DARIER DISEASE –A RETROSPECTIVE SERIES OF 67 CASES
Abstract
Introduction/Aim: Darier disease is a rare autosomal dominant genodermatosis caused by mutations in the ATP2A2 gene and characterized by distinct clinical and histopathological findings. The aim of this study was to present the epidemiological and therapeutic characteristics of patients with Darier disease treated at a tertiary care center over a fifteen-year period.
Methods: A retrospective cohort study including 67 patients diagnosed with Darier disease and treated at the Clinic of Dermatovenereology, University Clinical Center of Serbia, Belgrade, Republic of Serbia, was conducted. The diagnosis was established based on characteristic clinical presentation and histopathological confirmation. Epidemiological, clinical, and therapeutic characteristics were analyzed.
Results: Female predominance (66%) was observed in the study population, while the first skin lesions most commonly appeared during adolescence and early adulthood. Positive family history was recorded in 48% of patients, supporting the autosomal dominant inheritance pattern. Lesions were predominantly localized on the trunk (85%). Neuropsychiatric comorbidities were observed in 16% of patients. Topical therapy was used in all patients, whereas systemic retinoids were administered in 51% of patients, predominantly in generalized forms of the disease.
Conclusion: The results highlight the chronic course of the disease, marked phenotypic variability, and the need for individualized therapeutic approaches.
References
Takagi A, Kamijo M, Ikeda S. Darier disease. J Dermatol. 2016;43(3):275-279. doi:10.1111/1346-8138.13230
Moschella B, Busciglio S, Ambrosini E, Cesarini S, Caramanna L, Zanelli S, et al. Genetics of Darier’s Disease: New Insights into Pathogenic Mechanisms. Genes (Basel). 2025;16(6):619. https://doi.org/10.3390/genes16060619
Ettinger M, Kimeswenger S, Deli I, Traxler J, Altrichter S, Noack P, et al. Darier disease: Current insights and challenges in pathogenesis and management. J Eur Acad Dermatol Venereol. 2025 May;39(5):942-951. doi: 10.1111/jdv.20448.
Onozuka T, Sawamura D, Yokota K, Shimizu H. Mutational analysis of the ATP2A2 gene in two Darier disease families with intrafamilial variability. Br J Dermatol. 2004;150(4):652-7. doi:10.1111/j.0007-0963.2004.05868.x.
Beiu C, Giurcaneanu C, Mihai M, Popa L, Hage R. Darier Disease - A Clinical Illustration of Its High Variable Expressivity. Cureus. 2019;11(12):e6292. Published 2019 Dec 4. doi:10.7759/cureus.6292
Curman P, Jebril W, Larsson H, Bachar-Wikstrom E, Cederlöf M, Wikstrom JD. Darier disease is associated with neurodegenerative disorders and epilepsy. Sci Rep. 2024;14(1):7109. doi: 10.1038/s41598-024-57779-4.
Bachar-Wikstrom E, Curman P, Ahanian T, Leong IUS, Larsson H, Cederlöf M, Wikstrom JD. Darier disease is associated with heart failure: a cross-sectional case-control and population based study. Sci Rep. 2020;10(1):6886. doi: 10.1038/s41598-020-63832-9.
Ahanian T, Curman P, Leong IUS, Brismar K, Bachar-Wikstrom E, Cederlöf M, Wikstrom JD. Metabolic phenotype in Darier disease: a cross-sectional clinical study. Diabetol Metab Syndr. 2020;12:12. doi: 10.1186/s13098-020-0520-0.
Haber RN, Dib NG. Management of Darier disease: A review of the literature and update. Indian J Dermatol Venereol Leprol. 2021;87(1):14-21. doi:10.25259/IJDVL_963_19
Ruiz-Perez VL, Carter SA, Healy E, Todd C, Rees JL, Steijlen PM, et al. 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. 1999 Sep;8(9):1621-30. doi: 10.1093/hmg/8.9.1621.
Liang YH, Zhang QG, Liu QX. Two novel missense mutations of ATP2A2 in two Chinese patients with sporadic Darier disease. Clin Exp Dermatol. 2015 Mar;40(2):201-3. doi: 10.1111/ced.12452.
Godic A, Glavac D, Korosec B, Miljković J, Potocnik M, Kansky A. P160L mutation in the Ca(2+) ATPase 2A domain in a patient with severe Darier disease. Dermatology. 2004;209(2):142-4. doi: 10.1159/000079600.
Jacobsen NJ, Lyons I, Hoogendoorn B, Burge S, Kwok PY, O'Donovan MC, Craddock N, Owen MJ. ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. Hum Mol Genet. 1999 Sep;8(9):1631-6. doi: 10.1093/hmg/8.9.1631.
Hunt M, Wang N, Pupinyo N, Curman P, Torres M, Jebril W, Chatzinikolaou M, Lorent J, Silberberg G, Bansal R, Burner T, Zhou J, Kimeswenger S, Hoetzenecker W, Choate K, Bachar-Wikstrom E, Wikstrom JD. Dantrolene corrects cellular disease features of Darier disease and may be a novel treatment. EMBO Mol Med. 2024 Sep;16(9):1986-2001. doi: 10.1038/s44321-024-00104-3.
Smith-Pellegrin DL, Rivera-Vega M, Cazarín-Barrientos JR, Melgarejo-Gómez A, Messina-Baas OM, Cuevas-Covarrubias S. Naltrexone, a therapeutic alternative in Darier disease. Rev Med Hosp Gen Méx. 2021;84(4):177-80. doi:10.24875/hgmx.21000039