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Reminiscences on the occasion of the Whipple’s disease centenary: a summary paper


Authors: Z. Kojecký 1;  L. Benýšek 1;  I. Krč 1;  J. Ehrmann 1;  R. Koďousek 2;  J. Malinský 3
Authors‘ workplace: II. interní klinika Lékařské fakulty UP a FN Olomouc, přednosta doc. MUDr. Vlastimil Procházka, CSc. 1;  Ústav patologie Lékařské fakulty UP a FN Olomouc, přednosta doc. MUDr. Martin Tichý, CSc. 2;  Ústav histologie a embryologie Lékařské fakulty UP Olomouc, přednosta prof. MUDr. Václav Lichnovský, DrSc. 3
Published in: Vnitř Lék 2008; 54(3): 287-304
Category: From the History of Medicine

Overview

The disease referred to eponymically as Whipple’s disease (WD) in medical literature was thoroughly described by the American physician and pathologist George Hoyot Whipple (1878–1976) in 1907 and given a temporary denomination of „intestinal lipodystrophy“. According to literature, WD is rare, but its precise incidence has not yet been established. Familial incidence of the disease is acknowledged, and its immunogenetic pathogenesis is assumed. The incidence of WD is prevailingly observed in middle-aged men (mean age 55), exceptionally at child age – the ratio being 3 to 6 for men and women, respectively. 1. Clinical diagnosis is based on symptoms in the GIT region and, in rare cases, on extraintestinal symptoms. Clinical symptomatology includes: abdominal pain with persistent diarrhoea (steatorrhoea), symptoms typical of malabsorption connected with weight loss, fevers, polyarthritic symptoms, swollen lymph nodes and, in part of patients, skin hyperpigmentation. Anaemia and hypoalbuminaemia (reduced IgA) are typically detected in laboratory tests. Rarer extraintestinal symptoms of the disease are of a diverse nature: cardiac lesions, cerebral lesions, ocular symptoms, conspicuous or even tumour-like enlargement of lymph nodes, lesions of the hemopoietic system. The clinical course of WD is of progressive or remittent nature and the disease is fatal without treatment. Long-term therapy with antibiotics, especially a combination of tetracyclines (doxycyclin) and corticoids (dexametazone), or chloramphenicol in case of cerebral lesion, have a significantly positive effect on the course and prognosis of WD. From the point of view of pathology, WD is a multisystem infectious disease (Tropheryma whipplei) primarily affecting the GIT (39, 47, 52, 103) or different extraintestinal locations. Due to the known diversity of clinical symptoms, no clinical-diagnostic standard has been established for WD. Differential diagnosis includes different multisystem diseases, primarily malignant lymphomas (especially Hodgkin’s disease). From the pathogenetic point of view, we can either assume the effect of a particular cytokine (or TNFα) activating macrophage phagocytosis or, if its production is normal, a disorder or defect of the respective receptor in the macrophage cellular membrane. The identification of „Whipple’s bacteria“ – Tropheryma whipplei – gen. nov. et sp. nov. was made possible by modern molecular biology research methodologies. Its cultivation allows both for the acquisition of the specific antibody and of detailed knowledge of its genoma (PCR, 16S rRNA sequencing).

Key words:
Whipple’s disease – etiopathogenesis – Tropheryma whipplei – therapy with antibiotics


Sources

1. Adams CWM, Ayres J, Fagg NLK et al. Lymph-vesel embolism in case of Whipple’s diseages. Histopathology 1985; 9: 109-115.

2. Adams WR, Wolfsohn AW, Spiro HM. Some morphologic characteristics of Whipple’s disease. Amer J Path 1963; 42: 415-429.

3. Allchin WH, Hebb RG. Lymphangiectasis intestini. Trans Path Soc Lond 1895; 46: 221-223.

4. Altwegg MH, Fleish-Marx A, Goldenberger D et al. Spondylodiscitis caused by Tropheryma whippelii. Schweiz Med Wschr 1996; 126: 1495-1499.

5. Aust CH, Smith EB. Whipple’s disease in a 3-Month-Old Infant with involvement of bone marrow. Amer J Clin Path1962; 37: 66.

6. Baisden BL, Lepidi H, Raoult D et al. Diagnosis of Whipple disease by immunohistochemical analysis. A sensitive and specific method for detection of Tropheryma whipplei (the Whipple bacillus) in paraffin-embedded tissue. Amer J Clin Pathol 2002; 118: 742-748.

