Loricrin downregulation and epithelial-related disorders: a systematic review

Loricrin downregulation has been associated with age-related changes as well as inherited and inflammatory skin diseases. We hypothesize that changes in loricrin could be more related to altered barrier function and consequently disorders that affect epithelial cells, such as psoriasis, atopic dermatitis (AD), erythrokeratoderma, loricrin keratoderma (LK) and periodontitis. The aim of this review is to summarize what is known about the association between loricrin downregulation and epithelial-related disorders (ERDs). A search was performed on the following databases: Medline, Cochrane Library, PubMed, EMBASE, Lilacs, Scopus and Google Scholar, resulting in 16 included articles. Loricrin keratoderma was the ERD most frequently associated with loricrin mutations (730insG, 709insC and 578insG; 5/7 cases - 71.44 %). Atopic dermatitis was the ERD most frequently associated with loricrin downregulation (2/7 cases - 28.6 %). Mutilating palmoplantar keratoderma, progressive symmetrical erythrokeratoderma and a new type of erythrokeratoderma were not associated with any mutations. At the gene level, periodontitis patients showed the highest decrease (-6.89x), followed by AD (-6.5x) and psoriasis patients (-0.5x). In summary, loricrin mutation and downregulation were associated with several ERDs. The diversity in disease presentation is likely related to whether there is a total loss of loricrin, mislocalization and/or if the mutant form of loricrin causes dysfunction of other proteins and/or changes in cornification.