Eosinophilic esophagitis pathophysiology: Difference between revisions

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{{Eosinophilic esophagitis}}
{{Eosinophilic esophagitis}}
 
{{CMG}};{{AE}}{{Ajay}}
==Overview==
==Overview==
[[Eosinophilic esophagitis]] is an immunoallergic disorder resulting from the interaction between genetics and environmental triggers such as repeated exposure to food and aeroallergens. Patients presenting with [[Eosinophilic esophagitis|EoE]] have a history of elevated [[serum]] [[Immunoglobulin E|IgE]] levels, response to interventions such as diet restriction, history of food [[hypersensitivity]]. [[Eosinophils]] originate from CD34+ [[myeloid]] precursor cells in the [[bone marrow]], mature to a granulated state and migrate to [[vascular]] spaces. The [[eosinophils]] are absent in an otherwise normal [[esophagus]], the presence of the [[eosinophils]] in the [[esophagus]] suggests [[GERD]] or [[EoE]]. They tend to be present in all layers of the [[esophagus]] in [[Eosinophilic esophagitis|EoE]], but predominate in the [[lamina propria]] and [[Submucosa|submucosal]] regions. The documented [[cytokine]] expression profile in the [[esophageal]] [[tissue]] of [[EoE]] patients is that of a [[T helper cell|TH2]] [[inflammatory]] response. [[IL-5]] and [[Interleukin 13|IL-13]] are produced by the type-2 helper T cells ([[Th2]]) in response to the [[antigenic]] [[proteins]] from the [[food]] or [[inhalation]]. [[IL-13]] further stimulates the [[epithelial]] cells of the [[esophagus]] to produce large proteins to induce a gene called eotaxin-3, which in turn recruits [[eosinophils]] from the peripheral blood into the tissue. [[IL-5]] prolongs the survival of the [[eosinophils]]. The activated [[TH2-cells|TH2]] response leads to the recruitment and activation of [[Mast cells]] [[degranulate]] and cause tissue damage and repair. [[Cytokines]] produced by TH-1 cells are [[Tumour necrosis factor|tumor necrosis factor]] (TNF)-α, Interferon (IFN)-γ, [[TNF-α]] is expressed by the [[epithelial cells]] of the [[esophagus]] whereas the INF-γ is upregulated by the [[Peripheral T cells lymphoma|peripheral T cells.]] Delayed or type- IV [[hypersensitivity]] is the mechanism is involved in the [[Eosinophilic esophagitis|EoE]] rather than the non-IgE. It is postulated that the [[EoE]]-defining [[endoscopic]] and [[histologic]] manifestations are a culmination of the disease process which, may have debilitating long-term effects including [[strictures]] and food impactions in untreated or poorly managed cases of [[EoE]]. CD34+ [[myeloid]] precursor cells in the [[bone marrow]] produce [[eosinophils]] and then the [[eosinophils]] develop granulation and migrate to [[vascular]] spaces. [[Eosinophils]] although present in all the layers of the [[esophagus]] in patients with [[EoE]], they are predominant in the lamina propria and [[submucosa]] of the [[esophagus]]. The preformed [[granule]] [[proteins]] of the [[eosinophils]] are ECP- Eosinophil Cationic Protein, MBP- [[Major basic protein|Major Basic Protein]], EPO- Eosinophil [[Peroxidase]], EDN- [[Eosinophil]] Derived [[Neurotoxin]]. Upon the stimulation and the degranulation, the [[eosinophils]] release the [[granule]] [[proteins]] into the tissues. [[Eosinophils]] synthesize and release [[cytokines]] such as [[Interleukin 5|IL-5]], [[Interleukin 13|IL-13]], Transforming growth factor (TGF)-α and -β, [[Chemokines]] (eotaxins and RANTES), Lipid mediators such as platelet activating factor ([[PAF]]) and [[leukotriene]] C4. [[Interleukin 5|IL-5]], [[IL-13]], and [[granulocyte]]-[[macrophage]] colony stimulating factor ([[GM-CSF]]) can cause the [[maturation]] and migration of the [[eosinophils]]. [[Eosinophils]] cause [[inflammation]] in the [[EoE]] patients by the following mechanisms [[Angiogenic]] [[molecules]] from the [[eosinophils]] recruits the [[inflammatory]] [[cells]] and the increase the [[vascularity]]. [[Fibrogenic]] [[Mediator|mediators]] such as TGF-β1 and [[matrix]] [[metalloproteinase]] 9 (MMP)-9 causes the [[airway]] remodeling. MBP and MMP-9 disrupt the integrity of the [[epithelial cells]] of the [[esophageal]] through their involvement in [[smooth muscles]], [[fibroblasts]], and [[Cell adhesion molecule|cell-adhesion]] [[molecules]]. The above-mentioned processes lead to tissue remodeling eventually causing an overall [[esophageal]] [[Dysfunctional|dysfunction]]. [[TGF-β]] and [[eosinophilic]] [[granule]] [[proteins]] MBP and EPO are the key [[eosinophil]] [[Effector cell|effector]] [[proteins]]. The importance of [[eosinophils]] in mediating tissue [[fibrosis]] is supported by evidence in both [[murine]] and human models. These findings not only highlight the importance of targeting [[fibrosis]] reversal in treatment of [[EoE]], but also underline the importance of [[eosinophils]] in tissue remodeling.
