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BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood, and chronic EoE-directed therapy is therefore required to prevent long-term sequelae. OBJECTIVE: We investigated whether EoE patients in histologic remission have persistent dysregulation of esophageal gene expression. METHODS: Esophageal biopsy samples from 51 pediatric and 52 adult subjects with EoE in histopathologic remission (<15 eosinophils per high-power field [eos/hpf]) and control (48 pediatric and 167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE diagnostic panel, which comprises a set of 94 esophageal transcripts differentially expressed in active EoE. RESULTS: Defining remission as <15 eos/hpf, we identified 51 and 32 differentially expressed genes in pediatric and adult EoE patients compared to control individuals, respectively (false discovery rate < 0.05). Using the stringent definition of remission (0 eos/hpf), the adult and pediatric cohorts continued to have 18 and 25 differentially expressed genes (false discovery rate < 0.05). Among 6 shared genes between adults and children, CDH26 was upregulated in both children and adults; immunohistochemistry demonstrated increased cadherin 26 staining in the epithelium of EoE patients in remission compared to non-EoE controls. In the adult cohort, POSTN expression correlated with the endoscopic reference system score (Spearman r = 0.35, P = .011), specifically correlating with the rings' endoscopic reference system subscore (r = 0.53, P = .004). CONCLUSION: We have identified persistent EoE-associated esophageal gene expression in patients with disease in deep remission. These data suggest potential inflammation-induced epigenetic mechanisms may influence gene expression during remission in EoE and provide insight into possible mechanisms that underlie relapse in EoE.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Adulto , Humanos , Niño , Esofagitis Eosinofílica/patología , Eosinófilos/patología , Inflamación/patología , RecurrenciaRESUMEN
The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERS) organized a day-long symposium at the 2024 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research and debates on the mechanisms and management of eosinophilic gastrointestinal diseases (EGIDs). Updates on recent clinical trials and consensus guidelines were also presented. Herein, we summarize the updates on EGIDs presented at the symposium.
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Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy presenting with delayed onset of projectile vomiting in the absence of cutaneous and respiratory symptoms. The pathophysiology of FPIES remains poorly characterized. The first international consensus guidelines for FPIES were published in 2017 and provided clinicians with parameters on the diagnosis and treatment of FPIES. The guidelines have served as a resource in the recognition and management of FPIES, contributing to an increased awareness of FPIES. Since then, new evidence has emerged, shedding light on adult-onset FPIES, the different phenotypes of FPIES, the recognition of new food triggers, center-specific food challenge protocols and management of acute FPIES. Emerging evidence indicates that FPIES impacts both pediatric and adult population. As a result, there is growing need to tailor the consensus guidelines to capture diagnoses in both patient groups. Furthermore, it is crucial to provide food challenge protocols that meet the needs of both pediatric and adult FPIES patients, as well as the subset of patients with atypical FPIES. This review highlights the evolving clinical evidence relating to FPIES diagnosis and management published since the 2017 International FPIES Guidelines. We will focus on areas where recent published evidence may support evolution or revision of the guidelines.
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Enterocolitis , Hipersensibilidad a los Alimentos , Adulto , Niño , Humanos , Lactante , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/terapia , Hipersensibilidad a los Alimentos/epidemiología , Vómitos , Enterocolitis/diagnóstico , Enterocolitis/etiología , Enterocolitis/terapia , Alérgenos , Administración Cutánea , Proteínas en la Dieta/efectos adversosRESUMEN
Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus that occurs in both children and adults. Previous studies of affected tissue from pediatric cohorts have identified prominent signatures of eosinophilia and type 2 inflammation. However, the details of the immune response in adults with EoE are still being elucidated. To determine whether EoE in adults shares inflammatory profiles with those observed in children, we performed RNA sequencing of paired human esophageal biopsies and blood samples from adults with EoE or gastroesophageal reflux disease. Unbiased analysis of differentially expressed genes in tissue revealed a strong IFN signature that was significantly enriched in EoE patients as compared with patients with gastroesophageal reflux disease. Both type I and type II IFN-responsive genes were upregulated in adult biopsies, but not in blood. A similar increase in expression of IFN gene sets was observed in pediatric EoE biopsies as compared with non-EoE samples, and in public pediatric and adult RNA-sequencing data. Finally, we found that human peripheral CD4+ T cells from children with EoE produce IFN-γ upon activation with EoE-causal allergens. Together, this work identifies a conserved IFN signature in pediatric and adult EoE, highlighting a role for non-type 2 inflammatory networks in the disease process in humans.
