{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T11:26:07Z","timestamp":1787916367797,"version":"build-2784847793"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Whipple's disease is a chronic infectious disease that primarily affects the small intestine, but several organs can simultaneously be involved. The disease is caused by a gram-positive bacterium called\n                      <jats:italic>Tropheryma whipplei<\/jats:italic>\n                      . The disease is difficult to suspect because it is rare with unspecific and long-term symptoms; it can be lethal if not properly treated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We here present three patients who presented with a plethora of symptoms, mainly long-standing seronegative arthritis and gastrointestinal symptoms in the form of diarrhea with blood, weight loss, fever, and lymphadenopathy. They were after extensive investigations diagnosed with Whipple's disease, in two of them as long as 8\u00a0years after the first occurrence of joint manifestations. The diagnosis was made by PCR targeting the\n                      <jats:italic>T. whipplei<\/jats:italic>\n                      16S rRNA gene from small bowel specimen in all three patients, and, besides from histopathologic findings from the duodenum and distal ileum in one and mesenteric lymph nodes in another patient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This report aims to raise awareness of a very rare disease that presents with a combination of symptoms mimicking other and significantly more common diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12876-021-01664-1","type":"journal-article","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T07:02:33Z","timestamp":1616223753000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Whipple's disease: the great masquerader\u2014a high level of suspicion is the key to diagnosis"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6078-1764","authenticated-orcid":false,"given":"Nikolaos","family":"Melas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasjan","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Gyllemark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amil Haji","family":"Younes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9334-1821","authenticated-orcid":false,"given":"Sven","family":"Almer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,20]]},"reference":[{"key":"1664_CR1","first-page":"382","volume":"18","author":"GH Whipple","year":"1907","unstructured":"Whipple GH. A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Bull Johns Hopkins Hosp. 1907;18:382\u201391.","journal-title":"Bull Johns Hopkins Hosp"},{"issue":"1","key":"1664_CR2","first-page":"43","volume":"17","author":"M Pyrgioti","year":"2004","unstructured":"Pyrgioti M, Kyriakidis A. Whipple\u2019s disease: a review. Ann Gastroenterol. 2004;17(1):43\u201350.","journal-title":"Ann Gastroenterol"},{"key":"1664_CR3","first-page":"80","volume":"109","author":"J Yardley","year":"1961","unstructured":"Yardley J, Hendrix TR. Combined electron and light microscopy in Whipple\u2019s disease: demonstration of \u201cbacillary bones\u201d in the intestine. Bull Johns Hopkins Hosp. 1961;109:80\u201398.","journal-title":"Bull Johns Hopkins Hosp"},{"issue":"8765","key":"1664_CR4","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/0140-6736(91)90545-Z","volume":"338","author":"KH Wilson","year":"1991","unstructured":"Wilson KH, Blitchington R, Frothingham R, Wilson JA. Phylogeny of the Whipple\u2019s-disease-associated bacterium. Lancet. 1991;338(8765):474\u20135.","journal-title":"Lancet"},{"issue":"1","key":"1664_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/CDLI.8.1.1-8.2001","volume":"8","author":"F Fenollar","year":"2001","unstructured":"Fenollar F, Raoult D. Whipple\u2019s disease. Clin Diagn Lab Immunol. 2001;8(1):1\u20138.","journal-title":"Clin Diagn Lab Immunol"},{"issue":"7","key":"1664_CR6","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1007\/s10096-015-2357-2","volume":"34","author":"F Biagi","year":"2015","unstructured":"Biagi F, Balduzzi D, Delvino P, et al. Prevalence of Whipple\u2019s disease in north-western Italy. Eur J Clin Microbiol Infect Dis. 2015;34(7):1347\u20138.","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"1664_CR7","volume-title":"3rd Whipple\u2019s disease","author":"WO Dobbins","year":"1987","unstructured":"Dobbins WO. 3rd Whipple\u2019s disease. Springfield: Charles C. Thomas; 1987."},{"key":"1664_CR8","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3109\/00365529709025063","volume":"32","author":"A Von Herbay","year":"1997","unstructured":"Von Herbay A, Otto HF, Stolte M, et al. Epidemiology of Whipple\u2019s disease in Germany. Analysis of 110 patients diagnosed in 1965\u201395. Scand J Gastroenteol. 