Sustained clinical and histopathological remission in a patient with eosinophilic esophagitis and type-2 comorbidities at 18 months after discontinuation of dupilumab.

Eosinophilic esophagitis (EoE) is a chronic, allergen-mediated, type-2 inflammatory disease with the potential to significantly impact an individual's quality of life. Conventional treatments often result in varied responses, prompting the need for novel therapeutic approaches. We present the case of a 19-year-old male with a medical history marked by eosinophilic esophagitis, severe atopic dermatitis (AD), asthma, and allergic rhinitis. Despite undergoing diverse topical and systemic interventions to address his AD and EoE, the patient's symptoms persisted. However, following the initiation of dupilumab therapy-a dual IL-4 and IL-13 receptor antagonist-the patient experienced a substantial reduction in his Eczema Area and Severity Index score. Notably, a marked improvement was also seen regarding his symptoms of eosinophilic esophagitis. A subsequent esophageal biopsy revealed a significant decrease in eosinophilic inflammation, consistent with established clinical and histologic remission criteria. These findings corroborate the patient's reported relief from symptoms. This case underscores the potential efficacy of dupilumab as a promising therapeutic agent in managing eosinophilic esophagitis. Dupilumab offers a dual benefit of alleviating symptoms and achieving histologic and clinical remission. This novel approach presents a noteworthy advancement in the treatment of EoE.

Oesophageal squamous papilloma in paediatric population: a single-centre case series.

PURPOSE: Oesophageal squamous papilloma (OSP) is a rare epithelial lesion with an unclear aetiology, found incidentally in upper gastrointestinal endoscopy (UGE). We evaluate the epidemiology, general features and endoscopic and histological characteristics of OSP in children in a single centre. METHODS: We conducted a retrospective search of 3568 medical records of children under 18 years old who underwent UGE between 2004 and 2022, at Hospital Metropolitano de Quito, Ecuador. We described the general features of 15 patients diagnosed with OSP. Histopathology reports were analysed, including a chromogenic in situ hybridisation (CISH) for human papillomavirus (HPV) 6/11. RESULTS: OSP was diagnosed in 15 patients between 10 and 16 years of age, with an estimated prevalence of 0.4%. The gender ratio male to female was 1:1.1. Most patients (n=14) underwent UGE due to abdominal pain. Lesions were found predominantly in the upper and lower part of the oesophagus; 12 patients had isolated lesions, and none of the lesions tested positive for HPV on CISH 6/11 analysis. Additionally, Helicobacter pylori and eosinophilic oesophagitis (EoE) were diagnosed in one patient each. CONCLUSION: Our study describes the clinical features of paediatric OSP in a single centre. The prevalence was similar to that in the adult population but higher than in other paediatric populations, and none of our patients had HPV.

Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis.

OBJECTIVE: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls. METHODS: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons. RESULTS: One hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls. CONCLUSIONS: Dominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.

Seguridad de la endoscopia y biopsia esofágica en un paciente con esofagitis eosinofílica y enfermedad de Von Willebrand / Safety of esophageal endoscopy and biopsy in a patient with eosinophilic esophagitis and Von Willebrand disease

La esofagitis eosinofílica (EoE) es una enfermedad causada por una respuesta inmune frente a antígenos alimentarios en contacto con la mucosa esofágica; por su parte, la enfermedad de Von Willebrand (EVW) es el trastorno hemorrágico hereditario más común en los seres humanos. La característica central de todos los tipos de EVW, es la presencia de cantidades reducidas o de formas anormales del factor de Von Willebrand (FVW) en el torrente sanguíneo. Debido a que no se han reportado casos previos de EVW tipo 2A asociada a EoE, se describe este caso clínico con el objetivo principal de dar a conocer el hallazgo casual de estas dos patologías, la seguridad de la evaluación por endoscopia de vías digestivas altas y el pronóstico de posibles complicaciones

Eosinophilic esophagitis (EoE) is a disease caused by an immune response against food antigens in contact with the esophageal mucosa; alternatively, Von Willebrand disease (VWD) is the most common inherited bleeding disorder in humans. The central characteristic of all types of VWD is the presence of reduced amounts or abnormal forms of VWF in the bloodstream. Since no previous cases of VWD type 2A associated to EoE have been reported, this clinical case is described with the main objective to present the coincidental finding of these two pathologies, the safety of the evaluation by upper gastrointestinal endoscopy, and the prognosis of possible complications

