|[[image:LowKECG.png|thumb|700px|center|An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0]]
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==Overview==
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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]].<ref name="pmid18291339">{{cite journal |vauthors=Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D |title=Whipple's disease: new aspects of pathogenesis and treatment |journal=Lancet Infect Dis |volume=8 |issue=3 |pages=179–90 |year=2008 |pmid=18291339 |doi=10.1016/S1473-3099(08)70042-2 |url=}}</ref>
*[[Tropheryma whipplei]] is a [[periodic acid-Schiff stain]] positive, gram-positive [[bacillus]] of [[Actinomycetes]] family.<ref name="SchwartzmanSchwartzman2013">{{cite journal|last1=Schwartzman|first1=Sergio|last2=Schwartzman|first2=Monica|title=Whipple's Disease|journal=Rheumatic Disease Clinics of North America|volume=39|issue=2|year=2013|pages=313–321|issn=0889857X|doi=10.1016/j.rdc.2013.03.005}}</ref>
* 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. <ref name="KeitaDiatta2013">{{cite journal|last1=Keita|first1=Alpha Kabinet|last2=Diatta|first2=Georges|last3=Ratmanov|first3=Pavel|last4=Bassene|first4=Hubert|last5=Raoult|first5=Didier|last6=Roucher|first6=Clémentine|last7=Fenollar|first7=Florence|last8=Sokhna|first8=Cheikh|last9=Tall|first9=Adama|last10=Trape|first10=Jean-François|last11=Mediannikov|first11=Oleg|title=Looking for Tropheryma whipplei Source and Reservoir in Rural Senegal|journal=The American Journal of Tropical Medicine and Hygiene|volume=88|issue=2|year=2013|pages=339–343|issn=0002-9637|doi=10.4269/ajtmh.2012.12-0614}}</ref>
*It is transmitted through oro-oral and feco-oral routes. The poor sanitation is associated with [[Tropheryma whipplei|T. whipplei]] infection. <ref name="KeitaBrouqui2013">{{cite journal|last1=Keita|first1=Alpha Kabinet|last2=Brouqui|first2=Philippe|last3=Badiaga|first3=Sékéné|last4=Benkouiten|first4=Samir|last5=Ratmanov|first5=Pavel|last6=Raoult|first6=Didier|last7=Fenollar|first7=Florence|title=Tropheryma whipplei prevalence strongly suggests human transmission in homeless shelters|journal=International Journal of Infectious Diseases|volume=17|issue=1|year=2013|pages=e67–e68|issn=12019712|doi=10.1016/j.ijid.2012.05.1033}}</ref>
*It is believed that human being is the only host for this bacterium.<ref name="MarthMoos2016">{{cite journal|last1=Marth|first1=Thomas|last2=Moos|first2=Verena|last3=Müller|first3=Christian|last4=Biagi|first4=Federico|last5=Schneider|first5=Thomas|title=Tropheryma whipplei infection and Whipple's disease|journal=The Lancet Infectious Diseases|volume=16|issue=3|year=2016|pages=e13–e22|issn=14733099|doi=10.1016/S1473-3099(15)00537-X}}</ref>
*It invades [[Intestine|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]]. [[Tropheryma whipplei|T. whipplei]] multiplies in [[Macrophage|macrophages]] and [[Monocyte|monocytes]]. <ref name="pmid8903578">{{cite journal |vauthors=Marth T, Strober W |title=Whipple's disease |journal=Semin. Gastrointest. Dis. |volume=7 |issue=1 |pages=41–8 |year=1996 |pmid=8903578 |doi= |url=}}</ref> 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. <ref name="DolmansBoel2017">{{cite journal|last1=Dolmans|first1=Ruben A. V.|last2=Boel|first2=C. H. Edwin|last3=Lacle|first3=Miangela M.|last4=Kusters|first4=Johannes G.|title=Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections|journal=Clinical Microbiology Reviews|volume=30|issue=2|year=2017|pages=529–555|issn=0893-8512|doi=10.1128/CMR.00033-16}}</ref>
* [[Tropheryma whipplei]] infection causes four different clinical manifestations: acute infection, asymptomatic carrier state, the classic Whipple’s disease, and localized chronic infection.<ref name="Marth2009">{{cite journal|last1=Marth|first1=Thomas|title=New Insights into Whipple’s Disease – A Rare Intestinal Inflammatory Disorder|journal=Digestive Diseases|volume=27|issue=4|year=2009|pages=494–501|issn=1421-9875|doi=10.1159/000233288}}</ref> <ref name="StreetDonoghue1999">{{cite journal|last1=Street|first1=Sara|last2=Donoghue|first2=Helen D|last3=Neild|first3=GH|title=Tropheryma whippelii DNA in saliva of healthy people|journal=The Lancet|volume=354|issue=9185|year=1999|pages=1178–1179|issn=01406736|doi=10.1016/S0140-6736(99)03065-2}}</ref>
* It is believed that host immunologic response to the microorganism plays an important role on the clinical manifestation of the disease.<ref name="pmid8903578">{{cite journal |vauthors=Marth T, Strober W |title=Whipple's disease |journal=Semin. Gastrointest. Dis. |volume=7 |issue=1 |pages=41–8 |year=1996 |pmid=8903578 |doi= |url=}}</ref>
*
==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. <ref name="Marth2009">{{cite journal|last1=Marth|first1=Thomas|title=New Insights into Whipple’s Disease – A Rare Intestinal Inflammatory Disorder|journal=Digestive Diseases|volume=27|issue=4|year=2009|pages=494–501|issn=1421-9875|doi=10.1159/000233288}}</ref>
*
==Associated Conditions==
[[image:LowKECG.png|thumb|700px|right|An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0]]
The most important conditions associated with Whipple's disease include:
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* HLA-B27 individuals:
* Defective T-cell immunity:
==Gross Pathology==
{{#ev:youtube|7TWu0_Gklzo}}
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
==Microscopic Pathology==
==Table==
*On microscopic histopathological analysis, [[PAS stain|PAS]]-positive [[Macrophage|macrophages]] in the [[lamina propria]] containing non-acid-fast gram-positive [[bacilli]] are characteristic findings of Whipple's disease.<ref name="SchneiderMoos2008">{{cite journal|last1=Schneider|first1=Thomas|last2=Moos|first2=Verena|last3=Loddenkemper|first3=Christoph|last4=Marth|first4=Thomas|last5=Fenollar|first5=Florence|last6=Raoult|first6=Didier|title=Whipple's disease: new aspects of pathogenesis and treatment|journal=The Lancet Infectious Diseases|volume=8|issue=3|year=2008|pages=179–190|issn=14733099|doi=10.1016/S1473-3099(08)70042-2}}</ref>
Below images show the characteristic feature of Whipple's disease. foamy [[Macrophage|macrophages]] are present in the [[lamina propria]].<ref>https://commons.wikimedia.org</ref>
File:Whipple disease low mag.jpg| Low magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)<ref> CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357443</ref>
File:Whipple disease - intermed mag.jpg| Intermediate magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)<ref> CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357450</ref>
File:Whipple disease high mag.jpg| High magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)<ref> CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357481</ref>
File:Whipple disease very high mag.jpg| Very high magnification micrograph of Whipple's disease. H&E stain. Duodenal biopsy. By Nephron (Own work)<ref> CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15357462</ref>
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==References==
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Latest revision as of 02:27, 23 May 2019
pic
An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0
An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0
