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 1st 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.