[[Eosinophilic esophagitis]] is an immunoallergic disorder resulting from the interaction between genetics and environmental triggers such as repeated exposure to food and aeroallergens. Patients presenting with [[Eosinophilic esophagitis|EoE]] have a history of elevated [[serum]] [[Immunoglobulin E|IgE]] levels, response to interventions such as diet restriction, history of food [[hypersensitivity]]. [[Eosinophils]] originate from CD34+ [[myeloid]] precursor cells in the [[bone marrow]], mature to a granulated state and migrate to [[vascular]] spaces. The [[eosinophils]] are absent in an otherwise normal [[esophagus]], the presence of the [[eosinophils]] in the [[esophagus]] suggests [[GERD]] or [[EoE]]. They tend to be present in all layers of the [[esophagus]] in [[Eosinophilic esophagitis|EoE]], but predominate in the [[lamina propria]] and [[Submucosa|submucosal]] regions. The documented [[cytokine]] expression profile in the [[esophageal]] [[tissue]] of [[EoE]] patients is that of a [[T helper cell|TH2]] [[inflammatory]] response. [[IL-5]] and [[Interleukin 13|IL-13]] are produced by the type-2 helper T cells ([[Th2]]) in response to the [[antigenic]] [[proteins]] from the [[food]] or [[inhalation]]. [[IL-13]] further stimulates the [[epithelial]] cells of the [[esophagus]] to produce large proteins to induce a gene called eotaxin-3, which in turn recruits [[eosinophils]] from the peripheral blood into the tissue. [[IL-5]] prolongs the survival of the [[eosinophils]]. The activated [[TH2-cells|TH2]] response leads to the recruitment and activation of [[Mast cells]] [[degranulate]] and cause tissue damage and repair. [[Cytokines]] produced by TH-1 cells are [[Tumour necrosis factor|tumor necrosis factor]] (TNF)-α, Interferon (IFN)-γ, [[TNF-α]] is expressed by the [[epithelial cells]] of the [[esophagus]] whereas the INF-γ is upregulated by the [[Peripheral T cells lymphoma|peripheral T cells.]] Delayed or type- IV [[hypersensitivity]] is the mechanism is involved in the [[Eosinophilic esophagitis|EoE]] rather than the non-IgE. It is postulated that the [[EoE]]-defining [[endoscopic]] and [[histologic]] manifestations are a culmination of the disease process which, may have debilitating long-term effects including [[strictures]] and food impactions in untreated or poorly managed cases of [[EoE]]. CD34+ [[myeloid]] precursor cells in the [[bone marrow]] produce [[eosinophils]] and then the [[eosinophils]] develop granulation and migrate to [[vascular]] spaces. [[Eosinophils]] although present in all the layers of the [[esophagus]] in patients with [[EoE]], they are predominant in the lamina propria and [[submucosa]] of the [[esophagus]]. The preformed [[granule]] [[proteins]] of the [[eosinophils]] are ECP- Eosinophil Cationic Protein, MBP- [[Major basic protein|Major Basic Protein]], EPO- Eosinophil [[Peroxidase]], EDN- [[Eosinophil]] Derived [[Neurotoxin]]. Upon the stimulation and the degranulation, the [[eosinophils]] release the [[granule]] [[proteins]] into the tissues. [[Eosinophils]] synthesize and release [[cytokines]] such as [[Interleukin 5|IL-5]], [[Interleukin 13|IL-13]], Transforming growth factor (TGF)-α and -β, [[Chemokines]] (eotaxins and RANTES), Lipid mediators such as platelet activating factor ([[PAF]]) and [[leukotriene]] C4. [[Interleukin 5|IL-5]], [[IL-13]], and [[granulocyte]]-[[macrophage]] colony stimulating factor ([[GM-CSF]]) can cause the [[maturation]] and migration of the [[eosinophils]]. [[Eosinophils]] cause [[inflammation]] in the [[EoE]] patients by the following mechanisms [[Angiogenic]] [[molecules]] from the [[eosinophils]] recruits the [[inflammatory]] [[cells]] and the increase the [[vascularity]]. [[Fibrogenic]] [[Mediator|mediators]] such as TGF-β1 and [[matrix]] [[metalloproteinase]] 9 (MMP)-9 causes the [[airway]] remodeling. MBP and MMP-9 disrupt the integrity of the [[epithelial cells]] of the [[esophageal]] through their involvement in [[smooth muscles]], [[fibroblasts]], and [[Cell adhesion molecule|cell-adhesion]] [[molecules]]. The above-mentioned processes lead to tissue remodeling eventually causing an overall [[esophageal]] [[Dysfunctional|dysfunction]]. [[TGF-β]] and [[eosinophilic]] [[granule]] [[proteins]] MBP and EPO are the key [[eosinophil]] [[Effector cell|effector]] [[proteins]]. The importance of [[eosinophils]] in mediating tissue [[fibrosis]] is supported by evidence in both [[murine]] and human models. These findings not only highlight the importance of targeting [[fibrosis]] reversal in treatment of [[EoE]], but also underline the importance of [[eosinophils]] in tissue remodeling.


