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Vitamin D levels are lower in patients with eosinophilic esophagitis

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Key clinical point: The serum levels of vitamin D are significantly lower in patients with newly diagnosed eosinophilic esophagitis (EoE) than in control individuals without EoE; however, vitamin D levels are not strongly linked with the clinical, endoscopic, or histologic features of EoE.

Major finding: Mean serum 25-hydroxy-vitamin D3 levels were lower by 10.8 ng/mL in patients with EoE vs control individuals (95% CI −19.0 to −2.51). However, these levels were neither associated with differences in clinical or endoscopic features of EoE nor did they significantly correlate with EoE Endoscopic Reference Scores and eosinophil counts (Pearson’s R −0.28, P = .08; and −0.01, P = .93, respectively).

Study details: This secondary analysis of a prospective cohort study used the data of adults who underwent endoscopy and biopsy for upper gastrointestinal symptoms, of whom 40 were diagnosed with EoE and 40 were control individuals without EoE.

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cameron BA et al. Vitamin D levels as a potential modifier of eosinophilic esophagitis severity in adults. Dig Dis Sci. 2024 (Jan 6). doi: 10.1007/s10620-023-08264-x

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Key clinical point: The serum levels of vitamin D are significantly lower in patients with newly diagnosed eosinophilic esophagitis (EoE) than in control individuals without EoE; however, vitamin D levels are not strongly linked with the clinical, endoscopic, or histologic features of EoE.

Major finding: Mean serum 25-hydroxy-vitamin D3 levels were lower by 10.8 ng/mL in patients with EoE vs control individuals (95% CI −19.0 to −2.51). However, these levels were neither associated with differences in clinical or endoscopic features of EoE nor did they significantly correlate with EoE Endoscopic Reference Scores and eosinophil counts (Pearson’s R −0.28, P = .08; and −0.01, P = .93, respectively).

Study details: This secondary analysis of a prospective cohort study used the data of adults who underwent endoscopy and biopsy for upper gastrointestinal symptoms, of whom 40 were diagnosed with EoE and 40 were control individuals without EoE.

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cameron BA et al. Vitamin D levels as a potential modifier of eosinophilic esophagitis severity in adults. Dig Dis Sci. 2024 (Jan 6). doi: 10.1007/s10620-023-08264-x

Key clinical point: The serum levels of vitamin D are significantly lower in patients with newly diagnosed eosinophilic esophagitis (EoE) than in control individuals without EoE; however, vitamin D levels are not strongly linked with the clinical, endoscopic, or histologic features of EoE.

Major finding: Mean serum 25-hydroxy-vitamin D3 levels were lower by 10.8 ng/mL in patients with EoE vs control individuals (95% CI −19.0 to −2.51). However, these levels were neither associated with differences in clinical or endoscopic features of EoE nor did they significantly correlate with EoE Endoscopic Reference Scores and eosinophil counts (Pearson’s R −0.28, P = .08; and −0.01, P = .93, respectively).

Study details: This secondary analysis of a prospective cohort study used the data of adults who underwent endoscopy and biopsy for upper gastrointestinal symptoms, of whom 40 were diagnosed with EoE and 40 were control individuals without EoE.

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cameron BA et al. Vitamin D levels as a potential modifier of eosinophilic esophagitis severity in adults. Dig Dis Sci. 2024 (Jan 6). doi: 10.1007/s10620-023-08264-x

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Allergic phenotypes may predict low response to proton-pump inhibitors in eosinophilic esophagitis

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Key clinical point: Patients with eosinophilic esophagitis (EoE) who test positive for food and environmental allergens may report a lower response to proton-pump inhibitor (PPI) treatment, a first-line treatment for EoE.

Major finding: Positive food allergen testing predicted lower odds of histologic response (adjusted odds ratio [aOR] 0.15; P = .0006) and symptom response (aOR 0.22; P = .03) to PPI therapy. Patients with a higher number of positive environmental allergens detected on skin-prick testing (≥10 vs <10) were less likely to respond to PPI (21.0% vs 53.9%; P = .03).

Study details: Findings are from a retrospective study including 61 adults with newly diagnosed EoE who underwent formal allergy testing for food and environmental allergens and received PPI therapy twice daily after EoE diagnosis.

Disclosures: The corresponding author WW Chan declared serving on the scientific advisory board for a several pharmaceutical companies.

Source: Muftah M et al. Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis. J Gastroenterol Hepatol. 2024 (Jan 7). doi: 10.1111/jgh.16469

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Key clinical point: Patients with eosinophilic esophagitis (EoE) who test positive for food and environmental allergens may report a lower response to proton-pump inhibitor (PPI) treatment, a first-line treatment for EoE.

Major finding: Positive food allergen testing predicted lower odds of histologic response (adjusted odds ratio [aOR] 0.15; P = .0006) and symptom response (aOR 0.22; P = .03) to PPI therapy. Patients with a higher number of positive environmental allergens detected on skin-prick testing (≥10 vs <10) were less likely to respond to PPI (21.0% vs 53.9%; P = .03).

Study details: Findings are from a retrospective study including 61 adults with newly diagnosed EoE who underwent formal allergy testing for food and environmental allergens and received PPI therapy twice daily after EoE diagnosis.

Disclosures: The corresponding author WW Chan declared serving on the scientific advisory board for a several pharmaceutical companies.

Source: Muftah M et al. Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis. J Gastroenterol Hepatol. 2024 (Jan 7). doi: 10.1111/jgh.16469

Key clinical point: Patients with eosinophilic esophagitis (EoE) who test positive for food and environmental allergens may report a lower response to proton-pump inhibitor (PPI) treatment, a first-line treatment for EoE.

Major finding: Positive food allergen testing predicted lower odds of histologic response (adjusted odds ratio [aOR] 0.15; P = .0006) and symptom response (aOR 0.22; P = .03) to PPI therapy. Patients with a higher number of positive environmental allergens detected on skin-prick testing (≥10 vs <10) were less likely to respond to PPI (21.0% vs 53.9%; P = .03).

Study details: Findings are from a retrospective study including 61 adults with newly diagnosed EoE who underwent formal allergy testing for food and environmental allergens and received PPI therapy twice daily after EoE diagnosis.

Disclosures: The corresponding author WW Chan declared serving on the scientific advisory board for a several pharmaceutical companies.

Source: Muftah M et al. Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis. J Gastroenterol Hepatol. 2024 (Jan 7). doi: 10.1111/jgh.16469

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Histological categories do not help in predicting treatment response in eosinophilic esophagitis

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Key clinical point: Budesonide orodispersible tablet (BOT) induces clinicohistological remission irrespective of the distribution of esophageal eosinophilia. Histological categories are not predictors of treatment response in patients with eosinophilic esophagitis (EoE).

Major finding: Histological categories were not found to be significantly associated with treatment outcome (mid: adjusted odds ratio [aOR] 1.75; 95% CI 0.588-5.25; distal: aOR 1.42; 95% CI 0.535-3.60; diffuse: aOR 0.910; 95% CI 0.358-2.19).

Study details: This post hoc analysis of the phase 3 EOS-1 and EOS-2 trials included 263 patients with EoE having either proximal, mid, or distal esophagus predominant disease or diffuse disease who received a 6-week induction treatment with BOT.

Disclosures: This study was supported by the Swiss National Science Foundation and others. Some authors declared serving as consultants for or receiving speaker or consulting fees or travel grants from various sources.

Source: Godat A et al on behalf of the EoE eosinophil distribution research group. Eosinophil distribution in eosinophilic esophagitis and its impact on disease activity and response to treatment. Clin Gastroenterol Hepatol. 2023 (Dec 15). doi: 10.1016/j.cgh.2023.12.003

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Key clinical point: Budesonide orodispersible tablet (BOT) induces clinicohistological remission irrespective of the distribution of esophageal eosinophilia. Histological categories are not predictors of treatment response in patients with eosinophilic esophagitis (EoE).