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Esofagitis Eosinofílica/inmunología , Esófago/patología , Reflujo Gastroesofágico/inmunología , Interferón Tipo I/metabolismo , Interferón gamma/metabolismo , Adolescente , Adulto , Factores de Edad , Anciano , Biopsia , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Esofagitis Eosinofílica/sangre , Esofagitis Eosinofílica/patología , Esófago/inmunología , Femenino , Reflujo Gastroesofágico/sangre , Reflujo Gastroesofágico/patología , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ARN , Linfocitos T/inmunología , Linfocitos T/metabolismo , Transcriptoma/inmunología , Regulación hacia Arriba/inmunología , Adulto JovenRESUMEN
INTRODUCTION: The correlation between clinical and molecular treatment response thresholds in eosinophilic esophagitis (EoE) is not well understood. METHODS: We evaluated posttreatment EoE diagnostic panel gene expression profiles across histologic and endoscopic thresholds (EREFS) in a prospective adult EoE cohort. RESULTS: We observed a strong inverse correlation between posttreatment gene score and eosinophil count (R = -0.66; P < 0.001); biopsies with <15 eos/hpf had higher gene scores (≥425) vs those with ≥15 eos/hpf. Findings for EREFS were similar; EREFS ≤2 was associated with EoE diagnostic panel scores ≥395. DISCUSSION: Molecular signatures support the use of posttreatment response thresholds <15 eos/hpf and EREFS ≤2 in clinical practice and trials.
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Esofagitis Eosinofílica , Adulto , Biopsia , Endoscopía , Esofagitis Eosinofílica/diagnóstico , Eosinófilos/patología , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: Dupilumab has been approved to treat atopic dermatitis, asthma, and nasal polyps and is in active clinical trials for the treatment of eosinophilic esophagitis (EoE). Given its shared immunopathology, we hypothesized that EoE symptoms and inflammation would improve when dupilumab therapy was used for other allergic indications. OBJECTIVE: To measure the clinical and histologic response in EoE to dupilumab when treating other atopic diseases. METHODS: We completed a retrospective chart review of all patients at Children's Hospital of Philadelphia and Rady Children Hospital who were prescribed dupilumab for atopic dermatitis, asthma, or nasal polyps and had a concomitant clinical diagnosis of EoE. Demographic information along with histology, symptom scores, medications, and diet information were collected. Response to dupilumab was evaluated. RESULTS: A total of 45 patients were identified. Of which, 11 patients were prescribed dupilumab for asthma, 27 for atopic dermatitis, 3 for nasal polyps, and 4 for compassionate use for EoE. There was no follow-up data for 8 patients. Follow-up histology was available for 26 patients: 22 of 26 had less than 6 eosinophils per high power field after the initiation of dupilumab with significant improvement (pre: 52.9 + 35.1 to post: 4.5 + 10.9 eosinophils/high power field, P < .005). A total of 28 patients had improvement of symptoms, with 24 patients reporting complete resolution of symptoms after dupilumab initiation. Reductions in EoE treatment medications (swallowed steroids, proton pump inhibitors) or expansion of diet occurred in 29 patients treated with dupilumab. CONCLUSION: Dupilumab therapy initiated for atopic disease effectively induces symptomatic and histologic remission of esophageal disease and reduces the need for EoE-directed therapy in patients with concomitant EoE.
