Abstract
Annular epidermolytic ichthyosis (AEI; Online Mendelian Inheritance in Man [OMIM]# 607602) is a rare subtype of epidermolytic ichthyosis that is characterized by polycyclic, migratory erythematous and scaly plaques. It typically results from dominant mutations in the keratin 1 or keratin 10 genes. We present the case of a 5 year-old girl who developed intermittent eruptions of pink, round, scaly, migratory plaques with palmoplantar keratoderma and was originally diagnosed with erythrokeratodermia variabilis et progressiva (EKVP). Genetic analysis revealed a c.1436T>C transition mutation in the keratin 1 gene and histopathology showed epidermolysis and hyperkeratosis, confirming the diagnosis of AEI.
Keywords: Ichthyosis, Genetic diseases/mechanisms
CASE REPORT
A 5-year-old girl presented with pink, round, scaly plaques that migrated over her body and underwent spontaneous resolution and recurrence. She also experienced periodic peeling of the palms and soles and was predisposed to multiple skin infections.
At birth, she had thickened skin on her palms and soles, but was otherwise well. Within hours of birth, she developed bullae over her entire body that healed without evidence of scarring. She had no problems with hair, teeth, or nails, and development was normal. Her parents and one sibling were unaffected.
On physical examination, hyperkeratotic hyperpigmented and erythematous patches were appreciated on the chest (Figure 1a), and the popliteal and antecubital fossae. Well-defined thickened hyperkertotic scaly plaques were noted symmetrically bilaterally on the ankles and dorsal aspects of the feet, as well as the palmar and plantar surfaces consistent with a significant palmoplantar keratoderma (Figure 1b,c). No associated changes in hair, nails, or mucosae were appreciated. The initial clinical impression was that the subject had erythrokeratodermia variabilis et progressiva (EKVP), and a biopsy was performed from the left ventral wrist. Histopathologic findings included prominent orthohyperkeratosis overlying moderate psoriasiform hyperplasia, mild papillomatosis, and prominence of the granular layer. Cytoplasmic vacuolization and cytolysis were present within the granular and mid to upper spinous layers (Figure 2). Genetic analysis later revealed a 1436T-C transition mutation in the keratin 1 gene that predicted an amino acid change from isoleucine to threonine at codon 479, confirming a diagnosis of annular epidermolytic ichthyosis (AEI). Therapeutic trials demonstrated good response to emollients, tazarotene, and urea 40% with topical steroids employed for disease flares.
Figure 1: Clinical findings in AEI.
(a) Serpiginous, well-circumscribed erythematous scaly plaques over the torso. (b,c) Thick, yellow, waxy keratoderma on palms and soles.
Figure 2: Acanthosis, hyperkeratosis, and epidermolysis in AEI.
Lesional tissue shows prominent orthohyperkeratosis overlying moderate psoriasiform hyperplasia, mild papillomatosis and prominence of the granular layer. Cytoplasmic vacuolization and cytolysis (asterisk), is present within the granular and mid to upper spinous layers.
DISCUSSION
AEI is a rare phenotypic variant of epidermolytic ichthyosis (EI), an autosomal dominant disorder characterized by extensive erythroderma and blistering in early life. At birth, clinical features are similar to those of classical EI with erythroderma and blistering. However, in contrast to EI, an improvement of clinical symptoms occurs during early infancy after which patients develop outbursts of annular polycyclic, hyperkeratotic, and erythematous plaques on the trunk and extremities, along with palmoplantar keratoderma. [1]
There have been nine case reports in the English literature describing AEI. [2] The first molecular analyses performed in patients with AEI revealed novel mutations in the keratin 10 gene; subsequent molecular analyses in patients with similar clinical findings revealed mutations in the keratin 1 gene. [2] Palmoplantar keratoderma has been reported more commonly in keratin 1 mutations than keratin 10 mutations [3], consistent with this case.
The 1436T-C transition mutation in our patient resides in the highly conserved helix-termination motif of helix 2B of the keratin 1 gene. [4].
AEI can be confused with EKVP, an autosomal dominant skin disorder that is also characterized by erythrokeratoderma and migratory erythematous plaques. EKVP is typically associated with mutations in connexins 30.3, 31, and 43 (GBJ4, GJB3, and GJA1), but recent studies have suggested genetic heterogeneity. [5] Distinguishing features of EKVP include onset after infancy, absence of epidermal fragility, and histology without evidence of epidermolysis. In patients with suspected EKVP, AEI should be considered.
Footnotes
All the authors have read the manuscript and have approved this submission.
CONFLICTS OF INTEREST: No conflicts of interest
References
- 1.Sahn EE, Weimer CE Jr., and Garen PD, Annular epidermolytic ichthyosis: a unique phenotype. J Am Acad Dermatol, 1992. 27(2 Pt 2): p. 348–55. [DOI] [PubMed] [Google Scholar]
- 2.Jha A, et al. , Annular epidermolytic ichthyosis: a rare phenotypic variant of bullous congenital ichthyosiform erythroderma. Indian J Dermatol Venereol Leprol, 2015. 81(2): p. 194–7. [DOI] [PubMed] [Google Scholar]
- 3.DiGiovanna JJ and Bale SJ, Clinical heterogeneity in epidermolytic hyperkeratosis. Arch Dermatol, 1994. 130(8): p. 1026–35. [PubMed] [Google Scholar]
- 4.Sybert VP, et al. , Cyclic ichthyosis with epidermolytic hyperkeratosis: A phenotype conferred by mutations in the 2B domain of keratin K1. Am J Hum Genet, 1999. 64(3): p. 732–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Common JE, et al. , Clinical and genetic heterogeneity of erythrokeratoderma variabilis. J Invest Dermatol, 2005. 125(5): p. 920–7. [DOI] [PubMed] [Google Scholar]