==Pathophysiology==
==Pathophysiology==
* The [[pathophysiology]] of the [[Eosinophilic esophagitis|EoE]] is as follows:<ref name="pmid25499460">{{cite journal |vauthors=Malhotra N, Levine J |title=Eosinophilic esophagitis: an autoimmune esophageal disorder |journal=Curr Probl Pediatr Adolesc Health Care |volume=44 |issue=11 |pages=335–40 |year=2014 |pmid=25499460 |doi=10.1016/j.cppeds.2014.10.004 |url=}}</ref><ref name="pmid26051952">{{cite journal |vauthors=Martin LJ, Franciosi JP, Collins MH, Abonia JP, Lee JJ, Hommel KA, Varni JW, Grotjan JT, Eby M, He H, Marsolo K, Putnam PE, Garza JM, Kaul A, Wen T, Rothenberg ME |title=Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease |journal=J. Allergy Clin. Immunol. |volume=135 |issue=6 |pages=1519–28.e8 |year=2015 |pmid=26051952 |pmc=4460579 |doi=10.1016/j.jaci.2015.03.004 |url=}}</ref><ref name="pmid25216976">{{cite journal |vauthors=Lucendo AJ, Arias A, Tenias JM |title=Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis |journal=Ann. Allergy Asthma Immunol. |volume=113 |issue=6 |pages=624–9 |year=2014 |pmid=25216976 |doi=10.1016/j.anai.2014.08.004 |url=}}</ref><ref name="pmid22939463">{{cite journal |vauthors=López-Colombo A |title=[Eosinophilic esophagitis] |language=Spanish; Castilian |journal=Rev Gastroenterol Mex |volume=77 Suppl 1 |issue= |pages=1–3 |year=2012 |pmid=22939463 |doi=10.1016/j.rgmx.2012.07.002 |url=}}</ref><ref name="pmid24117638">{{cite journal |vauthors=Chehade M, Lucendo AJ, Achem SR, Souza RF |title=Causes, evaluation, and consequences of eosinophilic esophagitis |journal=Ann. N. Y. Acad. Sci. |volume=1300 |issue= |pages=110–8 |year=2013 |pmid=24117638 |doi=10.1111/nyas.12243 |url=}}</ref><ref name="pmid23797116">{{cite journal |vauthors=Straumann A |title=Eosinophilic esophagitis: a bulk of mysteries |journal=Dig Dis |volume=31 |issue=1 |pages=6–9 |year=2013 |pmid=23797116 |doi=10.1159/000347095 |url=}}</ref><ref name="pmid22307811">{{cite journal |vauthors=Straumann A |title=Eosinophilic esophagitis: rapidly emerging disorder |journal=Swiss Med Wkly |volume=142 |issue= |pages=w13513 |year=2012 |pmid=22307811 |doi=10.4414/smw.2012.13513 |url=}}</ref><ref name="pmid21429051">{{cite journal |vauthors=Schoepfer AM, Simon D, Straumann A |title=Eosinophilic oesophagitis: latest intelligence |journal=Clin. Exp. Allergy |volume=41 |issue=5 |pages=630–9 |year=2011 |pmid=21429051 |doi=10.1111/j.1365-2222.2011.03739.x |url=}}</ref><ref name="pmid21987875">{{cite journal |vauthors=Godat S, Moradpour D, Schoepfer A |title=[Eosinophilic esophagitis: update 2011] |language=French |journal=Rev Med Suisse |volume=7 |issue=307 |pages=1678–80, 1682 |year=2011 |pmid=21987875 |doi= |url=}}</ref><ref name="pmid14997131">{{cite journal |vauthors=Potter JW, Saeian K, Staff D, Massey BT, Komorowski RA, Shaker R, Hogan WJ |title=Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features |journal=Gastrointest. Endosc. |volume=59 |issue=3 |pages=355–61 |year=2004 |pmid=14997131 |doi= |url=}}</ref>