Eosinophilic esophagitis auxiliary diagnosis based on a peptide ligand to eosinophil cationic protein in esophageal mucus of pediatric patients.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by increased number of eosinophils. Currently, EoE diagnosis is based on endoscopic procedures for histopathological examination, eosinophils' counting and, often, in clinical practice, the challenge is the differentiation between EoE and gastroesophageal reflux disease (GERD). Our aim was to develop novel peptide ligand to Eosinophil cationic protein (ECP) present in EoE biopsies of patients with potential to be used for detection. We performed a comparative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of esophageal biopsies from pediatric patients with eosinophilic esophagitis, gastroesophageal reflux disease and control individuals. Then, phage display technology was used to select peptides against specific up-regulated protein from EoE patients. Twelve phage clones were selected after three biopanning rounds, and the best phage clone reactivity was evaluated by phage-ELISA assay using esophageal mucus samples from 94 pediatric patients. Mass spectrometry showed that eosinophil cationic protein (ECP) was one of the most up-regulated proteins in EoE patients, which is an eosinophil granule protein usually deposited on tissues to mediate remodeling, but in excess may cause fibrosis and hypertrophy, especially in allergic responses. A highly reactive ECP-ligand peptide (E5) was able to distinguish reactive mucus of EoE patients from GERD and the control individuals by Phage-ELISA, achieving a sensitivity of 84.62%, and a specificity of 82.72%. This is the first study that successfully demonstrated an antibody-like peptide targeting ECP at the esophagus mucus as a useful auxilliary tool for EoE diagnosis with a significant association with atopic disorders and dysphagia.ClinicalTrials.gov no.: NCT03069573.

Disodium cromoglycate treatment reduces TH2 immune response and immunohistopathological features in a murine model of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an emergent chronic disease of the esophagus. The immunopathological process in EoE is characterized by Th2 immune response and prominent eosinophilic influx, in response to common food allergens. The classical treatment consists of allergen elimination diet and systemic/topical corticosteroid therapy. Nevertheless, patients do not always comply to treatment, and the prolonged corticosteroid therapy can cause side effects, therefore, there is an immediate need for new therapeutic approach for EoE. Disodium cromoglicate (DSCG) is a substance broadly used in allergic asthma treatment, and a well-known mast cell activation stabilizer. However, its effect in EoE have not been evaluated yet. This study aimed to assess the effects of DSCG treatment in an EoE experimental model. Male Balb/C mice were subcutaneously sensitized for five days with OVA, and subsequently orally OVA-challenged, DSCG administration was performed between the OVA-challenges. DSCG treatment not only reduced eosinophilic and mast cell influx, as well as reduced fibrosis. In addition, tslp, GATA3, IL-5, FoxP3 and IL-10 mRNA expression were reduced in esophageal mucosa, associated with lower Th2 (CD3+CD4+GATA3+IL4+) and B cells (CD19+CD40+) number in peripheral lymphoid organs. In conclusion, the data demonstrate DSCG treatment was effective in reducing mast cell activation and Th2 immune response, important immunopathological EoE features. Therefore, the use of DSCG as an EoE treatment can be considered a promising therapeutic approach to treat this disease.

The potential for malignancy from atopic disorders and allergic inflammation: A systematic review and meta-analysis.

