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The causative agent is the gram-positive bacterium\n                    <jats:italic>Tropheryma whipplei<\/jats:italic>\n                    . The disease manifests with a wide range of clinical symptoms, including non-specific presentations such as diarrhea, arthralgia, and fever, as well as the more pathognomonic lipodystrophy. This diversity in presentation poses a significant diagnostic challenge even for experienced clinicians. Our review aims to provide an updated overview encompassing the latest insights into Whipple\u2019s disease, focusing on epidemiology, pathophysiology, genetic predisposition, clinical manifestations, diagnosis, immune reconstitution inflammatory syndrome, and treatment. Herein, we have additionally explored many of the confounding factors in the diagnosis and management of Whipple\u2019s disease, including the variable presentations among patients colonized by\n                    <jats:italic>Trophyrema whipplei<\/jats:italic>\n                    as well as the limitations of current treatment options, and underscore the need for further research and guidelines related to this complex disease process.\n                  <\/jats:p>","DOI":"10.1007\/s10238-026-02064-z","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T08:30:47Z","timestamp":1770366647000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Deciphering whipple\u2019s disease complexity"],"prefix":"10.1007","volume":"26","author":[{"given":"Jakub","family":"Korybski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Zelig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Narayanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Blonski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalina Milena","family":"Kazimierski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Hendrik","family":"Dierkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna Lidia","family":"Popiela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustin Patrick","family":"Gabriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"2064_CR1","doi-asserted-by":"publisher","unstructured":"Desmurs M, Petit H, Gottenberg J-E,\u00a0Sat0453 Joint Manifestations of Whipple\u2019s Disease: Clinical and Radiological Presentation of 19 Patients. 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