|Other names||Darier disease, Darier–White disease, Dyskeratosis follicularis, and Keratosis follicularis,:523:567|
|Linear Darier's disease|
Darier's disease (DAR) is an autosomal dominant disorder discovered by French dermatologist Ferdinand-Jean Darier. Darier's is characterized by dark crusty patches on the skin, sometimes containing pus. The crusty patches are also known as keratotic papules, keratosis follicularis, or dyskeratosis follicularis.
Mild forms of the disease are the most common, consisting solely of skin rashes that flare up under certain conditions such as high humidity, high stress, or tight-fitting clothes. Short stature, when combined with poorly-formed fingernails that contain vertical striations, is diagnostic even for mild forms of DAR.
Darier's disease affects both men and women and is not contagious. The disease often starts during or later than the teenage years, typically by the third decade. Short stature is common. The symptoms of the disease are thought to be caused by an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion.
Worldwide prevalence is estimated as between 1: 30,000 and 1: 100,000. Case studies have shown estimated prevalence by country to be 3.8: 100,000 in Slovenia, 1: 36,000 in north-east England, 1: 30,000 in Scotland, and 1: 100,000 in Denmark
It is clinically manifested by hyperkeratotic papules primarily affecting seborrheic areas on the neck, chest, back, ears, forehead, groin, and thorax, with less frequent involvement of the oral mucosa. When oral manifestations are present, they primarily affect the palatal and alveolar mucosa, are usually asymptomatic, and are discovered in routine dental examination. Histologically, the lesions present suprabasal clefts in the epithelium with acantholytic and dyskeratotic cells represented by corps ronds and corps grains. The rash associated with DAR often has a distinct odor. Palms & soles may become thickened, and sufferers may present intraoral papules. Fingernails become fragile, which helps in the diagnosis of the disease. The rash can be aggravated by heat, humidity, and exposure to sunlight. In some cases, sunlight makes it better, especially on the forehead.
Minor forms of the disease are the most common and may remain undiagnosed. These consist mainly of minor rashes without odor that are aggravated by heat, humidity, stress, and sunlight. Poorly-formed fingernails containing vertical striations are diagnostic, which is distinctive from simple nail-biting.
A recent study examined neuropsychiatric conditions in a non-random sample of 100 British individuals assessed as having DAR. There were high lifetime rates for mood disorders (50%), including depression (30%), bipolar disorder (4%), suicidal thoughts (31%), and suicide attempts (13%), suggesting a possible common genetic link. Scattered case studies also suggest a possible but unconfirmed link to learning disorders.
Darier's disease is inherited in an autosomal dominant manner, which indicates that the defective gene responsible for a disorder is located on an autosome. Only one copy of the gene is sufficient to cause the disorder.
The disorder is caused by a mutation in the gene ATP2A2. Family members with confirmed identical ATP2A2 mutations can exhibit differences in the clinical severity of disease, suggesting that other genes or environmental factors affect the expression of Darier's disease. With the discovery of the ATP2A2 gene, performing genetic tests to confirm the diagnosis of Darier's disease is now possible.
Darier's disease is sometimes mistaken for other skin conditions and is usually diagnosed by the appearance of the skin and the family history.
Patients present with the following signs:
1. Hyperkeratotic papules present over the seborrheic area of the body.
2. V-shaped nicking present at the tip of the nails.
3. Red and white longitudinal nail lines.
For minor forms, no specific treatment is required, but avoidance of excessive heat, humidity, stress, and tight-fitting clothes is advised, as well as maintaining good hygiene. Use of sunscreen is also important. Moisturizers such as topical urea or lactic acid can help symptomatically, and antiseptic washes can decrease the risk of skin bacteria. Topical creams (as above) are occasionally required to deal with flare-ups:
Treatment of choice for severe cases is oral retinoids. During flares, topical or oral antibiotics may be administered. Ciclosporin and prescription-only topical corticosteroids, e.g., betamethasone, have been used during acute flares. Some patients are able to prevent flares with use of topical sunscreens and oral vitamin C.
Options for systemic treatment include oral retinoids, which help to decrease the excess proliferation, and some examples include Acitretin, Isotretinoin, and Alitretinoin. Patients show clinical improvement with this treatment. Treatment options for surgery or destructive therapy is for lesions that don't respond to the above treatment. Some options may be dermabrasion, surgical excision, and photodynamic therapy.
A 1992 study of 163 affected persons found that most patients had no other medical problems, and most manage to lead a relatively normal life.
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