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Blood-culture negative infective endocarditis may complicate the course of classical Whipple\u2019s disease or appear as an isolated manifestation. The pathophysiology of this rare and complex disorder is still unclear, and the appropriate therapeutic management is debated. Recent reports have highlighted the role of biologic response modifiers in causing overt disease or in accelerating patient presentation by worsening pre-existing symptoms especially when administered in patients with isolated joint manifestations. In this clinical scenario, we describe the first reported case of classical Whipple\u2019s disease complicated with endocarditis in which patient symptoms were exacerbated by administration of IL-17 inhibitors. The patient presented with a history of long-standing fever and seronegative spondylarthritis and received a diagnosis of native aortic valve blood-culture negative infective endocarditis. Associated gastrointestinal symptoms prompted duodenal endoscopy with histology and molecular biology confirming the diagnosis. The following review provides valuable insights in the pathophysiology, diagnosis, treatment and long-term management of Whipple\u2019s disease and underlies how modern medicine and newer treatment options are shaping the host-pathogen interaction and presentation patterns of infectious diseases.\n                  <\/jats:p>","DOI":"10.1007\/s15010-026-02828-5","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:33:21Z","timestamp":1780468401000},"page":"2205-2214","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whipple\u2019s endocarditis and biologic response modifiers: a case-based review of an intricate host-pathogen interaction"],"prefix":"10.1007","volume":"54","author":[{"given":"Lorenzo","family":"Bertolino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria Carolina","family":"Peluso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Patauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana","family":"Infante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Luciano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Scarpulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Sannino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Vulcano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Panico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Durante-Mangoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"2828_CR1","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. 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