Erythrokeratodermia variabilis
Published Web Location
https://doi.org/10.5070/D38vj8c18fMain Content
Erythrokeratodermia variabilis
Bruce E Strober MD PhD
Dermatology Online Journal 9(4): 5
From the Ronald O. Perlman Department of Dermatology, New York University
Abstract
A 47-year-old woman presented with both transient, figurate, erythematous patches and fixed, hyperkeratotic plaques on the upper extremities. Her cutaneous disease began in childhood and affects numerous siblings and her daughter. Her clinical presentation, history, and histopathologic analysis were consistent with erythrokeratodermia variabilis, which is a genodermatosis linked to mutations in the gene encoding for the gap-junction protein, connexin 31.
Clinical summary
History.—A 47-year-old woman presented with a 35-year history of a dermatosis involving the upper extremities. At age 12, the patient developed on her trunk and extremities numerous, erythematous, mildly pruritic or asymptomatic patches that rapidly changed in shape or regressed over the course of hours. Simultaneously, fixed, scaly, brown plaques appeared on both the trunk and extremities. The condition waxed and waned without complete resolution and became worse during hot weather. Neither topical nor systemic medications have been effective in controlling the disease. The condition has improved steadily over the past 20 years and currently affects the upper extremities.
The patient was born in the Dominican Republic and has 11 siblings, 9 of whom are affected with an identical cutaneous disease. She does not recall whether either of her parents were affected. Her daughter developed the same condition as a child as did several nieces and nephews.
Approximately 20 years ago, Hansen disease was treated for 8 years with dapsone. Currently, she takes no medications, has no known drug allergies, and otherwise is in good health, with neither clinical nor histopathologic evidence of Hansen disease.
Physical examination.—Multiple, irregularly-shaped, well-demarcated, erythematous macules and patches and hyperpigmented, hyperkeratotic plaques were located on the upper extremities.
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Laboratory data.—A complete blood count with differential analysis, serum electrolytes, and liver profile were normal.
Histopathology—There is slight epidermal hyperplasia with abrupt parakeratosis under basket-weave orthokeratosis. The granular layer is absent in the areas of parakeratosis. A sparse, superficial, perivascular lymphocytic infiltrate is also present.
Diagnosis.—Erythrokeratodermia variabilis.
Comment
Erythrokeratodermia variabilis, described by Mendes da Costa in 1925, is a rare autosomal dominant disorder that usually appears within the first year of life but may arise later in childhood. Children display sharply demarcated, yet migratory, figurate, erythematous patches that appear, enlarge, or regress over minutes to hours. Concomitantly, there are persistent, well-demarcated, brown, hyperkeratotic plaques, which are scattered on the face, buttocks, trunk, and extremities. In some instances, the hyperkeratosis may be generalized. Approximately 50 percent of patients display a palmoplantar keratoderma associated with peeling. The transient erythematous patches develop independently of the hyperkeratotic plaques, and lesions may either sting or be asymptomatic. Both types of lesions may be precipitated by either trauma or changes in temperature. The disease displays marked intra- and interfamilial variability and tends to worsen until puberty and eventually enters a stable, chronic course. The overall health of the patient is unaffected with a normal life-span.[1]
Recent genetic linkage studies have established that mutations in the gene GJB3 encoding the gap-junction protein, connexin 31, are responsible for erythrokeratodermia variabilis.[2] A variety of different mutations within this gene account for the disease's clinical heterogeneity, with unique mutations found in different families.[3, 4] Specific mutations affecting connexin 31 may lead to either sensorineural deafness or peripheral neuropathy in the absence of skin manifestations.
Treatment with systemic retinoids such as acitretin can be very effective but is limited by long-term toxicities that are associated with the need for chronic therapy. Nevertheless, the minimum effective dose is often low. Agents such as urea, salicylic acid, or lactic acid are effective therapy for the hyperkeratotic plaques. Stinging and pruritus might be ameliorated with mildly sedating antihistamines.[1]
References
1. Hendrix JD Jr, Greer KE. Erythrokeratodermia variabilis present at birth: case report and review of the literature. Pediatr Dermatol 1995;12:351.2. Richard G, et al. Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis. Nature Genet 1998;20:366.
3. Richard G, et al. Clinical heterogeneity in EKV. J Invest Dermatol 1998;110:616.
4. Richard G, et al. The spectrum of mutations in erythrokeratodermias-novel and de novo mutations in GJB3. Hum Genet 2000;106:321.
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