* The [[pathophysiology]] of the EoE is as follows:<ref name="pmid25499460">{{cite journal |vauthors=Malhotra N, Levine J |title=Eosinophilic esophagitis: an autoimmune esophageal disorder |journal=Curr Probl Pediatr Adolesc Health Care |volume=44 |issue=11 |pages=335–40 |year=2014 |pmid=25499460 |doi=10.1016/j.cppeds.2014.10.004 |url=}}</ref><ref name="pmid26051952">{{cite journal |vauthors=Martin LJ, Franciosi JP, Collins MH, Abonia JP, Lee JJ, Hommel KA, Varni JW, Grotjan JT, Eby M, He H, Marsolo K, Putnam PE, Garza JM, Kaul A, Wen T, Rothenberg ME |title=Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease |journal=J. Allergy Clin. Immunol. |volume=135 |issue=6 |pages=1519–28.e8 |year=2015 |pmid=26051952 |pmc=4460579 |doi=10.1016/j.jaci.2015.03.004 |url=}}</ref><ref name="pmid25216976">{{cite journal |vauthors=Lucendo AJ, Arias A, Tenias JM |title=Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis |journal=Ann. Allergy Asthma Immunol. |volume=113 |issue=6 |pages=624–9 |year=2014 |pmid=25216976 |doi=10.1016/j.anai.2014.08.004 |url=}}</ref><ref name="pmid22939463">{{cite journal |vauthors=López-Colombo A |title=[Eosinophilic esophagitis] |language=Spanish; Castilian |journal=Rev Gastroenterol Mex |volume=77 Suppl 1 |issue= |pages=1–3 |year=2012 |pmid=22939463 |doi=10.1016/j.rgmx.2012.07.002 |url=}}</ref><ref name="pmid24117638">{{cite journal |vauthors=Chehade M, Lucendo AJ, Achem SR, Souza RF |title=Causes, evaluation, and consequences of eosinophilic esophagitis |journal=Ann. N. Y. Acad. Sci. |volume=1300 |issue= |pages=110–8 |year=2013 |pmid=24117638 |doi=10.1111/nyas.12243 |url=}}</ref><ref name="pmid23797116">{{cite journal |vauthors=Straumann A |title=Eosinophilic esophagitis: a bulk of mysteries |journal=Dig Dis |volume=31 |issue=1 |pages=6–9 |year=2013 |pmid=23797116 |doi=10.1159/000347095 |url=}}</ref><ref name="pmid22307811">{{cite journal |vauthors=Straumann A |title=Eosinophilic esophagitis: rapidly emerging disorder |journal=Swiss Med Wkly |volume=142 |issue= |pages=w13513 |year=2012 |pmid=22307811 |doi=10.4414/smw.2012.13513 |url=}}</ref><ref name="pmid21429051">{{cite journal |vauthors=Schoepfer AM, Simon D, Straumann A |title=Eosinophilic oesophagitis: latest intelligence |journal=Clin. Exp. Allergy |volume=41 |issue=5 |pages=630–9 |year=2011 |pmid=21429051 |doi=10.1111/j.1365-2222.2011.03739.x |url=}}</ref><ref name="pmid21987875">{{cite journal |vauthors=Godat S, Moradpour D, Schoepfer A |title=[Eosinophilic esophagitis: update 2011] |language=French |journal=Rev Med Suisse |volume=7 |issue=307 |pages=1678–80, 1682 |year=2011 |pmid=21987875 |doi= |url=}}</ref><ref name="pmid14997131">{{cite journal |vauthors=Potter JW, Saeian K, Staff D, Massey BT, Komorowski RA, Shaker R, Hogan WJ |title=Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features |journal=Gastrointest. Endosc. |volume=59 |issue=3 |pages=355–61 |year=2004 |pmid=14997131 |doi= |url=}}</ref>
* [[Eosinophilic esophagitis]] is an immunoallergic disorder resulting from the interaction between genetics and environmental triggers such as repeated exposure to food and aeroallergens.
* [[Eosinophilic esophagitis]] is an immunoallergic disorder resulting from the interaction between genetics and environmental triggers such as repeated exposure to food and aeroallergens.


