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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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BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains. CONCLUSIONS: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.
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BACKGROUND: Dupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents. METHODS: In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically. RESULTS: In Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B. CONCLUSIONS: Dupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.).
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Anticuerpos Monoclonales Humanizados , Esofagitis Eosinofílica , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/inmunología , Esofagitis Eosinofílica/patología , Eosinófilos/inmunología , Eosinófilos/patología , Esófago/efectos de los fármacos , Esófago/inmunología , Esófago/patología , Inyecciones Subcutáneas , Interleucina-13/antagonistas & inhibidores , Interleucina-4/antagonistas & inhibidores , Inducción de Remisión , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del TratamientoRESUMEN
Food security encompassess the concept of access by all people at all times to enough food for an active, healthy life. Conversely, food insecurity (FI) refers to household-level economic and social conditions of limited or uncertain access to adequate food. FI is a key social determinant of health that can negatively affect nutrition and health outcomes, as it is estimated that 10.2% of the US population meets criteria for FI. Recognizing the impact of FI on our patients and families is critical to promote health equity and optimize health outcomes. This review focuses on FI and allergic disease from the perspective of key multisector stakeholders within the field of allergy and immunology as well as from the larger health care arena, highlighting key resources and initiatives important to patients. Collectively, as specialists in allergy and immunology, and within the medical field more broadly, we must leverage our unique roles as we interface with patients and families and serve as committed advocates for change. Developing innovative strategies to promote health equity can provide a pathway forward for all children, adults, and families to gain access to healthy, nutritious food as part of their routine lifestyle. This is a call to action.
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Abastecimiento de Alimentos , Hipersensibilidad , Humanos , Niño , Adulto , Promoción de la Salud , Inseguridad Alimentaria , Estado NutricionalRESUMEN
The Consortium of Eosinophilic Gastrointestinal Diseases and The International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured a review of recent discoveries in the basic biology and pathogenesis of eosinophilic gastrointestinal diseases (EGIDs) in addition to advances in our understanding of the clinical features of EGIDs. Diagnostic and management approaches were reviewed and debated, and clinical trials of emerging therapies were highlighted. Herein, we briefly summarize the breakthrough discoveries in EGIDs.
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Asma , Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Estados Unidos , Enteritis/diagnóstico , Enteritis/terapia , Asma/diagnóstico , Asma/terapiaRESUMEN
BACKGROUND: Best practice guidelines for asthma management recommend education and spirometry at specific intervals. A written asthma action plan with education and spirometry is ordered at the discretion of physicians at our institution. An initial chart review revealed that asthma education and spirometry were not consistently ordered in the pediatric primary care clinics. This quality improvement study aimed to increase frequency of spirometry and asthma education in children with asthma seen in pediatric primary care through use of a respiratory therapist (RT)-driven protocol. METHODS: The protocol established that spirometry and education would be done annually for children ≥ 6 y of age with intermittent asthma and every 6 months for persistent asthma. RTs identified eligible subjects and placed the electronic medical record orders before the clinic visit. Physicians were invited to complete a questionnaire before and after protocol implementation to assess barriers and protocol satisfaction. RESULTS: Nine hundred and thirty-two children were included. Prior to protocol implementation, spirometry and education were completed in 64.9% and 62.6% of eligible children, respectively. Following protocol implementation, spirometry and education were significantly increased to 92.7% (P < .001) and 88.5% (P < .001), respectively. Physicians identified interruption in clinic flow as the primary barrier for ordering spirometry and were satisfied with the protocol. Physicians stated that communication with RT improved through use of this protocol. CONCLUSIONS: Implementation of an RT-driven protocol in an out-patient pediatric primary care setting significantly increased utilization of spirometry and education for children with asthma. RTs working in the pediatric out-patient primary care setting played a vital role in achieving best practices for asthma management. The implementation of the protocol enhanced interdisciplinary communication.
