Strictures in Eosinophilic Esophagitis
Strictures in Eosinophilic Esophagitis
We performed a retrospective analysis of the Swiss EoE database (SEED) and an extensive review of all patient records. The SEED was founded in 1989 by the senior author (AS) and currently includes data on 783 EoE patients from all over Switzerland. The data are stored in the Swiss EoE Clinic located in Olten, Switzerland. Of 783 patients, 323 patients (41.3%) are followed up and treated on a regular basis at the Swiss EoE Clinic by the senior author. In order to minimize the limitations of the retrospective design of this study, only data gathered in a structured manner on 323 patients who personally attended the Swiss EoE Clinic were used to carry out most of the analysis. The data on the remaining 460 EoE patients (58.7%), who were diagnosed externally by other gastroenterologists in Switzerland, were only used to examine the occurrence of strictures over time.
Patients whose data were included in the SEED had to meet the following criteria: report the presence of symptoms of esophageal dysfunction, exhibit predominant eosinophilic esophageal inflammation, either test negative by 24-hour pH-metric study or have esophageal eosinophilia that did not resolve after a completion of at least a 6-week double-dose proton pump inhibitor trial. Data on patients with histologically diagnosed eosinophilic gastroenteritis were not included into the SEED. For the purposes of inclusion into SEED, 4 biopsies from the distal esophagus (defined as the part lying >5 cm above the gastroesophageal junction) and 4 biopsies from the proximal esophagus were taken during each upper endoscopy from every patient. Between 1989 and 2007, the diagnostic criterion for EoE was met if ≥24 eosinophils per high-power field were observed in any of the fields examined. From the time of publication of the first consensus recommendation (2007), the diagnostic criterion for EoE was met if ≥15 eosinophils per high-power field were observed in any of the fields examined. In the SEED, items pertaining to demographics, disease-specific characteristics, EoE family history, history of allergies, EoE-related laboratory abnormalities, history of endoscopies, histologic findings, medications and complications, are recorded.
In addition, the records of all patients included in the analysis presented in this article were reviewed under the supervision of AMS and AS, and a new database was created in EpiData (version 3.1; The EpiData Association, Denmark). This database incorporates a total of 98 items, of which 22 are related to EoE patient history and 76 related to symptoms, endoscopic, laboratory, and histologic findings assessed and therapeutic decisions made during each visit. For the purposes of this study, diagnostic delay was defined as the time period from appearance of first symptoms to establishment of EoE diagnosis.
In addition to these criteria for SEED inclusion, patients were only included in this study if a complete dataset consisting of the following documents was obtained: a standardized symptom assessment questionnaire completed during each visit, a record of complete laboratory workup of samples obtained on the day of patient interview and endoscopy, an endoscopy report containing a structured description and photographic documentation of the endoscopic findings, and a histology report on the biopsies taken from the proximal and distal esophagus.
Since 1989, the following endoscopic signs were consistently described: edema (defined as reduced vascular pattern), white exudates (defined as white spots of the esophageal surface), furrows (defined as vertical lines), rings, crêpe-paper esophagus (lacerations), and strictures. The endoscopic features described in Swiss EoE Clinic visit records were identical to those that were used by Hirano et al for a novel grading system for endoscopic esophageal features of EoE.
For the purposes of this study, strictures were defined as narrowing of the esophageal diameter, irrespective of the length of the stricture. Stricture severity was classified as described elsewhere. Briefly, a stricture was classified as low grade if it could be passed with a standard endoscope (measured 9 mm in outer diameter) with some resistance, often inducing lacerations (also described as crêpe-paper esophagus). A stricture was classified as intermediate grade if it could not be passed with a 9-mm outer diameter endoscope, but could be passed with a 6-mm outer diameter endoscope. A stricture was classified as high grade if it could not be passed with a 6-mm outer diameter endoscope. If multiple strictures were found, the diameter of the narrowest stricture was reported. The length and location of strictures were recorded. Stricturing rings were assigned a length of 0.5 cm.
