Darier disease

Alternate names

Darier White Disease; Darier's disease; Keratosis follicularis

Definition

Darier disease is a skin condition characterized by wart-like blemishes on the body. The blemishes are usually yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor.

Summary

• A form of Darier disease known as the linear or segmental form is characterized by blemishes on localized areas of the skin.
• The blemishes are not as widespread as they are in typical Darier disease.
• Some people with the linear form of this condition have the nail abnormalities that are seen in people with classic Darier disease, but these abnormalities occur only on one side of the body.

Cause

• Darier disease is caused by mutations in the ATP2A2 gene.
• This gene gives the body instructions to make an enzyme known as SERCA2.
• This enzyme helps control the level of calcium ions inside cells.
• Calcium ions act as signals for many cell functions needed for normal development.

Gene mutations

• Mutations in the ATP2A2 gene affect the amount or function of the SERCA2 enzyme.
• This enzyme is expressed throughout the body, and it is unclear why mutations in this gene affect only the skin.
• The linear form of Darier disease is also caused by ATP2A2 gene mutations, but these mutations are acquired and arise in only some body cells after conception (somatic mutations).

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• Darier disease is inherited in an autosomal dominant manner.
• This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause symptoms of the disease.
• In some cases, a person inherits the mutated copy of the gene from a parent.
• In other cases, the mutation occurs for the first time in a person with no family history of Darier disease. While most people with a mutation develop symptoms, a small proportion of people do not.
• When a person with a mutated gene that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated gene.
• The linear form of the disease is typically not inherited and is due to acquired mutations that arise in only some cells of the body, after conception. These are called somatic mutations.

Signs and symptoms

• The blemishes are usually yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor.
• The most common sites for blemishes are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear.
• The mucous membranes can also be affected, with blemishes on the roof of the mouth (palate), tongue, inside of the cheek, gums, and throat.
• Other features of Darier disease include nail abnormalities, such as red and white streaks in the nails with an irregular texture, and small pits in the palms of the hands and soles of the feet.
• The wart-like blemishes characteristic of Darier disease usually appear in late childhood to early adulthood.
• The severity of the disease varies over time; affected people experience flare-ups alternating with periods when they have fewer blemishes.
• The appearance of the blemishes is influenced by environmental factors.
• Most people with Darier disease will develop more blemishes during the summertime when they are exposed to heat and humidity.
• UV light; minor injury or friction, such as rubbing or scratching; and ingestion of certain medications can also cause an increase in blemishes.
• On occasion, people with Darier disease may have neurological disorders such as mild intellectual disability, epilepsy, and depression.
• Learning and behavior difficulties have also been reported in people with Darier disease.
• Researchers do not know if these conditions, which are common in the general population, are associated with the genetic changes that cause Darier disease, or if they are coincidental.
• Some researchers believe that behavioral problems might be linked to the social stigma experienced by people with numerous skin blemishes.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Acrokeratosis
• Hypermelanotic macule(Hyperpigmented spots)
• Pruritus(Itching)
• Subungual hyperkeratotic fragments

30%-79% of people have these symptoms

• Abnormal hair morphology(Abnormality of the hair)
• Anal mucosal leukoplakia
• Palmoplantar keratoderma(Thickening of palms and soles)
• Plantar pits

5%-29% of people have these symptoms

• Skin vesicle

Diagnosis

• Darier disease is usually diagnosed by the appearance of the skin and the family history.
• It may be mistaken for other skin conditions. T
• he diagnosis may require a skin biopsy.
• Genetic testing to identify a mutation in the ATP2A2 gene can be used to confirm the diagnosis.

Treatment

• Basic measures to manage Darier disease may include using sunscreen, wearing cool cotton clothing, and avoiding hot environments.
• Moisturizers with urea or lactic acid can reduce scaling.
• A low- or mid-potency topical steroid is sometimes useful for inflammation.
• The affected skin may smell unpleasant, which may be due to bacteria growing in the rash.
• If bacterial overgrowth is suspected or there is a lot of crusting, it can be helpful to apply antiseptics or soak in astringents.
• Topical medications may include topical retinoids (i.e., adapalene, tazarotene gel, or tretinoin).
• Topical retinoids may reduce hyperkeratosis within 3 months.
• However, irritation is a side effect.
• Other medications may include acitretin, isotretinoin, cyclosporine, or oral retinoids (eg, acitretin, isotretinoin).
• Oral retinoids have been the most effective medical treatment for Darier disease, leading to reduction of symptoms in 90% of affected people.
• However, prolonged use is limited due to adverse effects.
• Other treatments may include oral antibiotics to clear bacterial infection, oral acyclovir to treat or suppress herpes simplex virus infection; dermabrasion; electrosurgery; and Mohs micrographic surgery for localized areas.

NIH genetic and rare disease info

• NIH info on Darier disease

Darier disease is a rare disease.

Darier disease Resources
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