Major finding: Histological categories were not found to be significantly associated with treatment outcome (mid: adjusted odds ratio [aOR] 1.75; 95% CI 0.588-5.25; distal: aOR 1.42; 95% CI 0.535-3.60; diffuse: aOR 0.910; 95% CI 0.358-2.19).

Study details: This post hoc analysis of the phase 3 EOS-1 and EOS-2 trials included 263 patients with EoE having either proximal, mid, or distal esophagus predominant disease or diffuse disease who received a 6-week induction treatment with BOT.

Disclosures: This study was supported by the Swiss National Science Foundation and others. Some authors declared serving as consultants for or receiving speaker or consulting fees or travel grants from various sources.

Source: Godat A et al on behalf of the EoE eosinophil distribution research group. Eosinophil distribution in eosinophilic esophagitis and its impact on disease activity and response to treatment. Clin Gastroenterol Hepatol. 2023 (Dec 15). doi: 10.1016/j.cgh.2023.12.003

Key clinical point: Budesonide orodispersible tablet (BOT) induces clinicohistological remission irrespective of the distribution of esophageal eosinophilia. Histological categories are not predictors of treatment response in patients with eosinophilic esophagitis (EoE).

Major finding: Histological categories were not found to be significantly associated with treatment outcome (mid: adjusted odds ratio [aOR] 1.75; 95% CI 0.588-5.25; distal: aOR 1.42; 95% CI 0.535-3.60; diffuse: aOR 0.910; 95% CI 0.358-2.19).

Study details: This post hoc analysis of the phase 3 EOS-1 and EOS-2 trials included 263 patients with EoE having either proximal, mid, or distal esophagus predominant disease or diffuse disease who received a 6-week induction treatment with BOT.

Disclosures: This study was supported by the Swiss National Science Foundation and others. Some authors declared serving as consultants for or receiving speaker or consulting fees or travel grants from various sources.

Source: Godat A et al on behalf of the EoE eosinophil distribution research group. Eosinophil distribution in eosinophilic esophagitis and its impact on disease activity and response to treatment. Clin Gastroenterol Hepatol. 2023 (Dec 15). doi: 10.1016/j.cgh.2023.12.003

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Eosinophil-derived neurotoxin can help diagnose eosinophilic esophagitis in exclusive distal eosinophilia

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Key clinical point: The levels of eosinophil-derived neurotoxin (EDN) may be used to track disease activity in patients with eosinophilic esophagitis (EoE) patients and may aid the diagnosis of EoE in patients with challenging conditions, such as distal eosinophilia.

Major finding: The average endoscopic reference score (EREFS; 3.4 vs 0.4; P < .001) and EDN concentrations (135.8 µg/mL vs 3.2 µg/mL; P < .001) were significantly higher in patients with active EoE vs control individuals. In patients with exclusive distant eosinophilia, positive (≥10 µg/mL) vs negative EDN concentrations correlated with significantly higher EREFS (3.33 vs 1.35, P < .001), which indicated a diagnosis of EoE.

Study details: Findings are from a retrospective study that included children and young adults who underwent routine endoscopy with biopsy and EDN esophageal epithelial brushings, of whom 140 had EoE and 91 were control individuals without EoE.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Thomas J et al. Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin. J Pediatr Gastroenterol Nutr. 2023 (Dec 27). doi: 10.1002/jpn3.12054

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Key clinical point: The levels of eosinophil-derived neurotoxin (EDN) may be used to track disease activity in patients with eosinophilic esophagitis (EoE) patients and may aid the diagnosis of EoE in patients with challenging conditions, such as distal eosinophilia.

Major finding: The average endoscopic reference score (EREFS; 3.4 vs 0.4; P < .001) and EDN concentrations (135.8 µg/mL vs 3.2 µg/mL; P < .001) were significantly higher in patients with active EoE vs control individuals. In patients with exclusive distant eosinophilia, positive (≥10 µg/mL) vs negative EDN concentrations correlated with significantly higher EREFS (3.33 vs 1.35, P < .001), which indicated a diagnosis of EoE.

Study details: Findings are from a retrospective study that included children and young adults who underwent routine endoscopy with biopsy and EDN esophageal epithelial brushings, of whom 140 had EoE and 91 were control individuals without EoE.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Thomas J et al. Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin. J Pediatr Gastroenterol Nutr. 2023 (Dec 27). doi: 10.1002/jpn3.12054

Key clinical point: The levels of eosinophil-derived neurotoxin (EDN) may be used to track disease activity in patients with eosinophilic esophagitis (EoE) patients and may aid the diagnosis of EoE in patients with challenging conditions, such as distal eosinophilia.

Major finding: The average endoscopic reference score (EREFS; 3.4 vs 0.4; P < .001) and EDN concentrations (135.8 µg/mL vs 3.2 µg/mL; P < .001) were significantly higher in patients with active EoE vs control individuals. In patients with exclusive distant eosinophilia, positive (≥10 µg/mL) vs negative EDN concentrations correlated with significantly higher EREFS (3.33 vs 1.35, P < .001), which indicated a diagnosis of EoE.

Study details: Findings are from a retrospective study that included children and young adults who underwent routine endoscopy with biopsy and EDN esophageal epithelial brushings, of whom 140 had EoE and 91 were control individuals without EoE.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Thomas J et al. Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin. J Pediatr Gastroenterol Nutr. 2023 (Dec 27). doi: 10.1002/jpn3.12054

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Eosinophil levels may predict concomitant non-EoE diseases in patients with EoE

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Key clinical point: Patients with eosinophilic esophagitis (EoE) may also present with non-EoE eosinophilic gastrointestinal diseases (EGID) with esophageal involvement (EI; EGID + EI) if they have high levels of peripheral blood eosinophils.

Major finding: Patients with EGID + EI vs EoE were more likely to have eczema (P = .003), food allergy (P < .001), abdominal pain (60.9% vs 45.0%; P = .002), and higher peripheral blood eosinophil levels (0.44 × 103/µL vs 0.38 × 103/µL; P = .027).

Study details: Findings are from an observational cohort study including 592 patients with isolated EoE and 190 patients with EGID + EI.

Disclosures: This study was supported by a grant from the US National Institutes of Health. ME Rothenberg and corresponding author T Shoda declared serving as a consultant or being inventors or co-inventors of patents.

Source: Sato H et al. Eosinophil involvement outside the esophagus in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2023 (Dec 14). doi: 10.1016/j.cgh.2023.12.004

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Key clinical point: Patients with eosinophilic esophagitis (EoE) may also present with non-EoE eosinophilic gastrointestinal diseases (EGID) with esophageal involvement (EI; EGID + EI) if they have high levels of peripheral blood eosinophils.

Major finding: Patients with EGID + EI vs EoE were more likely to have eczema (P = .003), food allergy (P < .001), abdominal pain (60.9% vs 45.0%; P = .002), and higher peripheral blood eosinophil levels (0.44 × 103/µL vs 0.38 × 103/µL; P = .027).

Study details: Findings are from an observational cohort study including 592 patients with isolated EoE and 190 patients with EGID + EI.

Disclosures: This study was supported by a grant from the US National Institutes of Health. ME Rothenberg and corresponding author T Shoda declared serving as a consultant or being inventors or co-inventors of patents.

Source: Sato H et al. Eosinophil involvement outside the esophagus in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2023 (Dec 14). doi: 10.1016/j.cgh.2023.12.004

Key clinical point: Patients with eosinophilic esophagitis (EoE) may also present with non-EoE eosinophilic gastrointestinal diseases (EGID) with esophageal involvement (EI; EGID + EI) if they have high levels of peripheral blood eosinophils.

Major finding: Patients with EGID + EI vs EoE were more likely to have eczema (P = .003), food allergy (P < .001), abdominal pain (60.9% vs 45.0%; P = .002), and higher peripheral blood eosinophil levels (0.44 × 103/µL vs 0.38 × 103/µL; P = .027).