The biopsies of all SEED patients followed up at the Swiss EoE Clinic were evaluated by CB. For the purposes of histologic examination, 4-μm sections were cut from the paraffin blocks and stained with H&E, van Gieson, Alcian blue, and Periodic acid-Schiff stain. All histologic examinations were performed using a standard pathology microscope (Zeiss Axiophot, Plan-Neofluar 40, ocular magnification 10×, area of microscopic field 0.260 mm). At least 10 sections of each esophageal biopsy specimen were surveyed, and the eosinophils in the most densely infiltrated area were counted (peak eosinophil count). The extent of subepithelial fibrosis was visualized using the van Gieson stain and semiquantiatively graded as either absent, mild/moderate, or severe.
The study was approved by the local ethics committee. Before inclusion into the SEED, a written informed consent was obtained from all patients.
Data from EpiData were imported into a statistical package program (STATA version 12, College Station, TX). Data distribution was analyzed using Normal-QQ-Plots. Results of quantitative data are presented as either mean ± SD and range (for parametric data) or median plus interquartile range (IQR) (for nonparametric data). Categorical data were summarized as the percentage of the group total. Differences in quantitative data distributions between the groups were assessed by the Student's t test (for parametric data) and by the Wilcoxon rank-sum test (for nonparametric data). Univariate logistic regression modeling was performed to identify risk factors for the outcome "presence of stricture(s) at the time of EoE diagnosis." As dependent variables for the outcome, the following items were evaluated: sex (coded as "male" and "female," binary variable), allergies (coded as "present" and "absent," binary variable), diagnostic delay (in years, continuous variable), age at EoE symptom onset (in years, continuous variable), EoE family history (coded as "present" and "absent," binary variable), blood eosinophilia at EoE diagnosis (defined as >0.3 g/L, coded as "present" and "absent," binary variable), elevated levels of IgE (defined as IgE level of >100 kU/L, coded as "present" and "absent," binary variable), and severe histologic activity (defined as peak eosinophil count of >100 per high-power field, coded as "present" and "absent," binary variable). For the purposes of this study, a P value of <.05 was considered statistically significant.
Methods
Swiss EoE Database
We performed a retrospective analysis of the Swiss EoE database (SEED) and an extensive review of all patient records. The SEED was founded in 1989 by the senior author (AS) and currently includes data on 783 EoE patients from all over Switzerland. The data are stored in the Swiss EoE Clinic located in Olten, Switzerland. Of 783 patients, 323 patients (41.3%) are followed up and treated on a regular basis at the Swiss EoE Clinic by the senior author. In order to minimize the limitations of the retrospective design of this study, only data gathered in a structured manner on 323 patients who personally attended the Swiss EoE Clinic were used to carry out most of the analysis. The data on the remaining 460 EoE patients (58.7%), who were diagnosed externally by other gastroenterologists in Switzerland, were only used to examine the occurrence of strictures over time.
Patients whose data were included in the SEED had to meet the following criteria: report the presence of symptoms of esophageal dysfunction, exhibit predominant eosinophilic esophageal inflammation, either test negative by 24-hour pH-metric study or have esophageal eosinophilia that did not resolve after a completion of at least a 6-week double-dose proton pump inhibitor trial. Data on patients with histologically diagnosed eosinophilic gastroenteritis were not included into the SEED. For the purposes of inclusion into SEED, 4 biopsies from the distal esophagus (defined as the part lying >5 cm above the gastroesophageal junction) and 4 biopsies from the proximal esophagus were taken during each upper endoscopy from every patient. Between 1989 and 2007, the diagnostic criterion for EoE was met if ≥24 eosinophils per high-power field were observed in any of the fields examined. From the time of publication of the first consensus recommendation (2007), the diagnostic criterion for EoE was met if ≥15 eosinophils per high-power field were observed in any of the fields examined. In the SEED, items pertaining to demographics, disease-specific characteristics, EoE family history, history of allergies, EoE-related laboratory abnormalities, history of endoscopies, histologic findings, medications and complications, are recorded.
