What are the other Names for this Condition? (Also known as/Synonyms)

• Darier Disease (DD)
• DD (Darier Disease)
• White Darier Disease 

What is Keratosis Follicularis? (Definition/Background Information)

• Keratosis Follicularis (Darier Disease) is a skin disorder caused by autosomal dominant type of genetic inheritance
• It is caused by the mutation of the ATP2A2 gene on chromosome 12. This gene is responsible for the formation of a calcium pump in a cell organelle (a functional component of a cell) called endoplasmic reticulum
• The condition is characteristic by greasy, hard papules (skin eruptions) over the head, scalp, face, chest, neck, and axilla. The correlation between the genetic mutation and the clinical features of the condition is not understood or explained
• A diagnosis of Keratosis Follicularis is made by skin biopsy (microscopic examination of the skin lesions) and gene sequencing test
• The most important complication of the condition is super-imposed bacterial and viral infections
• The treatment of Keratosis Follicularis include the use of topical moisturizers, steroids, and retinoid creams
• There is no effective prevention of Darier Disease. The disease usually persists throughout one’s life, with some individuals experiencing remissions with age, while others may experience exacerbations.

Who gets Keratosis Follicularis? (Age and Sex Distribution)

• Keratosis Follicularis is a genetic condition that is observed in children and young adults between 6-20 years of age
• The condition affects both males and females
• It is observed worldwide; all racial and ethnic groups may be affected

What are the Risk Factors for Keratosis Follicularis? (Predisposing Factors)

• The most important risk factor for Keratosis Follicularis is a positive family history of the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider. 

What are the Causes of Keratosis Follicularis? (Etiology)

Keratosis Follicularis is a genetic disorder inherited in an autosomal dominant manner. It is caused by ATP2A2 gene mutation on chromosome 12.

• This gene is involved in the synthesis of an intracellular calcium pump called SERCA2 (sarcoplasmic/endoplasmic reticulum calcium ATP isoform 2 protein). This pump is responsible for maintaining low levels of calcium within the sarcoplasmic reticulum
• Keratosis Follicularis manifests as a skin condition causing skin eruptions over the body. The microscopic examination of the skin lesions show adhesions between a type of cells in the skin, called keratinocytes, which secrete a protein called keratin
• The mutation in the intracellular calcium pump is thought to cause abnormal expression of a type of adhesion molecules between the epidermal cells (cells of epidermis, the outer most layer of the skin) called desmosomes
• The correlation between the genetic mutation and clinical presentations of the condition is still under investigation

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring. 

What are the Signs and Symptoms of Keratosis Follicularis?

The signs and symptoms associated with Keratosis Follicularis or Darier Disease include:

• Greasy, skin-colored, yellowish-brown papules present on the scalp, face, neck, ears, chest, back, and hand. Flexural regions, such as the groin, axilla, and genital regions, are also commonly involved
• The skin lesions are usually malodorous (foul-smelling) and associated with itching. The first lesions usually appears around puberty
• When the disease involves the hands and feet, the lesions over the dorsal aspect are warty, flat-topped papules called acrokeratosis verruciformis
• The palms and soles also show small pits and punctuated lesions called punctuated skin lesions. There may be multiple skin bumps with a small pit in the center
• Nail lesions: Involvement of the nails can also occur; the nails can become very weak and fragile causing longitudinal splitting. The base of the nail can become bumpy and thickened due to deposition of a protein called keratin. These findings are called subungual hyperkeratosis by the healthcare provider
• Mucosal lesions: The inner linings of the mouth (oral mucosa) can also show the presence of multiple white bumps with central depression. These are called punctuated leuco-papules
• Similar findings can also occur in the lining of the anogenital region
• Hot environment, sweating, sunlight exposure, and menstruation makes the condition worse

How is Keratosis Follicularis Diagnosed?

The diagnosis of Keratosis Follicularis may involve:

• A complete evaluation of medical history along with a thorough examination of the skin lesions
• Biopsy and microscopic examination  of the skin lesions: A small sample of the affected skin is taken and sent to the laboratory for examination under the microscope by a pathologist
• Gene sequencing: It is a confirmatory test to check for mutation in the ATP2A2 gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Keratosis Follicularis?

