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Progressive and symmetric erythrokeratoderma

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Progressive and symmetric erythrokeratoderma
David H Chu MD PhD, and Martha P Arroyo MD PhD
Dermatology Online Journal 9(4): 21

From the Ronald O. Perelman Department of Dermatology, New York University


A case of progressive and symmetric erythrokeratoderma in a 9-year-old boy is presented. The evidence for loricrin as a candidate gene for this disorder as well as the clinical features of this disease are reviewed.

Clinical summary

History.—A 9-year-old boy presented with a 7-year history of a dermatois involving the head, neck, trunk, and arms. The patient presented with progressive pigmentation over the face, neck, arms, and trunk that had been present since age 2. There was no associated migratory erythema. There were no hearing abnormalities. He is otherwise in good health and does not take any medications. His family is originally from the Virgin Islands, and his grandmother, mother, sister, and two of four brothers have similar lesions on their skin. He is in fourth grade, with normal developmental progression.

Physical examination.—Multiple, hyperpigmented, hyperkeratotic plaques in geographic shapes, were located symmetrically on the face, neck, chest, back, abdomen, and arms, including the axillae and antecubital fossae. There were no nail changes. The digits, palms, and soles were normal.

Figure 1 Figure 2

Laboratory data.—None

Histopathology.—There is papillated epidermal hyperplasia with hypergranulosis, parakeratosis, and compact orthokeratosis. In some foci, there is a layer of parakeratosis between the granular layer and the overlying orthokeratotic cornified layer.

Diagnosis.—Progressive and symmetric erythrokeratoderma.


The erythrokeratodermas are a heterogeneous collection of disorders that feature widespread erythematous plaques, which are either migratory or stationary. Some forms may be associated with palmoplantar keratoderma and neurologic defects. One rare type of erythrokeratoderma is progressive and symmetric erythrokeratoderma, which is inherited in an autosomal dominant fashion. This disease is characterized by nonmigratory, hyperpigmented, symmetric plaques that are usually distributed on the extremities, buttocks, and sometimes the face. This entity was first described by Darier in 1911; since that time only about thirty cases have appeared in the literature [1].

The use of oral retinoids to treat this disorder has been reported to be effective. Topical keratolytics, retinoids, and glucocorticoids have also been used with more variable effects [2].

Genetic analyses of large affected families, in conjunction with studies in transgenic mice, have suggested the loricrin gene is associated with the features of this disease. Loricrin is the major structural component of the cornified cell envelope that is formed beneath the plasma membrane of stratified squamous epithelial cells during terminal differentiation. Mutations in the loricrin gene also have been identified in Vohwinkel syndrome.

In one Japanese family, a single frame-shift mutation within the loricrin gene was identified in a patient with features of both progressive and symmetric erythrokeratoderma and Vohwinkel syndrome [1]. The mutations in loricrin for the two disorders map to similar regions of the gene, and both result in truncated gene products resulting from the introduction of a premature stop codon. Transgenic mice expressing such a mutant form of the loricrin gene develop generalized hyperkeratosis of the skin, constriction of the tail (similar to pseudoainhum), and thick footpads [3].


1. Ishida-Yamamoto A, et al. The molecular pathology of progressive symmetric erythrokeratoderma: A frameshift mutation in the loricrin gene and perturbations in the cornified cell envelope. Am J Human Genet 1997;61:581.

2. Gray LC, et al. Progressive symmetric erythrokeratodermia. J Am Acad Dermatol 1996;34:858.

3. Suga Y, et al. Transgenic mice expressing a mutant form of loricrin reveal the molecular basis of the skin diseases, Vohwinkel syndrome and progressive symmetric erythokeratoderma. J Cell Biol 2000;151:401.

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