* Patients presenting with [[Eosinophilic esophagitis|EoE]] have a history of:  
* Patients presenting with EoE have a history of:  
** Elevated [[serum]] [[Immunoglobulin E|IgE]] levels  
** Elevated [[serum]] [[Immunoglobulin E|IgE]] levels  
** Response to interventions such as diet restriction  
** Response to interventions such as diet restriction  
** History of food [[hypersensitivity]]
** History of food [[hypersensitivity]]


* [[Eosinophils]] originate from CD34+ [[myeloid]] precursor cells in the [[bone marrow]], mature to a granulated state and migrate to [[vascular]] spaces.
* [[Eosinophils]] originate from CD34+ [[myeloid]] precursor cells in the [[bone marrow]], mature to a granulated state and migrate to the [[vascular]] spaces.
* The [[eosinophils]] are absent in an otherwise normal [[esophagus]], the presence of the [[eosinophils]] in the [[esophagus]] suggests [[GERD]] or [[EoE]].
* The [[eosinophils]] are absent in an otherwise normal [[esophagus]], the presence of the [[eosinophils]] in the [[esophagus]] suggests [[GERD]] or EoE.
*They tend to be present in all layers of the [[esophagus]] in [[Eosinophilic esophagitis|EoE]], but predominate in the [[lamina propria]] and [[Submucosa|submucosal]] regions.  
*They tend to be present in all layers of the [[esophagus]] in EoE, but predominate in the [[lamina propria]] and [[Submucosa|submucosal]] regions.  
* The documented [[cytokine]] expression profile in the [[esophageal]] [[tissue]] of [[EoE]] patients is that of a [[T helper cell|TH2]] [[inflammatory]] response.
* The documented [[cytokine]] expression profile in the [[esophageal]] [[tissue]] of patients is that of a [[T helper cell|TH2]] [[inflammatory]] response.
* [[IL-5]] and [[Interleukin 13|IL-13]] are produced by the type-2 helper T cells ([[Th2]]) in response to the [[antigenic]] [[proteins]] from the [[food]] or [[inhalation]].  
* [[IL-5]] and [[Interleukin 13|IL-13]] are produced by the type-2 helper T cells ([[Th2]]) in response to the [[antigenic]] [[proteins]] from the [[food]] or [[inhalation]].  
* [[IL-13]] further stimulates the [[epithelial]] cells of the [[esophagus]] to produce large proteins to induce a gene called eotaxin-3, which in turn recruits [[eosinophils]] from the peripheral blood into the tissue.  
* [[IL-13]] further stimulates the [[epithelial]] cells of the [[esophagus]] to produce large proteins to induce a gene called eotaxin-3, which in turn recruits [[eosinophils]] from the peripheral blood into the tissue.  
Line 27: Line 27:
* [[Cytokines]] produced by TH-1 cells are  
* [[Cytokines]] produced by TH-1 cells are  
** '''[[Tumour necrosis factor|Tumor necrosis factor]] (TNF)-α'''  
** '''[[Tumour necrosis factor|Tumor necrosis factor]] (TNF)-α'''  
** '''Interferon (IFN)-γ'''  
** '''[[Interferon-gamma|Interferon (IFN)-γ]]'''  
* [[TNF-α]] is expressed by the [[epithelial cells]] of the [[esophagus]] whereas the INF-γ is upregulated by the [[Peripheral T cells lymphoma|peripheral T cells.]]
* [[TNF-α]] is expressed by the [[epithelial cells]] of the [[esophagus]] whereas [[Interferon-gamma|INF-γ]] is upregulated by the [[Peripheral T cells lymphoma|peripheral T cells.]]
* Delayed or type- IV [[hypersensitivity]] is the mechanism is involved in the [[Eosinophilic esophagitis|EoE]] rather than the non-IgE.
* Delayed or type- IV [[hypersensitivity]] is the mechanism is involved in the EoE.
*It is postulated that the [[EoE]]-defining [[endoscopic]] and [[histologic]] manifestations are a culmination of the disease process which, may have debilitating long-term effects including [[strictures]] and food impactions in untreated or poorly managed cases of [[EoE]].
*It is postulated that the EoE-defining [[endoscopic]] and [[histologic]] manifestations are a culmination of the disease process which, may have debilitating long-term effects including [[strictures]] and food impactions in untreated or poorly managed cases of EoE.
 
