About darier disease

What is darier disease?

Keratosis follicularis, also known as Darier disease, is a rare, genetic skin disorder. Affected individuals develop skin lesions that consist of thickened, rough bumps (papules) or plaques that may also be greasy or have a brown or yellow crust. These hardened, scaly lesions are progressive and may gradually grow bigger or spread. The nails and mucous membranes are also affected in most cases. Individuals may have periods of time when signs improve (remission), but the lesions usually recur (relapse). The specific problems vary from one individual to another. Keratosis follicularis is inherited as an autosomal dominant trait.

What are the symptoms for darier disease?

Bleeding under skin symptom was found in the darier disease condition

The disease is 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. 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.

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.

What are the causes for darier disease?

Mutations in the ATP2A2 gene cause Darier disease. The ATP2A2 gene provides instructions for producing an enzyme abbreviated as SERCA2. This enzyme acts as a pump that helps control the level of positively charged calcium atoms (calcium ions) inside cells, particularly in the endoplasmic reticulum and the sarcoplasmic reticulum. The endoplasmic reticulum is a structure inside the cell that is involved in protein processing and transport. The sarcoplasmic reticulum is a structure in muscle cells that assists with muscle contraction and relaxation by releasing and storing calcium ions. Calcium ions act as signals for a large number of activities that are important for the normal development and function of cells. SERCA2 allows calcium ions to pass into and out of the cell in response to cell signals.

Mutations in the ATP2A2 gene result in insufficient amounts of functional SERCA2 enzyme. A lack of SERCA2 enzyme reduces calcium levels in the endoplasmic reticulum, causing it to become dysfunctional. SERCA2 is expressed throughout the body; it is not clear why changes in this enzyme affect only the skin. Some researchers note that skin cells are the only cell types expressing SERCA2 that do not have a "back-up" enzyme for calcium transport. This dependence on the SERCA2 enzyme may make skin cells particularly vulnerable to changes in this enzyme.

The linear form of Darier disease is caused by ATP2A2 gene mutations that are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. There have been no known cases of people with the linear form of Darier disease passing it on to their children

What are the treatments for darier disease?

The treatment of keratosis follicularis is directed toward the specific symptoms that are apparent in each individual. For some individuals, sunscreen, loose clothing, moisturizing creams and avoiding excessive heat may reduce the severity of the disease.

Synthetic derivatives of vitamin A (retinoids) applied directly to the affected areas (topically) may help reduce scaly thickening of the skin (hyperkeratosis). Therapy that helps soften and shed hardened, abnormal skin (keratolytics) such as treatment with salicylic acid in propylene glycol gel may also help treat hyperkeratosis. Topical corticosteroids and substances that soothe and soften the skin (emollients) have also been used to alleviate inflammation in localized keratosis follicularis.

Retinoids taken by mouth (orally) have been effective in treating individuals with keratosis follicularis and are the drugs most often used to treat severe cases. Oral retinoids such as tretinoin and acitretin affect the entire body (systemic therapy). Oral retinoids can be associated with side effects. Women must not become pregnant when taking a retinoid because these drugs could damage the baby and pregnancy should be avoided for some time after stopping the drug (the exact time depends on which retinoid was prescribed). Retinoids should only be used under the supervision of a physician.

Antibiotics may be necessary to treat individuals with secondary bacterial infection. Antiviral agents such as acyclovir have been used to treat associated infection with the herpes simplex virus.

Genetic counseling is important for affected individuals and their families.

What are the risk factors for darier disease?

Darier disease, also called keratosis follicularis, is a genodermatosis. It is a rare genetic disorder inherited in an autosomal dominant manner.

  • The responsible mutations occur in the gene that encodes the calcium pump, in the endoplasmic reticulum.
  • The keratinocytes in the skin of the affected person lose cohesion among themselves, which leads to the manifestations.
  • The classic features of the disease are keratotic papules and longitudinal eyrthronychia.
  • However, the expressivity is highly variable, which means the severity, and features are not the same across all the affected persons.

Risk factors

  • The disease is transferred in an autosomal dominant inheritance. The affected parents are at high risk of transferring the disease to their children.
  • The genotypic severity that reflects in the phenotypic severity of the disease also depends on mosaicism. There are two types of mosaicism: type 1 and type 2. In type 1 mosaicism, the risk for the severity is less as the mutation occurs in only a part of the cells in the zygote.
  • In contrast, type 2 mosaicism leads to a mutation in all the cells of the zygote. Type 2 leads to a severe form of the disease. Hence, type 2 mosaicism is a risk factor for the disease.
  • Environmental factors
  • The UV radiation in the sunlight, sweat, friction, and heat induce the disease triggers that lead to apoptosis (programmed death) of keratinocytes. This event exacerbates the disease.

Greasy papules,Lesions,Small pits in palm,Bleeding under skin,V-shaped notches at the distal end of the nail plate,Higher rates of depression and mood disorders
Keratotic papules and longitudinal eyrthronychia,Acantholysis
5-fluorouracil,Retinoids including acitretin, alitretinoin, isotretinoin and etretinate

Is there a cure/medications for darier disease?

Darier disease is clinically called keratosis follicularis. It is a rare genetic disorder caused by the mutations in the gene ATP2A2 that encodes the calcium pump called SERCA2.

  • Calcium plays the role of maintaining calcium concentration inside the endoplasmic reticulum.
  • The defective pump leads to the failure of processing of proteins required for keratinocyte cohesion.
  • It leads to greasy, scaly papules that form warty lesions. Other skin manifestations include small pits on the palm and bleeding underneath the skin.


  • Avoidance of the factors such as sunlight, heat, friction, sweat, and occlusive clothes that trigger the exacerbation of the disease is a very important measure.
  • Use of sunscreen and lose clothing help to avoid the triggers.
  • Moisturizers containing urea lactic acid alleviate keratosis and scales.
  • Regular cleaning of affected skin areas prevents infection.
  • Oral retinoids are also treatment options. Retinoids include acitretin, alitretinoin, isotretinoin, and etretinate and, they reduce keratosis.
  • The topical application of 5-fluorouracil, in combination with a retinoid, is an effective treatment. 5-fluorouracil acts directly on the DNA of the cells and has its pharmacological effect.

Greasy papules,Lesions,Small pits in palm,Bleeding under skin,V-shaped notches at the distal end of the nail plate,Higher rates of depression and mood disorders
Keratotic papules and longitudinal eyrthronychia,Acantholysis
5-fluorouracil,Retinoids including acitretin, alitretinoin, isotretinoin and etretinate

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