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Whipple's disease Microchapters

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

Overview

Whipple’s disease is a very rare disease. Therefore, some aspects of pathogenesis have remained unclear. Tropheryma whipplei is usually transmitted through oral route to human hosts. There is no known causative genetic factor for Whipple's disease. However, genetic and immunologic factors play important roles on clinical manifestation of T. whipplei infection.

Pathophysiology

Pathogenesis

  • The bacterium lives in soil and wastewater. Farmers and everyone who has any contact with contaminated soil and water are at high risk of the infection. [3]
  • It is transmitted through oro-oral and feco-oral routes. The poor sanitation is associated with T. whipplei infection. [4]
  • It is believed that human being is the only host for this bacterium.[5]
  • It invades intestines primarily and then every other organ including the heart, CNS, joints, lymph nodes, skin, lungs and the eyes. Tissues are infected by macrophage infiltration contaminated by Tropheryma whipplei. T. whipplei multiplies in macrophages and monocytes. [6] Although there is a massive infiltration of the intestinal mucosa with the bacteria, the immunologic response is not adequate to limit the infection. Bacterium-infected macrophages express less CD11b which leads to inappropriate antigen presentation. These macrophages are unable to turn into mature phagosomes and lower the thioredoxin expression. The impairment in Th1 cells differentiation leads to the inability of the immune system to kill the bacteria. [7]
  • Tropheryma whipplei infection causes four different clinical manifestations: acute infection, asymptomatic carrier state, the classic Whipple’s disease, and localized chronic infection.[8] [9]
 
 
 
 
 
 
 
 
 
 
 
Contamination via oro-oral or feco-oral route
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acute infection
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Antibodies production
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Strong immune response
 
 
 
 
Insufficient immune response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete eradication
 
 
 
Chronic carrier
 
Chronic infection
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Classic Whipple's disease
 
 
 
Localized infection
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cure
 
Relapse
 
Re-infection
 
Death
 
 
 
 
 
 

Immunologic response

  • It is believed that host immunologic response to the microorganism plays an important role on the clinical manifestation of the disease.[6]

Genetics

There is no known causative genetic factor for Whipple's disease. However, there is an association between Whipple's disease and some immunologic defects.

  • Studies showed that individuals with specific HLA type (HLA alleles DRB1*13 and DQB1*06) have a higher risk of Whipple's disease. [8]

Associated Conditions

The most important conditions associated with Whipple's disease include:

  • HLA-B27 individuals:
  • Defective T-cell immunity:

Gross Pathology

  • On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

Below images show the characteristic feature of Whipple's disease. foamy macrophages are present in the lamina propria.[11]

  • Low magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[12]

    Low magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[12]

  • Intermediate magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[13]

    Intermediate magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[13]

  • High magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[14]

    High magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[14]

  • Very high magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[15]

    Very high magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)[15]

References

  1. ↑ Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D (2008). "Whipple's disease: new aspects of pathogenesis and treatment". Lancet Infect Dis. 8 (3): 179–90. doi:10.1016/S1473-3099(08)70042-2. PMID 18291339.
  2. ↑ Schwartzman, Sergio; Schwartzman, Monica (2013). "Whipple's Disease". Rheumatic Disease Clinics of North America. 39 (2): 313–321. doi:10.1016/j.rdc.2013.03.005. ISSN 0889-857X.
  3. ↑ Keita, Alpha Kabinet; Diatta, Georges; Ratmanov, Pavel; Bassene, Hubert; Raoult, Didier; Roucher, Clémentine; Fenollar, Florence; Sokhna, Cheikh; Tall, Adama; Trape, Jean-François; Mediannikov, Oleg (2013). "Looking for Tropheryma whipplei Source and Reservoir in Rural Senegal". The American Journal of Tropical Medicine and Hygiene. 88 (2): 339–343. doi:10.4269/ajtmh.2012.12-0614. ISSN 0002-9637.
  4. ↑ Keita, Alpha Kabinet; Brouqui, Philippe; Badiaga, Sékéné; Benkouiten, Samir; Ratmanov, Pavel; Raoult, Didier; Fenollar, Florence (2013). "Tropheryma whipplei prevalence strongly suggests human transmission in homeless shelters". International Journal of Infectious Diseases. 17 (1): e67–e68. doi:10.1016/j.ijid.2012.05.1033. ISSN 1201-9712.
  5. ↑ Marth, Thomas; Moos, Verena; Müller, Christian; Biagi, Federico; Schneider, Thomas (2016). "Tropheryma whipplei infection and Whipple's disease". The Lancet Infectious Diseases. 16 (3): e13–e22. doi:10.1016/S1473-3099(15)00537-X. ISSN 1473-3099.
  6. ↑ 6.0 6.1 Marth T, Strober W (1996). "Whipple's disease". Semin. Gastrointest. Dis. 7 (1): 41–8. PMID 8903578.
  7. ↑ Dolmans, Ruben A. V.; Boel, C. H. Edwin; Lacle, Miangela M.; Kusters, Johannes G. (2017). "Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections". Clinical Microbiology Reviews. 30 (2): 529–555. doi:10.1128/CMR.00033-16. ISSN 0893-8512.
  8. ↑ 8.0 8.1 Marth, Thomas (2009). "New Insights into Whipple's Disease – A Rare Intestinal Inflammatory Disorder". Digestive Diseases. 27 (4): 494–501. doi:10.1159/000233288. ISSN 1421-9875.
  9. ↑ Street, Sara; Donoghue, Helen D; Neild, GH (1999). "Tropheryma whippelii DNA in saliva of healthy people". The Lancet. 354 (9185): 1178–1179. doi:10.1016/S0140-6736(99)03065-2. ISSN 0140-6736.
  10. ↑ Schneider, Thomas; Moos, Verena; Loddenkemper, Christoph; Marth, Thomas; Fenollar, Florence; Raoult, Didier (2008). "Whipple's disease: new aspects of pathogenesis and treatment". The Lancet Infectious Diseases. 8 (3): 179–190. doi:10.1016/S1473-3099(08)70042-2. ISSN 1473-3099.
  11. ↑ https://commons.wikimedia.org
  12. ↑ CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357443
  13. ↑ CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357450
  14. ↑ CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357481
  15. ↑ CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357462

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