Pediatric Eosinophilic Esophagitis Is Associated With Increased Lamina Propria Immunoglobulin G4‐Positive Plasma Cells

Mohammad, Nur Farahiyah; Avinashi, Vishal; Chan, Edmond S.; Portales-Casamar, Élodie; Bush, Jonathan W.

doi:10.1097/mpg.0000000000001949

Cited by 22 publications

(31 citation statements)

References 19 publications

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“…15 Pediatric EoE patients with active esophagitis have been shown to be associated with increased levels of IgG4-positive plasma cells, particularly in those with a food allergy. 13 Esophageal IgG4 levels in children have also been found to correlate with peak eosinophil count; mean histologic grade; and esophageal IL4, IL13, and IL10 and had strong associations with a subset of the EoE transcriptome. 16 As our study cohort consists purely of adults, comparisons with the aforementioned studies may not be appropriate as the EoE disease process has been shown to be different in adults and children, with progression from an inflammatory to a fibrostenotic phenotype.…”

Section: Discussionmentioning

confidence: 96%

“…Although we confirm that IgG4 stain is significantly more prevalent in EoE than GERD, the specificity is not 100% and is consistent with most previous studies. [11][12][13][14][15][16] In the current study, less than 10% of GERD patients had a positive IgG4 stain, and up to a quarter of EoE patients had a negative IgG4 stain. Overall, our study suggests that the use of IgG4 stain has a positive predictive value of 92% for distinguishing EoE from GERD, which can be valuable in the clinical assessment of undifferentiated presentation.…”

Section: Discussionmentioning

confidence: 96%

“…17 Similarities have been noted between EoE-and IgG4-related disorders (IgG4-RD), such as the development of submucosal fibrosis. 13 However, obliterative phlebitis, which is often seen in IgG4-RD, is not seen in EoE. 13 Other similarities are responsiveness to steroids; a predilection to males; and an association with atopy, eosinophilic infiltration, IgG4 plasma cells, and granular IgG4 deposits.…”

Section: Discussionmentioning

confidence: 99%

“…13 However, obliterative phlebitis, which is often seen in IgG4-RD, is not seen in EoE. 13 Other similarities are responsiveness to steroids; a predilection to males; and an association with atopy, eosinophilic infiltration, IgG4 plasma cells, and granular IgG4 deposits. 14 IgG4 levels in EoE, however, are lower and more localized than in IgG4-RD, potentially due to a smaller affected tissue compartment.…”

Section: Discussionmentioning

confidence: 99%

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Distinguishing gastroesophageal reflux disease and eosinophilic esophagitis in adults: The role of esophageal mucosal immunoglobulin G4

et al. 2020

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Background and Aim: Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) can be difficult to distinguish as many of their clinical and histological features overlap. Preliminary data suggest a potential association between EoE and immunoglobulin G4 (IgG4) but not GERD. This study aimed to examine the role of esophageal mucosal IgG4 staining when differentiating EoE from GERD. Methods: Esophageal biopsy specimens from patients with proven EoE and GERD were evaluated, and immunohistochemical staining for IgG4 was performed by an experienced gastrointestinal pathologist blinded to the clinical and endoscopic data. The results on IgG4 staining were then correlated with clinical, endoscopic, and histological features. Results: Sixty patients were included in the study, with 30 EoE (38.8 AE 12.8 years, 23 M:7 F) and 30 GERD (50.7 AE 14.3 years, 14 M:16 F) patients. The prevalence of a positive intercellular IgG4 stain was significantly higher in the EoE patients than those with GERD (23/29 vs 2/30; P < 0.0001). Positive IgG4 stain had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 77%, 93%, 92%, and 80% for predicting the diagnosis of EoE, respectively. In both EoE and GERD patients, correlation was found between positive IgG4 staining and food bolus obstruction, dysphagia to solids, reflux, fixed rings, Barrett's esophagus, hiatus hernia, and esophagitis. In EoE patients, positive IgG4 staining was not correlated with the type of symptoms, endoscopic findings, histological findings, proton pump inhibitor therapy, or history of allergy/atopy. Conclusion: Given the high specificity and PPV of positive IgG4 staining in esophageal biopsies for EoE, this can be a useful marker to distinguish the disease from GERD.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Distinguishing gastroesophageal reflux disease and eosinophilic esophagitis in adults: The role of esophageal mucosal immunoglobulin G4

et al. 2020

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“…The presence of multiple foodspecific serum IgE antibodies correlates with esophageal eosinophilia in children with nonspecific gastrointestinal symptoms, which can be useful in stratifying potential EoE patients [56]. Esophageal and plasma food antigen-specific IgG4 antibodies are elevated in EoE [57][58][59][60]. Furthermore, serum epithelial-specific autoantibodies, specifically, antidesmoglein 3 (DSG3) IgG4 and anti-collagen XVII (NC16A) IgG4, are elevated in EoE.…”