Complications associated with Keratosis Follicularis include:

• Superimposed bacterial and viral infections of skin lesions: This super-infection is generally defined as occurrence of a second infection superimposed on an earlier one. The commonly associated viral infections include herpes simplex and pox virus infections. Because of the disruption of the barrier function of the skin already present in Darier Disease, these infections can readily become systemic. Skin infections in these patients must be attended to promptly and effectively
• Neurological abnormalities, such as epilepsy, mental impairment, and psychiatric conditions (schizophrenia and bi-polar disorder), have also been associated with Keratosis Follicularis
• Chronic itching and scaling of the skin that causes the skin to become thick, discolored, and leathery
• Increased psychological stress can occur due to the skin disorder, which may affect one’s performance at school and college. Parents and teachers should be alert and provide appropriate support to decrease the emotional stress
• The presence of skin infections and scarred skin, due to chronically-occurring nodules that ooze pus and form abscesses, can cause self-image issues, and emotional and psychological problems. If the emotional stress is great, it may even lead to severe depression
• Development of depression may further lead to social and cultural ostracism and social isolation

How is Keratosis Follicularis Treated?

The treatment options for Keratosis Follicularis include both medical and surgical treatment measures.

• The medical treatment for Keratosis Follicularis may include:
  • Avoiding hot environment
  • Use of moisturizers with urea or lactic acid to reduce scaling and hyperkeratosis
  • Topical retinoids and steroids
  • Topical 5 - Flurouracil
  • Topical tacrolimus or pimecrolimus
  • Oral retinoids for severe conditions
  • Antibacterial and antiviral medicines for any superimposed bacterial or viral infections respectively
• The surgical care for Keratosis Follicularis may include:
  • Dermabrasion - to smoothen the hyperkeratotic lesions
  • Electrosurgery for localized lesions
  • Ablation using CO2 or, Erbium:YAG laser
  • Electron beam therapy and photodynamic therapy may also be used

The following tips are helpful for Keratosis Follicularis:

• Keeping the skin moisturized can help in reducing the signs and symptoms caused by Keratosis Follicularis
• If any of the prescribed treatment causes new stinging or burning symptoms, then it is important to stop using them immediately and inform the physician’s office
• Taking care of oneself, being clean and hygienic (especially face and hands), avoiding the urge to touch/break the blisters, avoiding oily make-ups and creams, drinking lots of water, etc. are all simple practices that can ensure a faster recovery from the condition
• Avoid excessive washing and scrubbing of the skin
• Do not pop or lance the affected skin; this merely spreads bacteria and leads to excessive scarring
• Completely avoid scratching the affected areas

How can Keratosis Follicularis be Prevented?

• Currently, there are no specific methods or guidelines to prevent Keratosis Follicularis, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• In order to prevent aggravation of the condition and obtain relief from the signs and symptoms, one can practice certain self-care tips (outlined previously)

What is the Prognosis of Keratosis Follicularis? (Outcomes/Resolutions)

• The prognosis of Keratosis Follicularis depends on the severity of the signs and symptoms. Individuals with milder signs and symptoms have a better prognosis than those with severe signs and symptoms
• Keratosis Follicularis usually persist throughout life, with some individuals experiencing remissions with age, while others experiencing exacerbations
• Psychosocial consequences from the appearance and odor of the lesions also constitute the major morbidity of Keratosis Follicularis
• Due to its physical appearance, Keratosis Follicularis can impose a psychological trauma on the individuals, especially on teenagers, causing depression and reduced self-esteem. Family members should be alert for this possibility and early professional intervention will be beneficial
• Regular follow up visits with the healthcare providers are important

Additional and Relevant Useful Information for Keratosis Follicularis:

• There is no evidence to prove that oily foods and chocolate-based products have an influence on Keratosis Follicularis
• Cleaning the skin too hard with strong chemicals or soaps may aggravate the skin condition. Care must be taken avoid strong soaps and chemicals that could potentially worsen the condition
• The presence of dirt on the body is not a causative factor for Keratosis Follicularis. However, it helps to be clean and hygienic, which will help the condition from getting worse