What is Erythrokeratodermia Variabilis?
Erythrokeratodermia refers to a collection of inherited disorders typified by distinctive red skin areas and hard, rough plaques on the skin. The main cause for most cases of this condition, specifically Erythrokeratodermia variabilis (EKV), has been found to be mutations in the connexin genes. In this disorder, individuals usually see moving red patches along with hard plaques over the skin that could either be localized (restricted to a specific region) or generalized (over a wide area).
Erythrokeratodermia variabilis was also once called Mendes da Costa syndrome. Later on, symptoms of another condition, Progressive Symmetrical Erythrokeratodermia (PSEK) which causes red patches to progressively become more prominent, were observed within a family exhibiting EKV symptoms. This led medical professionals to believe that EKV and PSEK were actually different manifestations of the same inherited condition. Moreover, when the same gene modification was discovered in patients with both EKV and PSEK, some medical writers then suggested the term Erythrokeratodermia Variabilis Progressiva (EKVP) to cover the range of symptoms shown in both EKV and PSEK.
What Causes Erythrokeratodermia Variabilis?
Erythrokeratodermia variabilis (EKV) shows a pattern known as ‘dominant inheritance’, where a child can inherit the condition even if only one parent carries the gene for it. Genes containing mutations linked to EKV are typically those encoding for either the Cx31 (GJB3) or Cx30.3 (GJB4), and less frequently, the Cx43 (GJA1).
These coded proteins, namely connexin 31, connexin 30.3, and connexin 43, are part of the ‘gap junction’ proteins. Gap junction proteins belong to a large family of proteins that form communication channels between our cells. They help cells exchange substances like small molecules and ions, which are crucial for the cell’s functions. The human body contains at least 20 different types of connexin proteins, which are present in various cell types and tissues.
Connexin 31 is found in the skin, peripheral nerves (nerves outside the brain and spinal cord), and in the cochlea (the part of the inner ear involved in hearing). Connexin 30.3 is seen in the skin, kidneys and in blastocysts (early-stage embryos) before they implant in the womb. Connexin 43 is present almost everywhere in the body.
Mutations linked to EKV mostly result in altered amino acids, the building blocks of proteins. These altered proteins affect the skin’s normal development process.
There have been rare cases of EKV inherited in a ‘recessive’ manner, caused by both copies of the GJB3 gene being mutated. These patients also exhibit EKV, although it is primarily due to mutations in connexin proteins.
In one study investigating these gene mutations in several patients and families with EKV, it was found that mutations in the Cx31 or Cx30.3 were present in only three subjects. The study found no mutations in other genes associated with skin conditions. This suggests that EKV is a varied condition, with patients diagnosed with this disease carrying different mutations in Cx31 or Cx30.3.
Risk Factors and Frequency for Erythrokeratodermia Variabilis
Erythrokeratodermia variabilis, also known simply as EKV, is a rare skin disorder. It typically appears during the first year of a person’s life, although it has sometimes been seen at birth. However, it’s less common, but still possible, for EKV to appear later in childhood or even in early adulthood. EKV is usually inherited from parents in a manner called autosomal dominant, meaning you only need to get the abnormal gene from one parent in order to inherit the disease.
- Lesions from the EKV typically show in the first year of life, in some instances right from birth.
- It is less often that EKV appears later in childhood or in early adulthood.
- EKV is a rare skin disorder that is primarily passed down through genes, in a pattern known as autosomal dominant.
- Although there can be a fair amount of variability, the disease almost always shows up in people who have the gene (a concept known as “penetrance”).
- There are some documented cases where EKV has been inherited in an autosomal recessive manner, meaning a person needs to have two copies of the abnormal gene to have the disorder.
Signs and Symptoms of Erythrokeratodermia Variabilis
Erythrokeratodermia variabilis (EKV) is a skin condition that is primarily distinguished by two types of skin changes:
- Transient (temporary) red patches
- Long-lasting rough-textured plaques
In most cases, one of these features is more evident, and sometimes one might not even be present. Initially, the disorder presents as migratory red areas, well-defined with a map-like appearance. These areas can merge to form large patches of various shapes, sizes, and locations. In some cases, each patch may be surrounded by a lighter ring. Factors such as emotional stress, variation in temperature, friction, and sun exposure may enhance these red patches.
