Details of Disease

General Information of Disease (ID: DISR8WSB)

• Disease Name: Eosinophilic esophagitis
• Synonyms: EoE
• Disease Class: DA24: Oesophagitis
• Definition: Eosinophilic esophagitis (EoE) is a chronic, allergic disease of the esophagus characterized clinically by symptoms of esophageal dysfunction (including vomiting, dysphagia, feeding disorders, food impaction and abdominal pain) which persist after treatment with proton pump inhibitors (PPIs).
• Disease Hierarchy:
  DISHVC9B: Esophagitis
  DISZLHO0: Eosinophilic gastrointestinal disease
  DISR8WSB: Eosinophilic esophagitis
• ICD Code:
  ICD-11: ICD-11: DA24.1
  ICD-9: ICD-9: 530.13
  Expand ICD-11: 'DA24.1
  Expand ICD-9: 530.13
• Disease Identifiers:
  MONDO ID: MONDO_0005361
  MESH ID: D057765
  UMLS CUI: C0341106
  MedGen ID: 83318
  Orphanet ID: 73247
  SNOMED CT ID: 235599003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Cendakimab	DM9LSBJ	Phase 3	Monoclonal antibody	[1]
ABT-308	DM6WN2D	Phase 2	NA	[2]
SHP621	DMB2I83	Phase 2	NA	[2]
EUR-1100	DM6K4J8	Phase 1/2	NA	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 28 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABCB11	TTUXCAF	Limited	Altered Expression	[4]
CCR8	TTE836A	Limited	Altered Expression	[5]
CHIA	TTJB1O0	Limited	Biomarker	[6]
CRLF2	TTRMZ0N	Limited	Genetic Variation	[7]
IL15RA	TTGN89I	Limited	Altered Expression	[8]
KCNJ2	TTH7UO3	Limited	Altered Expression	[9]
KLK7	TTE6GTB	Limited	Altered Expression	[10]
LALBA	TTBRLU3	Limited	Biomarker	[11]
LCT	TTA0OSE	Limited	Genetic Variation	[12]
LRRC32	TT0FAYT	Limited	Biomarker	[13]
LTC4S	TTW7OTG	Limited	Altered Expression	[14]
PTGDR	TTNVEIR	Limited	Altered Expression	[15]
PTGDR2	TTQDMX5	Limited	Altered Expression	[16]
SGSH	TTPJ2SH	Limited	Biomarker	[17]
SLC9A3	TTFZVPO	Limited	Altered Expression	[18]
DNM1	TTE3JW9	moderate	Genetic Variation	[19]
STAT6	TTWOE1T	moderate	Posttranslational Modification	[20]
TNK2	TTIET93	moderate	Biomarker	[21]
AGXT	TTF5NVW	Strong	Biomarker	[22]
ATP4A	TTF1QVM	Strong	Biomarker	[23]
CCL11	TTCF05Y	Strong	Altered Expression	[24]
EPX	TTCIO0M	Strong	Biomarker	[25]
FFAR3	TTXDOHN	Strong	Biomarker	[26]
IL13	TT0GVCH	Strong	Altered Expression	[27]
IL5	TTPREZD	Strong	Altered Expression	[28]
IL5RA	TTXH9AD	Strong	Biomarker	[29]
POSTN	TT8ALTZ	Strong	Altered Expression	[30]
TSLP	TTHMW3T	Definitive	Genetic Variation	[31]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC9C2	DT2N5HO	Limited	Biomarker	[18]
ATP12A	DT5NLZA	Strong	Biomarker	[23]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CPA4	DEXKD7J	Strong	Biomarker	[32]

This Disease Is Related to 56 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AGA	OTNWT1WB	Limited	Biomarker	[33]
CAPN14	OTWKW0Y6	Limited	Genetic Variation	[31]
CEACAM8	OTLL9WWO	Limited	Altered Expression	[34]
CLC	OTYMYR85	Limited	Altered Expression	[16]
COL8A2	OTASWJ69	Limited	Biomarker	[35]
DEFB103B	OT8RWY64	Limited	Altered Expression	[36]
EMSY	OTBQ3KQE	Limited	Biomarker	[37]
FIP1L1	OTF91GTL	Limited	Genetic Variation	[38]
GFER	OTVK43OK	Limited	Biomarker	[17]
