Progressive Symmetric Erythrokeratoderma with Unusual Associations

Abstract

Sir, Progressive Symmetric Erythrokeratoderma (PSEK) or Gottron's syndrome is a rare cornification disorder (OMIM# 602036) with less than 100 cases reported worldwide, amongst which less than 10 were from India.[1] Most reported cases were inherited as an autosomal-dominant trait. The exact genetic basis has not been elucidated yet, though mutations in gene coding for cornified cell envelope (loricrin) have been implicated in majority of cases. We report a case of Gottron's syndrome in an 18-year-old boy for its rare presentation and unusual associations of narcolepsy, mental retardation, and bilateral cortical cataract. An 18-year-old man presented with mildly itchy, red, raised scaly lesions over face, neck, trunk, and limbs since he was one year of age. He was born after an uncomplicated pregnancy to non-consanguineous parents. Lesions started from trunk and gradually increased in size and number to involve face and limbs till the time of puberty, after which the disease stabilized. The lesions were persistent and non-migratory. There was no seasonal variation. No other member of the family tree was involved. Cutaneous examination revealed well-demarcated, hyperkeratotic, and erythematous plaques, covered with fine branny scales, present symmetrically over the face, neck, chest (sparing peri-areolar region), axillae, flexor aspect of arms and forearms [Figure 1], dorsa of hands, back, groin, buttocks, medial aspect of thighs, popliteal fossae, and flexor aspects of legs. Palms and soles were spared. There were no nails, teeth, or hair abnormalities. Figure 1 Progressive symmetric erythrokeratoderma: Classical lesions involving trunk (sparing peri-areolar area) and flexor aspects of arms and fore-arms Skin biopsy from a representative lesion showed hyperkeratosis, papillomatosis, and acanthosis in epidermis with an unremarkable dermis [Figure 2]. Ophthalmological examination revealed presence of bilateral cortical cataract. Psychiatric evaluation elicited mild mental retardation and narcolepsy. Hearing was normal. Other laboratory parameters were normal. Figure 2 Photomicrograph showing hyperkeratosis, papillomatosis, and acanthosis (H and E-stained section, ×40) As per the above clinical presentation and histological findings, patient was diagnosed to have progressive symmetric erythrokeratoderma. He was started on conservative therapy including topical emollients, urea, and salicylic acid with some beneficial effects. The erythrokeratodermias are a group of rare hereditary cornification disorders characterized by varying degrees of erythema and hyperkeratosis. They have been divided into two major non-syndromic types and some syndromes such as KID (Keratitis Ichthyosis Deafness) and HID (Hystrix like ichthyosis-deafness) syndrome.[2] The two major non-syndromic types have been described as PSEK and erythrokeratoderma variabilis (EKV). PSEK is clinically characterized by well-demarcated erythematous and hyperkeratotic plaques that are distributed with an almost perfect symmetry on the head, extremities, and buttocks. Onset is usually in early childhood, which progresses over the next few years and then remains stable over time with morphology, color, and site remaining constant. Rarely, they may partially regress after puberty. Patients are usually mentally and physically unaffected. Differential diagnoses include EKV, psoriasis, and pityriasis rubra pilaris (PRP). Though majority of genetic analyzes in affected individuals and transgenic mice have found mutations in gene for loricrin as the underlying defect, a recent report demonstrated connexin mutations in a PSEK patient.[3 4] Loricrin is the major structural component of the cornified cell envelope while connexins are the protein units of gap junctions distributed in skin, nervous system, internal ear, cornea, and lens. Due to unavailability of genetic testing in our institute, exact mutation in our patient could not be elucidated. Associated neurological abnormalities have been described recently.[5] We hypothesize that unusual association of ocular and neurological complaints in our patient could be due to underlying mutation of gap junction protein, connexin.