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Asma , Dermatitis Atópica , Esofagitis Eosinofílica , Pólipos Nasales , Anticuerpos Monoclonales Humanizados , Asma/complicaciones , Asma/tratamiento farmacológico , Niño , Ensayos de Uso Compasivo , Dermatitis Atópica/complicaciones , Dermatitis Atópica/tratamiento farmacológico , Esofagitis Eosinofílica/diagnóstico , Humanos , Pólipos Nasales/complicaciones , Estudios RetrospectivosRESUMEN
OBJECTIVE: To improve understanding of the heterogeneous presentation of eosinophilic esophagitis (EoE), and its different potential phenotypes and endotypes. DATA SOURCES: We reviewed studies addressing EoE genetics, risks, natural history, treatment, phenotype, or endotype to assess data relating to differences in the presentation of EoE in children and adults. This review was restricted to articles in the English language. STUDY SELECTIONS: Data source abstracts, pertinent articles, and book chapters meeting the objectives were critically reviewed. RESULTS: Data to support differing phenotypes and endotypes in EoE are emerging, but findings are based on multiple studies and therefore sometimes incomparable. Like other atopic disorders EoE is a complex disease with diverse clinical presentations (phenotypes) based on response to therapy, natural history, and association with atopic comorbidities. Different pathogenetic mechanisms (endotypes) may drive the multiple phenotypes. T Helper type 2 inflammation, epithelial barrier defects, enhanced fibrosis, and association with rare monogenetic diseases are the most described endotypes in EoE. CONCLUSION: Eosinophilic esophagitis is an atopic disorder that is increasing in prevalence and can be difficult to treat. Better understanding of phenotypes and endotypes in EoE may enable future care to be individualized more effectively, resulting in shorter time to remission and fewer endoscopies.
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Susceptibilidad a Enfermedades , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/etiología , Fenotipo , Alelos , Biomarcadores , Citocinas/metabolismo , Manejo de la Enfermedad , Esofagitis Eosinofílica/terapia , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
PURPOSE OF REVIEW: The purpose of this review is to provide a brief discussion on the differential diagnosis for peripheral eosinophilia. We will then focus on targeted immunotherapies for atopic disease, their effects on absolute peripheral eosinophil counts, and use of peripheral eosinophils as a predictor of treatment response. RECENT FINDINGS: In atopic disease, lower absolute peripheral eosinophil counts are typically associated with improved outcomes. Much of the current evidence on eosinophils as a biomarker comes from post hoc analyses in therapeutic immunotherapy. While changes in eosinophilia were not the primary outcome of interest in many studies, some patterns did emerge. Cytolytic monoclonal antibodies AK002 and benralizumab completely reduce peripheral and tissue eosinophil numbers. Dupilumab may have paradoxical transient eosinophilia despite observed clinical efficacy. Atopic inflammation is complex largely due to the various cytokines which affect eosinophil activation, proliferation, differentiation, and survival. This demonstrates the challenges of using peripheral eosinophilia alone as a biomarker for atopic disease activity. More attention should spotlight how different immunotherapy modalities affect eosinophil-driven responses.
