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Eosinophilic esophagitis and disease complications: register-based studies
Örebro University, School of Medical Sciences.
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis presents four studies on Eosinophilic Esophagitis (EoE). The overall aim is to grasp the basics of epidemiologic research and use this understanding on EoE disease complications. EoE is a fairly new inflammatory disease with clinicopathological diagnosis that increases in prevalence. It is considered a relatively mild disease, but the evidence concerning mortality and morbidity is scarce. Although EoE has a prevalence peak in childbearing age, pregnancy outcomes are poorly examined. 

In Study I, a random portion of 131 patient charts from the cohort werecollected for a diagnosis validation through a patient chart review. EoE was found in 99 patients, which corresponds to a positive predictive value of 89%. The cohort was predominately male, and the most common symptom was dysphagia. 

Study II examines mortality in EoE individuals compared to matched reference individuals using survival analysis. We performed sibling analysis to adjust for intrafamilial (genetic and environmental) confounding. We found no elevated risk for death. 

Study III uses a similar method to find higher risk of psychiatric comorbidity among EoE patients compared to matched reference individuals. Mean follow-up time was 4.03 years, and there were 106 events of psychiatric disease in the EoE-group, which corresponds to an elevated risk of 50% compared to reference individuals. 

Study IV investigates outcomes of pregnancy in EoE females versus comparators. The main outcome is premature birth; in secondary analyses, we examined both maternal and fetal outcomes. The only elevated risk was low birth weight; although a significant finding, it was still based on a small sample size and should be interpreted with caution.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2023. , p. 93
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 278
Keywords [en]
Eosinophilic esophagitis, dysphagia, cohort studies, mortality, psychiatric comorbidity, adverse pregnancy outcomes
National Category
General Practice
Identifiers
URN: urn:nbn:se:oru:diva-104228ISBN: 9789175294964 (print)OAI: oai:DiVA.org:oru-104228DiVA, id: diva2:1737144
Public defence
2023-05-17, Örebro universitet, Campus USÖ, Room X1, Södra Grev Rosengatan 32, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2023-02-15 Created: 2023-02-15 Last updated: 2023-05-08Bibliographically approved
List of papers
1. Validation of the diagnosis of eosinophilic esophagitis based on histopathology reports in Sweden
Open this publication in new window or tab >>Validation of the diagnosis of eosinophilic esophagitis based on histopathology reports in Sweden
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2021 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 126, no 1, article id e7687Article in journal (Refereed) Published
Abstract [en]

Background: Eosinophilic esophagitis (EoE) is a relatively new diagnosis, where until recently a specific international classification of disease code was missing. One way to identify patients with EoE is to use histopathology codes. We validated the clinicopathological EoE diagnosis based on histopathology reports and patient charts to establish these data sources as the basis for a nationwide EoE patient cohort.

Methods: Through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study, we randomly selected 165 patients from five Swedish health care regions with a histopathologic diagnosis of EoE. Patients were assigned a histopathology diagnosis of EoE if they had >= 15 eosinophils per high-power field or, in the absence of eosinophil quantification, the pathologist interpreted the biopsy as consistent with EoE. Patient charts were scrutinized to see if the other diagnostic criteria were fulfilled. Of the 131 received patient charts, 111 (85%) had sufficient information to be included in the study.

Results: Of the 111 validated patients, 99 had EoE, corresponding to a positive predictive value of 89% (95% confidence interval = 82-94%). Dysphagia was the most common symptom (n = 78, 70%), followed by food impaction (n = 64, 58%) and feeding difficulties (n = 37, 33%). Twelve patients had coexisting asthma (11%) and 16 allergic rhinitis (14%). Seventeen patients underwent esophageal dilatation (15%), of which seven had more than one dilatation. Ninety-seven (87%) patients had a proton-pump inhibitor treatment <= 2 years before or after the diagnosis. Forty-two patients (38%) had been prescribed inhalation steroids and 64 (58%) had undergone esophageal radiology.

Conclusion: Histopathology reports from the ESPRESSO cohort with esophageal eosinophilic inflammation are suggestive of EoE.

Place, publisher, year, edition, pages
Upsala Medical Society, 2021
Keywords
Eosinophilic esophagitis, inflammation, validation, histopathology
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-94122 (URN)10.48101/UJMS.V127.7687 (DOI)000689179400001 ()34471483 (PubMedID)2-s2.0-85114043167 (Scopus ID)
Funder
The Karolinska Institutet's Research Foundation
Note

Funding Agency:

Örebro University Hospital  

Available from: 2021-09-07 Created: 2021-09-07 Last updated: 2023-06-30Bibliographically approved
2. Mortality in Eosinophilic Esophagitis - a nationwide, population-based matched cohort study from 2005 to 2017
Open this publication in new window or tab >>Mortality in Eosinophilic Esophagitis - a nationwide, population-based matched cohort study from 2005 to 2017
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2021 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 126, no 1, article id e7688Article in journal (Refereed) Published
Abstract [en]

Background: There is a lack of knowledge about mortality in eosinophilic esophagitis (EoE). Therefore, this study aimed to examine the mortality in EoE.