Section: Diagnosis Of Eoementioning

confidence: 99%

New Developments in the Diagnosis and Treatment of Eosinophilic Esophagitis

Nhu

Moawad

2019

Curr Treat Options Gastro

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Purpose of Review: Eosinophilic esophagitis (EoE) is a chronic, allergen-driven, immunemediated disease of the esophagus that progresses to esophageal fibrostenosis if left untreated. The aim of this review is to provide a concise update on recent clinically relevant advances in the development of diagnostic and therapeutic approaches for EoE. Recent Findings-Current diagnostic and disease monitoring protocols for EoE rely on repetitive endoscopic evaluations and esophageal tissue acquisition for histopathologic analysis. Recent advancements in EoE diagnosis include endoscopic functional lumen imaging probe (FLIP), transnasal endoscopy (TNE), and the emergence of non-invasive diagnostic tools including cytosponge, esophageal string test, and mucosal impedance probe. Biomarkers for EoE have not yet proven their clinical utility. No Food and Drug Administration (FDA)-approved drugs currently exist for the treatment of EoE. Topical corticosteroid, proton-pump inhibitors (PPI), elimination diet, and dilation are the current treatment modalities for confirmed EoE. Promising results from clinical trials are emerging for biologic agents that target the interleukin (IL)-13 and the IL-4/IL-13 receptor, specifically, RPC4046 and dupilumab, respectively. Summary-New diagnostic algorithms, non-invasive diagnostic strategies, and treatment modalities for EoE are emerging. Patients with EoE continue to require a multimodal and multidisciplinary management approach.

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Esophageal epithelial immunoglobulin G is an important marker for the diagnosis and management of pediatric eosinophilic esophagitis

et al. 2022

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Background and Aim Our primary aim was to describe the prevalence of immunoglobulin G (IgG) and its subclass IgG4 in immunohistochemistry staining in esophageal biopsy specimens of children with eosinophilic esophagitis (EoE) compared with that of specimens from children with gastroesophageal reflux disease (GERD). Methods Esophageal biopsy specimens from children with EoE or GERD were stained prospectively for IgG and IgG4 antibodies. Subjects with EoE were divided into cohorts with either active EoE or EoE in remission. Active EoE cases were further divided into proton pump inhibitor responsive (PPI‐r) and PPI‐nonresponsive (PPI‐nr) subgroups. Demographic, clinical, and histologic data were compared among groups, including quantified IgG and IgG4 staining, peak eosinophil count, eosinophil‐derived neurotoxin levels, and EoE endoscopic reference score. Results Seventy‐nine children (aged 10.6 ± 5.6 years; 68% male) were enrolled. IgG‐positive cell counts were significantly elevated in those with active EoE (n = 29, 3 [interquartile range, IQR: 2–6]/high‐powered field [HPF]), compared with those having EoE remission (n = 25, 1 [IQR: 0–2]/HPF; P = 0.002) and those with GERD (n = 25, 0 [IQR: 0–0.25]/HPF, P = <0.0001). IgG‐positive cell counts were significantly higher in the PPI‐r (n = 15, 5 [IQR: 2.5–11]/HPF) subgroup, compared with the PPI‐nr subgroup (n = 11, 3 [IQR: 1.5–3.5]/HPF; P = 0.041) at baseline endoscopy. Conclusion Initial esophageal tissue biopsy specimens from pediatric subjects with active EoE showed a significant increase in IgG‐positive staining compared with tissue from subjects in EoE remission or with GERD. There was higher positivity of IgG‐stained cells in the PPI‐r subgroup compared with the PPI‐nr subgroup.

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Pediatric Eosinophilic Esophagitis Is Associated With Increased Lamina Propria Immunoglobulin G4‐Positive Plasma Cells

Cited by 22 publications

References 19 publications

Distinguishing gastroesophageal reflux disease and eosinophilic esophagitis in adults: The role of esophageal mucosal immunoglobulin G4

Distinguishing gastroesophageal reflux disease and eosinophilic esophagitis in adults: The role of esophageal mucosal immunoglobulin G4

New Developments in the Diagnosis and Treatment of Eosinophilic Esophagitis

Esophageal epithelial immunoglobulin G is an important marker for the diagnosis and management of pediatric eosinophilic esophagitis

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