{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:40:28Z","timestamp":1787020828736,"version":"build-2736575974"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011176","name":"Peking Union Medical College","doi-asserted-by":"publisher","award":["10023201700105"],"award-info":[{"award-number":["10023201700105"]}],"id":[{"id":"10.13039\/501100011176","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to\n                      <jats:italic>HPGD<\/jats:italic>\n                      and\n                      <jats:italic>SLCO2A1<\/jats:italic>\n                      gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The two patients were both males with complete-form PHO for more than 10\u2009years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of\n                      <jats:italic>SLCO2A1<\/jats:italic>\n                      according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u20090.001), hypoalbuminemia (16.7% vs. 0.9%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.003), and myelofibrosis (19.0% vs. 0.9%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.002) than those without. Most patients with gastrointestinal complication had\n                      <jats:italic>SLCO2A1<\/jats:italic>\n                      mutation (86.7%, 13 \/15).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn\u2019s disease but similar to CMUSE. Mutations in\n                      <jats:italic>SLCO2A1<\/jats:italic>\n                      might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-019-1264-5","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T12:02:34Z","timestamp":1577361754000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Primary hypertrophic osteoarthropathy related gastrointestinal complication has distinctive clinical and pathological characteristics: two cases report and review of the literature"],"prefix":"10.1186","volume":"14","author":[{"given":"Qiang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-he","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-le","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-xun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-ming","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-bo","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9430-9874","authenticated-orcid":false,"given":"Dong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"1264_CR1","first-page":"156","volume":"17","author":"IC Viola","year":"2000","unstructured":"Viola IC, Joffe S, Brent LH. Primary hypertrophic osteoarthropathy. J Rheumatol. 2000;17:156\u201362.","journal-title":"J Rheumatol"},{"key":"1264_CR2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1111\/j.1399-0004.2005.00533.x","volume":"68","author":"M Castori","year":"2005","unstructured":"Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: an update. Clin Genet. 2005;68:477\u201386.","journal-title":"Clin Genet"},{"key":"1264_CR3","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1038\/ng.153","volume":"40","author":"S Uppal","year":"2008","unstructured":"Uppal S, Diggle CP, Carr IM, Fishwick CWG, Ahmed M, Ibrahim GH, et al. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nat Genet. 2008;40:789\u201393.","journal-title":"Nat Genet"},{"key":"1264_CR4","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ajhg.2011.11.019","volume":"90","author":"Z Zhang","year":"2012","unstructured":"Zhang Z, Xia W, He J, Zhang Z, Ke Y, Yue H, et al. Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am J Hum Genet. 2012;90:125\u201332.","journal-title":"Am J Hum Genet"},{"key":"1264_CR5","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1007\/s00535-017-1426-y","volume":"53","author":"J Umeno","year":"2018","unstructured":"Umeno J, Esaki M, Hirano A, Fuyuno Y, Ohmiya N, Yasukawa S, Hirai F, et al. Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn's disease. J Gastroenterol. 2018;53:907\u201315.","journal-title":"J Gastroenterol"},{"key":"1264_CR6","doi-asserted-by":"publisher","first-page":"E923","DOI":"10.1210\/jc.2012-3568","volume":"98","author":"Z Zhang","year":"2013","unstructured":"Zhang Z, He J, Fu W, Zhang C, Zhang Z. Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a clinical and biochemical characterization. J Clin Endocrinol Metab. 2013;98:E923\u201333.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1264_CR7","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1111\/bjd.14480","volume":"180","author":"Z. Li","year":"2018","unstructured":"Li ZT, Wang D, Wang S. Successful treatment of pachydermoperiostosis with etoricoxib in a patient with a homozygous splice-site mutation in the SLCO2A1 gene. Br J Dermatol. 