Loss-of-function (LOF) variants in inducible T cell costimulator (ICOS), NFKB1, NFKB2, CTLA-4, LRBA, adenosine deaminase 2 (ADA2), IL-21 receptor (IL21-R), as well as gain-of-function (GOF) variants in PI3KCD associated with immune dysregulation clinical phenotypes, including autoimmune cytopenia, inflammatory skin disease, arthritis, lymphoproliferation, and endocrinopathies, were found in patients with liver disease, supporting the hypothesis of the heterogeneity of organ-specific hepatic disorders in monogenic IEI disorders [67]. Here, ICOS is linked to inflammatory skin disease.