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Recently, other more frequent forms of <jats:italic>Tropheryma whipplei<\/jats:italic> infection have been recognised. The clinical spectrum includes an acute, self\u2010limiting disease in children, localised forms affecting cardiac valves or the central nervous system without intestinal symptoms, and asymptomatic carriage of <jats:italic>T. whipplei<\/jats:italic> which is found in around 4% of Europeans. Genomic analysis has shown that <jats:italic>T. whipplei<\/jats:italic> represents a host\u2010dependent or opportunistic bacterium. It has been reported that the clinical course of <jats:italic>T.\u00a0whipplei<\/jats:italic> infection may be influenced by medical immunosuppression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To identify associations between immunomodulatory treatment and the clinical course of <jats:italic>T. whipplei<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A PubMed literature search was performed and 19 studies reporting on immunosuppression, particularly therapy with tumour necrosis factor inhibitors (<jats:styled-content style=\"fixed-case\">TNFI<\/jats:styled-content>) prior to the diagnosis in 41 patients with <jats:styled-content style=\"fixed-case\">Whipple?s disease<\/jats:styled-content>, were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As arthritis may precede the diagnosis of <jats:styled-content style=\"fixed-case\">WD<\/jats:styled-content> by many years, a relevant percentage (up to 50% in some reports) of patients are treated with immunomodulatory drugs or with <jats:styled-content style=\"fixed-case\">TNFI<\/jats:styled-content>. Many publications report on a complicated <jats:styled-content style=\"fixed-case\">Whipple?s disease<\/jats:styled-content> course or <jats:italic>T. whipplei<\/jats:italic> endocarditis following medical immunosuppression, particularly after <jats:styled-content style=\"fixed-case\">TNFI<\/jats:styled-content>. Standard diagnostic tests such as periodic acid\u2013Schiff stain used to diagnose <jats:styled-content style=\"fixed-case\">Whipple?s disease<\/jats:styled-content> often fail in patients who are pre\u2010treated by <jats:styled-content style=\"fixed-case\">TNFI<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In cases of doubt, <jats:styled-content style=\"fixed-case\">Whipple?s disease<\/jats:styled-content> should be excluded before therapy with <jats:styled-content style=\"fixed-case\">TNFI<\/jats:styled-content>. The fact that immunosuppressive therapy contributes to the progression of <jats:italic>T. whipplei<\/jats:italic> infection expands our pathogenetic view of this clinical entity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13140","type":"journal-article","created":{"date-parts":[[2015,2,19]],"date-time":"2015-02-19T08:16:29Z","timestamp":1424333789000},"page":"709-724","source":"Crossref","is-referenced-by-count":88,"title":["Systematic review: Whipple's disease (<i>Tropheryma whipplei<\/i> infection) and its unmasking by tumour necrosis factor inhibitors"],"prefix":"10.1111","volume":"41","author":[{"given":"T.","family":"Marth","sequence":"first","affiliation":[{"name":"Division of Internal Medicine Krankenhaus Maria Hilf Daun Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,19]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Whipple's Disease","author":"Dobbins WO","year":"1987"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12274-X"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra062477"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.10.041"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)64884-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.3.561-583.2001"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200211000-00005"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001403"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/655677"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1605.091801"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02335-06"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1806.111038"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.124"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr032"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9247461"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2089"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197904193001607"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.97"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(08)70042-2"},{"key":"e_1_2_11_21_1","first-page":"899","article-title":"Long\u2010term follow\u2010up in cerebral Whipple's disease","volume":"8","author":"Schnider PJ","year":"1996","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.05531-11"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp285"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivs116"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.03038.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/322666"},{"key":"e_1_2_11_27_1","first-page":"307","article-title":"Whipple's disease: etiopathogenesis, treatment, diagnosis, and clinical course. 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