HBS1L	OTA3U1N6	Limited	Genetic Variation	[39]
IL9R	OTILCLXA	Limited	Altered Expression	[40]
JAZF1	OTXTYSYD	Limited	Genetic Variation	[41]
KLF13	OTMIKHZ4	Limited	Biomarker	[42]
LRRC31	OT7VCU13	Limited	Altered Expression	[43]
MAPK8IP2	OTDUHLN0	Limited	Altered Expression	[9]
MPG	OTAHW80B	Limited	Altered Expression	[44]
OGDHL	OT1AZK6R	Limited	Biomarker	[45]
OXR1	OTPIDMT3	Limited	Biomarker	[46]
PANK2	OTFBW889	Limited	Biomarker	[17]
PRG2	OT0BCPQG	Limited	Biomarker	[47]
REEP5	OTZU4TJI	Limited	Altered Expression	[15]
RNASE2	OT8Z4FNE	Limited	Biomarker	[48]
RSAD2	OTCA9WCM	Limited	Altered Expression	[45]
SERPINB12	OTB44YPE	Limited	Biomarker	[49]
SPINK5	OT61IIAO	Limited	Altered Expression	[36]
SPRR3	OTN9QJKG	Limited	Altered Expression	[50]
SYNPO	OTICDJAB	Limited	Biomarker	[51]
TFDP1	OT6RZ7VT	Limited	Altered Expression	[15]
ANKRD27	OT5DCXIG	Strong	Genetic Variation	[52]
CAPN5	OTQ8QM7K	Strong	Genetic Variation	[53]
CCDC81	OTW49WA4	Strong	Genetic Variation	[53]
CCL26	OT2B7HR9	Strong	Biomarker	[54]
CEP295NL	OT35QUXS	Strong	Genetic Variation	[53]
CLDN1	OT27KV99	Strong	Altered Expression	[40]
CLDN7	OTNE0XHQ	Strong	Altered Expression	[40]
CLEC16A	OTLGV5SV	Strong	Genetic Variation	[41]
CPA3	OTOK8M0V	Strong	Altered Expression	[55]
DCC	OT2C1SHW	Strong	Genetic Variation	[53]
DHTKD1	OTDQLSNT	Strong	Genetic Variation	[56]
DSG1	OT11HC3A	Strong	Altered Expression	[57]
EPC2	OTTG0W9R	Strong	Biomarker	[58]
FLG	OTE9QDV6	Strong	Altered Expression	[10]
HSF2BP	OTWKP0JC	Strong	Genetic Variation	[53]
IFFO2	OT34XWYM	Strong	Genetic Variation	[53]
KIF17	OTHASX9G	Strong	Genetic Variation	[53]
MEAK7	OT9A8JSO	Strong	Genetic Variation	[59]
MID1	OTWN1PGU	Strong	Altered Expression	[44]
P2RX6	OT1FNTXA	Strong	Genetic Variation	[53]
RHOF	OTPA3F8Q	Strong	Altered Expression	[60]
SAFB	OTGRV2LW	Strong	Biomarker	[61]
SHROOM3	OTQKC5X2	Strong	Genetic Variation	[59]
SIGLEC8	OTQ5TRRV	Strong	Biomarker	[62]
SLC22A18	OT9C3KR4	Strong	Biomarker	[61]
SPINK7	OTK3VOI3	Strong	Biomarker	[63]
TIMP2	OT8S1RRP	Strong	Genetic Variation	[53]
TRIM8	OTS6JFR0	Strong	Biomarker	[64]

References

• [1] ClinicalTrials.gov (NCT05214768) A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Induction and Maintenance Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Japanese Subjects With Eosinophilic Gastroenteritis. U.S.National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] ClinicalTrials.gov (NCT01386112) Safety and Tolerability Study of Oral EUR-1100 to Treat Eosinophilic Esophagitis. U.S. National Institutes of Health.
• [4] Effect of YHHJ on the expression of the hepatocellular bile acid transporters multidrug resistance-associated protein 2 and bile salt export pump in ethinylestradiol-induced cholestasis.Exp Ther Med. 2018 Apr;15(4):3699-3704. doi: 10.3892/etm.2018.5891. Epub 2018 Feb 26.
• [5] Identification of human CCR8 as a CCL18 receptor.J Exp Med. 2013 Sep 23;210(10):1889-98. doi: 10.1084/jem.20130240. Epub 2013 Sep 2.
• [6] Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis.Int Immunopharmacol. 2014 Jan;18(1):35-42. doi: 10.1016/j.intimp.2013.10.026. Epub 2013 Nov 13.