Along with or following the red patches, stable rough-textured plaques can develop, appearing as well-defined, yellow to brown thickened areas. These areas also take on a geographic shape and sometimes become very thick and dark. Additionally, excessive hair growth, flaking skin like a collar, and scales resembling psoriasis may be present.
There are also some unusual signs of the disease that are considered to be variations of EKV. These include skin changes similar to erythema gyratum repens, which is associated with a mutation in the Cx30.3 gene. Erythrokeratodermia en cocarde, characterized by circular or spiral red patches, is linked to mutations in GJB4. Other cases may present with skin changes resembling erythema annulare centrifugum.
The affected areas usually include the outside parts of limbs, buttocks, and sides of the torso, often equally on both sides of the body. In half the patients, the skin thickening extends to the palms of the hands and soles of the feet. The skin on the face, scalp, and skin folds is typically unaffected, but any part of the skin can be involved. The hair, teeth, and nails are not affected by this disease and grow normally.
Some discomfort may be caused by a burning sensation in the red skin patches. While EKV generally becomes stable after puberty, it lasts lifelong. However, the skin may improve over time, and periods of skin clearing are possible.
Testing for Erythrokeratodermia Variabilis
Erythrokeratodermia variabilis is primarily a skin condition. However, it’s necessary to check for signs of other related health issues to rule out different types of erythrokeratodermia that might look like Erythrokeratodermia variabilis. One such condition is KID syndrome, which can create skin lesions similar to those of Erythrokeratodermia variabilis. In KID syndrome, individuals may experience inflammation of the cornea (‘keratitis’), hearing loss, hair loss (‘alopecia’), and a higher risk of infection. There have also been instances of reported neurological symptoms, such as coordination problems (‘ataxia’) and damage to the peripheral nerves (‘peripheral neuropathy’), that are associated with skin lesions similar to those seen in Erythrokeratodermia variabilis.
Treatment Options for Erythrokeratodermia Variabilis
The treatment for this skin condition, involving thickening of outer skin layer (known as hyperkeratosis), largely depends on its severity and extent. In simpler cases, specialists recommend using moisturizers, creams including retinoids (vitamin A-based substances), or keratolytic (skin-peeling) treatments that are applied directly onto the skin.
In more severe or extensive cases, you may be prescribed retinoids in pill form. These pills are often effective in improving, and sometimes completely clearing up, the thickening of the skin. However, they may not be as effective for red skin patches, which often cause individuals cosmetic concerns. For such cases, you might consider using makeup or other methods to improve appearances.
It’s also advisable to avoid sudden temperature changes, rubbing, and situations that could irritate the skin; these can make the condition worse.
It’s exciting to mention that new treatments are currently being studied. They involve targeting specific types of proteins within skin cells, and they may become a treatment option in the future. However, further research is needed to understand their potential benefits and risks.
What else can Erythrokeratodermia Variabilis be?
In simpler terms, the condition called erythrokeratodermia variabilis can look very similar to urticaria (also known as hives) in its early stages. However, you can tell them apart because erythrokeratodermia variabilis lasts longer and may occasionally show signs of scaling skin. In cases where the skin lesions become fixed plaques, the condition is distinguished from psoriasis by carrying out a microscopic study of the tissue.
When it comes to a condition like Netherton syndrome, the skin displays migratory and winding red patches with double-edged scaly borders, which is typical. Patients usually also show other signs such as abnormal hair shafts, eczema-like lesions, and itching. This condition and other rare types of scaly skin conditions, like erythrokeratolysis hiemalis, epidermolytic ichthyosis due to KRT1 and KRT10 gene mutations, and Greither syndrome, are among the important considerations when figuring out the correct diagnosis.
What to expect with Erythrokeratodermia Variabilis
Erythrokeratodermia variabilis is a condition that affects the skin’s appearance but does not have any serious health implications. It also does not affect any other parts of the body besides the skin.