1997;32:52\u20137.","journal-title":"Scand J Gastroenteol"},{"issue":"3","key":"1664_CR9","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1016\/S1473-3099(15)00537-X","volume":"16","author":"T Marth","year":"2016","unstructured":"Marth T, Moos V, Muller C, Biagi F, Schneider T. Tropheryma Whipplei infection and Whipple\u2019s disease. Lancet Infect Dis. 2016;16(3):e13\u201321.","journal-title":"Lancet Infect Dis"},{"key":"1664_CR10","unstructured":"Moos V, Fredricks ND. Tropheryma whippelii (Whipple's Disease). http:\/\/www.antimicrobe.org\/m07.asp."},{"issue":"12","key":"1664_CR11","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.3899\/jrheum.130328","volume":"40","author":"M Meunier","year":"2013","unstructured":"Meunier M, Puechal X, Hoppe E, et al. Rheumatic and musculoskeletal features of Whipple disease: a report of 29 cases. J Rheumatol. 2013;40(12):2061\u20136.","journal-title":"J Rheumatol"},{"issue":"7","key":"1664_CR12","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1097\/PAS.0b013e31825a2fa4","volume":"36","author":"CA Arnold","year":"2012","unstructured":"Arnold CA, Moreira RK, Lam-Himlin D, De Petris G, Montgomery E. Whipple disease a century after the initial description: increased recognition of unusual presentations, autoimmune comorbidities, and therapy effects. Am J Surg Pathol. 2012;36(7):1066\u201373.","journal-title":"Am J Surg Pathol"},{"issue":"1","key":"1664_CR13","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.athoracsur.2014.04.059","volume":"98","author":"MD Herrmann","year":"2014","unstructured":"Herrmann MD, Neumayr A, Essig A, Spless J, Merk J, M\u00f6ller P, Liebold A, Barth TF. Isolated Whipple\u2019s endocarditis: an underestimated diagnosis that requires molecular analysis of surgical material. Ann Thorac Surg. 2014;98(1):e1-3.","journal-title":"Ann Thorac Surg"},{"issue":"2","key":"1664_CR14","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1097\/MOG.0b013e3282f3f4f1","volume":"24","author":"T Marth","year":"2008","unstructured":"Marth T, Schneider T. Whipple disease. Curr Opin Gastroenterol. 2008;24(2):141\u20138.","journal-title":"Curr Opin Gastroenterol"},{"key":"1664_CR15","doi-asserted-by":"publisher","first-page":"bcr0220125882","DOI":"10.1136\/bcr.02.2012.5882","volume":"2012","author":"M Weisfelt","year":"2012","unstructured":"Weisfelt M, Oosterwerff E, Oosterwerff M, et al. Whipple\u2019s disease presenting with neurological symptoms in an immunosuppressed patient. BMJ Case Rep. 2012;2012:bcr0220125882.","journal-title":"BMJ Case Rep"},{"issue":"5","key":"1664_CR16","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1097\/MD.0b013e3181f204a8","volume":"89","author":"JC Lagier","year":"2010","unstructured":"Lagier JC, Lepidi H, Raoult D, Fenollar F. Systemic Tropheryma whipplei: clinical presentation of 142 patients with infections diagnosed or confirmed in a reference center. Medicine (Baltimore). 2010;89(5):337\u201345.","journal-title":"Medicine (Baltimore)"},{"issue":"3","key":"1664_CR17","doi-asserted-by":"publisher","first-page":"331","DOI":"10.15403\/jgld.2014.1121.273.fra","volume":"27","author":"V De Francesco","year":"2018","unstructured":"De Francesco V, Corsi F, Pennella A, et al. Whipple\u2019s disease: case report and review of the literature. J Gastrointestin Liver Dis. 2018;27(3):331\u20136.","journal-title":"J Gastrointestin Liver Dis"},{"issue":"8","key":"1664_CR18","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1111\/apt.13140","volume":"41","author":"T Marth","year":"2015","unstructured":"Marth T. Systematic review: Whipple\u2019s disease (Tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitors. Aliment Pharmacol Ther. 2015;41(8):709\u201324.","journal-title":"Aliment Pharmacol Ther"},{"issue":"15","key":"1664_CR19","doi-asserted-by":"publisher","first-page":"e714","DOI":"10.1097\/MD.0000000000000714","volume":"94","author":"U Gunther","year":"2015","unstructured":"Gunther U, Moos V, Offenmuller G, Oelkers G, Heise W, Moter A, Loddenkemper C, Schneider T. Gastrointestinal diagnosis of classical Whipple disease: clinical, endoscopic, and histopathologic features in 191 patients. Medicine (Baltimore). 2015;94(15):e714.","journal-title":"Medicine (Baltimore)"},{"key":"1664_CR20","unstructured":"Verouhis D, Pehrsson K. Whipples sjukdom \u2013 ovanlig, men sannolikt underdiagnostiserad. L\u00e4kartidningen nr 43, 2010 volym 107 (in Swedish)."