• [7] Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis.J Allergy Clin Immunol. 2010 Jul;126(1):160-5.e3. doi: 10.1016/j.jaci.2010.04.037.
• [8] Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice.Gastroenterology. 2010 Jul;139(1):182-93.e7. doi: 10.1053/j.gastro.2010.03.057. Epub 2010 Apr 8.
• [9] RNA sequencing confirms similarities between PPI-responsive oesophageal eosinophilia and eosinophilic oesophagitis.Aliment Pharmacol Ther. 2018 Jul;48(2):219-225. doi: 10.1111/apt.14825. Epub 2018 Jun 4.
• [10] Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis.Allergy. 2018 Jan;73(1):239-247. doi: 10.1111/all.13244. Epub 2017 Aug 6.
• [11] Specific IgG(4) antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis.J Allergy Clin Immunol. 2018 Jul;142(1):139-148.e12. doi: 10.1016/j.jaci.2018.02.049. Epub 2018 Apr 18.
• [12] The Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Hispanics Undergoing Endoscopy Is Infrequent Compared to Caucasians: A Cross-Sectional Study.Dig Dis Sci. 2017 Dec;62(12):3511-3516. doi: 10.1007/s10620-017-4791-8. Epub 2017 Oct 30.
• [13] Genetics of eosinophilic esophagitis.Mucosal Immunol. 2017 May;10(3):580-588. doi: 10.1038/mi.2017.4. Epub 2017 Feb 22.
• [14] Elevated levels of leukotriene C4 synthase mRNA distinguish a subpopulation of eosinophilic oesophagitis patients.Clin Exp Allergy. 2013 Aug;43(8):902-13. doi: 10.1111/cea.12146.
• [15] Involvement of EP2 and EP4 Receptors in Eosinophilic Esophagitis: A Pilot Study.Dig Dis Sci. 2019 Oct;64(10):2806-2814. doi: 10.1007/s10620-019-05623-5. Epub 2019 Apr 15.
• [16] Differences in eosinophil molecular profiles between children and adults with eosinophilic esophagitis.Allergy. 2017 Sep;72(9):1406-1414. doi: 10.1111/all.13140. Epub 2017 Mar 17.
• [17] Budesonide Oral Suspension Significantly Improves Eosinophilic Esophagitis Histology Scoring System Results: Analyses From a 12-Week, Phase 2, Randomized, Placebo-controlled Trial.Am J Surg Pathol. 2019 Nov;43(11):1501-1509. doi: 10.1097/PAS.0000000000001361.
• [18] Solute carrier family 9, subfamily A, member 3 (SLC9A3)/sodium-hydrogen exchanger member 3 (NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic esophagitis.J Allergy Clin Immunol. 2018 Dec;142(6):1843-1855. doi: 10.1016/j.jaci.2018.03.017. Epub 2018 May 4.
• [19] Independent Neuronal Origin of Seizures and Behavioral Comorbidities in an Animal Model of a Severe Childhood Genetic Epileptic Encephalopathy.PLoS Genet. 2015 Jun 30;11(6):e1005347. doi: 10.1371/journal.pgen.1005347. eCollection 2015 Jun.
• [20] 17-Estradiol protects the esophageal epithelium from IL-13-induced barrier dysfunction and remodeling.J Allergy Clin Immunol. 2019 Jun;143(6):2131-2146. doi: 10.1016/j.jaci.2018.10.070. Epub 2018 Dec 20.
• [21] Mutations in TNK2 in severe autosomal recessive infantile onset epilepsy. Ann Neurol. 2013 Sep;74(3):496-501. doi: 10.1002/ana.23934. Epub 2013 Sep 4.
• [22] Involvement of interleukin-18 in the pathogenesis of human eosinophilic esophagitis.Clin Immunol. 2015 Apr;157(2):103-13. doi: 10.1016/j.clim.2015.01.007. Epub 2015 Jan 28.
• [23] Refractory Heartburn: A Challenging Problem in Clinical Practice.Dig Dis Sci. 2018 Mar;63(3):577-582. doi: 10.1007/s10620-018-4927-5. Epub 2018 Jan 20.
• [24] Immunohistochemical differentiation of eosinophilic esophageal myositis from eosinophilic esophagitis.J Gastroenterol Hepatol. 2017 Jan;32(1):106-113. doi: 10.1111/jgh.13466.
• [25] Normalized serum eosinophil peroxidase levels are inversely correlated with esophageal eosinophilia in eosinophilic esophagitis.Dis Esophagus. 2018 Feb 1;31(2):dox139. doi: 10.1093/dote/dox139.
