Progressive Symmetric Erythrokeratoderma Having Overlapping Features With Erythrokeratoderma Variabilis and Lesional Hypertrichosis: Is Nomenclature “Erythrokeratoderma Variabilis Progressiva” More Appropriate?

Sir,

Erythrokeratodermas are rare genetic disorders of cornification with increased epidermal cell proliferation having phenotypic heterogeneity. They are currently classified into progressive symmetric erythrokeratoderma (PSEK) and erythrokeratoderma variabilis (EKV) with several overlapping features not only within the two (even among siblings), but also with other ichthyosiform dermatoses.[1,2] This lead some workers questioning existence of PSEK as a distinct entity or even to suggest alternative nomenclature “EKV progressiva.”[3,4]

This 8-year-old boy of nonconsanguineous parentage was brought with multiple skin lesions of progressive nature, which had started as a small erythematous plaque over buttocks within first perinatal week. The lesions evolved to multiple dusky red to brownish hyperkeratotic plaques with erythematous background and scant scaling, spreading symmetrically over elbows, knees, dorsal hands and feet within 2–3 months of age [Figure 1]. Some of the lesions also developed hair over them. The child occasionally felt mild pruritus and tightness from lesions, especially coinciding with exacerbations during winters. Mother also noticed mildly erythematous and scaly, ill-defined patches over cheeks, pinnae, and abdomen that used to disappear spontaneously within hours to days. All lesions tended to clear completely during summers leaving hyperpigmentation. He had no palmoplantar keratoderma, physical or mental retardation, neurological deficit, hair, nail or other systemic and laboratory abnormalities. His mother also had exactly similar skin problem ever since she remembers. Histology of a skin lesion was not pathognomic [Figure 2]. Genetic studies were not performed for want of in-house facility/affordability. Treatment with topical Daivobet^® (calcipotriol + betamethasone dipropionate) ointment softened his skin lesions.

Figure 1.

Well-defined hyperpigmented, hyperkeratotic plaques with geographical and polycyclic patterns present symmetrically over elbows, dorsal hands and feet, and knees in proband and his mother (a), right cheek and ear pinna (b), buttocks (c). Lesions over lower legs are extending over mid-calf regions and no erythematous plantar keratoderma is seen (d). Note scaling over pinna and ankles, and prominent hair growth over gluteal and leg lesions

Figure 2.

Histopathology of a skin lesion over left knee shows compact orthokeratotic hyperkeratosis, hypergranulosis, acanthosis, papillomatosis, broad rete ridges and mild lymphocytic infiltrate in the upper dermis (H and E, Panel a; × 10, Panel b; × 40)

Progressive symmetric erythrokeratoderma is inherited as autosomal dominant trait in 50% cases while others have spontaneous mutations (sporadic) or autosomal recessive transmission. However, the pathomechanism involved remains poorly understood as the disorder also shows genetic heterogeneity. A frameshift mutation in the loricrin (LOR) gene (loricrin is a major structural component of cross linked cell envelope of the epidermis) on chromosome 1q21 identified previously has been debated recently.[5,6] The mutations in connexin (CON) gene (connexin is a gap junction protein that maintains intracellular communication) have been identified more often in EKV than PSEK and include CON 31 (GJB3) and CON 30.3 (GJB4) mapped to chromosome 1p35.[7,8] However, CON mutations too have been absent in some cases.[9] Similarly, the candidate gene remains unidentified for a novel locus for PSEK mapped recently to chromosome 21q11.2-21q21.2.[9] As though genetic studies appear useful in diagnosis with little or doubtful certainty, no genetic mutation seems confirmatory for PSEK.

The lesions in PSEK are nonmigratory, well-demarcated, polycyclic, geographic shaped, erythematous, hyperkeratotic and mildly scaly plaques with striking symmetrical distribution over elbows, knees, dorsal hands and feet, buttocks and rarely face but typically spares the trunk. The plaques are slowly progressive and increase in number and size until puberty when they tend to stabilize or resolve spontaneously. Erythematous palmoplantar keratoderma occurs in 50% cases. Emotional stress, temperature extremes, friction and rarely sun exposure may exacerbate them. Only skin is affected and occasional associated neurological symptoms of delayed intellectual milestones, learning disability and convulsions appear fortuitous.[10] Contrarily, EKV presents at birth or 1^st year of life and involve abdomen and thorax, have migratory erythema, change shape and site over hours or days and often show seasonal variation. External mechanical pressure and temperature changes can induce new lesions. However, palmoplantar keratoderma and involvement of face, scalp and flexures is more characteristic of PSEK. Our patient had inherited the disorder in autosomal dominant fashion. While hypertrichosis over lesions appears unusual, his skin lesions were characteristic of PSEK with some clinical features overlapping with EKV. We tend to agree with Hirano and Harvey[11] that PSEK-diagnosed cases perhaps outgrow migratory erythema of EKV by the time diagnosis is made. As genetic studies may not always available in routine clinical settings, the diagnosis is mostly clinical and their differentiation remains difficult. This is true particularly in view of histopathologic features (hyperkeratosis, acanthosis, papillomatosis, variable perinuclear vacuolation of keratinocytes, sparse perivascular lymphocytic infiltrate in upper dermis) or electron microscopic features (granular cells containing swollen mitochondria, corneocytes with lipid-like vacuoles) being not pathognomic. In view of these diagnostic difficulties it has been even suggested that both PSEK and EKV perhaps represent varied presentations of a single disorder and should alternatively be termed as “EKV progressiva” instead of making a distinction between the two.[2,3,11] And we tend to agree.

Treatment is often difficult and benefit has been variable with systemic retinoids or topical emollients, keratolytics ointments (urea, salicylic acid, propylene glycol, lactic acid, alpha hydroxy acid), coal tar, retinoids, tacrolimus, and Vitamin D analogues with or without corticosteroid.[1,10,11,12,13,14] However, relapses are common after treatment withdrawal. Our patient benefited with topical Daivobet^® ointment.