OBJECTIVE: While chronic inflammation is a well-established risk factor for malignancy, studies evaluating the relationship between allergic inflammation and cancer have revealed conflicting results. Here, we aimed to assess the association between allergic inflammation in the lung (asthma), skin (eczema) or oesophagus (eosinophilic oesophagitis; EoE) and cancer at the organ site. DESIGN: We conducted a systematic review of the literature to identify observational studies (case-control, cohort and cross-sectional) evaluating the association between asthma and lung cancer, eczema and skin cancer, or EoE and oesophageal cancer. Random-effects meta-analysis was performed to define pooled estimates of effects. DATA SOURCES: PubMed, EMBASE and Web of Science. ELIGIBILITY CRITERIA FOR SELECTION: Included studies evaluated the incidence of cancer. RESULTS: Thirty-two studies met the inclusion criteria, 27 in the lung, four in the skin and one in the oesophagus. Meta-analysis of the three studies with prospective data collection of asthma diagnosis revealed a positive association with incident lung cancer (OR 1.27, 95% CI 1.09-1.44); however, this result was not consistently supported by the larger dataset of retrospective studies (OR 1.37, 95% CI 0.90-1.83). Overall, studies in the lung displayed significant heterogeneity (I2 98%, P < .0001), but no significant effect modification on the association between asthma and lung cancer was identified for the variables of sex, smoking or study design. Meta-analysis could not be applied to the four papers reviewed in the skin, but three suggested an association between eczema and non-melanoma skin cancer, while the remaining study failed to identify an association between melanoma and eczema. A single study meeting inclusion criteria showed no association between EoE and oesophageal malignancy. CONCLUSIONS: The current data cannot exclude the possibility of an association between atopy and malignancy the lung, skin and oesophagus. The relationship between allergy and cancer should be explored further in prospective studies that any association identified between these conditions has the potential for significant public health implications.

High-fat diet-induced obesity worsens TH2 immune response and immunopathologic characteristics in murine model of eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is an emergent chronic immune-mediated disease of the oesophagus, which affects both children and adults. It is clinically characterized by dysphagia, food impaction and oesophageal eosinophilia. Epidemiological studies indicate that obesity can worsen allergic symptoms; however, its effect on EoE immunopathological response has not been evaluated yet. This study aimed to assess the effect of obesity on allergic inflammation and T helper-2 profile in an EoE experimental model. METHODS: Obesity was induced by high-fat feeding. After 7 weeks of diet, male BALB/c mice were subcutaneously sensitized and orally challenged with OVA. RESULTS: Obesity itself induced a significant mast cell and eosinophil accumulation in the oesophagus, trachea, gut and lung. After allergy induction, this number was higher, when compared to lean-allergic mice. Moreover, obese-allergic mice showed higher remodelling area, in the oesophagus, associated with higher IL-5 and TSLP mRNA expression. In contrast, FoxP3 and IL-10 were less expressed in comparison with lean-allergic mice. In addition, the amount of CD11c+ MHCII+ PDL1+ dendritic cells was reduced, while the number of CD11c+ MHCII+ CD80+ DCs and CD3+ CD4+ GATA3+ IL-4+ cells was increased in obese-allergic mice in the spleen and lymph nodes when compared to lean-allergic mice. CONCLUSION: Obesity aggravated the immune histopathological characteristics in the EoE experimental model, which was associated with the reduction in the regulatory profile, and the increased inflammatory cells influx, related to the TH 2 profile. Altogether, the data provide new knowledge about obesity as a risk factor, worsening EoE symptoms, and contribute for future treatment strategies for this specific profile.

Association between endoscopic findings and histopathological confirmation in patients with suspicion of eosinophilic esophagitis.

BACKGROUND: The diagnosis of eosinophilic esophagitis (EoE) is performed by the detection of 15 or more eosinophils per field in an esophageal biopsy sample, but the endoscopic findings alone are not validated for a diagnosis of the disease. OBJECTIVE: To evaluate the association between the endoscopic findings and histopathological diagnosis in patients with suspected EoE in endoscopy. METHODS: A retrospective study of 24 patients with suspicion of EoE during endoscopy was held. The information was collected from databases of Endoscopy and Pathology services of the Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, from March 2012 to April 2018. The patients were divided into a group with positive biopsy (>15 Eosinophils/field, N=8) and a group with negative biopsy (<15 Eosinophils/field, N=16), and the endoscopic findings were compared between the two groups. RESULTS: From a total of 24 patients, 79.1% had longitudinal grooves, 20.8% white exudates, 33.3% mucosal pallor or loss of vascularity and 45.8% had more than one endoscopic finding. There was a significant difference (P<0.05) in the evaluation of the finding of mucosal pallor or decreased vasculature alone among the groups. The positive predictive value and negative predictive value of the presence of more than one endoscopic findings for the diagnosis of EoE was 54% and 84%, respectively. CONCLUSION: There was a low association between the presence of endoscopic findings and histopathological confirmation of the disease, which indicates that endoscopic findings alone are not reliable for the diagnosis of EoE.

