June 2002


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 DIAGNOSIS: Erythrokeratoderma variabilis (a.k.a. Mendes da Costa's syndrome)

Histopathology: Revealed hyperkeratosis, irregular acanthosis, papillomatosis and a mild superficial perivascular infiltrate of lymphocytes.

Discussion: Erythrokeratoderma variabilis (EKV) is a rare, autosomal dominant disease that was first described by Mendes da Costa in 1925. Clinically, this disease possesses two manifestations. Initially patients develop the erythematous component, which consists of bright red to brownish well-demarcated patches. These lesions frequently vary in severity and shape, and the distribution is known to change within minutes to days. Aggravating factors for this component include wind, cold, heat, or emotional stress. The second component is described as yellow-brown hyperkeratotic plaques with greasy scale that develop on normal or previously erythematous skin. The distribution is usually symmetrical, with a predilection for the extremities, buttocks, and face. Palmoplantar keratoderma may also be seen in some patients.

In most patients the first lesions occur between several months of life and 3 years, but up to 30% may have lesions present at birth. The vast majority of patients with erythrokeratoderma are otherwise healthy, but there have been reports of associated deafness, peripheral neuropathy, decreased tendon reflexes, nystagmus, dysarthria, cerebellar ataxia, and onychodystrophy.

The inheritance pattern of EKV is autosomal dominant with considerable variability of expression among family members. In recent years, investigation into the molecular biology of this disorder has yielded localization to chromosome 1p34-1p35, a region that has been found to house a cluster of connexin genes. There has also been further localization to mutations in gap junction protein beta-3, that encodes Connexin 31 on chromosome 1. Recently, a possible autosomal recessive variant of erythrokeratoderma variabilis has been reported.

The histologic features of EKV are generally nonspecific and include orthohyperkeratosis and acanthosis, with a normal granular layer, as well as dermal papillomatosis. Examination with electron microscopy has yielded inconsistent results, although several studies have reported a decreased number of keratinosomes in the stratum granulosum.

Erythrokeratoderma is a chronic, life-long disease, but treatment with topical and oral retinoids has achieved good therapeutic results in many patients. Etretinate 0.5-1.0 mg/kg/day is often effective, although symptoms rapidly recur with the discontinuation of therapy.

 

References

1. Armstrong DKB, Hutchinson TH, Walsh MY, McMillan JC. Autosomal recessive inheritance of erythrokeratoderma variabilis. Pediatric Dermatology 1997; 14(5): 355-358.

2. Brown J, Kierland RR. Erythrokeratodermia variabilis. Archives of Dermatology 1966; 93: 194-201.

3. Freedenberg IM, Eisen AZ, Wolff K, Austen ICF, Goldsmith LA, Katz SI, Fitzpatrick TB. Dermatology in General Medicine. McGraw-Hill, 1999, pp. 605-606.

4. Knipe RC, Flowers FP, Johnson FR, DeBusk FL, Ramos-Caro FA. Erythrokeratoderma variabilis: case report and review of the literature. Pediatric Dermatology 1995; 12(1): 21-23.

5. Rook A, Wilkinson D, Ebling F, Champion R, Burton J. Textbook of Dermatology. London, Blackwell Scientific, 1998, pp. 1533-1534.

6. Van der Wateren AR, Cormane RH. Oral retinoic acid as therapy for erythrokeratoderma variabilis. British Journal of Dermatology 1977; 97: 83-85.

7. Wilgoss A, Leigh I, Barnes M, Dopping-Hepenstal P, Eady RAJ, Walter J, Kennedy C, Kelsell D. Identification of a novel mutation R42P in the gap junction protein b-3 associated with autosomal dominant erythrokeratoderma variabilis. Journal of Investigative Dermatology 1999; 113(6): 1119-1122.

My thanks to Drs. Abena Ofari, Saadia Raza and Pui Kwok for their assistance in the preparation of this case.