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Eosinofilia/terapia , Eosinófilos/fisiología , Hipersensibilidad Inmediata/terapia , Inmunoterapia , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores , Eosinofilia/diagnóstico , Eosinofilia/inmunología , Humanos , Hipersensibilidad Inmediata/diagnóstico , Hipersensibilidad Inmediata/inmunología , Recuento de LeucocitosRESUMEN
BACKGROUND: Germline-encoded innate immune pattern recognition receptors (PRR) are expressed at epithelial surfaces and modulate epithelial defenses. Evidence suggests that stimulation of the Toll-like receptor (TLR) family of PRR may regulate epithelial barrier integrity by upregulating tight junction (TJ) complex protein expression, but it is not known whether this mechanism is utilized in esophageal epithelial cells. TJ complex proteins maintain intact barrier function and are dysregulated in atopic disorders including eosinophilic esophagitis. METHODS: Pattern recognition receptors expression was assessed in EoE and control primary esophageal epithelial cells, demonstrating robust expression of TLR2 and TLR3. The three-dimensional air-liquid interface culture (ALI) model was used to test whether TLR2 or TLR3 stimulation alters epithelial barrier function using an in vitro model of human epithelium. Transepithelial electrical resistance (TEER) and FITC-Dextran permeability were evaluated to assess membrane permeability. ALI cultures were evaluated by histology, immunohistochemistry, Western blotting, and chromatin immunoprecipitation (ChIP). RESULTS: TLR3 stimulation did not change TEER in the ALI model. TLR2 stimulation increased TEER (1.28- to 1.31-fold) and decreased paracellular permeability to FITC-Dextran, and this effect was abolished by treatment with anti-TLR2 blocking antibody. TJ complex proteins claudin-1 and zonula occludens-1 were upregulated following TLR2 stimulation, and ChIP assay demonstrated altered histone 4 acetyl binding at the TJP1 enhancer and CLDN1 enhancer and promoter following zymosan treatment, implying the occurrence of durable chromatin changes. CONCLUSIONS: Our findings implicate the TLR2 pathway as a potential regulator of esophageal epithelial barrier function and suggest that downstream chromatin modifications are associated with this effect.
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Mucosa Esofágica/metabolismo , Receptor Toll-Like 2/agonistas , Células Cultivadas , Células Epiteliales/metabolismo , Mucosa Esofágica/patología , Histonas/metabolismo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Receptores de Reconocimiento de Patrones/metabolismo , Uniones Estrechas , Receptores Toll-Like/metabolismoAsunto(s)
Enterocolitis , Hipersensibilidad a los Alimentos , Adulto , Humanos , Lactante , Alergólogos , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/terapia , Diagnóstico Diferencial , Enterocolitis/diagnóstico , Enterocolitis/terapia , Proteínas en la Dieta/efectos adversos , AlérgenosRESUMEN
PURPOSE: The point prevalence of underweight status and obesity in primary immunodeficiency disease (PID) is unknown, despite the described associations between PID and weight loss and failure to thrive. The goal of this study is to estimate the prevalence of underweight status and obesity in PID patients and to investigate the associations between abnormal body weight and complications of PID. METHODS: Using the US Immunodeficiency Network (USIDNET), we performed a retrospective analysis of 653 pediatric (age 2 to 20 years) and 514 adult (age > 20) patient records with information on patient body mass index (BMI). Prevalence of underweight and obese status in PID patients was compared to data from the National Health and Nutrition Examination Survey (NHANES). RESULTS: After separating BMI data by year of entry to the database, we demonstrated that both adult and pediatric patients with PID had significantly higher prevalence of underweight patients in multiple years of analysis. Further examination of underweight patients by PID diagnosis revealed that underweight status in adults with CVID was associated with granulomatous disease as well as earlier age of CVID diagnosis. In the pediatric CVID cohort, underweight status was significantly associated with lymphopenia. Examination of obesity in pediatric and adult PID patients compared to NHANES database revealed only a single year when obesity in PID patients was significantly less prevalent. In other 2-year time intervals from 2005 to 2014, the prevalence of obesity was unchanged in children and adults. CONCLUSIONS: These results quantify the prevalence of underweight status in PID in a North American population and demonstrate that whether as a result of weight loss or poor weight gain, underweight status is more prevalent in the PID population than in the general US population. The prevalence of obesity in PID patients was similar to that seen in the general population. This highlights the need for continued education on the association of low weight and PID. CLINICAL TRIAL REGISTRATION: NCT01953016.
