Holger Schäffler1, Theresia Blattmann2, Annette Findeisen3, Felix G Meinel4, Almut Meyer-Bahlburg5, Georg Lamprecht2, Lars Steinmüller-Magin6, Ralf Trauzeddel7, Steffen Emmert8. 1. Abteilung für Gastroenterologie und Endokrinologie, Klinik für Innere Medizin II, Universitätsklinikum Rostock, Ernst-Heydemann-Str. 6, 18057, Rostock, Deutschland. holger.schaeffler@med.uni-rostock.de. 2. Abteilung für Gastroenterologie und Endokrinologie, Klinik für Innere Medizin II, Universitätsklinikum Rostock, Ernst-Heydemann-Str. 6, 18057, Rostock, Deutschland. 3. Abteilung für Pädiatrische Gastroenterologie, Klinik für Pädiatrie, Universitätsklinikum Greifswald, Greifswald, Deutschland. 4. Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Rostock, Rostock, Deutschland. 5. Abteilung für Pädiatrische Rheumatologie, Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Greifswald, Greifswald, Deutschland. 6. Institut für Laboratoriumsmedizin und Humangenetik, Singen, Deutschland. 7. Abteilung für Pädiatrische Rheumatologie, Klinik für Pädiatrie, Helios Klinikum Berlin-Buch, Berlin, Deutschland. 8. Klinik und Poliklinik für Dermatologie und Venerologie, Universitätsklinikum Rostock, Rostock, Deutschland.
Abstract
BACKGROUND: The PAPA syndrome, an acronym for pyogenic sterile arthritis, pyoderma gangraenosum and acne, is an autosomal dominant hereditary disease which is caused by a mutation in the PSTPIP1 ("proline-serine-threonine phosphatase interacting protein 1") gene located on chromosome 15 and encodes the proline-serine-threonine phosphatase-interacting protein 1. An association with Crohn's disease (CD), autoimmune diseases of the liver and PAPA syndrome has not yet been reported in the literature. OBJECTIVE: To thoroughly investigate a family with three affected members (mother and 2 children) with newly diagnosed PAPA syndrome and intestinal and hepatobiliary symptoms. MATERIAL AND METHODS: We performed an in-depth phenotyping, dermatologic, radiologic, rheumatologic, gastroenterologic, histologic and genetic analysis in this family. RESULTS: 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 protein 2") gene could not be detected in any of the three persons affected. CONCLUSION: We extended the symptoms of PAPA syndrome to CD and autoimmune liver disease. These different disease entities might share a similar pathogenetic mechanism or even represent a new syndrome. This can be clarified in the future by screening patients with PAPA syndrome for intestinal and also hepatobiliary diseases.
BACKGROUND: The PAPA syndrome, an acronym for pyogenic sterile arthritis, pyoderma gangraenosum and acne, is an autosomal dominant hereditary disease which is caused by a mutation in the PSTPIP1 ("proline-serine-threonine phosphatase interacting protein 1") gene located on chromosome 15 and encodes the proline-serine-threonine phosphatase-interacting protein 1. An association with Crohn's disease (CD), autoimmune diseases of the liver and PAPA syndrome has not yet been reported in the literature. OBJECTIVE: To thoroughly investigate a family with three affected members (mother and 2 children) with newly diagnosed PAPA syndrome and intestinal and hepatobiliary symptoms. MATERIAL AND METHODS: We performed an in-depth phenotyping, dermatologic, radiologic, rheumatologic, gastroenterologic, histologic and genetic analysis in this family. RESULTS: 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 protein 2") gene could not be detected in any of the three persons affected. CONCLUSION: We extended the symptoms of PAPA syndrome to CD and autoimmune liver disease. These different disease entities might share a similar pathogenetic mechanism or even represent a new syndrome. This can be clarified in the future by screening patients with PAPA syndrome for intestinal and also hepatobiliary diseases.
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