• [26] Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis.J Clin Invest. 2019 Apr 8;129(5):2014-2028. doi: 10.1172/JCI125917. eCollection 2019 Apr 8.
• [27] RPC4046, a Monoclonal Antibody Against IL13, ReducesHistologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis.Gastroenterology. 2019 Feb;156(3):592-603.e10. doi: 10.1053/j.gastro.2018.10.051. Epub 2018 Nov 2.
• [28] Eosinophilic esophagitis.Allergy Asthma Proc. 2019 Nov 1;40(6):462-464. doi: 10.2500/aap.2019.40.4272.
• [29] Immunological and hematological effects of IL-5(R)-targeted therapy: An overview.Allergy. 2018 Oct;73(10):1979-1988. doi: 10.1111/all.13451. Epub 2018 Oct 8.
• [30] Integrin M activation and upregulation on esophageal eosinophils and periostin-mediated eosinophil survival in eosinophilic esophagitis.Immunol Cell Biol. 2018 Apr;96(4):426-438. doi: 10.1111/imcb.12018. Epub 2018 Mar 6.
• [31] Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications.Clin Rev Allergy Immunol. 2019 Aug;57(1):111-127. doi: 10.1007/s12016-019-08733-0.
• [32] Involvement of mast cells in eosinophilic esophagitis.J Allergy Clin Immunol. 2010 Jul;126(1):140-9. doi: 10.1016/j.jaci.2010.04.009. Epub 2010 Jun 9.
• [33] White Paper AGA: Drug Development for Eosinophilic Esophagitis.Clin Gastroenterol Hepatol. 2017 Aug;15(8):1173-1183. doi: 10.1016/j.cgh.2017.03.016. Epub 2017 Mar 22.
• [34] Immunophenotyping of peripheral eosinophils demonstrates activation in eosinophilic esophagitis.J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):40-7. doi: 10.1097/MPG.0b013e318212647a.
• [35] High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders.J Allergy Clin Immunol. 2013 Aug;132(2):378-86. doi: 10.1016/j.jaci.2013.02.030. Epub 2013 Apr 19.
• [36] Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.Allergy. 2015 Apr;70(4):443-52. doi: 10.1111/all.12570. Epub 2015 Jan 26.
• [37] From genetics to treatment of eosinophilic esophagitis.Curr Opin Allergy Clin Immunol. 2015 Oct;15(5):417-25. doi: 10.1097/ACI.0000000000000200.
• [38] Markers of tyrosine kinase activity in eosinophilic esophagitis: a pilot study of the FIP1L1-PDGFR fusion gene, pERK 1/2, and pSTAT5.Dis Esophagus. 2012 Feb;25(2):166-74. doi: 10.1111/j.1442-2050.2011.01230.x. Epub 2011 Aug 5.
• [39] Variability of hemoglobin F expression in hemoglobin EE disease: hematological and molecular analysis.Blood Cells Mol Dis. 2014 Jun-Aug;53(1-2):11-5. doi: 10.1016/j.bcmd.2014.02.005. Epub 2014 Feb 26.
• [40] Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis.J Pediatr Gastroenterol Nutr. 2019 Feb;68(2):225-231. doi: 10.1097/MPG.0000000000002144.
• [41] Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis.Genes Immun. 2019 Apr;20(4):281-292. doi: 10.1038/s41435-018-0034-z. Epub 2018 Jun 8.
• [42] Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis.J Allergy Clin Immunol. 2018 Feb;141(2):632-637.e5. doi: 10.1016/j.jaci.2017.07.010. Epub 2017 Oct 10.
• [43] LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium.Mucosal Immunol. 2016 May;9(3):744-56. doi: 10.1038/mi.2015.98. Epub 2015 Oct 14.
• [44] TRAIL deficiency and PP2A activation with salmeterol ameliorates egg allergen-driven eosinophilic esophagitis.Am J Physiol Gastrointest Liver Physiol. 2016 Dec 1;311(6):G998-G1008. doi: 10.1152/ajpgi.00151.2016. Epub 2016 Oct 13.
• [45] Whole-exome sequencing uncovers oxidoreductases DHTKD1 and OGDHL as linkers between mitochondrial dysfunction and eosinophilic esophagitis.JCI Insight. 2018 Apr 19;3(8):e99922. doi: 10.1172/jci.insight.99922. eCollection 2018 Apr 19.
