Erythrokeratodermia Variabilis with Hypertrichosis on the Lesions: A Case Report and Literature Review
Erythrokeratodermia variabilis (EKV) is a rare genodermatosis characterized by transient migratory erythematous patches and fixed hyperkeratotic plaques, predominantly affecting the distal extremities, trunk, and buttocks. While hyperkeratosis and erythema are hallmarks of the condition, the presence of hypertrichosis (excessive hair growth) on lesions is an exceedingly rare feature. This article presents a case of EKV with hypertrichosis and explores the clinical, histopathological, and molecular insights into this unusual manifestation.
Clinical Presentation
A 26-year-old Chinese male presented with widespread reddish-brown patches and hyperkeratotic plaques that first appeared at 5 months of age. The lesions exhibited a dynamic course, regressing spontaneously and reappearing in different areas over time. Notably, the patient reported worsening of lesions during colder temperatures, particularly in winter, with marked improvement during summer. Hypertrichosis was observed exclusively on hyperkeratotic plaques located on the arms and waist [Figure 1A–C], and this abnormal hair growth nearly disappeared in warmer months without therapeutic intervention. The patient denied using topical steroids or other medications that could induce hypertrichosis.
Physical examination revealed symmetrically distributed, sharply demarcated geographic or figurate-shaped reddish-brown patches and hyperpigmented hyperkeratotic plaques on the back, extremities, and waist. Palmoplantar keratoderma was also present, but no abnormalities were noted in the mucous membranes, nails, or teeth. Neurological assessments were unremarkable.
Histopathological and Laboratory Findings
A skin biopsy of lesional tissue demonstrated hyperkeratosis, moderate papillomatosis, and acanthosis in the epidermis [Figure 1D, 1E]. These findings are consistent with the histopathological profile of EKV. Routine laboratory investigations, including complete blood count, urinalysis, liver and kidney function tests, and sex hormone levels, were within normal limits. Adrenal gland ultrasound revealed no structural abnormalities. Genetic testing for mutations in GJB3 or GJB4—genes encoding connexin 31 and connexin 30.3, respectively—was not performed due to facility limitations and financial constraints.
Diagnosis and Management
The diagnosis of EKV was established based on clinical features, including migratory erythema, fixed hyperkeratosis, palmoplantar keratoderma, and temperature-dependent variability in lesion severity. The absence of similar symptoms in family members suggested a de novo mutation, though inheritance patterns (autosomal dominant or recessive) remain unclear without genetic confirmation.
Treatment included emollients to alleviate dryness and oral retinoids (specific type and dosage not detailed) combined with vitamin A supplementation. These interventions aimed to reduce hyperkeratosis and modulate epidermal differentiation. The patient reported seasonal improvement in lesions and associated hypertrichosis during summer, highlighting the influence of environmental factors on disease activity.
Discussion
Genetic Basis of EKV
EKV is linked to mutations in gap junction proteins, primarily GJB3 and GJB4, which disrupt intercellular communication in the epidermis. Connexins 31 and 30.3 are critical for maintaining epidermal homeostasis, and their dysfunction leads to impaired keratinocyte differentiation and aberrant cell signaling. While most EKV cases are familial, sporadic cases, like this one, suggest novel mutations or incomplete penetrance.
Hypertrichosis in EKV: Mechanisms and Implications
Hypertrichosis localized to hyperkeratotic plaques is a rare phenomenon in EKV. A similar finding was reported by Gupta et al. in a case of progressive symmetric erythrokeratodermia (PSEK), a distinct subtype of erythrokeratodermia. The absence of steroid use in both cases rules out iatrogenic causes. Shimizu et al. proposed that connexin expression patterns influence hair follicle morphogenesis, implying that mutations in GJB3 or GJB4 may alter signaling pathways in hair follicle stem cells. Increased hair density on plaques could reflect compensatory follicular activation secondary to chronic inflammation or epidermal remodeling.
Temperature-Dependent Variability
The patient’s lesions worsened in cold temperatures, a phenomenon documented in EKV. Cold exposure may exacerbate connexin dysfunction, leading to disrupted epidermal barrier function and increased keratinocyte proliferation. Seasonal improvement in hypertrichosis further underscores the role of environmental factors in modulating disease expression.
Differential Diagnosis and Clinical Overlaps
EKV must be distinguished from PSEK, which presents with non-migratory, symmetric hyperkeratotic plaques without erythema. However, overlaps exist, as both conditions may involve palmoplantar keratoderma and hypertrichosis. The dynamic nature of lesions in EKV, combined with genetic testing, aids differentiation.
Conclusion
This case highlights an unusual presentation of EKV with localized hypertrichosis, expanding the clinical spectrum of the disease. The coexistence of hypertrichosis and temperature-dependent lesion variability suggests a complex interplay between genetic mutations, environmental triggers, and follicular signaling pathways. Further studies are needed to elucidate the molecular mechanisms linking connexin mutations to hair follicle abnormalities.
doi.org/10.1097/CM9.0000000000000633
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