About white-darier disease

What is white-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 white-darier disease?

The symptoms of keratosis follicularis usually become apparent during the teen-age years often around puberty. Symptoms may develop in younger or older individuals, but rarely develop after the third or fourth decade of life. The severity of the disorder and the specific symptoms that develop vary, even among individuals within the same family.

The initial Lesions in keratosis follicularis are usually small, firm, greasy Bumps (papules) that are often skin-colored, brown or yellow-brown in color. The Lesions usually affect the areas of the body near sebaceous glands (sebaceous glands secrete oily grease) including the chest, back, forehead and scalp. Darier disease may also affect skin creases e.g. groin.

The skin Lesions associated with keratosis follicularis generally develop a brown, greasy crust and become thickened and warty (hyperkeratotic), scaly and darkened. The Lesions will slowly grow bigger eventually coming together (coalescing) to form discolored, warty Plaques that may cover extensive areas of the body particularly on the trunk. In extremely rare, severe cases, almost the entire body may be affected. The Lesions may cause persistent Itchiness (pruritus). Some patients have Fragile skin that Blisters or becomes raw (erosions) and painful.

The skin may develop bacterial, viral or fungal infections (secondary infections) that worsen (exacerbate) the condition. Infected skin Lesions may give off a distinct, unpleasant (malodorous) smell. The herpes simplex virus may be prone to infecting the Lesions and causes pain. Heat, exercise and sunlight may also worsen keratosis follicularis or cause a new outbreak of lesions.

Individuals with keratosis follicularis may have periods when few Lesions are present (remission). However, the Lesions tend to recur (relapse). Keratosis follicularis is usually worse in the summer and improves in the winter. Heat or sun often causes an outbreak.

Another common finding associated with keratosis follicularis is the development of multiple, small, yellow-brown, flattened wart-like (verrucous) Bumps (papules) on backs of the hands or feet. These Bumps may be the first sign of keratosis follicularis. Many affected individuals develop small horny Bumps called punctate keratoses or depressions (pits) on the palms and soles.

Most individuals with keratosis follicularis have abnormalities affecting the nails including fragile nails with splits along the length of the nail or red or white streaks that run up and down the nail with V-shaped notching at the free edge.

Sometimes the mucous membranes within the mouth develop small Bumps (papules). The roof of the mouth (palate) is most often affected. The gums, larynx and esophagus may also be affected. Darier disease can also affect the ducts of the salivary glands causing salivary gland obstruction. In some cases, Darier disease has developed on the mucous membranes of the anus and rectum.

Although in most people Darier disease is limited to the skin, additional symptoms have been reported in some cases including seizures, bipolar disorder, and learning disabilities.

Keratosis follicularis may -be restricted to a band of skin on one side of the body (segmental or linear keratosis follicularis).



What are the causes for white-darier disease?

Keratosis follicularis is a genetic disorder that occurs randomly as the result of a spontaneous genetic change (i.e., new mutation) or the mutation is inherited as an autosomal dominant trait.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females.

Investigators have determined that keratosis follicularis occurs due to mutations of the ATP2A2 gene. The ATP2A2 gene contains instructions for creating (encoding) a protein that acts as a calcium pump in the cell. This protein known as SERCA2 is responsible for carrying calcium ions from the semi-transparent fluid (cytoplasm) found in the interior of a cell into the extensive membrane network of a cell (endoplasmic reticulum) where proteins are processed. The exact process by which loss or improper function of the SERCA2 protein causes keratosis follicularis is unknown but SERCA2 is active (expressed) in keratinocytes, the main cell type of the outermost layer of the skin (epidermis). Calcium ions in the endoplasmic reticulum play an essential role in the formation of the proteins in the sticky junctions known as a desmosomes that hold the keratinocytes together. When the calcium pumps fail, the desmosomes do not hold cells together properly and the keratinocytes separate (acantholysis). Failure of keratinocytes to stick together also leads to abnormal maturation of the keratinocytes (abnormal keratinization) with the formation of the horny bumps. For this reason, keratosis follicularis is sometimes referred to as a disorder of abnormal keratinization or dyskeratosis.