Association between endoscopic findings and histopathological confirmation in patients with suspicion of eosinophilic esophagitis / Associação entre achados endoscópicos e confirmação histopatológica em pacientes com suspeita de esofagite eosinofílica

ABSTRACT BACKGROUND: The diagnosis of eosinophilic esophagitis (EoE) is performed by the detection of 15 or more eosinophils per field in an esophageal biopsy sample, but the endoscopic findings alone are not validated for a diagnosis of the disease. OBJECTIVE: To evaluate the association between the endoscopic findings and histopathological diagnosis in patients with suspected EoE in endoscopy. METHODS: A retrospective study of 24 patients with suspicion of EoE during endoscopy was held. The information was collected from databases of Endoscopy and Pathology services of the Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, from March 2012 to April 2018. The patients were divided into a group with positive biopsy (>15 Eosinophils/field, N=8) and a group with negative biopsy (<15 Eosinophils/field, N=16), and the endoscopic findings were compared between the two groups. RESULTS: From a total of 24 patients, 79.1% had longitudinal grooves, 20.8% white exudates, 33.3% mucosal pallor or loss of vascularity and 45.8% had more than one endoscopic finding. There was a significant difference (P<0.05) in the evaluation of the finding of mucosal pallor or decreased vasculature alone among the groups. The positive predictive value and negative predictive value of the presence of more than one endoscopic findings for the diagnosis of EoE was 54% and 84%, respectively. CONCLUSION: There was a low association between the presence of endoscopic findings and histopathological confirmation of the disease, which indicates that endoscopic findings alone are not reliable for the diagnosis of EoE.

RESUMO CONTEXTO: O diagnóstico da esofagite eosinofílica é realizado através da detecção, em amostra de biópsia esofágica, de 15 ou mais eosinófilos por campo, sendo que os achados endoscópicos isolados não são validados para o diagnóstico da doença. OBJETIVO: Avaliar a associação entre os achados endoscópicos com o diagnóstico histopatológico em pacientes com suspeita de esofagite eosinofílica na endoscopia. MÉTODOS: Estudo retrospectivo de 24 pacientes com suspeita de esofagite eosinofílica durante endoscopia digestiva alta. As informações foram colhidas de bancos de dados dos serviços de Endoscopia e Patologia do Hospital Universitário Walter Cantídio da Universidade Federal do Ceará, no período de março de 2012 a abril de 2018. Os pacientes foram divididos em grupo com biópsia positiva (>15 eosinófilos/campo, N=8) e grupo com biópsia negativa (<15 eosinófilos/campo, N=16), sendo comparados os achados endoscópicos entre os dois grupos. RESULTADOS: Do total de 24 pacientes, 79,1% tinham a presença de sulcos longitudinais, 20,8% exsudatos brancos, 33,3% palidez de mucosa ou perda da vascularização e 45,8% apresentaram mais de um achado endoscópico. Houve diferença significativa (P<0,05) na avaliação do achado de palidez ou perda da vascularização, isoladamente, entre os grupos. O valor preditivo positivo e valor preditivo negativo da presença de mais de um achado endoscópico para o diagnóstico de esofagite eosinofílica foi de 54% e 84%, respectivamente. CONCLUSÃO: Houve uma baixa associação entre a presença de achados endoscópicos e a confirmação histopatológica da doença, o que faz com que os achados endoscópicos isolados não sejam confiáveis para o diagnóstico de esofagite eosinofílica.

Low Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Patients with Esophageal Food Impaction in Mexican Population.

BACKGROUND: Eosinophilic esophagitis (EoE) is the most common cause of dysphagia and esophageal food impaction (EFI) in the USA, Western Europe, and Australia. In Mexico, the uncomplicated form of this disease is infrequent, and prevalence in patients with EFI is unknown. AIMS: To determine the prevalence and causes of EFI, endoscopic and therapeutic aspects, and establish the prevalence of biopsy-proven EoE in patients with EFI. METHODS: Diagnostic upper gastrointestinal endoscopy reports from January 2011 to December 2016 were retrospectively reviewed. Patients with therapeutic procedures, gastrointestinal hemorrhage, or non-food foreign body impaction were excluded. The number of patients with EFI was determined. Additionally, patients with esophageal biopsy were retained for EoE prevalence calculation. The diagnosis of EoE was defined with the presence of eosinophil infiltration count ≥ 15/high-power field with or without typical endoscopic abnormalities. RESULTS: A total of 4700 reports of the same number of patients were selected; 2209 were males (47%) with a mean age of 57.6 ± 12.3 years (range 14-93). We identified 36 patients with EFI (0.76, 95% CI 0.51-1.01), 16 males (44.4%) with a mean age of 54.9 ± 19.7 (range 22-92). Esophageal biopsies were obtained in 17/36 (47.2%) cases. The diagnosis of EoE was confirmed in 2 patients (11.7%). Peptic stenosis was the most frequent cause of EFI. CONCLUSIONS: EoE is an infrequent cause of EFI in the Mexican population (11.7%). EoE had the lowest prevalence compared to that reported in Caucasian populations. The prevalence of EFI was also low.