Study details: Findings are from an observational cohort study including 592 patients with isolated EoE and 190 patients with EGID + EI.

Disclosures: This study was supported by a grant from the US National Institutes of Health. ME Rothenberg and corresponding author T Shoda declared serving as a consultant or being inventors or co-inventors of patents.

Source: Sato H et al. Eosinophil involvement outside the esophagus in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2023 (Dec 14). doi: 10.1016/j.cgh.2023.12.004

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More comprehensive testing needed to characterize esophageal dysphagia

New approach to an old disorder
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The current approach to esophageal function testing is insufficient to characterize esophageal motility disorders, as many patients with esophageal dysphagia have abnormalities that are undetectable with routine tests, according to investigators.

More nuanced assessments of esophageal motility disorders could potentially lead to more accurate diagnoses, and more effective treatments, reported Ravinder K. Mittal, MD, and Ali Zifan, PhD, of the University of California San Diego.

Dr. Mittal
Dr. Ravinder K. Mittal

Esophageal motility disorders are currently divided into major and minor variants based on the contraction phase of peristalsis, Dr. Mittal and Dr. Zifan wrote in their report in Gastro Hep Advances. Yet the reason for dysphagia in many of these patients remains a puzzle, particularly in patients with supernormal contraction during peristalsis, like those with nutcracker esophagus. What’s more, up to half of patients with dysphagia have normal findings on high-resolution manometry impedance (HRMZ), the typical diagnostic modality, leaving many with the broad label of functional dysphagia.

This lack of clarity “suggests that the etiology in many patients remains unknown,” according to the investigators, which prompted them to publish the present review article.

After describing the shortcomings of current test methods, the investigators provided an overview of the physiology of esophageal peristalsis, then dove deeper into available data concerning luminal cross section measurements, esophageal distension during peristalsis, bolus flow, and distension contraction patterns in normal patients versus those with various kinds of dysphagia.

They highlighted two key findings.

First, in patients with functional dysphagia, esophagogastric junction outflow obstruction (EGJOO), and high amplitude esophageal peristaltic contractions (HAEC), the bolus must travel through a narrow esophageal lumen. Second, in patients with nonobstructive dysphagia and type 3 achalasia, the bolus moves against distal luminal occlusion.

“These findings indicate a relative dynamic obstruction to bolus flow and reduced distensibility of the esophageal wall in patients with several primary esophageal motility disorders,” the investigators wrote. “We speculate that the dysphagia sensation experienced by many patients may result from a normal or supernormal contraction wave pushing the bolus against resistance.”

Yet routine esophageal function testing fails to capture these abnormalities, Dr. Mittal and Dr. Zifan noted.

“[C]urrent techniques used to measure esophageal distension during peristalsis are not adequate,” they wrote. “The high-resolution manometry and current scheme of classifying esophageal motor disorders in the current format emphasize only half of the story of peristalsis, probably the less important of the two halves, i.e., the contraction phase of peristalsis.”

More focus is needed on esophageal distension, they suggested, noting that relaxation is first needed to accommodate a bolus before contraction, no matter how powerful, can push it down the esophagus.

“A simple analogy is that of a car — it cannot get through a roadway that is smaller than its own width, irrespective of the horsepower of its engine,” they wrote.

The solution may lie in a more comprehensive approach to esophageal function testing.

“Integrating representations of distension and contraction, along with objective assessments of flow timing and distensibility, complements the current classification of esophageal motility disorders that are based on the contraction characteristics,” the investigators wrote, predicting that these efforts could improve diagnostic accuracy.

What to do about those diagnoses is another mystery.

“The question though remains regarding the optimal treatment for the impaired distension function of the esophagus, and whether improvement in the distension function will lead to improvement in dysphagia symptoms,” the investigators concluded.

The review was supported by the National Institutes of Health. The investigators reported copyright/patent protection for the computer software (Dplots) used to evaluate the distension contraction plots.

Body

Medicine is strewn with diseases first labeled as functional or psychologically induced that have been recategorized into clear non-sensory disorders of which functional dysphagia is one.

In this review article, Dr. Mittal and Dr. Zifan discuss a summary and new paradigm for esophageal motility disorders and the origin of functional dysphagia (FD). As with other functional disorders, the predominance of research has suggested that functional dysphagia is in large part a sensory disorder in which patient are sensing normally sub-threshold events of normal bolus transit interpreted as dysphagia.

Dr. David A. Katzka
In this review, largely a summary of Dr. Mittal’s work, the role of more subtle characteristics of esophageal motility are examined. Several novel findings are observed including the role of increased esophageal wall tension and failure of relaxation with luminal narrowing as a cause of dysphagia. This may be due to inhibition or impaired relaxation or dyscoordination of the circular and longitudinal muscle layers during peristalsis. These novel findings are reinforced by a multidisciplinary approach blending the pressure findings on high resolution manometry, the motor and distensibility data from impedance planimetry (EndoFLIP), the anatomic findings of endoscopic ultrasound, and the bolus and anatomic information from barium esophagography, providing as complete a picture as possible for understanding dysphagia.

Will this lead to recategorization of all functional dysphagia as a perturbation in motor function and the discovery of new therapies? Certainly, to some degree, though sensory dysfunction will likely remain a prominent mechanism in some patients. Nevertheless, it is always exciting when a new approach to an old disorder emerges. With the work from Dr. Mittal’s laboratory and many others, functional dysphagia may soon drop the functional!
 

David A. Katzka, MD, is a gastroenterologist at New York–Presbyterian/Columbia University Irving Medical Center, New York, where he leads the Esophagology and Swallowing Center. He has performed research for Medtronic, but has no other relevant disclosures.

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Medicine is strewn with diseases first labeled as functional or psychologically induced that have been recategorized into clear non-sensory disorders of which functional dysphagia is one.

In this review article, Dr. Mittal and Dr. Zifan discuss a summary and new paradigm for esophageal motility disorders and the origin of functional dysphagia (FD). As with other functional disorders, the predominance of research has suggested that functional dysphagia is in large part a sensory disorder in which patient are sensing normally sub-threshold events of normal bolus transit interpreted as dysphagia.

Dr. David A. Katzka
In this review, largely a summary of Dr. Mittal’s work, the role of more subtle characteristics of esophageal motility are examined. Several novel findings are observed including the role of increased esophageal wall tension and failure of relaxation with luminal narrowing as a cause of dysphagia. This may be due to inhibition or impaired relaxation or dyscoordination of the circular and longitudinal muscle layers during peristalsis. These novel findings are reinforced by a multidisciplinary approach blending the pressure findings on high resolution manometry, the motor and distensibility data from impedance planimetry (EndoFLIP), the anatomic findings of endoscopic ultrasound, and the bolus and anatomic information from barium esophagography, providing as complete a picture as possible for understanding dysphagia.

Will this lead to recategorization of all functional dysphagia as a perturbation in motor function and the discovery of new therapies? Certainly, to some degree, though sensory dysfunction will likely remain a prominent mechanism in some patients. Nevertheless, it is always exciting when a new approach to an old disorder emerges. With the work from Dr. Mittal’s laboratory and many others, functional dysphagia may soon drop the functional!
 

David A. Katzka, MD, is a gastroenterologist at New York–Presbyterian/Columbia University Irving Medical Center, New York, where he leads the Esophagology and Swallowing Center. He has performed research for Medtronic, but has no other relevant disclosures.

Body

Medicine is strewn with diseases first labeled as functional or psychologically induced that have been recategorized into clear non-sensory disorders of which functional dysphagia is one.

In this review article, Dr. Mittal and Dr. Zifan discuss a summary and new paradigm for esophageal motility disorders and the origin of functional dysphagia (FD). As with other functional disorders, the predominance of research has suggested that functional dysphagia is in large part a sensory disorder in which patient are sensing normally sub-threshold events of normal bolus transit interpreted as dysphagia.