7. Bentley SD, Mainwald M, Murphy LD et al. Sequencing and analysis of the genome of the Whipple´s disease bacterium Tropheryma whipplei. Lancet 2003; 361:637-644.

8. Black-Schäffer B. The tinctorial demonstration of a glykoprotein in Whipple’s disease. Soc Exp Biol Med 1949; 72: 225-227.

9. Cabot RC. New Engl J Med 1997; 337: 1612-1619.

10. Caroli J, Prévot A-R, Julien C et al. L’étiologie bactérienne de la maladie de Whipple. III. A propos d’une nouvelle observation. Isolement de Corynebacterium anaerobium. Arch Mal Appar Digest 1963; 52: 177.

11. Cohen AS, Schimmel EM, Holt PR et al. Ultrastructural abnormalities in Whipple’s disease. Proc Soc Exp Biol Med 1960; 105: 411.

12. Crane J, Aguilar MJ. Obliterative lymphangitis of the mesentery in Whipple’s disease. Gastroenterology 1957; 32: 513.

13. DeBoulay CE. An immunohistochemical study of Whipple’s disease using the immunoperoxidase technique. Hum Pathol 1982; 13: 925-929.

14. Deriban G, Marth T. Current concepts of immunopathogenesis, diagnosis and therapy in Whipple´s disease. Curr Med Chem 2006; 13/24: 2921-2926.

15. Desnues B, Ihring M, Raoult D et al. Whipple’s disease: a macrophage disease. Clin Vaccine Imunology 2006; 13/2: 170-178.

16. Desnues B, Lepidi H, Raoult D et al. Whipple disease: intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated macrophages. J Infect Dis 2005; 192: 1642-1646.

17. Desnues B, Raoult D, Mede JL. IL-16 is critical for Tropheryma whipplei replication in Whipple’s disease. The Journ of Immunology 2005; 175: 4575-4582.

18. Dreier J, Szabados F, von Herbay A et al. Tropheryma whipplei of an acellular porcine heart valve bioprosthesis in a patient who did not have intestinal Whipple’s disease. J Clin Microbiol 2004; 42/10: 4487-4493.

19. Durand DV, Lecomte C, Cathelras P et al. Whipple disease. Clinical review of 52 cases. Medicine (Baltimore) 1997; 76: 170-184.

20. Dušek J, Koďousek R, Myšák J et al. Diseminovaná infekce vyvolaná Mycobacterium intracellulareavium. Cesk Patol 1981; 17/2: 101-108.

21. Dušek J, Tichý T, Koďousek R. Postižení srdce u Whippleovy choroby. Přednáška na XXVI.Vědeckém sjezdu Čs. patologů, Praha 16.-17.6.1999.

22. Dulty F, Altwegg M. Whipple’s disease and „Tropheryma whippelii“. Clin Microbiol Rev 2001; 14: 561-583.

23. Dutly F, Hinrikson HP, Seidel T et al. Tropheryma whippelii DNA in saliva of patients without Whipple’s disease. Infection 2000; 28: 219-222.

24. Dvořáček Č, Mores A, Neoral L. Generalizovaná BCG vakcína. Rozhl Tuberk 1959; 19: 107.

25. Dybkaer R, Kok N. Bacteria in Whipple’s disease 3. Studies in two patients of antibodies in serum and cutaneous hypersensitivity against some bacterial antigens. Acta Path Microbiol Scand 1965; 64: 373.

26. Eck M, Kreipe H, Harmsen D et al. Invasion and destruction of mucosal plasma cells by Tropheryma whippelii. Hum Pathol 1997; 28/12: 1424-1428.

27. Ehrbar HU, Bauerfeind P, Dutly F et al. PCR-positive tests for Tropheryma whippelii in patients without Whipple’s disease. Lancet 1999; 353: 2214.

28. Elliott GB, Hill M, Howard DLG. Whipple’s disease associated with benign Thymoma. Canad Med Ass J 1961; 85: 1340.

29. Fenollar F, Fournier PE, Robert C et al. Use of genome selected repeated sequences increases the sensitivity of PCR detection of Tropheryma whipplei. J Clin Microbiol 2004; 42: 401-403.

30. Fenollar F, Raoult D Whipple’s disease. Cur Gastroenterol Rep 2003; 5(5): 379-385.

31. Finďo P, Valach V, Fukal J. Whippleova choroba. Vnitř Lék 1986; 32: 715-719.

32. Frič P, Šobra J, Bednář B et al. Whippleova choroba. Vnitř Lék 1963; 9(8): 782-790.

33. Genot S, Stein A, Lepidi H et al. Murine model of infection by Tropheryma whipplei. Inf a Immun 2006; 74(8): 4915-4917.

