NIPAL4 deletion identified in an American Bully with autosomal recessive congenital ichthyosis and response to topical therapy

Abstract

Ichthyoses represent a heterogeneous group of hereditary cornification disorders characterized by generalized scaling of the skin. An autosomal recessive congenital ichthyosis ( ARCI ) has been described in American Bulldogs and is caused by a variant in the NIPAL 4 gene encoding for the ICHTHYIN protein. So far, this variant has not been described in other breeds. A 1.5‐year‐old female pedigreed American Bully was referred for generalized scaling and bad coat quality since adoption at 8 weeks of age. Clinical examination, cytological and histopathological examination, and DNA testing were performed. Clinical examination revealed a generalized scaling; cytological evaluation using impression with acetate tapes showed a secondary Malassezia dermatitis. Histopathological examination revealed a moderate to marked, diffuse, compact orthokeratotic hyperkeratosis with the formation of large scales. Few Malassezia were observed in the stratum corneum associated with minimal mixed perivascular inflammation and moderate epidermal hyperplasia. DNA testing of the dog revealed that he carries two defective alleles of the NIPAL 4 gene previously described in the American Bulldog. We performed a commercially available breed detection test which, although not specifically testing for “American Bully” signatures, revealed a high probability of American Bulldog DNA signature within the past three generations. Topical treatment using a combination of keratolytic and keratomodulator shampoo, emollient and moisturizers spray and antimicrobial wipes achieved a marked clinical improvement after only 1 month. Continuous topical treatment was necessary to maintain clinical improvement. To the authors’ knowledge, this is the first description of the deleterious NIPAL 4 variant in an American Bully as well as the first description of clinical management and follow‐up of ARCI in this breed.

Epidermal barrier dysregulation in atopic skin predisposes for excessive growth of the allergy-associated yeastMalassezia

“…In further support of the causal relationship between loss of barrier integrity and enhanced fungal control, a case report found topical treatment improving the skin barrier function to coincide with a reduction in the fungal load. 96 No consistent data exist for differential Malassezia colonization levels on human skin. 13,97 Amplicon and metagenomic sequencing studies generally report relative abundances of individual genera or species.…”

Ichthyosis and hereditary cornification disorders in dogs

“…Some success with topical treatment has been reported for ARCI in the American bulldog and golden retriever. 53,54 For the American bulldog, the author suggests addressing the Malassezia proliferation with topical treatment with or without systemic azoles. Continued research into pathogenesis-based therapy offers hope for improved outcomes.…”

Heterozygous ASPRV1 frameshift variant in a Pembroke Welsh Corgi with ichthyosis

“…Further subdivision into epidermolytic and non‐epidermolytic ichthyoses is based on the presence or absence of light microscopic findings of vacuoles and lysis of keratinocytes (Mauldin, 2013). In dogs, several breed‐specific ichthyoses have been described, and, to date, causal variants in nine different genes have been identified (Affolter et al., 2022; Bauer et al., 2017; Briand et al., 2019; Casal et al., 2017; Credille et al., 2005, 2009; Grall et al., 2012; Kiener et al., 2022; Kiener, Åhman, et al., 2023; Kiener, Castilla, et al., 2023; Metzger et al., 2015). These genes are mainly involved in the biosynthesis, metabolism, and transport of lipids required for skin barrier function or the intracellular protein network responsible for the integrity of skin structure (Gutiérrez‐Cerrajero et al., 2023).…”