In addition, the records of all patients included in the analysis presented in this article were reviewed under the supervision of AMS and AS, and a new database was created in EpiData (version 3.1; The EpiData Association, Denmark). This database incorporates a total of 98 items, of which 22 are related to EoE patient history and 76 related to symptoms, endoscopic, laboratory, and histologic findings assessed and therapeutic decisions made during each visit. For the purposes of this study, diagnostic delay was defined as the time period from appearance of first symptoms to establishment of EoE diagnosis.
In addition to these criteria for SEED inclusion, patients were only included in this study if a complete dataset consisting of the following documents was obtained: a standardized symptom assessment questionnaire completed during each visit, a record of complete laboratory workup of samples obtained on the day of patient interview and endoscopy, an endoscopy report containing a structured description and photographic documentation of the endoscopic findings, and a histology report on the biopsies taken from the proximal and distal esophagus.
Description of Endoscopic Findings
Since 1989, the following endoscopic signs were consistently described: edema (defined as reduced vascular pattern), white exudates (defined as white spots of the esophageal surface), furrows (defined as vertical lines), rings, crêpe-paper esophagus (lacerations), and strictures. The endoscopic features described in Swiss EoE Clinic visit records were identical to those that were used by Hirano et al for a novel grading system for endoscopic esophageal features of EoE.
For the purposes of this study, strictures were defined as narrowing of the esophageal diameter, irrespective of the length of the stricture. Stricture severity was classified as described elsewhere. Briefly, a stricture was classified as low grade if it could be passed with a standard endoscope (measured 9 mm in outer diameter) with some resistance, often inducing lacerations (also described as crêpe-paper esophagus). A stricture was classified as intermediate grade if it could not be passed with a 9-mm outer diameter endoscope, but could be passed with a 6-mm outer diameter endoscope. A stricture was classified as high grade if it could not be passed with a 6-mm outer diameter endoscope. If multiple strictures were found, the diameter of the narrowest stricture was reported. The length and location of strictures were recorded. Stricturing rings were assigned a length of 0.5 cm.
Histologic Analyses
The biopsies of all SEED patients followed up at the Swiss EoE Clinic were evaluated by CB. For the purposes of histologic examination, 4-μm sections were cut from the paraffin blocks and stained with H&E, van Gieson, Alcian blue, and Periodic acid-Schiff stain. All histologic examinations were performed using a standard pathology microscope (Zeiss Axiophot, Plan-Neofluar 40, ocular magnification 10×, area of microscopic field 0.260 mm). At least 10 sections of each esophageal biopsy specimen were surveyed, and the eosinophils in the most densely infiltrated area were counted (peak eosinophil count). The extent of subepithelial fibrosis was visualized using the van Gieson stain and semiquantiatively graded as either absent, mild/moderate, or severe.
Ethics
The study was approved by the local ethics committee. Before inclusion into the SEED, a written informed consent was obtained from all patients.
Statistical Analysis
Data from EpiData were imported into a statistical package program (STATA version 12, College Station, TX). Data distribution was analyzed using Normal-QQ-Plots. Results of quantitative data are presented as either mean ± SD and range (for parametric data) or median plus interquartile range (IQR) (for nonparametric data). Categorical data were summarized as the percentage of the group total. Differences in quantitative data distributions between the groups were assessed by the Student's t test (for parametric data) and by the Wilcoxon rank-sum test (for nonparametric data). Univariate logistic regression modeling was performed to identify risk factors for the outcome "presence of stricture(s) at the time of EoE diagnosis." As dependent variables for the outcome, the following items were evaluated: sex (coded as "male" and "female," binary variable), allergies (coded as "present" and "absent," binary variable), diagnostic delay (in years, continuous variable), age at EoE symptom onset (in years, continuous variable), EoE family history (coded as "present" and "absent," binary variable), blood eosinophilia at EoE diagnosis (defined as >0.3 g/L, coded as "present" and "absent," binary variable), elevated levels of IgE (defined as IgE level of >100 kU/L, coded as "present" and "absent," binary variable), and severe histologic activity (defined as peak eosinophil count of >100 per high-power field, coded as "present" and "absent," binary variable). For the purposes of this study, a P value of <.05 was considered statistically significant.