34. Ghigo E, Capo C, Aurouze M et al. Survival of the Tropheryma whipplei, the agent of Whipple’s disease, requires phagosome acidification. Infect Immun 2002; 70: 1501-1506.

35. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23-35.

36. Greenberger NJ, DeLor CJ, Fisher J et al. Whipple’s disease. Characterization of anaerobic Corynebacteria and demonstration of bacilli in vascular endothelium. Digestive Dis 1971; 16/12: 1127-1136.

37. Haubrich WS, Watson JHL, Sieracki JC. Unique morphologic features of Whipple’s disease. Gastroenterology 1960; 39: 454.

38. Hinrikson HP, Dutly F, Nair S et al. Detection of three different types of Tropheryma whippelii directly from clinical specimens by sequencing,single-strand conformation polymorphism (SSCP) analysis and type-specific PCR of their 16S-23S ribosomal intergenic spacer region. Int J Syst Bacteriol 1999; 49: 1701-1706.

39. Chears WC, Ashworth CT. Electron microscopic study of the intestinal mucosa in Whipple’s disease. Demonstration of encapsulated bacilliform bodies in the lesion. Gastroenterology 1961; 41: 129-138.

40. Cho CW, Linscheer MA, Hirschkorn A et al. Sarcoid-like granulomas as an early manifestion of Whipple disease. Gastroenterology 1984; 87: 941-947.

41. Julien C, Caroli J, Etévé J. Considerations thérapeutiques et pathogéniques sur la maladie de Whipple. I. La guérison de la maladie de Whipple par les antibiotiques? A propos d’un cas personel traité par l’auréomycine. Arch Mal Appar Digest 1963; 52: 31.

42. Kjaerheim A et al. Bacteria in Whipple’s disease.Isolation of a haemophillus strain from the jejunal propria. Acta Path Micr Scand 1966; 66: 135-142.

43. Koďousek R. Encefalopatie při Whippleově nemoci. Přednáška Komise pro neuropatologii, Praha 6. 12. 1968.

44. Koďousek R, Kojecký Z. Die Encephalopathie bei der Whipple’schen Krankheit. Acta Univ Palacki Olom (fac med) 1968; 51: 153-161.

45. Koďousek R, Kojecký Z. Beitrag zur Pathologie und Pathogenese der Encephalopathie bei der Whipple’schen Krankheit. 1. Donau-Symposium für Neuropathologie, Wien 7. 5. 1969.

46. Koďousek R, Kojecký Z. On the basic of cerebral lesions in Whipple’s disease. Rev of czechoslovak medicine 1971; 17(3): 137-143.

47. Koďousek R, Malínský J, Kojecký Z et al. Nové bioptické a elmi nálezy u Whippleovy choroby (včetně průkazu grampozitivních bakterií ve střevní sliznici). Předn. v Čs. gastroenterol. 1963; 7/5: 290-294.

48. Koďousek R, Kojecký Z, Blatný J et al. Příspěvek histochemie a elektronové mikroskopie k problematice Whippleovy choroby. Čsl gastroenterologie 1963; 17/5: 290-294.

49. Koďousek R, Kojecký Z, Blatný J et al. Histochemical and electronoptic analysis of the intestinal mucosa and its clinical importance. Acta Univ Palacki Olom (fac med) 1963; 33: 41-54.

50. Kojecký Z, Benýšek L, Koďousek R. Vlastní sonda pro biopsii tenkého střeva. (New designet tube for biopsy of the small intestine). Čs Gastroenterol 1962; 16: 520-523.

51. Kojecký Z, Koďousek R. Études histo-enzymatiques de la muquese intestinala dans les carcinoïdes malins. Archive des Maladie de l’Appareil Digestif et des Maladies de la Nutrition 1961; 50: 1194-1196.

52. Kojecký Z, Malínský J, Koďousek R et al. Frequence of ocurrence of microbes in the intestinal mucosa and in the lymph nodes during a long term observation of a patient suffering from Whipple’s disease. Gastroenterologia (Basel) 1964; 101: 163-172.

53. Kojecký Z, Malínský J, Koďousek R et al. Observation de l’existence de microbes dans la muqueuse intestinale chez un malade atteint de maladine de Whipple survivant pendant deux ans. Acta Gastroenterol Belg 1964; 27/10: 502.