Frequency of Esophageal Eosinophilia in a Pediatric Population from Central Brazil.

Here we report a retrospective cross-sectional study on Esophageal eosinophilia (EsEo) frequency in Brazil, for 2, 425 pediatric patients with symptoms associated with gastroesophageal diseases in 2012. EsEo is defined by ≥15 eosinophils per high power field (400x) and confirmed through histological analyses of esophageal biopsies. Overall, 126 patients had EsEo equating to a frequency of 5.2%. There was a significant difference between the endoscopic features of patients with EsEo, where 10.7% had erosive esophagitis, 3.0% had non-erosive esophagitis and 1% showed normal esophageal mucosa. According to the interaction of the variables in the Classification and Regression Tree Analysis, most patients diagnosed with EsEo were older males with erosive esophagitis. On the other hand, the lowest frequency of EsEo was found among younger females with non-erosive esophagitis/normal mucosa. Environmental conditions, including climate variation and changes, were observed in association with EsEo, supporting a potential role for environmental factors in its pathogenesis. There was an inverse correlation between the number of EsEo, rainfall and humidity. EsEo is a relatively frequent finding in the pediatric population of Brazil with symptoms of gastroesophageal diseases. Both clinical and histological examinations of patients are important for a reliable diagnostic of EsEo cases and to patient care.

Caracterização histopatológica da esofagite eosinofílica em crianças e adolescentes / Histological features of eosinophilic esophagitis in children and adolescents

ABSTRACT BACKGROUND: Eosinophilic esophagitis is an emerging disease featured by eosinophilic esophageal infiltrate not responsive to proton pump inhibitors. OBJECTIVE: To characterize histological features of children and adolescents with eosinophilic esophagitis. METHODS: Cross-sectional study in a tertiary hospital. Biopsies from each esophageal third from 14 patients (median age 7 years) with eosinophilic esophagitis were evaluated. Histological features evaluated included morphometry of esophageal epithelium, esophageal density (per high power field), extracellular eosinophilic granules, eosinophilic microabscesses, surface disposition of eosinophils, epithelial desquamation, peripapillary eosinophilia, basal layer hyperplasia and papillary elongation. RESULTS: Several patients presented a normal esophageal macroscopy in the upper digestive endoscopy (6, 42.8%), and the most common abnormality were vertical lines (7, 50%) and whitish spots over esophageal mucosa (7, 50%). Basal layer hyperplasia was observed in 88.8%, 100% e 80% of biopsies from proximal, middle and lower esophagus, respectively (P=0.22). Esophageal density ranges from 0 to more than 50 per hpf. Extracellular eosinophilic granules (70%-100%), surface disposition of eosinophils (60%-93%), epithelial desquamation (60%-100%), peripapillary eosinophilia (70%-80%) were common, but evenly distributed among each esophageal third. Just one patient did not present eosinophils in the lower third, four in the middle third and four in the upper esophageal third. CONCLUSION: In the absence of hypereosinophilia, other histological features are present in eosinophilic esophagitis and may contribute to diagnosis. Eosinophilic infiltrate is focal, therefore multiple biopsies are needed for diagnosis.