Methods: A nationwide, population- based matched cohort study was conducted of all EoE patients in Sweden diagnosed between July 2005 and December 2017. Individuals with EoE (n = 1,625) were identified through prospectively recorded histopathology codes from all gastrointestinal pathology-reports in Sweden, representing 28 pathology departments (the ESPRESSO study). Each individual with EoE was then matched with up to five reference individuals from the general population (n = 8,003) for age, sex, year of birth, and place of residence. We used the Cox proportional hazard modeling to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) while adjusting for other potential confounders. In sensitivity analyses, mortality in EoE patients was compared with mortality in their siblings.

Results: Through December 2017, 34 deaths were confirmed in EoE patients (4.60 per 1,000 person-years) compared with 165 in reference individuals (4.57 per 1,000 person-years). This rate corresponds to an aHR of 0.97 (95% CI = 0.67-1.40). HRs were similar in males (aHR = 1.00 [0.66-1.51]) and females (aHR = 0.92 [0.38-2.18]). We observed no increased risk in mortality due to esophageal or other gastrointestinal cancers in patients with EoE (aHR = 1.02 [0.51- 2.02]). Mortality was similar in EoE patients and their siblings (aHR = 0.91 [0.44-1.85]).

Conclusion: In this nationwide, population-based matched cohort study in Sweden, there was no -increased risk of death in patients with EoE compared with their siblings and the general population.

Place, publisher, year, edition, pages
Uppsala Medical Society, 2021
Keywords
death, cancer, eosinophilic esophagitis, mortality, population-based
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-94670 (URN)10.48101/ujms.v126.7688 (DOI)000696239000001 ()34540144 (PubMedID)2-s2.0-85121935835 (Scopus ID)
Funder
The Karolinska Institutet's Research Foundation
Note

Funding agency:

Örebro University Hospital

Available from: 2021-09-29 Created: 2021-09-29 Last updated: 2023-05-08Bibliographically approved
3. Individuals With Eosinophilic Esophagitis Are at Greater Risk of Later Psychiatric Disorder
Open this publication in new window or tab >>Individuals With Eosinophilic Esophagitis Are at Greater Risk of Later Psychiatric Disorder
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2022 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 117, no 7, p. 1046-1055Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Several gastrointestinal and allergic diseases have been linked to psychiatric disease, but there are limited data on psychiatric disease in eosinophilic esophagitis (EoE). Our aim was to study the association between EoE and later psychiatric disorders.

METHODS: This was a population-based nationwide cohort study. Individuals with EoE diagnosed during 1989-2017 in Sweden (n = 1,458) were identified through the ESPRESSO histopathology cohort that represents all gastrointestinal biopsy reports in Sweden's 28 pathology departments. Individuals with EoE were matched with up to 5 reference individuals on sex, age, county, and calendar year (n = 6,436). Cox proportional hazard modeling estimated adjusted hazard ratios (HRs). In a secondary analysis, we compared individuals with EoE with their siblings to adjust for intrafamilial confounding.

RESULTS: The median age at EoE diagnosis was 39 years, and 76% of the enrolled individuals with EoE were male. During a median follow-up of 4 years, 106 individuals with EoE (15.96/1,000 person-years) developed a psychiatric disorder compared with 331 reference individuals (10.93/1,000 person-years), corresponding to an HR of 1.50 (95% confidence interval = 1.20-1.87). The increased risk was seen in the first 5 years of follow-up, but not thereafter. The highest relative risks were seen in individuals diagnosed with EoE in childhood. Compared with siblings, individuals with EoE were at an increased risk of psychiatric disease (HR = 1.62; 95% confidence interval = 1.14-2.31). EoE was linked to mood disorders, anxiety disorder, and attention-deficit hyperactivity disorder.

DISCUSSION: Individuals with EoE may be at greater risk of psychiatric disease than their siblings and the general population. This risk needs to be considered in clinical care to detect, prevent, and treat comorbidity.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2022
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-100455 (URN)10.14309/ajg.0000000000001749 (DOI)000818997600015 ()35347093 (PubMedID)2-s2.0-85133144026 (Scopus ID)
Available from: 2022-08-22 Created: 2022-08-22 Last updated: 2023-04-24Bibliographically approved
4. Pregnancy outcomes in females with eosinophilic esophagitis: a nationwide population-based study
Open this publication in new window or tab >>Pregnancy outcomes in females with eosinophilic esophagitis: a nationwide population-based study
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(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-105671 (URN)
Available from: 2023-04-24 Created: 2023-04-24 Last updated: 2023-04-24Bibliographically approved

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