PAPA syndrome with Crohn's disease and primary sclerosing cholangitis/autoimmune hepatitis overlap syndrome

Abstract

The PAPA syndrome, an acronym for pyogenic sterile arthritis, pyoderma gangraenosum and acne, is an autosomal dominant hereditary disease which is caused by amutation in the PSTPIP1 ("proline-serine-threonine phosphatase interacting protein1") gene located on chromosome15 and encodes the proline-serine-threonine phosphatase-interacting protein1. An association with Crohn's disease (CD), autoimmune diseases of the liver and PAPA syndrome has not yet been reported in the literature. To thoroughly investigate afamily with three affected members (mother and 2children) with newly diagnosed PAPA syndrome and intestinal and hepatobiliary symptoms. We performed an in-depth phenotyping, dermatologic, radiologic, rheumatologic, gastroenterologic, histologic and genetic analysis in this family. All three family members could be newly diagnosed as suffering from PAPA syndrome and carried the known disease-causing mutation c.688G > A (p.Ala230Thr) in the PSTPIP1 gene. The younger son suffered from CD in addition to PAPA syndrome. The mother additionally suffered from ulcerative colitis (UC) and an overlap syndrome between autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). A mutation in in the NOD2 ("nucleotide binding oligomerization domain containing protein2") gene could not be detected in any of the three persons affected. We extended the symptoms of PAPA syndrome to CD and autoimmune liver disease. These different disease entities might share asimilar pathogenetic mechanism or even represent anew syndrome. This can be clarified in the future by screening patients with PAPA syndrome for intestinal and also hepatobiliary diseases.