54. Kopřiva F, Michál V, Paroulek J et al. Cervival adenitis caused by Mycobacterium chelonae. Čs pediatr. 1998; 53(Suppl 1): 56-57.

55. Krč I, Ehrmann J, Kojecký Z et al. Whippleova choroba. Postgrad Med 1999; 1(4): 39-43.

56. Kurtz M, Davis TD, Ruffin JM. Light and electron microscopic studies of Whipple’s disease. Lab Investig 1962; 11: 653.

57. Lamberty J, Varela PY, Font RG et al. Whipple’s disease, light and electron microscopic study. Arch Pathol 1974; 97: 325-330.

58. Lammas DA, DeHeer E, Edgar JD et al. Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutation in the Interleukin 12- dependent Interferon gamma production pathway. Int J Exper Pathol 2002; 83: 1-20.

59. Lampert P, Tom M, Cumings JN. Encephalopathy in Whipple’s disease. Neurology 1962; 12: 65-71.

60. LaScola B, Fenollar F, Fournier PE et al. Description of Tropheryma whipplei gen. nov., sp. nov. The Whipple’s disease bacillus. Internat Journ of Systematic and Evolutionary Microbiology 2001; 51: 1471-1479.

61. Levaditi JC, Prévot AR, Caroli J et al. Histological peculiarities of the experimental disease induced in rabbits by inoculation of Corynebacterium anaerobium strains isolated from Whipple’s disease. Ann Inst Pasteur (Paris) 1965; 109/1: 144-147.

62. Maiwald M. Detection of Tr. whipplei DNA in a patient with AIDS. J Clin Microbiol 1995; 33: 1354-1356.

63. Mainwald M, Schuhmacher F, Ditton HJ et al. Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 1968; 64: 760-762.

64. Mainwald M, von Herbay A, Fredricks DN et al. Cultivation of Tropheryma whipplei from cerebrospinal fluid. J Infect Dis 2003; 188: 801-808.

65. Maizel H, Ruffin M, Dobbins WO Whipple’s disease. A review of 19 patients from one Hospital and Review of the Literature since 1950. Medicine 1970; 49: 175-205.

66. Marín M, Muñoz P, Sánchez M et al. Tropheryma whipplei infective endocarditis as the only manifestation of Whipple’s disease. J Clin Microbiol 2007; 45/6: 2078-2081.

67. Maršálek E, Kojecký Z et al. Nocardia pulm. sp. in Whipple’s disease. Gastroenterologia (Basel) 1964; 101: 163-172.

68. Marth T, Raoult D. Whipple’s disease. Lancet 2003; 361: 239-246.

69. Maxwell JD et al. M. Whipple. Lancet 1968; 1: 887.

70. Misbach SA, Mapstone NP. Whipple’s disease revisited. J Clin Pathol 2000; 53: 750-755.

71. Morgan AD. The first recorded case of Whipple’s disease? Gut 1961; 2: 370-372.

72. Müller SA, Vogt P, Altwegg M et al. Deadly carousal or difficult interpretation of new diagnostic tools for Whipple’s disease: case report and review of the literature. Infection 2005; 33/1: 39-42.

73. Ortiz-Hidalgo C George H. Whipple. Nobel Price in 1934, Whipple’s disease, pernicious anemia and other contributions to medicine. Gac Med Mex 2002; 138/4: 371-376.

74. Paulley JW. Whipple’s disease. Acta Gastroenterol Belg 1964; 27: 519.

75. Prévot AR, Morel C. Noveau cas de maladine de Whipple a Corynebacterium anaerobium guérie par antibiotherapie. Bull Acad Nat Med (Paris) 1964; 148: 540.

76. Ramzan NN, Loftus E, Burgart LF et al. Diagnosis and monitoring of Whipple’s disease by polymerase chain reaction. Ann Intern Med 1997; 126: 520-527.

77. Raoult D, Birg ML, LaScola B et al. Cultivation of the bacillus of Whipple’s disease. N Engl J Med 2000; 342: 620-625.

78. Raoult D, LaScola B, Lecocq P et al. Culture and immunological detection of Tropheryma whippelii from duodenum of a patient with Whipple’s disease. JAMA 2001; 285: 1039-1049.

79. Raoult D, Ogata H, Audic S et al. Tropheryma whipplei twist: a human pathogenic actinobacteria with a reduced genome. Genome Res 2003; 13: 1800-1809.

80. Ratliff NB, McMahon IT, Naab TJ et al. Whipple’s disease in the porcine leaflets of a Carpentier-Edwards prosthetic mitral valve. N Engl J Med 1984; 311: 902-903.