Dr. David A. Katzka
In this review, largely a summary of Dr. Mittal’s work, the role of more subtle characteristics of esophageal motility are examined. Several novel findings are observed including the role of increased esophageal wall tension and failure of relaxation with luminal narrowing as a cause of dysphagia. This may be due to inhibition or impaired relaxation or dyscoordination of the circular and longitudinal muscle layers during peristalsis. These novel findings are reinforced by a multidisciplinary approach blending the pressure findings on high resolution manometry, the motor and distensibility data from impedance planimetry (EndoFLIP), the anatomic findings of endoscopic ultrasound, and the bolus and anatomic information from barium esophagography, providing as complete a picture as possible for understanding dysphagia.

Will this lead to recategorization of all functional dysphagia as a perturbation in motor function and the discovery of new therapies? Certainly, to some degree, though sensory dysfunction will likely remain a prominent mechanism in some patients. Nevertheless, it is always exciting when a new approach to an old disorder emerges. With the work from Dr. Mittal’s laboratory and many others, functional dysphagia may soon drop the functional!
 

David A. Katzka, MD, is a gastroenterologist at New York–Presbyterian/Columbia University Irving Medical Center, New York, where he leads the Esophagology and Swallowing Center. He has performed research for Medtronic, but has no other relevant disclosures.

Title
New approach to an old disorder
New approach to an old disorder

The current approach to esophageal function testing is insufficient to characterize esophageal motility disorders, as many patients with esophageal dysphagia have abnormalities that are undetectable with routine tests, according to investigators.

More nuanced assessments of esophageal motility disorders could potentially lead to more accurate diagnoses, and more effective treatments, reported Ravinder K. Mittal, MD, and Ali Zifan, PhD, of the University of California San Diego.

Dr. Mittal
Dr. Ravinder K. Mittal

Esophageal motility disorders are currently divided into major and minor variants based on the contraction phase of peristalsis, Dr. Mittal and Dr. Zifan wrote in their report in Gastro Hep Advances. Yet the reason for dysphagia in many of these patients remains a puzzle, particularly in patients with supernormal contraction during peristalsis, like those with nutcracker esophagus. What’s more, up to half of patients with dysphagia have normal findings on high-resolution manometry impedance (HRMZ), the typical diagnostic modality, leaving many with the broad label of functional dysphagia.

This lack of clarity “suggests that the etiology in many patients remains unknown,” according to the investigators, which prompted them to publish the present review article.

After describing the shortcomings of current test methods, the investigators provided an overview of the physiology of esophageal peristalsis, then dove deeper into available data concerning luminal cross section measurements, esophageal distension during peristalsis, bolus flow, and distension contraction patterns in normal patients versus those with various kinds of dysphagia.

They highlighted two key findings.

First, in patients with functional dysphagia, esophagogastric junction outflow obstruction (EGJOO), and high amplitude esophageal peristaltic contractions (HAEC), the bolus must travel through a narrow esophageal lumen. Second, in patients with nonobstructive dysphagia and type 3 achalasia, the bolus moves against distal luminal occlusion.

“These findings indicate a relative dynamic obstruction to bolus flow and reduced distensibility of the esophageal wall in patients with several primary esophageal motility disorders,” the investigators wrote. “We speculate that the dysphagia sensation experienced by many patients may result from a normal or supernormal contraction wave pushing the bolus against resistance.”

Yet routine esophageal function testing fails to capture these abnormalities, Dr. Mittal and Dr. Zifan noted.

“[C]urrent techniques used to measure esophageal distension during peristalsis are not adequate,” they wrote. “The high-resolution manometry and current scheme of classifying esophageal motor disorders in the current format emphasize only half of the story of peristalsis, probably the less important of the two halves, i.e., the contraction phase of peristalsis.”

More focus is needed on esophageal distension, they suggested, noting that relaxation is first needed to accommodate a bolus before contraction, no matter how powerful, can push it down the esophagus.

“A simple analogy is that of a car — it cannot get through a roadway that is smaller than its own width, irrespective of the horsepower of its engine,” they wrote.

The solution may lie in a more comprehensive approach to esophageal function testing.

“Integrating representations of distension and contraction, along with objective assessments of flow timing and distensibility, complements the current classification of esophageal motility disorders that are based on the contraction characteristics,” the investigators wrote, predicting that these efforts could improve diagnostic accuracy.

What to do about those diagnoses is another mystery.

“The question though remains regarding the optimal treatment for the impaired distension function of the esophagus, and whether improvement in the distension function will lead to improvement in dysphagia symptoms,” the investigators concluded.

The review was supported by the National Institutes of Health. The investigators reported copyright/patent protection for the computer software (Dplots) used to evaluate the distension contraction plots.

The current approach to esophageal function testing is insufficient to characterize esophageal motility disorders, as many patients with esophageal dysphagia have abnormalities that are undetectable with routine tests, according to investigators.

More nuanced assessments of esophageal motility disorders could potentially lead to more accurate diagnoses, and more effective treatments, reported Ravinder K. Mittal, MD, and Ali Zifan, PhD, of the University of California San Diego.

Dr. Mittal
Dr. Ravinder K. Mittal

Esophageal motility disorders are currently divided into major and minor variants based on the contraction phase of peristalsis, Dr. Mittal and Dr. Zifan wrote in their report in Gastro Hep Advances. Yet the reason for dysphagia in many of these patients remains a puzzle, particularly in patients with supernormal contraction during peristalsis, like those with nutcracker esophagus. What’s more, up to half of patients with dysphagia have normal findings on high-resolution manometry impedance (HRMZ), the typical diagnostic modality, leaving many with the broad label of functional dysphagia.

This lack of clarity “suggests that the etiology in many patients remains unknown,” according to the investigators, which prompted them to publish the present review article.

After describing the shortcomings of current test methods, the investigators provided an overview of the physiology of esophageal peristalsis, then dove deeper into available data concerning luminal cross section measurements, esophageal distension during peristalsis, bolus flow, and distension contraction patterns in normal patients versus those with various kinds of dysphagia.

They highlighted two key findings.

First, in patients with functional dysphagia, esophagogastric junction outflow obstruction (EGJOO), and high amplitude esophageal peristaltic contractions (HAEC), the bolus must travel through a narrow esophageal lumen. Second, in patients with nonobstructive dysphagia and type 3 achalasia, the bolus moves against distal luminal occlusion.

“These findings indicate a relative dynamic obstruction to bolus flow and reduced distensibility of the esophageal wall in patients with several primary esophageal motility disorders,” the investigators wrote. “We speculate that the dysphagia sensation experienced by many patients may result from a normal or supernormal contraction wave pushing the bolus against resistance.”

Yet routine esophageal function testing fails to capture these abnormalities, Dr. Mittal and Dr. Zifan noted.

“[C]urrent techniques used to measure esophageal distension during peristalsis are not adequate,” they wrote. “The high-resolution manometry and current scheme of classifying esophageal motor disorders in the current format emphasize only half of the story of peristalsis, probably the less important of the two halves, i.e., the contraction phase of peristalsis.”

More focus is needed on esophageal distension, they suggested, noting that relaxation is first needed to accommodate a bolus before contraction, no matter how powerful, can push it down the esophagus.

“A simple analogy is that of a car — it cannot get through a roadway that is smaller than its own width, irrespective of the horsepower of its engine,” they wrote.

The solution may lie in a more comprehensive approach to esophageal function testing.

“Integrating representations of distension and contraction, along with objective assessments of flow timing and distensibility, complements the current classification of esophageal motility disorders that are based on the contraction characteristics,” the investigators wrote, predicting that these efforts could improve diagnostic accuracy.

What to do about those diagnoses is another mystery.

“The question though remains regarding the optimal treatment for the impaired distension function of the esophagus, and whether improvement in the distension function will lead to improvement in dysphagia symptoms,” the investigators concluded.