RESUMO CONTEXTO: Esofagite eosinofílica é uma doença emergente caracterizada por infiltrado eosinofílico esofágico não responsivo a inibidores de bomba de prótons. OBJETIVO: Caracterizar os achados histopatológicos de uma coorte de crianças e adolescentes com diagnóstico de esofagite eosinofílica. MÉTODOS: Estudo transversal conduzido em hospital terciário. Biópsias de terços proximal, médio e distal de 14 pacientes (idade mediana 7 anos) com diagnóstico de esofagite eosinofílica. Estudo morfométrico e variáveis histológicas analisadas em fragmentos de biópsias nos terços esofágicos: contagem de eosinófilos/CGA, grânulos eosinofílicos extracelulares, microabscessos eosinofílicos, disposição superficial de eosinófilos, descamação epitelial, eosinofilia peripapilar, hiperplasia da camada basal e alongamento de papilas. RESULTADOS: Vários pacientes apresentaram aspecto macroscópico normal da mucosa esofágica à endoscopia (6, 42.8%), e a anormalidade mais comumente observada foi linhas verticais (7, 50%) e exsudato branco (7, 50%). Hiperplasia da camada basal foi observada em 88,8%, 100% e 80% das biópsias do terço proximal, médio e distal respectivamente (P=0,22); contagem de eosinófilos nos terços variou de 0 a ≥50/CGA, grânulos eosinofílicos extracelulares (70%-100%), disposição superficial de eosinófilos (60%-93%), descamação epitelial (60%-100%), eosinofilia peripapilar (70%-80%), sem diferença estatística entre os terços esofágicos. Ausência de eosinofilia ocorreu raramente em terço distal (uma do distal, quatro do proximal, quatro do médio). CONCLUSÃO: Na ausência de hipereosinofilia, outros achados histopatológicos de inflamação eosinofílica estão presentes. A infiltração eosinofílica apresentou caráter focal, sugerindo-se a realização de múltiplas biópsias de diversos segmentos.

HISTOLOGICAL FEATURES OF EOSINOPHILIC ESOPHAGITIS IN CHILDREN AND ADOLESCENTS.

BACKGROUND: Eosinophilic esophagitis is an emerging disease featured by eosinophilic esophageal infiltrate not responsive to proton pump inhibitors. OBJECTIVE: To characterize histological features of children and adolescents with eosinophilic esophagitis. METHODS: Cross-sectional study in a tertiary hospital. Biopsies from each esophageal third from 14 patients (median age 7 years) with eosinophilic esophagitis were evaluated. Histological features evaluated included morphometry of esophageal epithelium, esophageal density (per high power field), extracellular eosinophilic granules, eosinophilic microabscesses, surface disposition of eosinophils, epithelial desquamation, peripapillary eosinophilia, basal layer hyperplasia and papillary elongation. RESULTS: Several patients presented a normal esophageal macroscopy in the upper digestive endoscopy (6, 42.8%), and the most common abnormality were vertical lines (7, 50%) and whitish spots over esophageal mucosa (7, 50%). Basal layer hyperplasia was observed in 88.8%, 100% e 80% of biopsies from proximal, middle and lower esophagus, respectively (P=0.22). Esophageal density ranges from 0 to more than 50 per hpf. Extracellular eosinophilic granules (70%-100%), surface disposition of eosinophils (60%-93%), epithelial desquamation (60%-100%), peripapillary eosinophilia (70%-80%) were common, but evenly distributed among each esophageal third. Just one patient did not present eosinophils in the lower third, four in the middle third and four in the upper esophageal third. CONCLUSION: In the absence of hypereosinophilia, other histological features are present in eosinophilic esophagitis and may contribute to diagnosis. Eosinophilic infiltrate is focal, therefore multiple biopsies are needed for diagnosis.

Mastócitos discriminam esofagite eosinofílica em pacientes pediátricos / Mast cells distinguish eosinophilic esophagitis in pediatric patients