81. Relman DA, Schmidt TM, MacDermott RP et al. Identification of the uncultured bacillus of Whipple’s disease. N Engl J Med 1992; 327: 293-301.

82. Renesto P, Crapoulet N, Ogata H et al. Genome - based design of a cell-free culture medium for Tropheryma whipplei. Lancet 2003; 362: 447-449.

83. Rickman DS et al. Uveitis caused by Tr. whipplei (Whipple’s bacillus). N Engl J Med 1995; 332: 363-366.

84. Rodarte JR, Garrison CO, Holley KE et al. Whipple’s disease simulating sarcoidosis. A case with unique clinical and histological features. Arch Int Med 1972; 129: 479-482.

85. Rolain JM, Fenollar F, Raoult D. False positive PCR detection of Tropheryma whipplei in the saliva of healthy people. BMC Microbiol 2007; 7: 48.

86. Rouillon A, Menkes CJ, Gerstner JC et al. Sarcoid-like forms of Whipple’s disease. Report of 2 cases. J Rheumatol 1993; 20: 1070-1072.

87. Rutishauser E, Borer F. Cellules histiocytaires PAS-positives dans la maladine de Whipple. Schweiz Med Wschr 1959; 89: 397.

88. Rutishuser E, deWeck A. Réticulo-endothéliose cutanée dans la maladine de Whipple. Dermatologica 1957; 115: 358.

89. Sharma OP. Unusual systemic disorders associated with interstitial lung disease. Curr Opin Pulm Med 2001; 7(5): 291-294.

90. Schneider T, Stallmach A, von Herbay A et al. Treatment of refractory Whipple’s disease with interferon-gamma. Ann Intern Med 1998; 129: 875-877.

91. Schoedon G, Goldenberger D, Forrer R et al. Deactivation of macrophages with Interleukin-4 is the key to isolation of Tropheryma whippelii. J Infect Dis 1997; 176: 672-677.

92. Schochet SS, Lampert PW Granulomatous encephalitis in Whipple’s disease. Acta Neuropathol (Berl) 1969; 13: 1-11.

93. Sieracki JC Whipple’s disease; Observations on systemic involvement I. Cytologic observations. Arch Pathol 1958; 66: 464-467.

94. Sieracki JC, Fine G, Horn RC et al. Central nervous system involvement in Whipple’s disease. J Neuropathol Exper Neurol 1960; 19: 70-75.

95. Silva MT, Macedo PM, Moura Nues JF. Ultrastructure of bacilli and bacillary origin of the macrophagic inclusions in Whipple’s disease. J Gen Microbiol 1985; 131: 1001-1013.

96. Southern JF, Moscicki RA, Magro C et al. Lymphedema, lymphocytic myocarditis and sarcoid-like granulomatosis. Manifestations of Whipple’s disease. JAMA 1989; 261: 1467-1470.

97. Street S, Donoghu HD, Neild GH Tropheryma whippelii DNA in saliva of healthy people. Lancet 1999; 354: 1178-1179.

98. Upton AC. Histochemical investigations of the mesenchymal lesions in Whipple’s disease. Amer J Clin Pathol 1952; 22: 775.

99. Vorreith M, Vitovská M, Pazderka V. Intestinální lipodystrofie (Whippleova choroba). Čas Lék Čes 1958; 97: 1250.

100. Whipple GH. A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Johns Hopk Hosp Bull 1907; 18: 382-391.

101. Wilson KH, Blitchinton R, Frothingham R et al. Phylogeny of the Whipple’s disease associated bacterium. Lancet 1991; 338: 474-475.

102. Yardley JH, Fleming WH. Whipple’s disease: A note regarding PAS-positive granules in the original case. Johns Hopkins Hosp Bull 1961; 109: 86.

103. Yardley JH, Hendrix TR. Combined electron and light microscopy in Whipple’s disease. Demonstration of „bacillary bodies“ in the intestine. Johns Hopkins Hosp Bull 1961; 109: 80.

104. Zinkernagel AS, Gmur R, Fenner L et al. Marginal and subgingival plaque - a natural habitat of Tropheryma whipplei? Infection 2003; 31: 86-91.

105. Dobbins WO. The diagnosis of Whipple’s disease. N Engl J Med 1995; 332: 390-392.

106. Amsler L, Bauerfeind P, Nigg C et al. Prevalence of Tr. whipplei DNA in patients with various gastrointestinal diseases and in healthy controls. Infection 2003; 31: 81-85.

107. Mainwald M, Ditton HJ, 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.

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