a SERCA2b SERCA2c Heart, slow twitch skeletal muscle, brain All tissues (e.g.epidermis) Epithelial, mesenchymal and hematopoietic cell lines, monocytes Darier disease (dominant)... 

Why does Darier disease affect skin only ... 

Dode, L., Andersen, J. P., Leshe, N., Dhitavat, J., Vilsen, B., and Hovnanian, A., 2003, Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 2 isoforms and characterization of Darier disease (SERCA2) mutants by steady-state and transient kinetic analyses. J Biol Chem, 278 47877—89. 

Frezzini, C., Cedro, M., Feao, J. C., and Porter, S., 2006, Darier disease affecting die gingival and oral mucosal surfaces. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 102 e29—33. 

Hafner, O., and Vakilzadeh, F., 1997, [Acrokeratosis verruciformis-like changes in Darier disease]. 

Leinonen, P. T., Myllyla, R. M., Hagg, P. M., Tuukkanen, J., Koivunen, J., Peltonen, S., Oikarinen, A., Korkiamaki, T., and Peltonen, J., 2005, Keratinocytes cultured from patients with Hailey-Hailey disease and Darier disease display distinct patterns of calcium regulation. Br J Dermatol, 153 113—7. 

Miyauchi, Y., Daiho, T., Yamasaki, K., Takahashi, H., Ishida-Yamamoto, A., Danko, S., Suzuki, H., and Iizuka, H., 2006, Comprehensive analysis of expression and function of 51 sarco(endo)plasmic reticulum Ca2+-ATPase mutants associated with Darier disease. J Biol Chem, 281 22882-95. 

Onozuka, T., Sawamura, D., Yokota, K., and Shimizu, H., 2004, Mutational analysis of the ATP2A2 gene in two Darier disease families with intrafamilial variability. Br J Dermatol, 150 652—7. 

Reese, D. A., Paul, A. Y., and Davis, B., 2005, Unilateral segmental Darier disease following Blaschko lines a case report and review of the literature. Cutis, 76 197—200. 

Ringpfeil, F., Raus, A., DiGiovanna, J. J., Korge, B., Harth, W., Mazzanti, C., Uitto, J., Bale, S. J., and Richard, G., 2001, Darier disease-novel mutations in ATP2A2 and genotype-phenotype correlation. 

Yang, Y., Li, G., Bu, D., and Zhu, X., 2001, Novel point mutations of the ATP2A2 gene in two Chinese families with Darier disease. J Invest Dermatol, 116 482-3. 

Histologically, the disease is characterized by a loss of adhesion between suprabasal keratinocytes (acantholysis) and abnormal keratinisation (dyskeratosis) of the epidermis. In HHD, acantholysis is the most prominent histological feature while in the clinically related Darier disease (OMIM 124200), dyskeratosis is much more apparent. Ultrastructural analysis of acantholytic cells reveals perinuclear aggregates of keratin filaments that have retracted from desmosomes (Harada et al., 1994 Hashimoto et al., 1995 Metze et al., 1996). 

The precise link between altered expression or functionality of SPCA1 and the development of skin lesions has not yet been established. First, we do not know whether the symptoms are due to a defect in Ca2+ or Mn2+ transport by SPCA1. However, the similarity between HHD and Darier disease points to a major role of Ca2+ ions because SERCA2 is hardly capable of transporting Mn2+relative to... 

Darier disease (keratosis follicularis) is an autosomal dominant disorder of keratinization, which usually starts at puberty. Mutations in an endoplasmatic ATPase, which pumps calcium ions across membranes in keratinocytes, have been found to cause the disease.43... 

People with a history or current outbreak of eczema or atopic dermatitis People with Darier disease (keratosis follicularis) are also at risk for eczema vaccinatum and should not receive the vaccine. 

Gordon-Smith K, Jones LA, Burge SM, Munro CS, Tavadia S, Craddock N. The neuropsychiatric phenotype in Darier disease. Br J Dermatol 2010 163(3) 515-22. 

---