2016. https:\/\/doi.org\/10.1111\/bjd.14480.","journal-title":"British Journal of Dermatology"},{"key":"1264_CR8","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008865","volume":"96","author":"H Zhang","year":"2017","unstructured":"Zhang H, Yang B. Successful treatment of pachydermoperiostosis patients with etoricoxib, aescin, and arthroscopic synovectomy: two case reports. Medicine. 2017;96:e8865.","journal-title":"Medicine"},{"key":"1264_CR9","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/RHU.0000000000000647","volume":"24","author":"F Sun","year":"2018","unstructured":"Sun F, Guo L, Ye S. Primary hypertrophic osteoarthropathy with SLCO2A1 mutation in a Chinese patient successfully treated with Etoricoxib. J Clin Rheumatol. 2018;24:164\u20137.","journal-title":"J Clin Rheumatol"},{"key":"1264_CR10","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s11845-009-0346-0","volume":"181","author":"X Chen","year":"2012","unstructured":"Chen X, Zou C, Dong G, Liang L, Zhao Z. Cranio-osteoarthropathy: a rare variant of hypertrophic osteoarthropathy. Ir J Med Sci. 2012;181:257\u201361.","journal-title":"Ir J Med Sci"},{"key":"1264_CR11","doi-asserted-by":"publisher","first-page":"E923","DOI":"10.1210\/jc.2012-3568","volume":"98","author":"Z Zhang","year":"2013","unstructured":"Zhang Z, He J, Fu W, Zhang C, Zhang Z. Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a clinical and biochemical characterization. J Clin Endocrinol Metab. 2013;98:E923\u201333.","journal-title":"J Clin Endocrinol Metab"},{"key":"1264_CR12","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1007\/s00296-013-2732-1","volume":"33","author":"Y Ren","year":"2013","unstructured":"Ren Y, Leng X, Yang B, Zhang X. Aberrant cd200\/cd200r1 expression contributes to painful synovium hyperplasia in a patient with primary hypertrophic osteoarthropathy. Rheumatol Int. 2013;33:2509\u201312.","journal-title":"Rheumatol Int"},{"key":"1264_CR13","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1007\/s00223-015-0024-3","volume":"97","author":"L Yuan","year":"2015","unstructured":"Yuan L, Chen L, Liao R, Lin Y, Jiang Y, Wang O, et al. A common mutation and a novel mutation in the HPGD gene in nine patients with primary hypertrophic osteoarthropathy. Calcifi Tissue Int. 2015;97:336\u201342.","journal-title":"Calcifi Tissue Int"},{"key":"1264_CR14","first-page":"1467","volume":"8","author":"S Li","year":"2015","unstructured":"Li S, Li Q, Wang Q, Chen D, Li J. Primary hypertrophic osteoarthropathy with myelofibrosis and anemia: a case report and review of literature. Int J Clin Exp Med. 2015;8:1467\u201371.","journal-title":"Int J Clin Exp Med"},{"key":"1264_CR15","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.3892\/mmr.2017.6391","volume":"15","author":"T Guo","year":"2017","unstructured":"Guo T, Yang K, Liu L, Tan Z, Luo H. Identification of two novel mutations in the SLCO2A1 prostaglandin transporter gene in a Chinese patient with primary hypertrophic osteoarthropathy. Mol Med Rep. 2017;15:2977\u201382.","journal-title":"Mol Med Rep"},{"key":"1264_CR16","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.ejmg.2017.06.001","volume":"60","author":"W Ma","year":"2017","unstructured":"Ma W, Guo S, Li Y, Li Z. Pachydermoperiostosis of the complete type: a novel missense mutation c.101T > C in the SLCO2A1 gene. Eur J Med Genet. 2017;60:433\u20136.","journal-title":"Eur J Med Genet"},{"key":"1264_CR17","doi-asserted-by":"publisher","first-page":"761","DOI":"10.2340\/00015555-2645","volume":"97","author":"X Wen","year":"2017","unstructured":"Wen X, Li Y, Hamblin MR, Jiang X. Facial manifestations of pachydermoperiostosis treated with botulinum toxin type-a: report of 3 cases. Acta Derm Venereol. 2017;97:761\u20132.","journal-title":"Acta Derm Venereol"},{"key":"1264_CR18","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.bone.2017.09.015","volume":"106","author":"Y Hou","year":"2018","unstructured":"Hou Y, Lin Y, Qi X, Yuan L, Liao R, Pang Q, et al. Identification of mutations in the prostaglandin transporter gene SLCO2A1 and phenotypic comparison between two subtypes of primary hypertrophic osteoarthropathy (PHO): a single-center study. Bone. 2018;106:96\u2013102.","journal-title":"Bone."