Differential Diagnosis of Chronic Diarrhea
New Insights into Whipple’s Disease – A Rare Intestinal Inflammatory DisorderMarth T.
Division of Internal Medicine, Krankenhaus Maria Hilf, Daun, Germany
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Whipple’s disease (WD) is a rare systemic infectious disor- der caused by the actinomycete Tropheryma whipplei. This chronic disease, first described by Whipple as ‘intestinal lipodystrophy’, affects preferentially middle-aged white men who may present with weight loss, diarrhea, abdominal pain and arthralgia. Thus, it represents an important differential diagnosis of chronic diarrhea. A variety of other clinical patterns, such as involvement of the heart, lung, or central nervous system (CNS), are frequent. In addition, individuals with isolated heart valve involvement or asymptomatic carriers may be observed. The diagnosis often is established by small bowel biopsy, which is characterized by periodic acid-Schiff-positive inclusions representing the causative bacteria. T. whipplei can be detected by specific polymerase chain reaction, immunohistochemistry or electron microscopy and was cultured a few years ago. Several studies show that subtle defects of the cell-mediated immunity exist in active and inactive WD which may predispose individuals with a certain HLA type to a clinical manifestation of T. whipplei infection. As confirmed in a recent controlled trial, most patients respond well to a prolonged antibiotic treatment, but some patients with relapsing disease or CNS manifestation may have a poor prognosis. In the presentation, the relevance of WD in the differential diagnosis of chronic diarrhea and the new findings of this enigmatic rare disorder will be discussed.
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Dobbins WO III: Whipple’s Disease. Springfield, Thomas, 1987.
- Dobbins WO III, Ruffin JM: A light- and electron-microscopic study of bacterial invasion in Whipple’s disease. Am J Pathol 1967;51:225–242.
- Trier JS, Phelps PC, Eidelmann S, Rubin CE: Whipple’s disease: light and electron microscope correlation of jejunal mucosal histology with antibiotic treatment and clinical status. Gastroenterology 1965;48:684– 707.
- Relman DA, Schmidt TM, MacDermot RP, Falkow S: Identification of the uncultured bacillus of Whipple’s disease. N Engl J Med 1992;30:293–301.
- Maiwald M, Ditton HJ, von Herbay A, Rainey FA, Stackerbrandt E: 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.
- Raoult D, Birg ML, La Scola B, Fournier PE, Enea M, Lepidi H, Roux V, Piette JC, Vandenesch F, Vital Durand D, Marrie TJ: Cultivation of the bacillus of Whipple’s disease. N Engl J Med 2000;342:620–625.
- Renesto P, Crapoulet N, Ogata H, La Scola B, Vestris G, Claverie JM, Raoult D: Genome-based design of a cell-free culture medium for Tropheryma whipplei. Lancet 2003;362:447–449.
- Maiwald M, Ditton HJ, von Herbay A, Rainey FA, Stackerbrandt E: Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 1999;64:760–762.
- Schöniger-Hekele M, Petermann D, Weber B, Müller CT: Whipplei in the environment: survey of sewage plant influxes and sewage plant workers. Appl Environ Microbiol 2007;73:2033–2035.
- Marth T, Raoult D: Whipple’s disease. Lancet 2003;361:239–246.
- Fenollar F, Fournier PE, Raoult D, Gérolami R, Lepidi H, Poyart C: Quantitative detection of Tropheryma whipplei DNA by real-time PCR. J Clin Microbiol 2002;3:1119–1120.
Maiwald M, von Herbay A, Persing DH, Mitchell PP, Abdelmalek MF, Thorvilson JN, Fredricks DN, Relman DA: Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of Whipple disease. Ann Intern Med 2001;2:115–119.
- Amsler L, Bauernfeind P, Nigg C, Maibach RC, Steffen R, Altwegg M: Prevalence of T. whipplei DNA in patients with various gastrointestinal diseases and in healthy controls. Infection 2003;31:81–85.
- Martinetti M, Biagi F, Badulli C, Feurle GE, Müller C, Moos V, Schneider T, Marth T, Marchese A, Trotta L, Sachetto S, Pasi A, De Silvestri A, Salvaneschi L, Corazza GR: The HLA alleles DRB1*13 and DQB1*06 are associated to Whipple’s disease. Gastroenterology 2009;136:2289–2294.
- Marth T, Roux M, von Herbay A, Meuer SC, Feurle GE: Persistent reduction of complement receptor-3 α-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple’s disease. Clin Immunol Immunopathol 1994;72:217–226.
- Marth T, Neurath M, Cuccherini BA, Stro-ber M: Defects of monocyte interleukin-12 production and humoral immunity in Whipple’s disease. Gastroenterology 1997;113:442–448.
- Eck M, Kreipe H, Harmsen D, Müller-Hermelink HK: Invasion and destruction of mucosal plasma cells by Tropheryma whippelii. Hum Pathol 1997;28:1424–1428.
- Dobbins WO III: Is there a immune deficit in Whipple’s disease? Dig Dis Sci 1981;26:247–252.