* CD34+ [[myeloid]] precursor cells in the [[bone marrow]] produce [[eosinophils]] and then the [[eosinophils]] develop granulation and migrate to [[vascular]] spaces.
* [[Eosinophils]] although present in all the layers of the [[esophagus]] in patients with [[EoE]], they are predominant in the lamina propria and [[submucosa]] of the [[esophagus]].
* The preformed [[granule]] [[proteins]] of the [[eosinophils]] are
* The preformed [[granule]] [[proteins]] of the [[eosinophils]] are
**'''ECP'''- Eosinophil Cationic Protein
**'''ECP'''- Eosinophil Cationic Protein
Line 43: Line 40:
**'''[[Interleukin 5|IL-5]]'''
**'''[[Interleukin 5|IL-5]]'''
**'''[[Interleukin 13|IL-13]]'''  
**'''[[Interleukin 13|IL-13]]'''  
**'''Transforming growth factor (TGF)-α and -β'''  
**'''[[Transforming growth factor]] [[TGF alpha|(TGF)-α]] and [[TGF beta|-β]]'''  
**'''[[Chemokines]] (eotaxins and RANTES)'''
**'''[[Chemokines]] (eotaxins and RANTES)'''
**'''Lipid mediators such as platelet activating factor ([[PAF]]) and [[leukotriene]] C4'''
**'''Lipid mediators such as platelet activating factor ([[PAF]]) and [[leukotriene]] C4'''
* [[Interleukin 5|IL-5]], [[IL-13]], and [[granulocyte]]-[[macrophage]] colony stimulating factor ([[GM-CSF]]) can cause the [[maturation]] and migration of the [[eosinophils]].
* [[Interleukin 5|IL-5]], [[IL-13]], and [[granulocyte]]-[[macrophage]] colony stimulating factor ([[GM-CSF]]) can cause the [[maturation]] and migration of the [[eosinophils]].


* [[Eosinophils]] cause [[inflammation]] in the [[EoE]] patients by the following mechanisms
* [[Eosinophils]] cause [[inflammation]] in the EoE patients by the following mechanisms
** [[Angiogenic]] [[molecules]] from the [[eosinophils]] recruits the [[inflammatory]] [[cells]] and the increase the [[vascularity]].  
** [[Angiogenic]] [[molecules]] from the [[eosinophils]] recruits the [[inflammatory]] [[cells]] and increase the [[vascularity]].  
** [[Fibrogenic]] [[Mediator|mediators]] such as TGF-β1 and [[matrix]] [[metalloproteinase]] 9 (MMP)-9 causes the [[airway]] remodeling.
** [[Fibrogenic]] [[Mediator|mediators]] such as [[TGF beta|TGF-β1]] and [[matrix]] [[metalloproteinase]] 9 (MMP)-9 causes the [[airway]] remodeling.
** MBP and MMP-9 disrupt the integrity of the [[epithelial cells]] of the [[esophageal]] through their involvement in [[smooth muscles]], [[fibroblasts]], and [[Cell adhesion molecule|cell-adhesion]] [[molecules]].  
** MBP and MMP-9 disrupt the integrity of the [[epithelial cells]] of the [[esophageal|esophagus]] through their involvement in the [[smooth muscles]], [[fibroblasts]], and [[Cell adhesion molecule|cell-adhesion]] [[molecules]].  
** The above-mentioned processes lead to tissue remodeling eventually causing an overall [[esophageal]] [[Dysfunctional|dysfunction]].
** The above-mentioned processes lead to tissue remodeling eventually, causing an overall [[esophageal]] [[Dysfunctional|dysfunction]].
**[[TGF-β]] and [[eosinophilic]] [[granule]] [[proteins]] MBP and EPO are the key [[eosinophil]] [[Effector cell|effector]] [[proteins]]. The importance of [[eosinophils]] in mediating tissue [[fibrosis]] is supported by evidence in both [[murine]] and human models.  
**[[TGF-β]] and [[eosinophilic]] [[granule]] [[proteins]] MBP and EPO are the key [[eosinophil]] [[Effector cell|effector]] [[proteins]]. The importance of [[eosinophils]] in mediating tissue [[fibrosis]] is supported by evidence in both [[murine]] and human models.  
**These findings not only highlight the importance of targeting [[fibrosis]] reversal in treatment of [[EoE]], but also underline the importance of [[eosinophils]] in tissue remodeling.
**These findings not only highlight the importance of targeting [[fibrosis]] reversal in the treatment of EoE, but also underline the importance of [[eosinophils]] in tissue remodeling.