The review was supported by the National Institutes of Health. The investigators reported copyright/patent protection for the computer software (Dplots) used to evaluate the distension contraction plots.

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Commentary: Risks for Eosinophilic Esophagitis: IBD, Eczema, Diet, and Acid Suppressants, January 2024

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Dr Puerta scans the journals so you don't have to!

Cristian Puerta, M.D.
A recent nationwide Swedish population cohort study investigated the link between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD), revealing a fourfold increased risk of developing IBD subsequent to an EoE diagnosis.

 

Although there exists a recognized association between IBD and secondary EoE diagnoses, studies focusing on the primary diagnosis of EoE alongside IBD have yielded conflicting results. Dr Amiko Uchida, from the University of Utah Department of Medicine, working with colleagues from the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm, Sweden, led by Dr Jonas F. Ludvigsson, conducted a comprehensive study spanning 1990-2019 to explore the relationship between these two diseases.

 

Dr Uchida and colleagues assessed the association among Swedish patients diagnosed with biopsy-verified EoE (n = 1587) between 1990 and 2017. These patients were age- and sex-matched with up to five reference individuals from the general population (n = 7808). The primary focus was to discern the relationship between the primary diagnosis of EoE and the subsequent diagnosis of IBD.

 

The study's findings underscore the importance of heightened awareness among healthcare professionals regarding the potential association between EoE and the development of subsequent IBD. Collaborative efforts between physicians, gastroenterologists, and specialists in allergic diseases are crucial to ensure comprehensive care and timely identification of gastrointestinal complications in patients with EoE.

 

These results indicate a potential interplay between EoE and the pathogenesis of IBD, particularly Crohn's disease. In patients with EoE, careful consideration of gastrointestinal symptoms suggestive of IBD, such as abdominal pain, diarrhea, and rectal bleeding, is pivotal, necessitating further evaluation and appropriate monitoring for early detection and management of IBD.

 

Upon diagnosis, clinicians must develop a management plan for this chronic and critical disease. This study aids in planning future screenings for these patients, because one third of those diagnosed with EoE are at risk of developing IBD within a year. Therefore, primary physicians must remain vigilant for the development of gastrointestinal symptoms leading to a diagnosis of Crohn's disease or ulcerative colitis. Additionally, family awareness is crucial owing to observed associations between siblings, suggesting a potential role of genetics or early environmental factors in EoE development and future IBD diagnoses.

 

Further research is necessary to elucidate the shared pathophysiologic mechanisms connecting EoE and IBD. It is important to consider certain details, however; for instance, 31% of all subsequent IBD cases were diagnosed within the first year after an EoE diagnosis, potentially indicating a role of detection bias in these findings. Using a validated nationwide cohort and comparing study individuals with their siblings helped control for potential intrafamilial confounders as well as some environmental confounders, minimizing such biases as selection bias due to socioeconomic status. This strengthens the observed association in this study.

 

These insights into the increased risk for IBD, notably Crohn's disease, among patients with EoE underscore the need for thorough clinical evaluation and vigilant monitoring for gastrointestinal complications in this population.

 

A retrospective study conducted in pediatric patients presenting with an aerodigestive manifestation aimed to assess the factors associated with EoE and the diagnostic role of triple endoscopy. The results suggested a potential association between a family history of eczema and a diet lacking allergenic foods with a future diagnosis of EoE.

 

This study by Sheila Moran and colleagues, led by Dr Christina J. Yang from the Department of Otorhinolaryngology, Head and Neck Surgery at the Albert Einstein College of Medicine, Bronx, New York, aimed to identify preoperative risk factors linked to an EoE diagnosis in children undergoing triple endoscopy. They evaluated 119 pediatric patients aged 0-21 years who underwent triple endoscopy (including flexible bronchoscopy, rigid direct laryngoscopy and bronchoscopy, and esophagoscopy with biopsy) at the Children's Hospital at Montefiore between January 1, 2015, and December 31, 2019.

 

The study underscored the significance of both genetic predisposition and dietary influences in EoE development. Understanding the interplay between familial atopic conditions and dietary choices among pediatric patients with aerodigestive dysfunction is crucial for early identification and implementing preventive strategies against EoE.

 

As clinicians, it's essential to consider rare diseases like EoE when patients present with mixed symptoms, including aerodigestive symptoms, a family history of eczema, and a history of environmental allergies, given the association between these conditions. The potential link between a family history of eczema and increased EoE risk suggests a shared genetic susceptibility among allergic conditions. Therefore, clinicians evaluating children with aerodigestive dysfunction, particularly those with a familial history of eczema, should maintain a high index of suspicion for EoE, prompting vigilant monitoring and appropriate diagnostic assessments.

 

When contemplating advanced procedures, such as triple endoscopy or biopsy sampling, considering the patient's previous medical history and the effect of dietary modifications, such as incorporating or excluding dairy from the diet, warrants further investigation in the context of EoE prevention. Clinicians should consider providing dietary counseling and personalized nutritional plans based on evidence-based approaches to potentially mitigate EoE risk in susceptible pediatric populations.

 

Additionally, it's crucial to consider EoE in minority racial groups and underserved communities and encourage the use of diagnostic tests, such as triple endoscopy, to facilitate early diagnosis. Healthcare providers should contemplate integrating family history assessments, particularly regarding eczema, into the evaluation of children with aerodigestive dysfunction. This information can assist in risk assessment and early identification of individuals at a higher risk of developing EoE, enabling prompt intervention and management.

 

The increasing incidence of EoE across different nations, including the United States, has underscored the need for a deeper understanding of its causes, early diagnosis, and treatment. A novel population-based study conducted in Denmark aimed to explore the relationship between maternal and infant use of antibiotics and acid suppressants in the development of EoE. The study yielded significant results based on a population of 392 cases. Dr Elizabeth T. Jensen, MPH, PhD, from the Department of Epidemiology & Prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, conducted a comprehensive study spanning the last 20 years to decipher potential causes contributing to the rising incidence of EoE.

 

Dr Jensen and her colleagues evaluated the association between maternal and infant use of antibiotics and acid suppressants in Denmark. They used pathology, prescription, birth, inpatient, and outpatient health registry data, ensuring complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. The research obtained a census of cases from a registered sample of approximately 1.4 million children, matching EoE cases to controls using a 1:10 ratio through incidence density sampling. A total of 392 patients with EoE and 3637 control patients were enrolled. The primary outcome of the study focused on the development of EoE, revealing a dose-response association between maternal and infant antibiotic and acid suppressant use and increased EoE risk.

 

This study demonstrated a robust correlation between the dosage of antibiotics and acid suppressants and the development of EoE in offspring during childhood. These findings hold significance because these medications represent some of the most common prescriptions in clinical practice. Pregnancy triggers significant physiologic changes in women, including increased hormonal effects and abdominal pressure on the lower esophageal sphincter, making pregnant individuals more prone to esophageal reflux and necessitating the use of gastric acid suppressants. As clinicians, it's crucial to consider lifestyle modifications and dietary adjustments before resorting to acid suppressants, reserving their use for only when absolutely necessary.

 

Postpregnancy, emphasizing exclusive breastfeeding for the first 6 months and proper feeding techniques can aid in reducing the likelihood of reflux disease in newborns. Acid suppressants have been linked to alterations in infant microbiome colonization, potentially increasing the susceptibility to immunoreactive diseases, such as asthma, atopic dermatitis, and allergic rhinitis. Given that exclusive breastfeeding in the initial 6 months has demonstrated preventive benefits against such diseases, primary physicians play a crucial role in advocating its importance. Although gastric acid suppressants and antibiotics are essential for managing various health conditions, including infections and gastroesophageal reflux disease (GERD), their potential impact on EoE development should not be overlooked.

 

Though this study had a relatively small sample size, the strong population registry of Denmark significantly reduced recall bias. However, cultural differences and over-the-counter access to drugs, such as acid suppressants, in other countries, including the United States, warrant further research to ascertain their effect on EoE development.