ABSTRACT BACKGROUND: Mast cells exert a substantial role in gastrointestinal allergic diseases. Therefore, it is reasonable to presume that mast cell may aid diagnosis in eosinophilic gastroenteropathy. OBJECTIVE: To evaluate whether mast cell count in the esophageal epithelium can discriminate eosinophilic esophagitis, proton-pump inhibitor (PPI)-responsive eosinophilic esophagitis and gastroesophageal reflux esophagitis. METHODS: Retrospectively we reviewed the files of 53 consecutive patients (age: 7.8 years; range: 8-14 years) with definitive diagnose established during clinical follow up in a universitary outpatient clinic as follow: eosinophilic esophagitis (N=23), PPI-responsive eosinophilic esophagitis (N=15) and gastroesophageal reflux esophagitis (N=15). Eosinophil count in the esophageal epithelium in slides stained with H-E was reviewed and immunohistochemistry for mast cell tryptase was performed. RESULTS: Count of eosinophils/high-power field (HPF) higher than 15 were found in 14 out of 15 reflux esophagitis patients. The mean count of eosinophils/HPF was similar in eosinophilic esophagitis patients and in those with PPI-responsive eosinophilic esophagitis (42 and 39 eosinophils/HPF, respectively, P=0.47). Values of mast cell tryptase (+) were higher in eosinophilic esophagitis [median: 25 mast cells/HPF; range (17-43) ] and in PPI-responsive eosinophilic esophagitis patients [25 (16-32) ], compared to reflux esophagitis [4 (2-14) ], P<0.001. There was no difference between the mean count of mast cells/HPF in the esophageal epithelium of eosinophilic esophagitis patients and PPI-responsive eosinophilic esophagitis patients, respectively, 26 and 24 mast cells/HPF, P=0.391. CONCLUSION: Tryptase staining of mast cells differentiates eosinophilic esophagitis from reflux esophagitis.

RESUMO CONTEXTO: Os mastócitos detêm papel fundamental na resposta imuno-alérgica gastrintestinal. Assim, é razoável admitir que essas células sejam úteis no diagnóstico diferencial das gastroenteropatias eosinofílicas. OBJETIVO: Determinar se a análise quantitativa de mastócitos na mucosa esofágica permite discernir esofagite eosinofílica, esofagite eosinofílica responsiva ao inibidor de bomba de prótons e esofagite péptica por doença de refluxo gastroesofágico. MÉTODOS: Revisamos retrospectivamente os prontuários 53 crianças (idade: 7,8 anos; variação: 8-14 anos), atendidas consecutivamente, num serviço terciário e cujos diagnósticos definitivos estabelecidos após seguimento clínico foram esofagite eosinofílica (N=23), esofagite eosinofílica responsiva ao inibidor de bomba de prótons (N=15) e esofagite péptica por doença de refluxo gastroesofágico (N=15). As amostras histológicas foram revisadas quanto à contagem de eosinófilos na coloração de H-E e processadas para imunoistoquímica da triptase de mastócitos. RESULTADOS: Valores de eosinófilos/campo de maior aumento (CMA; 400X) >15 foram encontrados em 14 dos 15 pacientes com refluxo gastroesofágico. A média de eosinófilos/CMA foi similar nos pacientes com esofagite eosinofílica e com esofagite eosinofílica responsiva ao inibidor de bomba de prótons, respectivamente, 42 e 39 eosinófilos/CMA, P=0,47). Os valores de mastócitos triptase (+) foram superiores no epitélio esofágico dos pacientes com esofagite eosinofílica [mediana: 25 mastócitos/CMA; variação (17- 43) ] e na esofagite eosinofílica responsiva ao inibidor de bomba de prótons [25 (16-32) ], comparados aos pacientes com refluxo gastroesofágico [4(2-14) ], P<0,001. Não houve diferença entre a média de mastócitos/CMA nos pacientes com esofagite eosinofílica comparados aos com esofagite eosinofílica responsiva ao inibidor de bomba de prótons, respectivamente, 26 e 24 mastócitos/CMA, P=0,391. CONCLUSÃO: A coloração para mastócitos pela imunoistoquímica da triptase diferencia as esofagites eosinofílicas da esofagite péptica.

MAST CELLS DISTINGUISH EOSINOPHILIC ESOPHAGITIS IN PEDIATRIC PATIENTS.

