Whipple's disease historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]


Whipple described the disease for the first time in 1907 as a gastrointestinal disorder and named it as "intestinal lipodystrophy." Light and electron microscopy on small bowel biopsy were used to detect bacilli inside the intestinal mucosa. In 1952, systemic antibiotics were used to treat the disease which confirmed the infective nature of the disease. It took almost 100 years for investigators to cultivate the bacterium and sequenced the genome.

Historical Perspective

Year Investigator Landmark event
1907 George Hoyt Whipple Described the Whipple's disease for the first time and named it as "intestinal lipodystrophy".
1947 Oliver-Pascual Reported a case of “intestinal lipodystrophy” before the death of a patient.
1949 Black-Schaffer Strained the bacilli with periodic acid-Schiff stain; renamed to "Whipple's disease."
1952 Pauley Successfully used systemic antibiotics for treatment of the "Whipple's disease."
1958 Bolt Used small bowel biopsy to differentiate malabsorption diseases and confirm the Whipple's disease.
1961 Chears and Ashworth Used electron microscopy and cytochemical study to detect the bacilli inside the intestinal macrophages.
1961 Yardley and Hendrix  Used combined electron and light microscopy to detect the rod-shaped structures in the intestinal mucosa.
1991 Wilson Sequenced a 16S rRNA of a new bacterium partially and classified it within the Actinomycetes clade.
1992 Relman Confirmed the previous result and extended the 16S rRNA sequence by using PCR; named the bacterium “Tropheryma whippleii” for the first time.
2000 Raoult Reported isolation and cultivation of “Tropheryma whippleii” for the first time.
2001 La Scola Characterized the bacterium phenotypically; slightly renamed it to “Tropheryma whipplei.”
2003 Bentley


Analyzed and sequenced the genome of two different strains of Tropheryma whipplei.

Landmark Events in the Development of Treatment Strategies


  1. Whipple G H. 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;198:383.
  2. OLIVER-PASCUAL E, GALAN J (1947). "[Not Available]". Rev Esp Enferm Apar Dig Nutr (in Undetermined). 6 (3): 213–26. PMID 20251637.
  3. BLACK-SCHAFFER B (1949). "The tinctoral demonstration of a glycoprotein in Whipple's disease". Proc. Soc. Exp. Biol. Med. 72 (1): 225–7. PMID 15391722.
  4. 4.0 4.1 PAULLEY JW (1952). "A case of Whipple's disease (intestinal lipodystrophy)". Gastroenterology. 22 (1): 128–33. PMID 12980233.
  5. Bolt, Robert J.; Pollard, H. Marvin; Standaert, Ludovic (1958). "Transoral Small-Bowel Biopsy as an Aid in the Diagnosis of Malabsorption States". New England Journal of Medicine. 259 (1): 32–34. doi:10.1056/NEJM195807032590107. ISSN 0028-4793.
  6. CHEARS WC, ASHWORTH CT (1961). "Electron microscopic study of the intestinal mucosa in Whipple's disease. Demonstration of encapsulated bacilliform bodies in the lesion". Gastroenterology. 41: 129–38. PMID 13692693.
  7. YARDLEY JH, HENDRIX TR (1961). "Combined electron and light microscopy in Whipple's disease. Demonstration of "bacillary bodies" in the intestine". Bull Johns Hopkins Hosp. 109: 80–98. PMID 13787237.
  8. Wilson KH, Blitchington R, Frothingham R, Wilson JA (1991). "Phylogeny of the Whipple's-disease-associated bacterium". Lancet. 338 (8765): 474–5. PMID 1714530.
  9. Relman, David A.; Schmidt, Thomas M.; MacDermott, Richard P.; Falkow, Stanley (1992). "Identification of the Uncultured Bacillus of Whipple's Disease". New England Journal of Medicine. 327 (5): 293–301. doi:10.1056/NEJM199207303270501. ISSN 0028-4793.
  10. Raoult, Didier; Birg, Marie L.; Scola, Bernard La; Fournier, Pierre E.; Enea, Maryse; Lepidi, Hubert; Roux, Veronique; Piette, Jean-Charles; Vandenesch, François; Vital-Durand, Denis; Marrie, Tom J. (2000). "Cultivation of the Bacillus of Whipple's Disease". New England Journal of Medicine. 342 (9): 620–625. doi:10.1056/NEJM200003023420903. ISSN 0028-4793.
  11. La Scola, B; Altwegg, M; Mallet, M N; Fournier, P E; Fenollar, F; Raoult, D (2001). "Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple's disease bacillus". International Journal of Systematic and Evolutionary Microbiology. 51 (4): 1471–1479. doi:10.1099/00207713-51-4-1471. ISSN 1466-5026.
  12. Bentley, Stephen D; Maiwald, Matthias; Murphy, Lee D; Pallen, Mark J; Yeats, Corin A; Dover, Lynn G; Norbertczak, Halina T; Besra, Gurdyal S; Quail, Michael A; Harris, David E; von Herbay, Axel; Goble, Arlette; Rutter, Simon; Squares, Robert; Squares, Stephen; Barrell, Bart G; Parkhill, Julian; Relman, David A (2003). "Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei". The Lancet. 361 (9358): 637–644. doi:10.1016/S0140-6736(03)12597-4. ISSN 0140-6736.
  13. Raoult D, Ogata H, Audic S, Robert C, Suhre K, Drancourt M, Claverie JM (2003). "Tropheryma whipplei Twist: a human pathogenic Actinobacteria with a reduced genome". Genome Res. 13 (8): 1800–9. doi:10.1101/gr.1474603. PMC 403771. PMID 12902375.