===Gross Pathology===
===Gross Pathology===
Line 74: Line 71:
===Histopathology===
===Histopathology===
*Characteristic features are as follows:
*Characteristic features are as follows:
**Criteria is: > 20 eosinophils/0.24 mm2.  
**> 20 eosinophils/0.24 mm2.  
**Papillae are elongated
**Papillae are elongated
**Papillae reach into the top 1/3 of the epithelial layer
**Papillae reach into the top 1/3 of the epithelial layer

Latest revision as of 20:43, 19 December 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ajay Gade MD[2]]

Overview

Eosinophilic esophagitis is an immunoallergic disorder resulting from the interaction between genetics and environmental triggers such as repeated exposure to food and aeroallergens. Patients presenting with EoE have a history of elevated serum IgE levels, response to interventions such as diet restriction, history of food hypersensitivity. Eosinophils originate from CD34+ myeloid precursor cells in the bone marrow, mature to a granulated state and migrate to vascular spaces. The eosinophils are absent in an otherwise normal esophagus, the presence of the eosinophils in the esophagus suggests GERD or EoE. They tend to be present in all layers of the esophagus in EoE, but predominate in the lamina propria and submucosal regions. The documented cytokine expression profile in the esophageal tissue of EoE patients is that of a TH2 inflammatory response. IL-5 and IL-13 are produced by the type-2 helper T cells (Th2) in response to the antigenic proteins from the food or inhalation. IL-13 further stimulates the epithelial cells of the esophagus to produce large proteins to induce a gene called eotaxin-3, which in turn recruits eosinophils from the peripheral blood into the tissue. IL-5 prolongs the survival of the eosinophils. The activated TH2 response leads to the recruitment and activation of Mast cells degranulate and cause tissue damage and repair. Cytokines produced by TH-1 cells are tumor necrosis factor (TNF)-α, Interferon (IFN)-γ, TNF-α is expressed by the epithelial cells of the esophagus whereas the INF-γ is upregulated by the peripheral T cells. Delayed or type- IV hypersensitivity is the mechanism is involved in the EoE rather than the non-IgE. It is postulated that the EoE-defining endoscopic and histologic manifestations are a culmination of the disease process which, may have debilitating long-term effects including strictures and food impactions in untreated or poorly managed cases of EoE. CD34+ myeloid precursor cells in the bone marrow produce eosinophils and then the eosinophils develop granulation and migrate to vascular spaces. Eosinophils although present in all the layers of the esophagus in patients with EoE, they are predominant in the lamina propria and submucosa of the esophagus. The preformed granule proteins of the eosinophils are ECP- Eosinophil Cationic Protein, MBP- Major Basic Protein, EPO- Eosinophil Peroxidase, EDN- Eosinophil Derived Neurotoxin. Upon the stimulation and the degranulation, the eosinophils release the granule proteins into the tissues. Eosinophils synthesize and release cytokines such as IL-5, IL-13, Transforming growth factor (TGF)-α and -β, Chemokines (eotaxins and RANTES), Lipid mediators such as platelet activating factor (PAF) and leukotriene C4. IL-5, IL-13, and granulocyte-macrophage colony stimulating factor (GM-CSF) can cause the maturation and migration of the eosinophils. Eosinophils cause inflammation in the EoE patients by the following mechanisms Angiogenic molecules from the eosinophils recruits the inflammatory cells and the increase the vascularity. Fibrogenic mediators such as TGF-β1 and matrix metalloproteinase 9 (MMP)-9 causes the airway remodeling. MBP and MMP-9 disrupt the integrity of the epithelial cells of the esophageal through their involvement in smooth muscles, fibroblasts, and cell-adhesion molecules. The above-mentioned processes lead to tissue remodeling eventually causing an overall esophageal dysfunction. TGF-β and eosinophilic granule proteins MBP and EPO are the key eosinophil effector proteins. The importance of eosinophils in mediating tissue fibrosis is supported by evidence in both murine and human models. These findings not only highlight the importance of targeting fibrosis reversal in treatment of EoE, but also underline the importance of eosinophils in tissue remodeling.

