Superficial epidermolytic ichthyosis: A rare disorder with the unusual absence of blistering

Superficial epidermolytic ichthyosis (SEI), formerly known as ichthyosis bullosa of Siemens (IBS), is an extremely rare keratinization disorder with superficial peeling, with an estimated prevalence of 1:500,000, caused by a variety of mutations in the keratin 2E gene. The clinical features include hyperkeratosis and blistering, but these are milder than in epidermolytic hyperkeratosis. The treatment is symptomatic and involves keratolytics and emollients. Herein, we report a case of SEI with the unusual absence of spontaneous blistering.

ABHD5 frameshift deletion in Golden Retrievers with ichthyosis

Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we investigated 14 Golden Retrievers with scales that were not homozygous for the mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis and mildly hyperplastic epidermis that led to the diagnosis of a non-epidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 non-affected family members delimited a critical interval of ∼12.7 Mb on chromosome 23. Whole-genome sequencing of an affected dog revealed a single protein-changing variant within this region that was not present in 795 control genomes. The identified variant is a 14 bp deletion in the ABHD5 gene (c.1006_1019del), leading to a frameshift and altering the last 14 codons p.(Asp336Serfs*6). The genotypes at this variant showed perfect co-segregation with the ichthyosis phenotype in a large family comprising 14 cases and 72 controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid storage disease with ichthyosis. Our data in dogs together with the knowledge on the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as candidate causative genetic variant for a new canine form of ichthyosis, which we propose to designate as Golden Retriever ichthyosis type 2 (ICH2).

Ichthyosis in Dogs—Congenital Dermatologic Disorder

The skin provides protective functions, such as thermoregulation, resorption, provision of immune responses, storage and sensory functions, which all play an important role in the internal stability of the organism. The skin has 3 major layers: the epidermis, the dermis and subcutis. The outermost protective layer of the epidermis, the stratum corneum, consists of 20 to 30 overlapping layers of anucleate cells, the corneocytes. Ichthyosis is an autosomal recessive congenital skin disease, in which the corneocytes form defects that appear like individual steps of the stratum corneum. Ichthyosis is characterized by excessive scaling over the entire body surface and is not curable; the symptoms can only be alleviated. Several genetic variants have been identified in specific dog breeds: PNPLA1 in the Golden Retrievers, SLC27A4 in the Great Danes, NIPAL4 in the American Bulldogs, TGM1 in the Jack Russel Terriers, ASPRV1 in the German Shepherds, which cause different forms of nonepidermolytic ichthyosis and KRT10 in the Norfolk Terriers, which causes epidermolytic ichthyosis. When classifying breeds of dogs predisposed to ichthyosis, it is necessary to determine the presence of defective genes in the genome of the individual animals involved in mating.

Recalibrated Scales: The Use of Low-dose Isotretinoin in a Case of Epidermolytic Ichthyosis-NPS1 in a Filipino Child

Epidermolytic Ichthyosis (EI) is a rare non-syndromic keratinopathic ichthyosis without definitive treatment. This is a case of EI in a 5-year-old Filipino female who presented with hyperkeratotic scales sparing the palms and soles. Histopathology revealed epidermolytic hyperkeratosis. A trial of treatment with isotretinoin 0.3 mg/kg/day, together with keratolytic agents, urea lotion and lactic acid lotion, resulted in a marked decrease in the thickness of the scales and odor. Interestingly, rebound effects were noted at 0.6 mg/kg/day. Taking into account that EI presents with more skin fragility compared to non-EHK ichthyosis, the authors surmise that there may be a smaller treatment window for patients with EI, which is notably lower than recommended for ichthyosis in general.

Ichthyoses—A Clinical and Pathological Spectrum from Heterogeneous Cornification Disorders to Inflammation

Ichthyoses are inborn keratinization disorders affecting the skin only (non-syndromic) or are associated with diseases of internal organs (syndromic). In newborns, they can be life-threatening. The identification of the gene defects resulted in reclassification and a better understanding of the pathophysiology. Histopathologic patterns include orthohyperkeratosis with a reduced or well-developed stratum granulosum, hyperkeratosis with ortho- and parakeratosis with preserved or prominent stratum granulosum, and epidermolytic ichthyosis. Another pattern features “perinuclear vacuoles and binucleated keratinocytes”, which is associated with keratin mutations. Some ichthyoses are histologically defined by psoriasis-like features, and distinct subtypes show follicular hyperkeratosis. In addition to histological and immunohistochemical methods, these patterns allow a better histopathologic diagnosis.