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Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/epidemiología , Delgadez/complicaciones , Delgadez/epidemiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/etiología , Masculino , América del Norte/epidemiología , Prevalencia , Vigilancia en Salud Pública , Sistema de Registros , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is a multifactorial, non-IgE-mediated inflammatory disorder of the esophagus and is the most common cause of food impaction in the pediatric population. The purpose of this review is to describe the current recommendations for diagnosis and management of EoE. RECENT FINDINGS: New data has associated EoE with other allergic disorders of the atopic march as well as several risk factors, which predispose to allergic conditions. A subset of patients with esophageal eosinophilia respond to proton pump inhibitor (PPI) therapy with a partial or complete resolution of esophageal eosinophilia. Therefore, some patients can be treated with PPI alone. If this is unsuccessful, dietary elimination and swallowed steroid therapy are recommended for long-term management. There is a growing appreciation that untreated esophageal inflammation can lead to complications of fibrosis and stricture formation. SUMMARY: The current review will focus on the diagnosis and management of EoE in the pediatric population. Identification and diagnosis of pediatric patients with EoE is critical to prevent long-term esophageal complications.
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Antiinflamatorios/uso terapéutico , Dietoterapia , Dilatación , Esofagitis Eosinofílica/diagnóstico , Reflujo Gastroesofágico/etiología , Glucocorticoides/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Niño , Endoscopía Gastrointestinal , Esofagitis Eosinofílica/epidemiología , Esofagitis Eosinofílica/fisiopatología , Esofagitis Eosinofílica/terapia , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/terapia , Humanos , Guías de Práctica Clínica como Asunto , Atención Primaria de Salud , Estados UnidosRESUMEN
BACKGROUND: Pediatric asthma is a major contributor to emergency room utilization and hospital readmission rates. OBJECTIVE: To develop an allergy departmentâbased intervention to improve follow-up appointment scheduling processes for pediatric asthma patients after discharge for asthma exacerbation. METHODS: This quality improvement study was conducted in the allergy clinic of an urban, tertiary children's hospital. Children receiving subspecialty allergy care for asthma were included into the intervention group during the intervention period. The quality improvement intervention consisted of 3 attempts by telephone to reach the family to schedule the follow-up appointment. If this was unsuccessful or if the appointment was not kept, then a reminder letter was sent to the family. The primary outcome of interest in this study was the percent of postdischarge follow-up appointments scheduled within 30 days of discharge. Secondary outcomes measured were the percent of allergy appointments attended within 30 days of discharge and the 30-day hospital readmission rate. RESULTS: Demographics did not differ significantly between the intervention and baseline preintervention year. The initial baseline scheduled allergy follow-up visit rate was 48.8 ± 13.3% of patients discharged per month. This increased to an overall rate of 75.7 ± 20.1% patients scheduling allergy follow-up within 30 days of discharge during the intervention year. We also observed a significant increase in attended allergy visits 30 days postdischarge from 35.5 ± 15.6% in year 1 to 53.9 ± 25.5% during the intervention year and a significant decrease in the 30-day readmission rate on the allergy service. CONCLUSION: These data suggests that minor changes in allergy practice organization can significantly affect posthospitalization follow-up rates and decrease asthma readmission rates.
