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Epidermolytic Ichthyosis

Epidermolytic Ichthyosis


DISEASE OVERVIEW

Epidermolytic ichthyosis (EI) is a genetic skin disorder that is characterized by varying degrees of blistering and scaling of the skin. The symptoms of the disease are often noticed at birth or shortly after, and symptoms change as the patient ages. Symptoms may vary from mild blistering upon friction to severe erosions or widespread warty scaling. Hair and nail abnormalities, reduced sweating and the formation of calluses on the palms or soles (palmoplantar keratoderma) of the feet can also occur. Under a microscope, the skin may show mid-epidermal splitting and skin thickening (hyperkeratosis). Current treatments address the specific symptoms and can include topical treatments, medications and antiseptic washes for skin infections. The cosmetic issues and sometimes unpleasant odor associated with EI can lead to stress and psychological distress.

SIGNS & SYMPTOMS

The symptoms of EI progress with the patient’s age. Infants more commonly show signs of red, blistering skin and will usually develop thickened skin (cornification) and scaling into adulthood. Infants may also show growths on the inner surface of the eyelid (conjunctival hamartoma). Scales tend to form in parallel rows of spines or ridges. Reddened skin (erythroderma), itchiness (pruritus) and abnormal dryness (xerosis) are common symptoms. Skin ulcers and other damage can lead to bacterial infections. Heat intolerance and sensitivity to sunlight may also occur. A palmoplantar keratoderma may be present and can be so severe as to limit movement and hand function. Milder cases usually show minimal blistering in areas subject to friction or have only a palmoplantar keratoderma.

CAUSES

EI is caused by harmful changes (variants) in the KRT1 or KRT10 genes. These variants result in improper expression of keratin 1 and keratin 10, which are structural proteins specifically found in epithelial and epidermal cells. The malfunctioning proteins result in barrier abnormalities that can lead to epidermal inflammation, causing the various symptoms seen with the disease.

Some patients have some cells with the harmful gene variant and other cells without the harmful gene variant (somatic mosaicism). This can cause blistering and hyperkeratotic lesions specific to certain areas of the skin. The severity of the disease in these patients is directly correlated to the percentage of cells affected. In somatic mosaicism, the gene change is not inherited.

EI is an autosomal dominant genetic disorder. Dominant genetic disorders occur when only a single copy of a harmful gene variant is necessary to cause a particular disease. EI can be inherited or sporadic, meaning the gene variant can be the result of a new mutation (gene change) in the affected individual. About 50% of cases are caused by spontaneous changes in the KRT1 or KRT10 genes, and the variant can then be passed down to children. The risk of passing the harmful gene variant from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

DISORDERS WITH SIMILAR SYMPTOMS

Epidermolytic ichthyosis can resemble different diseases depending on the stage it is in. Early stages of EI can resemble diseases that involve the extreme onset of blisters and lesions in infants. Specific disorders include toxic epidermal necrolysis (TEN), epidermolysis bullosa (EB) and incontinentia pigmenti (IP). Blister presentation associated with TEN is caused by the first-time exposure to drugs during infancy. EB is a group of diseases, each characterized by the fragility and blistering of skin and mucosae. IP is an X-linked dominant skin disease caused by variants in the IKBKG gene. IP is a multisystem disorder, and the skin is most commonly affected in infants.

Later stages can resemble other conditions, such as Curth Macklin-type ichthyosis hystrix and superficial EI. KPI’s, or keratinopathic ichthyoses, includes a group of multiple diseases that involve variants in the genes KRT1, KRT2, and KRT10. Curth Macklin-type ichthyosis hystrix is caused by a variant in KRT1 and presents similar skin conditions to EI. However, Curth Macklin-type ichthyosis hystrix also includes nail dystrophy and chronic loss of joint function (flexion contracture). Superficial EI is caused by a variant in KRT2 and is characterized by much milder skin thickening and scaling that remains superficial.

Erythrokeratodermia variabilis (EKV) and keratitis-ichthyosis-deafness (KID) like disorders exhibit autosomal dominant inheritance and are caused by variants in genes coding for gap junction proteins. EKV is caused by variants in genes GJB3 and GJB4 while KID is caused by variants in GJB2. These disorders can cause skin thickening and redness, as well as the formation of plaques. EKV can also mimic the cyclic nature of annular epidermolytic ichthyosis.

The spine-like scaling (hystrix-like scaling) that can be present with EI must be distinguished from Lelis syndrome. Lelis syndrome is a very rare hyperkeratotic presentation of hypohidrotic ectodermal dysplasia (XHED). XHED is an X-linked recessive condition that can present with sparse hair and abnormal teeth. Lelis syndrome can also present discolored and thickened skin. However, unlike EI, Lelis syndrome is accompanied with a lack of sweating (hypohidrosis).

Psoriasis is a common and chronic disorder characterized by dry, well-circumscribed silvery-gray scaling spots (papules) or plaques that usually appear on the scalp, elbows or knees. The cause is not well understood but it is thought to be immune mediated and genetic. Sometimes it can be difficult to distinguish from the palmoplantar keratodermas caused by a KRT1 gene variant. However, psoriasis does not follow autosomal dominant inheritance like EI.

DIAGNOSIS

EI is diagnosed by clinical signs and symptoms. Histopathology tests and electron microscopy assessments may be used but are not the most definitive. Genetic testing for harmful variants in the KRT1 and KRT10 genes can confirm a diagnosis.

STANDARD THERAPIES

The main goal of treating EI is to ease the presenting symptoms. This can be challenging as it may require a combination of treatments and therapies. The medications that help to remove the excess thickened skin (topical keratolytics or oral retinoids) can leave the very fragile epidermis (underlying living cell layers) exposed. Therefore, application of a barrier repair formula containing ceramides or cholesterol, or topical emollients, may be used in conjunction to relieve and protect the vulnerable skin. Since bacterial infections are a cause of concern, it is recommended that patients wash with antiseptic soap 2-3 times per week. Many patients find baths with salt or sodium bicarbonate, as well as bleach, beneficial as it helps to descale and prevent bacterial overgrowth. If symptoms are seen at birth, the newborn is recommended to be transferred to the neonatal ICU for proper monitoring and care.

TYPE OF DOCTOR AND DEPARTMENT: Dermatology SPECIALIST CAN DIAGNOSE THIS DISEASE. 

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