 

In light of these findings, clinicians should carefully weigh the risks and benefits of prescribing antibiotics and acid suppressants during pregnancy and infancy. Adherence to evidence-based guidelines and considering alternative treatment options, such as lifestyle modifications, should be prioritized. Prescribing antibiotics only when medically necessary and using nonpharmacologic strategies for managing GERD in infants should be considered to mitigate potential risks associated with these medications.

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Dr Puerta scans the journals so you don't have to!
Dr Puerta scans the journals so you don't have to!

Cristian Puerta, M.D.
A recent nationwide Swedish population cohort study investigated the link between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD), revealing a fourfold increased risk of developing IBD subsequent to an EoE diagnosis.

 

Although there exists a recognized association between IBD and secondary EoE diagnoses, studies focusing on the primary diagnosis of EoE alongside IBD have yielded conflicting results. Dr Amiko Uchida, from the University of Utah Department of Medicine, working with colleagues from the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm, Sweden, led by Dr Jonas F. Ludvigsson, conducted a comprehensive study spanning 1990-2019 to explore the relationship between these two diseases.

 

Dr Uchida and colleagues assessed the association among Swedish patients diagnosed with biopsy-verified EoE (n = 1587) between 1990 and 2017. These patients were age- and sex-matched with up to five reference individuals from the general population (n = 7808). The primary focus was to discern the relationship between the primary diagnosis of EoE and the subsequent diagnosis of IBD.

 

The study's findings underscore the importance of heightened awareness among healthcare professionals regarding the potential association between EoE and the development of subsequent IBD. Collaborative efforts between physicians, gastroenterologists, and specialists in allergic diseases are crucial to ensure comprehensive care and timely identification of gastrointestinal complications in patients with EoE.

 

These results indicate a potential interplay between EoE and the pathogenesis of IBD, particularly Crohn's disease. In patients with EoE, careful consideration of gastrointestinal symptoms suggestive of IBD, such as abdominal pain, diarrhea, and rectal bleeding, is pivotal, necessitating further evaluation and appropriate monitoring for early detection and management of IBD.

 

Upon diagnosis, clinicians must develop a management plan for this chronic and critical disease. This study aids in planning future screenings for these patients, because one third of those diagnosed with EoE are at risk of developing IBD within a year. Therefore, primary physicians must remain vigilant for the development of gastrointestinal symptoms leading to a diagnosis of Crohn's disease or ulcerative colitis. Additionally, family awareness is crucial owing to observed associations between siblings, suggesting a potential role of genetics or early environmental factors in EoE development and future IBD diagnoses.

 

Further research is necessary to elucidate the shared pathophysiologic mechanisms connecting EoE and IBD. It is important to consider certain details, however; for instance, 31% of all subsequent IBD cases were diagnosed within the first year after an EoE diagnosis, potentially indicating a role of detection bias in these findings. Using a validated nationwide cohort and comparing study individuals with their siblings helped control for potential intrafamilial confounders as well as some environmental confounders, minimizing such biases as selection bias due to socioeconomic status. This strengthens the observed association in this study.

 

These insights into the increased risk for IBD, notably Crohn's disease, among patients with EoE underscore the need for thorough clinical evaluation and vigilant monitoring for gastrointestinal complications in this population.

 

A retrospective study conducted in pediatric patients presenting with an aerodigestive manifestation aimed to assess the factors associated with EoE and the diagnostic role of triple endoscopy. The results suggested a potential association between a family history of eczema and a diet lacking allergenic foods with a future diagnosis of EoE.

 

This study by Sheila Moran and colleagues, led by Dr Christina J. Yang from the Department of Otorhinolaryngology, Head and Neck Surgery at the Albert Einstein College of Medicine, Bronx, New York, aimed to identify preoperative risk factors linked to an EoE diagnosis in children undergoing triple endoscopy. They evaluated 119 pediatric patients aged 0-21 years who underwent triple endoscopy (including flexible bronchoscopy, rigid direct laryngoscopy and bronchoscopy, and esophagoscopy with biopsy) at the Children's Hospital at Montefiore between January 1, 2015, and December 31, 2019.

 

The study underscored the significance of both genetic predisposition and dietary influences in EoE development. Understanding the interplay between familial atopic conditions and dietary choices among pediatric patients with aerodigestive dysfunction is crucial for early identification and implementing preventive strategies against EoE.

 

As clinicians, it's essential to consider rare diseases like EoE when patients present with mixed symptoms, including aerodigestive symptoms, a family history of eczema, and a history of environmental allergies, given the association between these conditions. The potential link between a family history of eczema and increased EoE risk suggests a shared genetic susceptibility among allergic conditions. Therefore, clinicians evaluating children with aerodigestive dysfunction, particularly those with a familial history of eczema, should maintain a high index of suspicion for EoE, prompting vigilant monitoring and appropriate diagnostic assessments.

 

When contemplating advanced procedures, such as triple endoscopy or biopsy sampling, considering the patient's previous medical history and the effect of dietary modifications, such as incorporating or excluding dairy from the diet, warrants further investigation in the context of EoE prevention. Clinicians should consider providing dietary counseling and personalized nutritional plans based on evidence-based approaches to potentially mitigate EoE risk in susceptible pediatric populations.

 

Additionally, it's crucial to consider EoE in minority racial groups and underserved communities and encourage the use of diagnostic tests, such as triple endoscopy, to facilitate early diagnosis. Healthcare providers should contemplate integrating family history assessments, particularly regarding eczema, into the evaluation of children with aerodigestive dysfunction. This information can assist in risk assessment and early identification of individuals at a higher risk of developing EoE, enabling prompt intervention and management.

 

The increasing incidence of EoE across different nations, including the United States, has underscored the need for a deeper understanding of its causes, early diagnosis, and treatment. A novel population-based study conducted in Denmark aimed to explore the relationship between maternal and infant use of antibiotics and acid suppressants in the development of EoE. The study yielded significant results based on a population of 392 cases. Dr Elizabeth T. Jensen, MPH, PhD, from the Department of Epidemiology & Prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, conducted a comprehensive study spanning the last 20 years to decipher potential causes contributing to the rising incidence of EoE.

 

Dr Jensen and her colleagues evaluated the association between maternal and infant use of antibiotics and acid suppressants in Denmark. They used pathology, prescription, birth, inpatient, and outpatient health registry data, ensuring complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. The research obtained a census of cases from a registered sample of approximately 1.4 million children, matching EoE cases to controls using a 1:10 ratio through incidence density sampling. A total of 392 patients with EoE and 3637 control patients were enrolled. The primary outcome of the study focused on the development of EoE, revealing a dose-response association between maternal and infant antibiotic and acid suppressant use and increased EoE risk.

 

This study demonstrated a robust correlation between the dosage of antibiotics and acid suppressants and the development of EoE in offspring during childhood. These findings hold significance because these medications represent some of the most common prescriptions in clinical practice. Pregnancy triggers significant physiologic changes in women, including increased hormonal effects and abdominal pressure on the lower esophageal sphincter, making pregnant individuals more prone to esophageal reflux and necessitating the use of gastric acid suppressants. As clinicians, it's crucial to consider lifestyle modifications and dietary adjustments before resorting to acid suppressants, reserving their use for only when absolutely necessary.

 

Postpregnancy, emphasizing exclusive breastfeeding for the first 6 months and proper feeding techniques can aid in reducing the likelihood of reflux disease in newborns. Acid suppressants have been linked to alterations in infant microbiome colonization, potentially increasing the susceptibility to immunoreactive diseases, such as asthma, atopic dermatitis, and allergic rhinitis. Given that exclusive breastfeeding in the initial 6 months has demonstrated preventive benefits against such diseases, primary physicians play a crucial role in advocating its importance. Although gastric acid suppressants and antibiotics are essential for managing various health conditions, including infections and gastroesophageal reflux disease (GERD), their potential impact on EoE development should not be overlooked.