BACKGROUND:: Mast cells exert a substantial role in gastrointestinal allergic diseases. Therefore, it is reasonable to presume that mast cell may aid diagnosis in eosinophilic gastroenteropathy. OBJECTIVE:: To evaluate whether mast cell count in the esophageal epithelium can discriminate eosinophilic esophagitis, proton-pump inhibitor (PPI)-responsive eosinophilic esophagitis and gastroesophageal reflux esophagitis. METHODS:: Retrospectively we reviewed the files of 53 consecutive patients (age: 7.8 years; range: 8-14 years) with definitive diagnose established during clinical follow up in a universitary outpatient clinic as follow: eosinophilic esophagitis (N=23), PPI-responsive eosinophilic esophagitis (N=15) and gastroesophageal reflux esophagitis (N=15). Eosinophil count in the esophageal epithelium in slides stained with H-E was reviewed and immunohistochemistry for mast cell tryptase was performed. RESULTS:: Count of eosinophils/high-power field (HPF) higher than 15 were found in 14 out of 15 reflux esophagitis patients. The mean count of eosinophils/HPF was similar in eosinophilic esophagitis patients and in those with PPI-responsive eosinophilic esophagitis (42 and 39 eosinophils/HPF, respectively, P=0.47). Values of mast cell tryptase (+) were higher in eosinophilic esophagitis [median: 25 mast cells/HPF; range (17-43) ] and in PPI-responsive eosinophilic esophagitis patients [25 (16-32) ], compared to reflux esophagitis [4 (2-14) ], P<0.001. There was no difference between the mean count of mast cells/HPF in the esophageal epithelium of eosinophilic esophagitis patients and PPI-responsive eosinophilic esophagitis patients, respectively, 26 and 24 mast cells/HPF, P=0.391. CONCLUSION:: Tryptase staining of mast cells differentiates eosinophilic esophagitis from reflux esophagitis.

How to improve the diagnosis of eosinophilic esophagitis: Experience from a case series in Mexico. / Cómo mejorar el diagnóstico de esofagitis eosinofílica: experiencia de una serie de casos en México.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, immune disorder mediated largely by food antigens. It shares nonspecific symptoms with gastroesophageal reflux disease (GERD). EoE is rarely reported in Mexico, perhaps due to the racial characteristics of the population or because of insufficient diagnostic suspicion. AIMS: Our aim was to describe a Mexican cohort with EoE and evaluate the usefulness of the clinical history and endoscopy in the EoE diagnosis, in comparison with GERD patients. MATERIALS AND METHODS: A retrospective study was carried out on the clinical characteristics and endoscopic and histopathologic findings in patients with EoE, along with a case-control study on patients with GERD. The endoscopic images obtained were interpreted in a blind and randomized manner by 4 gastroenterologists, before and after providing them with information on the characteristic alterations of EoE. The esophageal biopsies were also blinded to 2 pathologists that evaluated their diagnostic correlation. The Fisher's exact test and Mann-Whitney U test were used in the statistical analysis. RESULTS: Fourteen patients with EoE were included in the study. Ten (71%) of them were men and the mean age of the patients was 35 years. There were more subjects with a personal history of asthma (p=0.0023) and food impaction (p=0.04) in the EoE group. The initial evaluation of the endoscopic findings showed 53% correct EoE interpretations and rose to 96% in the second revision (sensitivity 100%, specificity 71%, PPV 65%, NPV 100%). CONCLUSIONS: Mexican patients with EoE have similar characteristics to those of patients in western case series. Clinical awareness of the disorder increases endoscopic diagnosis in up to 40% of cases.

Lack of compliance with consensus recommendations on the diagnosis of eosinophilic esophagitis (EoE) in published prevalence studies. A clinical and systematic review.

OBJECTIVE: According to consensus recommendations, the presence of esophageal symptoms, >15 eosinophils/high-power field and unresponsiveness to proton pump inhibitors are required for a diagnosis of eosinophilic esophagitis (EoE). Nevertheless, inconsistency in using these guidelines has been reported in recent publications. The objective of this study was to assess compliance with EoE diagnostic guidelines in published studies on EoE prevalence and to evaluate other clinical and methodological parameters. METHODS: A systematic review was conducted in articles published between 2008 and 2015 on the prevalence of EoE in unselected adults. Studies using EoE diagnostic definitions were judged to be compliant if they included all three components of the definition, partially compliant if they included two and non-compliant if they included one or none. Esophageal biopsy protocol differences and descriptions of patients' characteristics were determined. RESULTS: Among the 20 studies included, eight were performed in a hospital setting and 12 in the general population. Only 40.0% of studies were compliant, 35.0% were partially compliant and 25.0% were non-compliant with the EoE diagnostic definition guidelines. In 60.0% of the studies a proton pump inhibitor trial was not administered. Only 30.0% adhered to the recommendations in the esophageal biopsy protocol. A lack of description of the history of atopia and endoscopic characteristics was observed in many studies. CONCLUSIONS: Partial or non-compliance with the EoE diagnostic definition was observed in most of the published prevalence studies after the publication of the first consensus. The results of these studies might be interpreted taking into account this context.