Abstract
Whipple’s disease is an infectious disease caused by a grampositive bacterium, Tropheryma whipplei. The first case was reported in 1907 by GH Whipple. Its classic symptoms are diarrhea and arthralgias, but symptoms can be various. Cardiac or central nervous system involvement, not always associated with digestive symptoms, may also be observed. For a long time, diagnosis has been based on duodenal biopsy, which is positive using periodic acid-Schiff staining. However, for patients without digestive symptoms, results can be negative, leading to a delay in diagnosis. For 10 years, a tool based on polymerase chain reaction targeting the 16S rDNA sequence has been used. In vitro culture of the bacterium, achieved 3 years ago, has allowed new perspectives for diagnosis and treatment. The natural evolution of the disease without treatment is always fatal. Current treatment is based on administration of trimethoprim-sulfamethoxazole for at least 1 year.
Similar content being viewed by others
References and Recommended Reading
Whipple G: 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, 18:382–393.
Fenollar F, Raoult D: Whipple’s disease. Clin Diag Lab Immunol 2001, 8:1–8.
Misbah S, Mapstone N: Whipple’s disease revisited. J Clin Pathol 2000, 53:750–755.
Dutly F, Altwegg M: Whipple’s disease and ‘Tropheryma whippelii’. Clin Microbiol Rev 2001, 14:561–583.
Maiwald M, Relman D: Whipple’s disease and Tropheryma whippelii: secrets slowly revealed. Clin Infect Dis 2001, 32:457–463.
Marth T, Raoult D: Whipple’s disease. Lancet 2003, 361:239–246.
Dobbins, WO III: Whipple’s Disease. Springfield, IL: Thomas; 1987.
La Scola B, Rolain J, Maurin M, Raoult D: Can Whipple’s disease be transmitted by gastroscopes? Infect Control Hosp Epidemiol 2003, 191–194.
Gross M, Jung C, Zoller W: Detection of Tropheryma whippelii (Whipple’s disease) in faeces. Ital J Gastroenterol 1999, 31:70–72.
Maibach R, Dutly F, Altwegg M: Detection of Tropheryma whipplei DNA in feces by PCR using a target capture method. J Clin Microbiol 2002, 40:2466–2471.
Maiwald M, Schuhmacher F, Ditton H, von Herbay A: Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 1998, 64:60–62.
Maiwald M, von Herbay A, Persing D, et al.: Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of Whipple disease. Ann Intern Med 2001, 134:115–119.
Dutly F, Hinrikson H, Seidel T, et al.: Tropheryma whippelii DNA in saliva of patients without Whiple’s disease. Infection 2000, 28:219–222.
Street S, Donoghue H, Neild G: Tropheryma whippelii DNA in saliva of healthy people. Lancet 1999, 354:1178–1179. Another report of the possible presence of T. whipplei DNA in saliva of healthy subjects.
Ehrbar H, Bauerfeind P, Dutly F, et al.: PCR-positive tests for Tropheryma whippelii in patients without Whipple’s disease. Lancet 1999, 353:2214. This paper reports for the first time the possible presence of T. whipplei DNA in duodenal biospy of healthy subjects.
Fenollar F, Fournier P, Gerolami R, et al.: Quantitative detection of Tropheryma whipplei DNA by real-time PCR. J Clin Microbiol 2002, 40:1119–1120.
Amsler L, Bauerfeind P, Nigg C, et al.: Prevalence of Tropheryma whipplei DNA in patients with various gastrointestinal disease and in healthy controls. Infection 2003, 31:81–85.
Marth T, Neurath M, Cuccherini B, Strober W: Defects of monocyte interleukin 12 production and humoral immunity in Whipple’s disease. Gastroenterology 1997, 113:442–448.
Fenollar F, Lepidi H, Gerolami R, et al.: Whipple’s disease associated with giardiasis. J Infect Dis 2003, in press.
Wilson K, Blitchington R, Frothingham R, Wilson J: Phylogeny of the Whipple’s-disease associated bacterium. Lancet 1991, 338:474–475.
Hinrikson H, Dutly F, Altwegg M: Evaluation of a specific nested PCR targeting domain III of the 23S rRNA gene of ‘Tropheryma Whippelii’ and proposal of a classification system for its molecular variants. J Clin Microbiol 2000, 38:595–599.
Maiwald M, Ditton H, von Herbay A, et al.: Reassessment of the phylogenetic position of the bacterium associated with Whipple’s disease and determination of the 16S-23S ribosomal intergenic spacer sequence. Int J Syst Bacteriol 1996, 46:1078–1082.
Hinrikson H, Dutly F, Altwegg M: Homogeneity of 16S-23S ribosomal intergenic spacer regions of Tropheryma whippelii in Swiss patients with Whipple’s disease. J Clin Microbiol 1999, 37:152–166.
Bentley S, Maiwald M, Murphy L, et al.: Sequencing and analysis of the genome of the Whipple’s disease bacterium Tropheryma whipplei. Lancet 2003, 361:637–644. This paper describes the full genome sequence of a strain of T. whipplei.
Raoult D, Audic S, Robert C, et al.: The Tropheryma whipplei genome illustrates the diversity of gene loss patterns in small genome bacterial pathogens. Genome Res 2003, in press. Another paper describing the full genome sequence of a strain of T. whipplei.