- Desnues B, Raoult D, Mege JL: IL-16 is critical for T. whipplei replication in Whipple’s disease. J Immunol 2005;175:4575–4582.
- (a) Desnues B, Lepidi H, Raoult D, Mege JL: Whipple disease: intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated macrophages. J Infect Dis 2005;9:1642–1646. (b) Moos V, Schmidt C, Geelhaar A, Kunkel D, Allers K, Schinnerling K, Loddenkemper C, Fenollar F, Moter A, Raoult D, Ignatius R, Schneider T: Impaired immune functions of monocytes and macrophages in Whipple’s disease. Gastroenterology 2009, Aug 4 [Epub ahead of print].
- Marth T, Kleen N, Stallmach A, Ring S, Aziz S, Schmidt C, Strober W, Zeitz M, Schneider T: Dysregulated peripheral and mucosal Th1/Th2 response in Whipple’s disease. Gastroenterology 2002;123:1468–1477.
- Moos V, Kunkel D, Marth T, Feurle GE, La-Scola B, Ignatius R, Zeitz M, Schneider T: Reduced peripheral and mucosal T. whipplei-specific Th1 response in patients with Whipple’s disease. J Immunol 2006;177:2015–2022.
Fenollar F, Puechal X, Raoult D: Whipple’s disease N Engl J Med 2007;356:55–66.
- Feurle GE, Marth T: An evaluation of antimicrobial treatment for Whipple’s disease: Tetracycline versus trimethoprim-sulfomethoxazole. Dig Dis Sci 1994;39:1642–1648.
- Mahnel R, Kalt A, Ring S, Stallmach A, Strober W, Marth T: Immunosuppressive therapy in Whipple’s disease patients is associated with the appearance of gastrointestinal manifestations. Am J Gastroenterol 2005;100:1167–1173.
- Marth T, Strober W: Whipple’s disease. Semin Gastrointest Dis 1996;7:41–48.
- 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.
- Geissdörfer W, Wittmann I, Seitz G, Cesnjevar R, Röllinghoff M, Schoerner C, Bogdan C: A case of aortic valve disease associated with Tropheryma whippelii infection in the absence of other signs of Whipple’s disease. Infection 2001;29:44–47.
- Gerard A, Sarrot-Reynauld F, Liozon E: Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore) 2002;81:443–457.
- Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D: Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis 2008;8:179–190.
- Louis ED, Lynch T, Kaufmann P, Fahn S, Odel J: Diagnostic guidelines in central nervous system Whipple’s disease. Ann Neurol 1996;40:561–568.
Marth T: Whipple’s disease; in Mandell GL, Dolin JE, Bennett R (eds): Principles and Practice of Infectious Disease, ed 6. Philadelphia, Churchill Livingstone, 2005, pp 1306–1310.
- Rodarte JR, Garrison CO, Holley KE, Fontana RS: Whipple’s disease simulating sarcoidosis. Arch Intern Med 1972;129:479–482.
- Dzirlo L, Hubner M, Mueller C, Blaha B, Formann E, Dellinger C, Petzelbauer P, Muell-auer L, Huber K, Kneussl M, Gschwantler M: A mimic of sarcoidosis. Lancet 2007;369:1832.
- Gillen CD, Coddington R, Monteith PG, Taylor RH: Extraintestinal lymphoma in association with Whipple’s disease. Gut 1993;11:1627–1629.
Fest T, Pron B, Lefranc MP, Pierre C, Angonin R, de Wazières B, Soua Z, Dupond JL: Detection of a clonal BCL2 gene rearrangement in tissues from a patient with Whipple disease. Ann Intern Med 1996;8:738–740.
- Autran B, Gorin I, Leibowitch M, Laroche L, Escande JP, Hewitt J, Marche C: AIDS in a Haitian woman with cardiac Kaposi’s sarcoma and Whipple’s disease. Lancet 1983;8327:767–768.
- Meier-Willersen HJ, Maiwald M, von Herbay A: Whipple’s disease associated with opportunistic infections. Dtsch Med Wochenschr 1993;23:854–860.
- Fenollar F, Lepidi H, Gérolami R, Drancourt H, Raoult D: Whipple disease associated with giardiasis. J Infect Dis 2003;188:828–834.
Geboes, K, Ectors N, Heidbuchel H, Rut-geerts P, Desmet V, Vantrappen G: Whipple’s disease: the value of upper gastrointestinal endoscopy for the diagnosis and follow-up. Acta Gastroenterol Belg 1992;2:209–219.
- Von Herbay A, Ditton HJ, Schuhmacher F, Maiwald M: Whipple’s disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid. Gastroenterology 1997;113:434–441.
- Boulos A, Rolain JM, Raoult D: Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells. Antimicrob Agents Chemother 2004;48:747–752.
- Raoult D, Ogata H, Audic S, Robert C, Suhre K, Drancourt M: Tropheryma whipplei Twist: a human pathogenic Actinobacteria with a reduced genome. Genome Res 2003;13:1800–1809.
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