Darier Disease

What It Is, Causes, Signs and Symptoms, and More

Author: Emily Miao, MD, PharmD

Editor: Ian Mannarino, MD, MBA

Editor: Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator: Abbey Richard, MSc

Copyeditor: David G. Walker

Modified: Jan 28, 2026

What is Darier disease?

Darier disease, also known as Darier-White disease or keratosis follicularis, is a rare genetic disorder characterized by a defect in skin keratinization, causing characteristic red or brown papules with abnormal keratosis and nail abnormalities. Keratinization (i.e., the process in which skin cells undergo maturation) is essential for maintaining the structural integrity of the skin and for providing a protective moisture barrier. It is also required in the formation of hair and nails.

An infographic detailing the background, signs and symptoms, diagnosis, and treatment of Darier disease.

What causes Darier disease?

Darier disease is primarily caused by mutations in the ATP2A2 gene, which encodes for a Ca2+ ATPase Type II (SERCA2) protein that is located in the endoplasmic reticulum (i.e., the eukaryotic organelle responsible for protein synthesis and lipid metabolism). More specifically, SERCA2 proteins regulate calcium levels within the intracellular and extracellular space and maintain desmosomes, which are structures responsible for cell-to-cell adhesion. Without a properly functioning SERCA2 protein, calcium signaling is altered in keratinocytes (i.e., skin cells), resulting in acantholysis (the loss of cell adhesion).

Darier disease is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene needs to be passed on by a parent to cause disease. Darier disease has a high penetrance, meaning that most affected individuals will exhibit signs and symptoms of the disorder. However, the condition also has high variable expressivity, meaning these signs and symptoms will vary greatly in each affected individual despite carrying the same mutation.

What are the signs and symptoms of Darier disease?

The signs and symptoms of Darier disease primarily include skin manifestations, nail abnormalities, and mucous membrane involvement. Skin manifestations are characterized by red and brown hyperkeratotic (i.e. thickening and scaling of skin) papules (i.e., circumscribed solid lesion up to one centimeter [cm]) and plaques (i.e., circumscribed solid lesion greater than one cm) with or without fissures or cracks. These skin findings are found in areas of the body where there are high concentrations of sebaceous glands, such as the chest, back, forehead, and scalp, and may be greasy and malodorous. Skin manifestations usually begin in the upper trunk or neck and may spread to high-friction, intertriginous areas (e.g., groin, armpit, neck, elbow). Sun exposure, friction, heat, and sweat can worsen the skin involvement.

Nail abnormalities include nail pitting and longitudinal leukonychia, which is the presence of longitudinal white bands on the nail plate. Approximately 50% of affected individuals will have oral mucous membrane involvement where they will have oral lesions consisting of white patches and painful sores that may crust or ulcerate.

How is Darier disease diagnosed?

Diagnosis of Darier disease begins with a thorough review of symptoms and medical and family history. A referral to a dermatologist may be helpful for the identification of characteristic features seen in Darier disease. A head-to-toe skin evaluation may be performed using a dermatoscope (i.e., an instrument used to magnify skin lesions) to identify affected areas, morphology, and distribution patterns. A skin biopsy of an affected lesion may reveal characteristic histopathologic features, such as acantholysis throughout the epidermis and dyskeratosis, characterized by corps ronds (i.e., round keratinocytes with basophilic stained nuclei). Darier disease may reveal similar histopathologic findings as Hailey-Hailey disease, which is another rare skin condition characterized by abnormal keratinization. When comparing a case of Darier disease to Hailey-Hailey disease, the former often exhibit a higher proportion of dyskeratosis and it is more pronounced in histopathology. If superinfection is suspected, a skin culture or laboratory examination of a skin scraping may help exclude bacterial and fungal infections, respectively. Genetic testing for mutations in the ATP2A2 gene is often not necessary for the diagnosis, but it can help assess the future risk of passing the pathogenic variant onto offspring.

How is Darier disease treated?

There is currently no cure for Darier disease and treatment consists of a combination of supportive measures and pharmacotherapy aimed at improving skin hygiene, decreasing the severity of symptoms, and improving the affected individuals’ quality of life. Supportive measures can be provided to help individuals reduce the impact of aggravating factors, including avoidance of direct sunlight, excessive heat, moisture, and friction through reduction of body weight (if appropriate). Individuals may also wear lightweight and breathable clothing to avoid chafing in intertriginous areas. Additionally, regular use of moisturizers and emollients containing keratolytics, such as topical urea or lactic acid, may help reduce skin irritation, decrease hyperkeratosis, and improve skin appearance.