},{"key":"1264_CR19","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1002\/jbmr.3157","volume":"32","author":"S Li","year":"2017","unstructured":"Li S, He J, Fu W, Liu Y, Hu Y, Zhang Z. Clinical, biochemical, and genetic features of 41 Han Chinese families with primary hypertrophic osteoarthropathy, and their therapeutic response to Etoricoxib: results from a six-month prospective clinical intervention. J Bone Miner Res. 2017;32:1659\u201366.","journal-title":"J Bone Miner Res"},{"key":"1264_CR20","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1023\/A:1014725024519","volume":"47","author":"T Kunikata","year":"2002","unstructured":"Kunikata T, Tanaka A, Miyazawa T, Kato S, Takeuchi K. 16,16-dimethyl prostaglandin E2 inhibits indomethacin-induced small intestinal lesions through EP3 and EP4 receptors. Dig Dis Sci. 2002;47:894\u2013904.","journal-title":"Dig Dis Sci"},{"key":"1264_CR21","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1254\/jphs.10R06CR","volume":"114","author":"K Takeuchi","year":"2010","unstructured":"Takeuchi K, Kato S, Amagase K. Prostaglandin EP receptors involved in modulating gastrointestinal mucosal integrity. J Pharmacol Sci. 2010;114:248\u201361.","journal-title":"J Pharmacol Sci"},{"key":"1264_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005581","volume":"11","author":"J Umeno","year":"2015","unstructured":"Umeno J, Hisamatsu T, Esaki M, Hirano A, Kubokura N, Asano K, et al. A hereditary enteropathy caused by mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. PLoS Genet. 2015;11:e1005581.","journal-title":"PLoS Genet"},{"key":"1264_CR23","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jdermsci.2014.05.008","volume":"75","author":"H Niizeki","year":"2014","unstructured":"Niizeki H, Shiohama A, Sasaki T, Seki A, Kabashima K, Otsuka A, et al. The complete type of pachydermoperiostosis: a novel nonsense mutation p.E141* of the SLCO2A1 gene. J Dermatol Sci. 2014;75:193\u20135.","journal-title":"J Dermatol Sci"},{"key":"1264_CR24","first-page":"193","volume":"53","author":"C Debray","year":"1964","unstructured":"Debray C, Besancon F, Hardouin JP, Martin E, Marche C, Khoury K. Cryptogenetic plurifocal ulcerative stenosing enteritis. Arch Mal Appar Dig Mal Nutr. 1964;53:193\u2013206.","journal-title":"Arch Mal Appar Dig Mal Nutr"},{"key":"1264_CR25","doi-asserted-by":"publisher","first-page":"370","DOI":"10.5946\/ce.2016.090","volume":"49","author":"JM Lee","year":"2016","unstructured":"Lee JM, Lee KM. Endoscopic diagnosis and differentiation of inflammatory bowel disease. Clin Endosc. 2016;49:370\u20135.","journal-title":"Clin Endosc"},{"key":"1264_CR26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1136\/gutjnl-2012-303581","volume":"63","author":"MA Brooke","year":"2014","unstructured":"Brooke MA, Longhurst HJ, Plagnol V, Kirkby NS, Mitchell JA, R\u00fcschendorf F, et al. Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-alpha. Gut. 2014;63:96\u2013104.","journal-title":"Gut."},{"key":"1264_CR27","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.3899\/jrheum.150364","volume":"42","author":"G Giancane","year":"2015","unstructured":"Giancane G, Diggle CP, Legger EG, Tekstra J, Prakken B, Brenkman AB, et al. Primary hypertrophic osteoarthropathy: an update on patient features and treatment. J Rheumatol. 2015;42:2211\u20134.","journal-title":"J Rheumatol"},{"key":"1264_CR28","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S0889-8553(05)70223-5","volume":"30","author":"JL Wallace","year":"2001","unstructured":"Wallace JL. Prostaglandin biology in inflammatory bowel disease. Gastroenterol Clin N Am. 2001;30:971\u201380.","journal-title":"Gastroenterol Clin N Am"},{"key":"1264_CR29","doi-asserted-by":"publisher","first-page":"821","DOI":"10.18433\/J3VW2F","volume":"16","author":"S Harirforoosh","year":"2013","unstructured":"Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16:821\u201347.","journal-title":"J Pharm Pharm Sci"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-019-1264-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-019-1264-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-019-1264-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T19:22:01Z","timestamp":1608837721000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-019-1264-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1264"],"URL":"https:\/\/doi.org\/10.1186\/s13023-019-1264-5","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"5 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The Ethics Committee of the hospital approved the use of the clinical data and genetic test results of the two patients. A consensus had been obtained from both patients to use their pictures, notes and lab investigations for publication on the condition that their personal information was kept confidential.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"297"}}