 

Though this study had a relatively small sample size, the strong population registry of Denmark significantly reduced recall bias. However, cultural differences and over-the-counter access to drugs, such as acid suppressants, in other countries, including the United States, warrant further research to ascertain their effect on EoE development.

 

In light of these findings, clinicians should carefully weigh the risks and benefits of prescribing antibiotics and acid suppressants during pregnancy and infancy. Adherence to evidence-based guidelines and considering alternative treatment options, such as lifestyle modifications, should be prioritized. Prescribing antibiotics only when medically necessary and using nonpharmacologic strategies for managing GERD in infants should be considered to mitigate potential risks associated with these medications.

Cristian Puerta, M.D.
A recent nationwide Swedish population cohort study investigated the link between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD), revealing a fourfold increased risk of developing IBD subsequent to an EoE diagnosis.

 

Although there exists a recognized association between IBD and secondary EoE diagnoses, studies focusing on the primary diagnosis of EoE alongside IBD have yielded conflicting results. Dr Amiko Uchida, from the University of Utah Department of Medicine, working with colleagues from the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm, Sweden, led by Dr Jonas F. Ludvigsson, conducted a comprehensive study spanning 1990-2019 to explore the relationship between these two diseases.

 

Dr Uchida and colleagues assessed the association among Swedish patients diagnosed with biopsy-verified EoE (n = 1587) between 1990 and 2017. These patients were age- and sex-matched with up to five reference individuals from the general population (n = 7808). The primary focus was to discern the relationship between the primary diagnosis of EoE and the subsequent diagnosis of IBD.

 

The study's findings underscore the importance of heightened awareness among healthcare professionals regarding the potential association between EoE and the development of subsequent IBD. Collaborative efforts between physicians, gastroenterologists, and specialists in allergic diseases are crucial to ensure comprehensive care and timely identification of gastrointestinal complications in patients with EoE.

 

These results indicate a potential interplay between EoE and the pathogenesis of IBD, particularly Crohn's disease. In patients with EoE, careful consideration of gastrointestinal symptoms suggestive of IBD, such as abdominal pain, diarrhea, and rectal bleeding, is pivotal, necessitating further evaluation and appropriate monitoring for early detection and management of IBD.

 

Upon diagnosis, clinicians must develop a management plan for this chronic and critical disease. This study aids in planning future screenings for these patients, because one third of those diagnosed with EoE are at risk of developing IBD within a year. Therefore, primary physicians must remain vigilant for the development of gastrointestinal symptoms leading to a diagnosis of Crohn's disease or ulcerative colitis. Additionally, family awareness is crucial owing to observed associations between siblings, suggesting a potential role of genetics or early environmental factors in EoE development and future IBD diagnoses.

 

Further research is necessary to elucidate the shared pathophysiologic mechanisms connecting EoE and IBD. It is important to consider certain details, however; for instance, 31% of all subsequent IBD cases were diagnosed within the first year after an EoE diagnosis, potentially indicating a role of detection bias in these findings. Using a validated nationwide cohort and comparing study individuals with their siblings helped control for potential intrafamilial confounders as well as some environmental confounders, minimizing such biases as selection bias due to socioeconomic status. This strengthens the observed association in this study.

 

These insights into the increased risk for IBD, notably Crohn's disease, among patients with EoE underscore the need for thorough clinical evaluation and vigilant monitoring for gastrointestinal complications in this population.

 

A retrospective study conducted in pediatric patients presenting with an aerodigestive manifestation aimed to assess the factors associated with EoE and the diagnostic role of triple endoscopy. The results suggested a potential association between a family history of eczema and a diet lacking allergenic foods with a future diagnosis of EoE.

 

This study by Sheila Moran and colleagues, led by Dr Christina J. Yang from the Department of Otorhinolaryngology, Head and Neck Surgery at the Albert Einstein College of Medicine, Bronx, New York, aimed to identify preoperative risk factors linked to an EoE diagnosis in children undergoing triple endoscopy. They evaluated 119 pediatric patients aged 0-21 years who underwent triple endoscopy (including flexible bronchoscopy, rigid direct laryngoscopy and bronchoscopy, and esophagoscopy with biopsy) at the Children's Hospital at Montefiore between January 1, 2015, and December 31, 2019.

 

The study underscored the significance of both genetic predisposition and dietary influences in EoE development. Understanding the interplay between familial atopic conditions and dietary choices among pediatric patients with aerodigestive dysfunction is crucial for early identification and implementing preventive strategies against EoE.

 

As clinicians, it's essential to consider rare diseases like EoE when patients present with mixed symptoms, including aerodigestive symptoms, a family history of eczema, and a history of environmental allergies, given the association between these conditions. The potential link between a family history of eczema and increased EoE risk suggests a shared genetic susceptibility among allergic conditions. Therefore, clinicians evaluating children with aerodigestive dysfunction, particularly those with a familial history of eczema, should maintain a high index of suspicion for EoE, prompting vigilant monitoring and appropriate diagnostic assessments.

 

When contemplating advanced procedures, such as triple endoscopy or biopsy sampling, considering the patient's previous medical history and the effect of dietary modifications, such as incorporating or excluding dairy from the diet, warrants further investigation in the context of EoE prevention. Clinicians should consider providing dietary counseling and personalized nutritional plans based on evidence-based approaches to potentially mitigate EoE risk in susceptible pediatric populations.

 

Additionally, it's crucial to consider EoE in minority racial groups and underserved communities and encourage the use of diagnostic tests, such as triple endoscopy, to facilitate early diagnosis. Healthcare providers should contemplate integrating family history assessments, particularly regarding eczema, into the evaluation of children with aerodigestive dysfunction. This information can assist in risk assessment and early identification of individuals at a higher risk of developing EoE, enabling prompt intervention and management.

 

The increasing incidence of EoE across different nations, including the United States, has underscored the need for a deeper understanding of its causes, early diagnosis, and treatment. A novel population-based study conducted in Denmark aimed to explore the relationship between maternal and infant use of antibiotics and acid suppressants in the development of EoE. The study yielded significant results based on a population of 392 cases. Dr Elizabeth T. Jensen, MPH, PhD, from the Department of Epidemiology & Prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, conducted a comprehensive study spanning the last 20 years to decipher potential causes contributing to the rising incidence of EoE.

 

Dr Jensen and her colleagues evaluated the association between maternal and infant use of antibiotics and acid suppressants in Denmark. They used pathology, prescription, birth, inpatient, and outpatient health registry data, ensuring complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. The research obtained a census of cases from a registered sample of approximately 1.4 million children, matching EoE cases to controls using a 1:10 ratio through incidence density sampling. A total of 392 patients with EoE and 3637 control patients were enrolled. The primary outcome of the study focused on the development of EoE, revealing a dose-response association between maternal and infant antibiotic and acid suppressant use and increased EoE risk.

 

This study demonstrated a robust correlation between the dosage of antibiotics and acid suppressants and the development of EoE in offspring during childhood. These findings hold significance because these medications represent some of the most common prescriptions in clinical practice. Pregnancy triggers significant physiologic changes in women, including increased hormonal effects and abdominal pressure on the lower esophageal sphincter, making pregnant individuals more prone to esophageal reflux and necessitating the use of gastric acid suppressants. As clinicians, it's crucial to consider lifestyle modifications and dietary adjustments before resorting to acid suppressants, reserving their use for only when absolutely necessary.

 

Postpregnancy, emphasizing exclusive breastfeeding for the first 6 months and proper feeding techniques can aid in reducing the likelihood of reflux disease in newborns. Acid suppressants have been linked to alterations in infant microbiome colonization, potentially increasing the susceptibility to immunoreactive diseases, such as asthma, atopic dermatitis, and allergic rhinitis. Given that exclusive breastfeeding in the initial 6 months has demonstrated preventive benefits against such diseases, primary physicians play a crucial role in advocating its importance. Although gastric acid suppressants and antibiotics are essential for managing various health conditions, including infections and gastroesophageal reflux disease (GERD), their potential impact on EoE development should not be overlooked.