Pharmacotherapy for Darier disease consists of a stepwise approach. Individuals with mild, localized disease begin with a combination of supportive measures and intermittent use of medium-potency topical corticosteroids (e.g., triamcinolone, mometasone). Topical retinoids (e.g., tretinoin), which regulate skin cell turnover and proliferation, may also be used. Individuals with more severe or extensive disease may be initiated on a stronger, systemic treatment regimen of oral retinoids (e.g., acitretin, isotretinoin) instead. Individuals should receive appropriate counseling for the use of oral retinoids, including avoidance of pregnancy during treatment and appropriate use of contraception due to the known teratogenicity of retinoids.

The malodor that may occur secondary to microbial colonization is treated with topical antibiotics (e.g., gentamicin, mupirocin) or topical antifungals (e.g., ketoconazole). Antibacterial washes, such as chlorhexidine, may also be used. Finally, since the disorder has a profound impact on often visible portions of the skin, discussion with a mental health professional may be necessary to manage any depression and anxiety. Genetic counseling may also be offered to individuals who wish to learn more about the risk of passing the genetic mutation to offspring.

What are the most important facts to know about Darier disease?

Darier disease, also known as Darier-White disease or keratosis follicularis, is a rare genetic disorder characterized by a defect in skin keratinization, an essential process in which the skin cells undergo maturation. It is primarily caused by mutations in the ATP2A2 gene, which results in acantholysis (the loss of cell adhesion between keratinocytes). The signs and symptoms of Darier disease primarily include skin manifestations, nail abnormalities, and mucous membrane involvement. A referral to a dermatologist may be helpful for the identification and diagnosis of characteristic features seen in Darier disease. There is currently no cure for Darier disease, and management consists of a combination of supportive measures and pharmacotherapy aimed at improving skin hygiene, decreasing the severity of symptoms, and improving the affected individuals’ quality of life.

Key Takeaways

Definition	Darier disease, also known as Darier-White disease or keratosis follicularis, is a rare genetic disorder characterized by a defect in skin keratinization, causing characteristic red or brown papules with abnormal keratosis and nail abnormalities.
Causes	- Mutations in ATP2A2 gene - Ca2+ ATPase Type II (SERCA2) protein of endoplasmic reticulum - Mutation → altered calcium signaling in keratinocytes → acantholysis (loss of cell adhesion) - Autosomal dominant inheritance - High penetrance - Variable expressivity (varying signs and symptoms in each affected individual)
Signs and Symptoms	- Skin manifestations - Red and brown hyperkeratotic papules and plaques - Mostly in areas with high concentration of sebaceous glands (chest, back, forehead, scalp) - Usually begin in upper trunk or neck and spread to high-friction, intertriginous areas - Sun exposure, friction, heat, sweat can worsen skin involvement - Nail abnormalities - Nail pitting - Longitudinal leukonychia - Mucous membrane involvement (50%) - White patches and painful sores - May crust or ulcerate
Diagnosis	- Review of symptoms - Medical and family history - Dermatologist referral → dermatoscopic examination - Skin biopsy - Useful for differentiation with Hailey-Hailey disease - If superinfection suspected: skin culture or skin scraping laboratory examination - Genetic testing (to assess future risk of passing the variant)
Treatment	- No cure - Supportive measures (reduce impact of aggravating factors): - Avoid direct sunlight, excessive heat, moisture, and friction (reduction of body weight if appropriate) - Wear lightweight and bearable clothing - Regular use of moisturizers and emollients containing keratinolytic (topical urea, lactic acid) - Pharmacotherapy: - Mild, localized disease: - Supportive measures - Intermittent use of medium-potency topical corticosteroids - Topical retinoids - Severe or extensive disease: - Systemic treatment regimen with oral retinoids (with appropriate counseling and appropriate use of contraception) - Topical antibiotics or antifungals (malodor from microbial colonization) - Counseling from mental health professional - Genetic counseling

References

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

Hanna N, Lam M, Fleming P, Lynde CW. Therapeutic options for the treatment of Darier's disease: A comprehensive review of the literature. J Cutan Med Surg. 2022;26(3):280-290. doi:10.1177/12034754211058405

Savignac M, Simon M, Edir A, Guibbal L, Hovnanian A. SERCA2 dysfunction in Darier disease causes endoplasmic reticulum stress and impaired cell-to-cell adhesion strength: Rescue by Miglustat. J Invest Dermatol. 2014;134(7):1961-1970. doi:10.1038/jid.2014.8

Suryawanshi H, Dhobley A, Sharma A, Kumar P. Darier disease: A rare genodermatosis. J Oral Maxillofac Pathol. 2017;21(2):321. doi:10.4103/jomfp.JOMFP_170_16

Wang Y, Bruce AT, Tu C, et al. Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. J Cell Sci. 2011;124(Pt 21):3568-3580. doi:10.1242/jcs.084053