The linear or segmental forms of keratosis follicularis are caused by genetic mosaicism meaning that the ATP2A2gene mutation is only present in some of the cells in one part of the skin but most of the skin is not affected. Mosaicism is caused by a mutation in a single cell after fertilization (postzygotic mutation) and is not inherited.



What are the treatments for white-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 white-darier disease?

White Darier disease is also named as Keratosis Follicularis.

  • It is a very rare skin disorder and is genetic.
  • It is characterized by lesions on the skin that have thickened, rough bumps i.e., papules that appear greasy, yellow or skin color or brown crust.
  • These lesions may spread and grow over time. This may vary from person to person. This mostly affects scalp, forehead, upper arms, chest, back, knees, elbows, ear and also sometimes mucous membranes, tongue, gums, larynx, esophagus, throat, etc.
  • It also affects nails; there occur red and white streaks in the nails that have an irregular texture
  • White Darier disease may affect skin creases i.e., groin. In severe cases, it may also affect the entire body.
  • The skin lesions cause itchiness and are very painful. Also, bacterial, viral or fungal infections worsen the condition.
  • This lesion creates a bad odor.
  • Excess heat, and exercise may create more trouble. This means that white darier disease worsens the condition in summer and improves in winter.
  • There occur horny bumps that are known as punctate keratosis on palms, and soles.
  • Some cases with white darier disease also complain about seizures, bipolar disorder, and learning disabilities.
  • White darier disease occurs due to mutation inherited as an autosomal dominant trait. This occurs because of mutations of ATP2A2 gene.
  • Keratosis Follicularis is also sometimes called as a disorder of abnormal keratinization or dyskeratosis.
  • People having white darier disease can also have neurological disorders like mild intellectual disability, epilepsy, and depression.


Symptoms
Wart-like blemishes on the body that are yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor,Blemishes are found on the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear,Itching,Cystic acne
Conditions
Acrokeratosis verruciformis,Pruritus
Drugs
Sunscreen,Moisturizing lotions,Antiseptics,Astringents,Antibiotics,Benzoyl peroxide,Topical diclofenac sodium,Adapalene,Tazarotene gel,Tretinoin



Is there a cure/medications for white-darier disease?

White Darier disease is also known as Keratosis Follicularis (Darier disease). This is a rare genetic disorder. Darier disease is an autosomal dominant inherited disorder.

  • In this disease, hyperkeratotic seborrheic regions, nail abnormalities and changes in mucous membranes occur.
  • Blemishes are characterized on the body. They are hard to touch, yellow-colored and, contain a strong odor, and occur on body parts like the forehead, upper arms, knees, elbows, chest, back.
  • Nail abnormalities like the irregular texture of red, and white color and small pits in soles, and palms are the other features of this disease. This condition usually appears in late childhood to adulthood.
  • Environmental factors also boost symptoms of this disease, like heat and humidity. Some neurological disorders also occur in this disease.
  • Mutations in ATP2A2 gene cause this disease. This results in a reduction of calcium levels in the endoplasmic reticulum.
  • Treatment for this disease is directed towards its particular symptoms that vary for every patient. Using sunscreen, moisturizing creams can be used to reduce the effect on the skin.
  • Synthetic derivatives of Vitamin A are applied to reduce the thickness to the skin.
  • Salicylic acid in propylene glycol gel treatment is also used, and topical corticosteroids are used to make skin softer.
  • Oral medications with keratosis follicularis are often used for treatment.
  • Oral retinoids like tretinoin and acitretin affect the entire body treatment.
  • They also have their own side effects. For secondary bacterial infection, antibiotics are necessary for treatment.
  • Antibiotics like acyclovir are used to treat the infection.
  • Genetic counseling is also important for affected families and affected individuals.


Symptoms
Wart-like blemishes on the body that are yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor,Blemishes are found on the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear,Itching,Cystic acne
Conditions
Acrokeratosis verruciformis,Pruritus
Drugs
Sunscreen,Moisturizing lotions,Antiseptics,Astringents,Antibiotics,Benzoyl peroxide,Topical diclofenac sodium,Adapalene,Tazarotene gel,Tretinoin



Video related to white-darier disease