 

Though this study had a relatively small sample size, the strong population registry of Denmark significantly reduced recall bias. However, cultural differences and over-the-counter access to drugs, such as acid suppressants, in other countries, including the United States, warrant further research to ascertain their effect on EoE development.

 

In light of these findings, clinicians should carefully weigh the risks and benefits of prescribing antibiotics and acid suppressants during pregnancy and infancy. Adherence to evidence-based guidelines and considering alternative treatment options, such as lifestyle modifications, should be prioritized. Prescribing antibiotics only when medically necessary and using nonpharmacologic strategies for managing GERD in infants should be considered to mitigate potential risks associated with these medications.

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H pylori Infection Linked to Increased Alzheimer’s Risk

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H pylori Infection Linked to Increased Alzheimer’s Risk

 

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

  • Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
  • The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
  • Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

  • Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
  • The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
  • Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
  • The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

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TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

  • Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
  • The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
  • Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

  • Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
  • The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
  • Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
  • The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

 

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

  • Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
  • The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
  • Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

  • Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
  • The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
  • Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
  • The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

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Does residential proximity to swine farms increase odds of developing eosinophilic esophagitis?

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Key clinical point: People from a tertiary care center database were at a significantly increased risk of getting eosinophilic esophagitis (EoE) when they lived close (<1 mile) to a commercial swine farm or in an area with a high density of swine farm operations.

Major finding: Odds of EoE were ~2.5 times higher in participants who had undergone upper endoscopy and lived in an area with <1 mile proximity to a permitted swine facility (adjusted odds ratio [aOR] 2.56; 95% CI 1.33-4.95) or where the density of swine farms was >10 farms per census tract (aOR 2.76; 95% CI 1.30-5.84).

Study details: This case-control study including 401 patients with EoE and 1852 control individuals who had undergone endoscopy but did not show any esophageal pathology from a tertiary care center and 904 patients with EoE and 4074 endoscopy-based control participants from a pathology database.

Disclosures: This study was partly funded by a grant from the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cotton CC et al. Proximity to swine farming operations as a risk factor for eosinophilic esophagitis. JPGN Rep. 2023;4(4):e391 (Nov 8). doi: 10.1097/PG9.0000000000000391

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Key clinical point: People from a tertiary care center database were at a significantly increased risk of getting eosinophilic esophagitis (EoE) when they lived close (<1 mile) to a commercial swine farm or in an area with a high density of swine farm operations.

Major finding: Odds of EoE were ~2.5 times higher in participants who had undergone upper endoscopy and lived in an area with <1 mile proximity to a permitted swine facility (adjusted odds ratio [aOR] 2.56; 95% CI 1.33-4.95) or where the density of swine farms was >10 farms per census tract (aOR 2.76; 95% CI 1.30-5.84).

Study details: This case-control study including 401 patients with EoE and 1852 control individuals who had undergone endoscopy but did not show any esophageal pathology from a tertiary care center and 904 patients with EoE and 4074 endoscopy-based control participants from a pathology database.

Disclosures: This study was partly funded by a grant from the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cotton CC et al. Proximity to swine farming operations as a risk factor for eosinophilic esophagitis. JPGN Rep. 2023;4(4):e391 (Nov 8). doi: 10.1097/PG9.0000000000000391

Key clinical point: People from a tertiary care center database were at a significantly increased risk of getting eosinophilic esophagitis (EoE) when they lived close (<1 mile) to a commercial swine farm or in an area with a high density of swine farm operations.

Major finding: Odds of EoE were ~2.5 times higher in participants who had undergone upper endoscopy and lived in an area with <1 mile proximity to a permitted swine facility (adjusted odds ratio [aOR] 2.56; 95% CI 1.33-4.95) or where the density of swine farms was >10 farms per census tract (aOR 2.76; 95% CI 1.30-5.84).

Study details: This case-control study including 401 patients with EoE and 1852 control individuals who had undergone endoscopy but did not show any esophageal pathology from a tertiary care center and 904 patients with EoE and 4074 endoscopy-based control participants from a pathology database.

Disclosures: This study was partly funded by a grant from the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Cotton CC et al. Proximity to swine farming operations as a risk factor for eosinophilic esophagitis. JPGN Rep. 2023;4(4):e391 (Nov 8). doi: 10.1097/PG9.0000000000000391

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Eosinophilic esophagitis histology scoring system predicts response to PPI therapy in pediatric EoE

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Tue, 01/02/2024 - 21:06

Key clinical point: The eosinophilic esophagitis (EoE) histology scoring system (HSS) can predict the response to proton pump inhibitor (PPI) therapy in pediatric patients with EoE.

Major finding: The final EoEHSS grade score for the middle segment of the esophagus was significantly lower in patients who responded (peak eosinophil count < 15/high-power field on esophageal biopsy) vs did not respond to PPI therapy (0.3 vs 0.5; P = .037). Responders vs nonresponders had significantly lower grade values for the individual EoEHSS parameters eosinophilic abscesses (P = .044) and eosinophil surface layering (P = .046) for the middle esophagus.

Study details: Findings are from a cross-sectional study including 89 pediatric patients with EoE (age 0-18 years) who received PPI daily and were either responsive (n = 17) or nonresponsive (n = 72) at 3 months of therapy.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Jevtić J et al. The usefulness of the eosinophilic esophagitis histology scoring system in predicting response to proton pump inhibitor monotherapy in children with eosinophilic esophagitis. Diagnostics (Basel). 2023; 13(22):3445 (Nov 15). doi: 10.3390/diagnostics13223445

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Key clinical point: The eosinophilic esophagitis (EoE) histology scoring system (HSS) can predict the response to proton pump inhibitor (PPI) therapy in pediatric patients with EoE.

Major finding: The final EoEHSS grade score for the middle segment of the esophagus was significantly lower in patients who responded (peak eosinophil count < 15/high-power field on esophageal biopsy) vs did not respond to PPI therapy (0.3 vs 0.5; P = .037). Responders vs nonresponders had significantly lower grade values for the individual EoEHSS parameters eosinophilic abscesses (P = .044) and eosinophil surface layering (P = .046) for the middle esophagus.

Study details: Findings are from a cross-sectional study including 89 pediatric patients with EoE (age 0-18 years) who received PPI daily and were either responsive (n = 17) or nonresponsive (n = 72) at 3 months of therapy.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Jevtić J et al. The usefulness of the eosinophilic esophagitis histology scoring system in predicting response to proton pump inhibitor monotherapy in children with eosinophilic esophagitis. Diagnostics (Basel). 2023; 13(22):3445 (Nov 15). doi: 10.3390/diagnostics13223445

Key clinical point: The eosinophilic esophagitis (EoE) histology scoring system (HSS) can predict the response to proton pump inhibitor (PPI) therapy in pediatric patients with EoE.

Major finding: The final EoEHSS grade score for the middle segment of the esophagus was significantly lower in patients who responded (peak eosinophil count < 15/high-power field on esophageal biopsy) vs did not respond to PPI therapy (0.3 vs 0.5; P = .037). Responders vs nonresponders had significantly lower grade values for the individual EoEHSS parameters eosinophilic abscesses (P = .044) and eosinophil surface layering (P = .046) for the middle esophagus.

Study details: Findings are from a cross-sectional study including 89 pediatric patients with EoE (age 0-18 years) who received PPI daily and were either responsive (n = 17) or nonresponsive (n = 72) at 3 months of therapy.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Jevtić J et al. The usefulness of the eosinophilic esophagitis histology scoring system in predicting response to proton pump inhibitor monotherapy in children with eosinophilic esophagitis. Diagnostics (Basel). 2023; 13(22):3445 (Nov 15). doi: 10.3390/diagnostics13223445

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