},{"issue":"5","key":"1664_CR21","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1590\/S0036-46652012000500010","volume":"54","author":"VP Renon","year":"2012","unstructured":"Renon VP, Appel-Da-Silva MC, D\u2019Incao RB. Whipple\u2019s disease: rare disorder and late diagnosis. Rev Inst Med Trop Sao Paulo. 2012;54(5):293\u20137.","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"1664_CR22","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1056\/NEJMra062477","volume":"356","author":"F Fenollar","year":"2007","unstructured":"Fenollar F, Puechal X, Raoult D. Whipple\u2019s disease. N Engl J Med. 2007;356:55\u201366.","journal-title":"N Engl J Med"},{"issue":"1","key":"1664_CR23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1093\/qjmed\/92.1.61","volume":"92","author":"SA Misbah","year":"1999","unstructured":"Misbah SA, Stirzaker D, Ozols B, et al. Anonymous survey of blood donors by polymerase chain reaction for Tropheryma whippelii. QJM. 1999;92(1):61.","journal-title":"QJM"},{"issue":"3","key":"1664_CR24","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S1473-3099(08)70042-2","volume":"8","author":"T Schneider","year":"2008","unstructured":"Schneider T, Moos V, Loddenkemper C, et al. Whipple\u2019s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008;8(3):179\u201390.","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"1664_CR25","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/apm.12782","volume":"126","author":"A Loiodice","year":"2018","unstructured":"Loiodice A, Losurdo G, Iannone A, et al. Transmission electron microscopy helpfulness in Whipple\u2019s disease masked by immunosuppressant therapy for arthritis. APMIS. 2018;126(1):92\u20136.","journal-title":"APMIS"},{"issue":"5","key":"1664_CR26","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1086\/590559","volume":"47","author":"F Fenollar","year":"2008","unstructured":"Fenollar F, Laouira S, Lepidi H, et al. Value of Tropheryma whipplei quantitative polymerase chain reaction assay for the diagnosis of Whipple disease: usefulness of saliva and stool specimens for first-line screening. Clin Infect Dis. 2008;47(5):659\u201367.","journal-title":"Clin Infect Dis"},{"issue":"2","key":"1664_CR27","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1136\/gut.18.2.152","volume":"18","author":"S Moorthy","year":"1977","unstructured":"Moorthy S, Nolley G, Hermos JA. Whipple\u2019s disease with minimal intestinal involvement. Gut. 1977;18(2):152\u20135.","journal-title":"Gut"},{"issue":"2","key":"1664_CR28","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1053\/gast.1997.v113.pm9247461","volume":"113","author":"A Von Herbay","year":"1997","unstructured":"Von Herbay A, Ditton HJ, Schuhmacher F, Malwald M. Whipple\u2019s disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid. Gastroenterology. 1997;113(2):434\u201344.","journal-title":"Gastroenterology"},{"key":"1664_CR29","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1053\/j.gastro.2009.10.041","volume":"138","author":"GE Feurle","year":"2010","unstructured":"Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapiews in Whipple\u2019s disease. Gastroenterology. 2010;138:478\u201386.","journal-title":"Gastroenterology"},{"key":"1664_CR30","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1086\/588706","volume":"198","author":"N Bakkali","year":"2008","unstructured":"Bakkali N, Fenolar F, Biswas S, et al. Acquired resistance to trimethoprim-sulfamethoxazole during Whipple disease and expression of the causative target gene. J Infect Dis. 2008;198:101\u20138.","journal-title":"J Infect Dis"},{"issue":"3","key":"1664_CR31","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1097\/MEG.0000000000000539","volume":"28","author":"E Ruggiero","year":"2016","unstructured":"Ruggiero E, Zurlo A, Giantin V, et al. Short article: relapsing Whipple\u2019s disease: a case report and literature review. Eur J Gastroenterol Hepatol. 2016;28(3):267\u201370.","journal-title":"Eur J Gastroenterol Hepatol"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-021-01664-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12876-021-01664-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-021-01664-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T07:02:49Z","timestamp":1616223769000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgastroenterol.biomedcentral.com\/articles\/10.1186\/s12876-021-01664-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,20]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1664"],"URL":"https:\/\/doi.org\/10.1186\/s12876-021-01664-1","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,20]]},"assertion":[{"value":"5 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written consent for publication was given by all three patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"128"}}