• [46] Environmental Enrichment During Adulthood Reduces Sucrose Binge-Like Intake in a High Drinking in the Dark Phenotype (HD) in C57BL/6J Mice.Front Behav Neurosci. 2019 Feb 15;13:27. doi: 10.3389/fnbeh.2019.00027. eCollection 2019.
• [47] Eosinophil granule major basic protein 1 deposition in eosinophilic esophagitis correlates with symptoms independent of eosinophil counts.Dis Esophagus. 2019 Dec 30;32(11):doz055. doi: 10.1093/dote/doz055.
• [48] Blind esophageal brushing offers a safe and accurate method to monitor inflammation in children and young adults with eosinophilic esophagitis.Dis Esophagus. 2018 Dec 1;31(12). doi: 10.1093/dote/doy056.
• [49] SERPINB12 as a possible marker of steroid dependency in children with eosinophilic esophagitis: A pilot study.Dig Liver Dis. 2020 Feb;52(2):158-163. doi: 10.1016/j.dld.2019.08.018. Epub 2019 Oct 23.
• [50] Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis.J Immunol. 2010 Apr 1;184(7):4033-41. doi: 10.4049/jimmunol.0903069. Epub 2010 Mar 5.
• [51] Synaptopodin is upregulated by IL-13 in eosinophilic esophagitis and regulates esophageal epithelial cell motility and barrier integrity.JCI Insight. 2017 Oct 19;2(20):e96789. doi: 10.1172/jci.insight.96789.
• [52] GWAS identifies four novel eosinophilic esophagitis loci.Nat Commun. 2014 Nov 19;5:5593. doi: 10.1038/ncomms6593.
• [53] Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.Nat Genet. 2014 Aug;46(8):895-900. doi: 10.1038/ng.3033. Epub 2014 Jul 13.
• [54] One-Hour Esophageal String Test: A Nonendoscopic Minimally Invasive Test That Accurately Detects Disease Activity in Eosinophilic Esophagitis.Am J Gastroenterol. 2019 Oct;114(10):1614-1625. doi: 10.14309/ajg.0000000000000371.
• [55] A Distinct Esophageal mRNA Pattern Identifies Eosinophilic Esophagitis Patients With Food Impactions.Front Immunol. 2018 Nov 5;9:2059. doi: 10.3389/fimmu.2018.02059. eCollection 2018.
• [56] Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Both Generate Superoxide/H(2)O(2) in a Side Reaction and Each Could Contribute to Oxidative Stress in Mitochondria.Neurochem Res. 2019 Oct;44(10):2325-2335. doi: 10.1007/s11064-019-02765-w. Epub 2019 Mar 7.
• [57] Impedance and Histologic Characteristics of the Sub-Laryngeal Esophagus Distinguish Eosinophilic Esophagitis From Other Esophageal Disorders.Clin Gastroenterol Hepatol. 2020 Jul;18(8):1727-1735.e2. doi: 10.1016/j.cgh.2019.09.032. Epub 2019 Oct 4.
• [58] Identification of anoctamin 1 (ANO1) as a key driver of esophageal epithelial proliferation in eosinophilic esophagitis.J Allergy Clin Immunol. 2020 Jan;145(1):239-254.e2. doi: 10.1016/j.jaci.2019.07.049. Epub 2019 Oct 21.
• [59] Common variants at 5q22 associate with pediatric eosinophilic esophagitis.Nat Genet. 2010 Apr;42(4):289-91. doi: 10.1038/ng.547. Epub 2010 Mar 7.
• [60] KLF4 activates NFB signaling and esophageal epithelial inflammation via the Rho-related GTP-binding protein RHOF.PLoS One. 2019 Apr 18;14(4):e0215746. doi: 10.1371/journal.pone.0215746. eCollection 2019.
• [61] FGF9-induced proliferative response to eosinophilic inflammation in oesophagitis.Gut. 2009 Feb;58(2):166-73. doi: 10.1136/gut.2008.157628. Epub 2008 Oct 31.
• [62] Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis.JCI Insight. 2019 Oct 3;4(19):e126219. doi: 10.1172/jci.insight.126219.
• [63] Role of genetics, environment, and their interactions in the pathogenesis of eosinophilic esophagitis.Curr Opin Immunol. 2019 Oct;60:46-53. doi: 10.1016/j.coi.2019.04.004. Epub 2019 May 25.
• [64] De novo mutations in epileptic encephalopathies. Nature. 2013 Sep 12;501(7466):217-21. doi: 10.1038/nature12439. Epub 2013 Aug 11.