Whipple's disease pathophysiology: Difference between revisions
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{{Family tree | | | | | | | | | A01 | {{Family tree | | | | | | | | | A01 | | | | | | | | |A01= Contamination via oro-oral or feco-oral route}} | ||
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{{Family tree | | | | | | | | | B01 | {{Family tree | | | | | | | | | B01 | | | | | | | | |B01= Acute infection}} | ||
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{{Family tree | | | | | | | | | C01 | {{Family tree | | | | | | | | | C01 | | | | | | | | |C01= Antibodies production}} | ||
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{{Family tree | | | | | D01 | | | | | | D02 | {{Family tree | | | | | D01 | | | | | | D02 | | | | |D01= Strong immune response| D02= Insufficient immune response}} | ||
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{{Family tree | | E01 | | | | E02 | | | E03 | {{Family tree | | E01 | | | | E02 | | | E03 | | | | |E01= Complete eradication|E02= Chronic carrier|E03= Chronic infection}} | ||
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{{Family tree | | | | | | | | | | F01 | | | | F02 | {{Family tree | | | | | | | | | | F01 | | | | F02 | |F01= Classic Whipple's disease|F02= Localized infection}} | ||
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{{family tree | | | | |,|-|-|-|v|-|^|-|v|-|-|-|. | {{Family tree | | | | G01 | | G02 | | G03 | | G04 | |G01= Cure|G02= Relapse|G03= Re-infection|G04= Death}} | ||
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Revision as of 15:06, 6 November 2017
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Whipple's disease Microchapters |
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Whipple's disease pathophysiology On the Web |
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American Roentgen Ray Society Images of Whipple's disease pathophysiology |
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Risk calculators and risk factors for Whipple's disease pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]
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
- Whipple's disease is a rare bacterial systemic infection caused by Tropheryma whipplei.[1]
- Tropheryma whipplei is a periodic acid-Schiff stain positive, gram-positive bacillus of Actinomycetes family.[2]
- 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 Tropheryma whipplei infection.[4]
- It is believed that human being is the only host for this bacterium.[5]
- Tropheryma whipplei invades intestines primarily and then every other organ including the heart, CNS, joints, lymph nodes, lungs, eyes, kidneys, bone marrow, and skin. Tissues are infected by macrophage infiltration contaminated by Tropheryma whipplei. Tropheryma 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 T-helper 1 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 Tropheryma whipplei 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 cellular immunity
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of Whipple's disease.
Microscopic Pathology
- On microscopic histopathological analysis, PAS-positive macrophages in the lamina propria containing non-acid-fast gram-positive bacilli are characteristic findings of Whipple's disease.[10]
Below images show the characteristic feature of Whipple's disease. foamy macrophages are present in the lamina propria.[11]
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 6.0 6.1 Marth T, Strober W (1996). "Whipple's disease". Semin. Gastrointest. Dis. 7 (1): 41–8. PMID 8903578.
- ↑ 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.
- ↑ 8.0 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.
- ↑ 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.
- ↑ 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.
- ↑ https://commons.wikimedia.org