Pathophysiology

  • Patients presenting with EoE have a history of:

Gross Pathology

  • Endoscopy of the esophagus: Eosinophilic esophagitis Source: Wikimedia

    Endoscopy of the esophagus: Eosinophilic esophagitis
    Source: Wikimedia


Histopathology

  • Characteristic features are as follows:
    • > 20 eosinophils/0.24 mm2.
    • Papillae are elongated
    • Papillae reach into the top 1/3 of the epithelial layer
    • Basal cell hyperplasia; > 3 cells thick or >15% of epithelial thickness
H&E stain of esophagus biopsy showing eosinophilic esophagitis, manifested by an infiltration of eosinophils in the lamina propria

References

  1. ↑ Malhotra N, Levine J (2014). "Eosinophilic esophagitis: an autoimmune esophageal disorder". Curr Probl Pediatr Adolesc Health Care. 44 (11): 335–40. doi:10.1016/j.cppeds.2014.10.004. PMID 25499460.
  2. ↑ Martin LJ, Franciosi JP, Collins MH, Abonia JP, Lee JJ, Hommel KA, Varni JW, Grotjan JT, Eby M, He H, Marsolo K, Putnam PE, Garza JM, Kaul A, Wen T, Rothenberg ME (2015). "Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease". J. Allergy Clin. Immunol. 135 (6): 1519–28.e8. doi:10.1016/j.jaci.2015.03.004. PMC 4460579. PMID 26051952.
  3. ↑ Lucendo AJ, Arias A, Tenias JM (2014). "Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis". Ann. Allergy Asthma Immunol. 113 (6): 624–9. doi:10.1016/j.anai.2014.08.004. PMID 25216976.
  4. ↑ López-Colombo A (2012). "[Eosinophilic esophagitis]". Rev Gastroenterol Mex (in Spanish; Castilian). 77 Suppl 1: 1–3. doi:10.1016/j.rgmx.2012.07.002. PMID 22939463.
  5. ↑ Chehade M, Lucendo AJ, Achem SR, Souza RF (2013). "Causes, evaluation, and consequences of eosinophilic esophagitis". Ann. N. Y. Acad. Sci. 1300: 110–8. doi:10.1111/nyas.12243. PMID 24117638.
  6. ↑ Straumann A (2013). "Eosinophilic esophagitis: a bulk of mysteries". Dig Dis. 31 (1): 6–9. doi:10.1159/000347095. PMID 23797116.
  7. ↑ Straumann A (2012). "Eosinophilic esophagitis: rapidly emerging disorder". Swiss Med Wkly. 142: w13513. doi:10.4414/smw.2012.13513. PMID 22307811.
  8. ↑ Schoepfer AM, Simon D, Straumann A (2011). "Eosinophilic oesophagitis: latest intelligence". Clin. Exp. Allergy. 41 (5): 630–9. doi:10.1111/j.1365-2222.2011.03739.x. PMID 21429051.
  9. ↑ Godat S, Moradpour D, Schoepfer A (2011). "[Eosinophilic esophagitis: update 2011]". Rev Med Suisse (in French). 7 (307): 1678–80, 1682. PMID 21987875.
  10. ↑ Potter JW, Saeian K, Staff D, Massey BT, Komorowski RA, Shaker R, Hogan WJ (2004). "Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features". Gastrointest. Endosc. 59 (3): 355–61. PMID 14997131.
  11. ↑ "Vertical lines in distal esophageal mucosa (VLEM): a true endoscopic manifestation of esophagitis in children? - PubMed - NCBI".
  12. ↑ "Fragility of the esophageal mucosa: a pathognomonic endoscopic sign of primary eosinophilic esophagitis? - PubMed - NCBI".
  13. ↑ "Eosinophilic esophagitis: red on microscopy, white on endoscopy. - PubMed - NCBI".
  14. ↑ "The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis. - PubMed - NCBI".


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