Erythrokeratoderma Variabilis - Causes, Symptoms, and Management

Introduction

Erythrokeratoderma, also known as erythrokeratodermia, is a rare group of keratinization disorders. The various strata of the epidermis, the skin's top layer, are formed through this process. Well-defined plaques of erythema (redness) and hyperkeratosis (abnormal thickening of the skin) are features of the various erythrokeratodermas. Erythrokeratoderma variabilis is one of the specific types of erythrokeratoderma.

What Is Erythrokeratoderma Variabilis?

• Erythrokeratodermia variabilis (EKV) is a skin condition that either manifests at birth or infancy. The illness is distinguished by two main characteristics, even though its signs and symptoms differ.

• The first essential characteristic of EKVP is erythematous regions, which are areas of reddened skin. In contrast to the hyperkeratosis that characterizes this illness, the erythematous parts are typically transitory; they appear and go. They can appear anywhere on the body and differ in size, shape, and location. Children are more likely to experience this redness, which trauma, discomfort, unexpected temperature changes, or emotional stress can bring on. It typically disappears in a few hours to days.

• The second is hyperkeratosis, characterized by rough, thick skin. These patches, which are often reddish-brown, might appear anywhere on the body or only in a limited area. They frequently remain stationary, rarely spread or disappear. The patches, however, can come in different sizes and shapes and, in some affected individuals, enlarge with time. The locations of the hyperkeratosis are typically symmetric, meaning they are present on both sides of the body at the same places.

What Are the Other Names of Erythrokeratoderma Variabilis?

The other names are as follows:

• Erythrokeratodermia variabilis of Mendes da Costa

• Erythrokeratodermia, progressive symmetric

• Progressive symmetrical erythrokeratoderma of Gottron

How Is It Inherited?

The most frequent inheritance type for EKV is autosomal dominant, which means that only one mutated copy of a gene needs to exist in a cell for the illness to manifest. Therefore, affected individuals often receive the mutation from one affected parent. In other circumstances, people without a family history of the condition experience the disorder due to new gene changes.

What Are the Causes of Erythrokeratoderma Variabilis?

• Mutations in various genes, including GJB3, GJB4, and GJA1, can lead to EKV.

• Connexins 31, 30.3, and 43 are made according to the instructions provided by these three genes, respectively.

• These proteins are a subset of the connexin family, a collection of proteins that organize into channels on the surface of cells termed gap junctions. To control the flow of nutrition, charged elements (ions), and other biochemical compounds from one cell to another, gap junctions open and close. They are necessary for direct interaction between cells next to one another.

• Connexins 31, 30.3, and 43 are used to create gap junctions, which are present in various tissues, including the epidermis (the outermost layer of the skin).

• The EKV-causing GJB3, GJB4, and GJA1 gene mutations modify the structure or position of the connexins generated by these genes.

• Some GJB3 or GJB4 gene mutations result in the development of aberrant connexins, which can accumulate in the endoplasmic reticulum (ER), a cell structure that can cause ER stress. Researchers believe ER stress harms and causes the early death of epidermal cells. In addition, the flow of molecules through gap junctions is altered by further GJB3 or GJB4 gene mutations, which may also cause premature death of epidermal cells. Unknown mechanisms underlie how hyperkeratosis and erythematous regions are caused by epidermal damage and cell death.

• Connexin 43 protein produced due to GJA1 gene mutations is aberrant and unable to form gap junctions at the cell surface. Instead, after being created, the unusual protein is contained in the Golgi apparatus, a part of the cell. Therefore, it is unknown how changes to the epidermis's gap junction structure brought on by a lack of connexin 43 contribute to the skin abnormalities associated with EKVP.

• Some EKVP patients lack a recognized mutation in one of the three connexin genes mentioned above. In addition, a tiny percentage of affected individuals have been found to have mutations in at least one non-connexin gene. According to studies, EKVP may also result from alterations in unidentified genes.

What Are the Symptoms of Erythrokeratoderma Variabilis?

• The first presenting symptom is red spots with migratory patterns.

• These lesions typically have a circular or map-like appearance and are well-defined.

• Large erythematous patches that fluctuate in size, shape, number, and location can form over minutes, hours, or, more frequently, days.

• More pronounced erythematous lesions may be triggered by emotional stress, environmental heat or cold, mechanical friction, and sun exposure.

• In parallel with or after the emergence of migratory red spots, stable hyperkeratotic plaques with scaling of the skin form.

• These lesions are typically well-defined, from yellow to brown, and frequently have a red base.

• They are morphologically geographical plaques that have thickened.

• The condition does not affect the growth and development of the skin's appendages, such as hair, teeth, and nails.

• Some people may experience discomfort from symptoms, including a burning feeling in erythematous lesions.

• After puberty, EKV usually stabilizes.

• Although the ailment lasts a lifetime, it is still possible for the skin to occasionally clear up and improve over time.

How Is Erythrokeratoderma Variabilis Diagnosed?

• Erythrokeratodermia variabilis primarily affects the skin.

• It is diagnosed mainly by physical examination of the patient.

• The systemic symptoms are evaluated to rule out additional erythrokeratodermia subtypes that can clinically resemble EKV. These include the erythrokeratodermia-like lesions of the KID syndrome. In addition, alopecia, hearing loss, keratitis, and an elevated risk of infection are all symptoms of this illness.

What Are the Differential Diagnosis?

It includes the following.

• Urticaria: A skin rash that appears as an itchy red rash or lumps known as weals.

• Psoriasis: A skin condition that typically affects the knees, elbows, trunk, and scalp, resulting in a rash with itchy, scaly spots.

• Greither Syndrome: It is characterized by reddish-yellow, mild to severe hyperkeratosis of the palms and soles, spreading to the backs of the hands, feet, and wrists, as well as affecting the skin above the Achilles tendon.

How Is Erythrokeratoderma Variabilis Treated?

• Treatment is almost symptomatic, depending on the degree and severity of the hyperkeratosis.

• Emollients, topical retinoids, and keratolytics are the topical treatments recommended for mild forms.

• In some severe and widespread conditions, systemic retinoids administered at levels significantly lower than those needed for other keratinization disorders may be effective.

• These medications frequently result in a notable improvement and, in rare instances, a complete disappearance of the hyperkeratosis.

• However, retinoids exhibit a less effective response when treating erythematous lesions.

• Innovative medicines that directly inhibit connexin hemichannels and gap junctions are currently being researched and possibly made available.

Conclusion

Erythrokeratoderma variabilis is a rare skin condition with erythematous patches and skin thickening. Treatment is to reduce the symptoms of the disorder. When experiencing any sign of this disorder, consult a physician to rule out other diseases that resemble this condition.