Raoult D, Birg M, La Scola B, et al.: Cultivation of the bacillus of Whipple’s disease. N Engl J Med 2000, 342:620–625. This paper describes the isolation and establishment of the first strain of T. whipplei. This important discovery has led to a better understanding of Whipple’s disease.
Raoult D, La Scola B, Lecocq P, et al.: Culture and immunological detection of Tropheryma whippelii from the duodenum of a patient with Whipple disease. JAMA 2001, 285:1039–1043. This paper describes the first isolation of a strain of T. whipplei from a duodenal biopsy.
Ghigo E, Capo C, Aurouze M, et al.: The survival of Tropheryma whipplei, the agent of Whipple’s disease, requires phagosome acidification. Infect Immun 2002, 70:1501–1506.
Misbah S, Ozols B, Franks A, Mapstone N: Whipple’s disease without malabsorption: new atypical features. Q J Med 1997, 90:765–772.
Pu’echal X: Whipple’s disease and arthritis. Curr Opin Rheumatol 2001, 13:74–79.
Mur Villacampa M: Presentacion inusual de la enfermedad de Whipple. Rev Esp Enf Digest 1987, 72:183.
Schultz M, Hartmann A, Dietmaier W, et al.: Massive steatosis hepatis: an unusual manifestation of Whipple’s disease. Am J Gastroenterol 2002, 97:771–772.
Gerard A, Sarrot-Reynaud F, Liozon E, et al.: Neurologic presentation of Whipple: report of 12 cases and review of the literature. Medicine 2002, 81:443–457.
Fenollar F, Lepidi H, Raoult D: Whipple’s endocarditis: review of the literature and comparisons with Q fever, Bartonella infection, and blood culture-positive endocarditis. Clin Infect Dis 2001, 33:1309–1316.
Khairy P, Graham A: Whipple’s disease and the heart. Can Cardiol 1996, 12:831–834.
Chan R, Yannuzzi L, Foster C: Ocular Whipple’s disease: earlier definitive diagnosis. Ophtalmology 2001, 108:2225–2231.
Drancourt M, Bodaghi B, Le Hoang P, et al.: Culture of Tropheryma whipplei from the vitreous fluid of a patient presenting with unilateral uveitis. Ann Intern Med 2003, in press.
Liang Z, La Scola B, Raoult D: Monoclonal antibodies to immunodominant epitope of Tropheryma whipplei. Clin Diagn Lab Immunol 2002, 9:156–159.
Lepidi H, Fenollar F, Gerolami R, et al.: Whipple’s disease: immunospecific and quantitative immunohistochemical study of intestinal biopsies. Human Pathol 2003, 34:589–596.
Lepidi H, Costedoat N, Piette J, et al.: Immunohistological detection of Tropheryma whipplei (Whipple bacillus) in lymph nodes. Am J Med 2002, 113:334–336.
Baisden B, Lepidi H, Raoult D, et al.: Diagnosis of Whipple disease by immunohistochemical analysis: a sensitive and specific method for the detection of Tropheryma whipplei (the Whipple bacillus) in paraffin-embedded tissue. Am J Clin Pathol 2002, 118:742–748.
Dumler J, Baisden S, Raoult D: Immunodetection of Tropheryma whipplei intestinal tissues of Dr Whipple’s patient. N Engl J Med 2003, 348:1411–1412. This paper describes the positivity of the immunochemistry performed on the duodenal biopsy sampled in 1907 in the patient described by GH Whipple.
Fenollar F, Raoult D: Molecular techniques in Whipple’s disease. Expert Rev Mol Diagn 2001, 1:299–309.
Ramzan N, Loftus E, Burgart L, et al.: Diagnosis and monitoring of Whipple disease by polymerase chain reaction. Ann Intern Med 1997, 126:520–527.
La Scola B, Fenollar F, Fournier P, et al.: Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple’s disease bacillus. Int J Syst Evol Microbiol 2001, 51:1471–1479.
Fenollar F, Birg ML, Gauduchon V, Raoult D: Culture of Tropheryma whipplei from human samples: a three year experience from 1999 to 2002. J Clin Microbiol 2003, in press.
Morgenegg S, Maibach R, Chaperon D, et al.: Antibodies against recombinant heat shock protein 65 of Tropheryma whipplei in patients with and without Whipple’s disease. J Microbiol Met 2001, 47:299–306.
Feurle G, Marth T: An evaluation of antimicrobial treatment for Whipple’s disease-tetracyline versus trimethoprim-sulfamethoxazole. Dig Dis Sci 1994, 39:1642–1648.
Vital-Durand D, Lecomte C, Cathebras P, et al.: Whipple’s disease-clinical review of 52 cases. The SNFMI Research Group On Whipple Disease. Societe Nationale Francaise de Medecine Interne. Medicine 1997, 76:170–184.
Masselot F, Boulos A, Maurin M, et al.: Molecular evaluation of antibiotic susceptibility: Tropheryma whipplei paradigm. Antimicrob Agents Chemoter 2003, 47:1658–1664.
Schneider T, Stallmach A, von Herbay A, et al.: Treatment of refractory Whipple disease with interferon-gamma. Ann Intern Med 1998, 129:875–877.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fenollar, F., Raoult, D. Whipple’s disease. Curr Gastroenterol Rep 5, 379–385 (2003). https://doi.org/10.1007/s11894-003-0050-6
Issue Date:
DOI: https://doi.org/10.1007/s11894-003-0050-6