Darier disease

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Darier disease is a skin condition characterized by wart-like blemishes on the body. The blemishes are usually yellowish in color, are hard to the touch, can appear 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 ears. The mucous membranes can also be affected, with blemishes occurring on the roof of the mouth (palate), tongue, gums, and inside the cheeks 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 and 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 summer when they are exposed to heat and humidity. The number of blemishes can also increase when an affected person is exposed to ultraviolet light; experiences minor injury or friction, such as rubbing or scratching; or takes certain medications.

On occasion, people with Darier disease may have neurological disorders such as mild intellectual disabilities, 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.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the ATP2A2 gene cause Darier disease. .cf0{font-style:italic;font-family:Segoe UI;font-size:9pt;}The ATP2A2 gene provides instructions for making an enzyme called sarco(endo)plasmic reticulum calcium-ATPase 2 (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.

ATP2A2 gene variants result in insufficient amounts of functional SERCA2 enzyme. A lack of functional 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 that express 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 variants that are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic variants and are not inherited. Currently, no cases of people with the linear form of Darier disease passing it on to their children have been reported in the scientific literature.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the variant from one affected parent. Other cases result from a new (de novo) variant in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or in early embryonic development. These affected individuals have no history of the disorder in their family.

The linear form of Darier disease is generally not inherited but arises from a variant in the gene that occurs after conception. This alteration is called a somatic variant.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The worldwide prevalence of Darier disease is unknown. The prevalence of Darier disease is estimated to be 1 in 30,000 people in Scotland, 1 in 36,000 people in northern England, and 1 in 100,000 people in Denmark.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal nail morphology · Very frequent (99-80%)

Abnormal structure or appearance of the nail.

Acrokeratosis · Very frequent (99-80%)

Overgrowth of the stratum corneum characterized by flesh-coloured or slightly pigmented smooth or warty papules on the upper surface of hands and feet.

Hyperkeratotic papule · Very frequent (99-80%)

A circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point that is composed of localized hyperkeratosis (the latter may be demonstrated histopathologically).

Hypermelanotic macule · Very frequent (99-80%)

A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size.

Pruritus · Very frequent (99-80%)

Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.

Subungual hyperkeratotic fragments · Very frequent (99-80%)

Abnormality of skin pigmentation · Frequent (79-30%)

An abnormality of the pigmentation of the skin.

Abnormality of the hair · Frequent (79-30%)

An abnormality of the hair.

Other findings in the same source

From: Orphanet

Additional reported features include Anal mucosal leukoplakia (Frequent (79-30%)); Blepharitis (Frequent (79-30%)); Cobblestone-like hyperkeratosis (Frequent (79-30%)); Fragile nails (Frequent (79-30%)); Keratoconjunctivitis sicca (Frequent (79-30%)); Longitudinal erythronychia (Frequent (79-30%)); Palmoplantar keratoderma (Frequent (79-30%)); Plantar pits (Frequent (79-30%)); Thickened skin (Frequent (79-30%)); Palmar pits (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Darier disease is Dermatology, with a dermatologist as the relevant type of clinician. Dermatologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which features of the skin, hair or nails distinguish the possibilities?
• Would photographs over time help document the changes?
• What should be expected from treatment, and how will irritation or other adverse effects be managed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Darier disease. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.