Darier Disease - Facts and Information

Introduction

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Defining Darier Disease

Darier disease is a form of skin condition that is characterized by wart-like blemishes that appear on the affected person's body. The blemishes are commonly yellow in color, are mildly greasy, hard, and may produce a strong odor. The most common places the blemishes appear on a person's body include the knees, elbows, back, chest, upper arms, forehead and behind the person's ears. The affected person's mucous membranes may also be affected; blemishes can appear on the person's tongue, the roof of their mouth, the inside of their cheeks, their gums or in their throat. Additional features of Darier disease involve nail abnormalities like white and read streaks in the person's nails combined with an irregular texture, as well as small pits in the soles of their feet or the palms of their hands.

The blemishes that characterize Darier disease often appear during late childhood or in early adulthood. The severity of the disease tends to vary over a period of time, with persons who are affected by the disease experiencing flare-ups that alternate with periods when they have fewer blemishes. Environmental factors influence the appearance of these blemishes. The majority of people with Darier disease develop a greater amount of blemishes during the summertime upon being exposed to humidity and heat. Ultraviolet light, friction or a minor injury such as scratching or rubbing, or ingestion of certain forms of medications, may also cause an increased number of blemishes.

Occasionally, people who have Darier disease also experience a form of neurological disorder, such as epilepsy, depression, or a mild intellectual disability. Learning and behavioral difficulties have also been reported among persons with Darier disease. The medical community is not sure if the co-existing conditions, which are also common among the general population, are associated with genetic changes that cause Darier disease or if they are coincidental. There are some researchers who are of the belief that behavioral issues may be linked to the social stigma experienced by persons with numerous skin blemishes.

Linear, or, 'segmental,' Darier disease is a form of the disease that is characterized by blemishes on areas of the person's skin that are localized. The blemishes in this instance are not as widespread as they are in the more typical form of Darier disease. Some persons with the linear form of the condition experience nail abnormalities which are found in persons with classic Darier disease, yet these abnormalities happen on only one side of the person's body.

Another name that Darier disease is referred to by is, 'Keratosis Follicularis.' Darier disease is a rare form of genetic disorder. A single gene is passed from one parent, causing the condition. The chance that a child inheriting the gene if one parent is affected is approximately one in two, but not everyone with the gene will develop symptoms of the disease. The gene involved in Darier disease has been identified as ATP2A2, which is found on chromosome 12q23-24.1. The exact mechanism through which this gene causes the disease is under investigation, although it appears that the way in which skin cells join together might be disrupted. Skin cells stick together through structures referred to as, 'desmosomes;' it appears that the desmosomes do not assemble appropriately if there is an insufficient amount of calcium present.

Diagnosing Darier Disease

In most cases, Darier disease is diagnosed by its appearance and the person's family history, although it is many times mistaken for other forms of skin issues. A diagnosis may require a skin biopsy. The histology associated with Darier disease is characteristic; it is referred to as, 'focal acantholytic dyskeratosis,' and is associated with varying degrees of skin thickening. The pathology is similar to Grover's disease.

Symptoms of Darier's Disease

The signs and symptoms of Darier disease differ markedly between people. Some people have very subtle signs, ones that are asymptomatic and are found only upon a careful inspection. Other people experience lesions that are extensive and can cause them a considerable amount of distress. The severity of the disease in persons who are affected can fluctuate over time.

Skin lesions, which are characterized by persistent, greasy, and small bumps that usually occur of areas of the person's face, ears, forehead, eyebrows, as well as the sides of their nose, beard area, neck, back and chest area, are the main symptoms of the disease. The natural folds of the skin around the person's joints; around their groin or armpits, or under their breasts or between their buttocks, are other areas that may be affected. These lesions are either yellow or brown in color and have a sandpaper texture. A number of these lesions can grow together, forming larger, wart-like lesions that may present a strong odor; commonly within skin folds.

The person's scalp is many times affected as well, with a crusty rash that is similar to seborrhoeic dermatitis, although it is usually harsher to the touch. Some people affected by Darier disease experience freckle-like lesions that are flat, while others can experience raise and large, warty lesions. Others may experience cystic acne, or a blistered pattern. Some people develop a linear pattern to the rash, many times with lines of embyonal development of their skin.

Darier Disease Genetic Information

Mutations of the ATP2A2 gene are responsible for Darier disease. The gene provides instructions for the production of an enzyme that is abbreviated as SERCA2, which acts as a pump that helps to control the level of positively charged calcium atoms inside of cells, most notably in Endoplasmic reticulum and sarcoplasmic reticulum. Endoplasmic reticulum is a structure within the cell which is involved in the processing and transport of protein. Sarcoplasmic reticulum is a structure in muscle cells that aids in muscle contraction and relaxation through release and storage of calcium ions. Calcium ions act as signals for a number of activities which are important for the development and function of cells.

SERCA2 permits calcium ions to both pass in and out of cells in response to cell signals.
Mutations in the ATP2A2 gene result in a lack of sufficient amounts of functional SERCA2 enzyme, reducing calcium levels in the Endoplasmic reticulum - the result is that it becomes dysfunctional. SERCA2 is something that is expressed throughout a person's body, and it is not known why the enzyme only affects a person's skin. There are some researchers who note that skin cells are the only cell types that express SERCA2 which do not have a form of, 'back-up,' enzyme for the transportation of calcium. The dependence on the SERCA2 enzyme might make skin cells especially vulnerable to changes in the enzyme.

The linear form of Darier disease is caused by mutations in the ATP2A2 gene that are acquired during a person's lifetime; they are present only in certain cells. The changes are referred to as, 'somatic mutations,' and are not ones that are inherited. There has not been a documented case of a person with the linear form of Darier disease passing it to one of their children.

Darier disease is inherited in an autosomal dominant pattern, meaning that once copy of the altered gene in each cell is enough to cause the disorder. Some persons inherit the mutations from one parent who is affected. Other times, a new mutation of the gene is responsible, and happen in people who do not have a history of the disorder in their family.