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Citas y Horarios , Asma/terapia , Servicio de Urgencia en Hospital , Hospitales Pediátricos , Readmisión del Paciente/estadística & datos numéricos , Adolescente , Niño , Preescolar , Continuidad de la Atención al Paciente/normas , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Evaluación de Resultado en la Atención de Salud , Alta del Paciente , Atención Primaria de Salud , Modelos de Riesgos Proporcionales , Mejoramiento de la Calidad/organización & administraciónRESUMEN
BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Esophageal biopsy specimens are characterized by eosinophilia and expression of TH2 cytokines. OBJECTIVE: To ascertain whether TH2 cells can exist in the peripheral blood in patients with milk-induced EoE. METHODS: Peripheral blood mononuclear cells from 20 children with milk-induced EoE were collected during active EoE (EoE-A) while consuming milk and inactive EoE (EoE-I) while not consuming milk, and 8 healthy patients without EoE were used as controls. The samples were analyzed for T-cell phenotype, including intracellular cytokines before and after incubation with milk antigens and assessed by flow cytometry. RESULTS: We found a significant increase in CD4+ TH2 cells in the peripheral blood of patients with EoE-A compared with the controls. Furthermore, we observed a significant mean (SD) increase in the activation marker of CD154+ T cells (0.17% [0.047%]) in patients with EoE-A compared with control patients (0.034% [0.007%]) and EoE-I (0.025% [0.008]). These CD4+ T cells expressed significantly increase levels of TH2 cytokines (interleukins 4, 5, and 13) compared with the EoE-I and control groups. CD3+CD4+CD154+IL-5+ cells were significantly increased by milk antigens in both milk-induced EoE-A (0.050% [0.008%] to 0.079% [0.017%]) and EoE-I (0.0045% [0.002%] to 0.014% [0.008%]) compared with the controls (0.008% [0.003%] to 0.003% [0.001%]). CONCLUSION: Our findings indicate that in EoE peripheral T cells have specific activation to milk allergens.
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Esofagitis Eosinofílica/inmunología , Eosinófilos/inmunología , Esófago/patología , Hipersensibilidad a la Leche/inmunología , Células Th2/inmunología , Adolescente , Alérgenos/inmunología , Animales , Biopsia , Bovinos , Niño , Preescolar , Citocinas/metabolismo , Femenino , Humanos , Inmunofenotipificación , Activación de Linfocitos , Masculino , Leche , Proteínas de la Leche/inmunologíaRESUMEN
PURPOSE OF REVIEW: EoE is a significant cause of gastrointestinal morbidity affecting 1:2000. Patients with EoE typically have multiple atopic comorbidities, and additionally, many patients with EoE can be controlled well with elimination diets. The purpose of this review is to summarize the care of pediatric eosinophilic esophagitis patients. RECENT FINDINGS: EoE represents a distinct clinical syndrome which is characterized by esophageal dysfunction and eosinophil-predominant inflammation of the esophageal mucosa. Patients with EoE can present with varying symptoms depending on their age; in this review, we review the presenting features of eosinophilic esophagitis in children as well as a diagnostic algorithm for EoE. The mucosal inflammation in EoE is driven by exposure to food antigens in many patients with EoE. Therefore, for the majority of patients, the mainstays of treatment remain food elimination diets or swallowed steroids. This review summarizes the diagnostic approach to eosinophilic esophagitis (EoE) in pediatric patients, focusing on the importance of accurate diagnosis and selection of appropriate therapy.
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Esofagitis Eosinofílica , Animales , Niño , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/inmunología , Esofagitis Eosinofílica/terapia , HumanosAsunto(s)
Alérgenos/administración & dosificación , Cateterismo Periférico/métodos , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/inmunología , Enterocolitis/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Alérgenos/inmunología , Antieméticos/uso terapéutico , Enterocolitis/tratamiento farmacológico , Enterocolitis/inmunología , Hipersensibilidad a los Alimentos/inmunología , Humanos , Ondansetrón/uso terapéuticoRESUMEN
Recent advances in the understanding of immune dysregulation in autoimmune diseases have enabled the development of new monoclonal antibody-based drugs called biologics. Biologics have been used to target aberrant immune responses in many diseases, but patients with rheumatologic and other autoimmune diseases have benefited the most and improvements in outcomes have been significant. The use of biologics is not without hazard, however, as these agents block immune pathways adapted to protect the host. This has been borne out by increased rates of infections as well as induction of new autoimmune and hematologic adverse effects. As new drugs for the treatment of autoimmune conditions are entering the pipeline, it is incumbent on the practicing immunologist to understand the mechanism of these biologics and the implications of clinical use.