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Asma , Pacientes Ambulatorios , Humanos , Niño , Lactante , Asma/diagnóstico , Asma/terapia , Espirometría , Registros Electrónicos de Salud , Atención Primaria de SaludRESUMEN
BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population. METHODS: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160. FINDINGS: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy. INTERPRETATION: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy. FUNDING: National Institute of Allergy and Infectious Disease, Immune Tolerance Network.
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Alérgenos/administración & dosificación , Arachis/inmunología , Desensibilización Inmunológica , Hipersensibilidad al Cacahuete/prevención & control , Administración Oral , Alérgenos/inmunología , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Tolerancia Inmunológica , Masculino , Hipersensibilidad al Cacahuete/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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Esofagitis Eosinofílica/terapia , Medición de Resultados Informados por el Paciente , Adulto , Anciano , Niño , Esofagitis Eosinofílica/patología , Esofagitis Eosinofílica/psicología , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Calidad de VidaRESUMEN
BACKGROUND: Little is known about the endoscopic and histologic findings of non-esophageal eosinophilic gastrointestinal diseases (EGID). AIM: To characterize the presenting endoscopic and histologic findings in patients with eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) at diagnosis and 6 months after initiating the treatment. METHODS: We conducted a retrospective cohort study at 6 US centers associated with the Consortium of Eosinophilic Gastrointestinal Researchers. Data abstracted included demographics, endoscopic findings, tissue eosinophil counts, and associated histologic findings at diagnosis and, when available, after initial treatment. RESULTS: Of 373 subjects (317 children and 56 adults), 142 had EG, 123 EGE, and 108 EC. Normal endoscopic appearance was the most common finding across all EGIDs (62% of subjects). Baseline tissue eosinophil counts were quantified in 105 (74%) EG, 36 (29%) EGE, and 80 (74%) EC subjects. The mean peak gastric eosinophil count across all sites was 87 eos/hpf for EG and 78 eos/hpf for EGE. The mean peak colonic eosinophil count for EC subjects was 76 eos/hpf (range 10-500). Of the 29% of subjects with post-treatment follow-up, most had an improvement in clinical, endoscopic, and histologic findings regardless of treatment utilized. Reductions in tissue eosinophilia correlated with improvements in clinical symptoms as well as endoscopic and histologic findings. CONCLUSIONS: In this large cohort, normal appearance was the most common endoscopic finding, emphasizing the importance of biopsy, regardless of endoscopic appearance. Decreased tissue eosinophilia was associated with improvement in symptoms, endoscopic, and histologic findings, showing that disease activity is reversible.
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Colitis/patología , Endoscopía Gastrointestinal , Enteritis/patología , Eosinofilia/patología , Eosinófilos/patología , Gastritis/patología , Adolescente , Adulto , Anciano , Biopsia , Niño , Preescolar , Estudios de Cohortes , Colon/patología , Eritema/patología , Femenino , Humanos , Lactante , Intestino Delgado/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estómago/patología , Úlcera/patología , Adulto JovenAsunto(s)
Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Guías de Práctica Clínica como Asunto , Enteritis/diagnóstico , Enteritis/inmunología , Enteritis/terapia , Eosinofilia/diagnóstico , Eosinofilia/inmunología , Eosinofilia/terapia , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/inmunología , Esofagitis Eosinofílica/terapia , Gastritis/diagnóstico , Gastritis/inmunología , Gastritis/terapia , HumanosRESUMEN
OBJECTIVE: To review novel therapeutics in development for treatment of eosinophilic gastrointestinal disorders (EGIDs). DATA SOURCES: Clinical trial data (clinicaltrials.gov) and literature search on PubMed. STUDY SELECTIONS: Studies on treatment and clinical trials in EGIDs were included in this review. RESULTS: During the past decade, significant progress has been made in understanding disease mechanisms in EGIDs. As a result, a variety of novel therapeutics have been developed for treatment of these disorders. Several monoclonal antibodies against targets, including interleukin (IL) 4, IL-5, IL-13, integrins, and siglec-8, have shown promise in early trials. Novel formulations of corticosteroids are also in development. CONCLUSION: The field of EGID research has advanced rapidly, and disease-modifying therapeutics are closer to clinical application.
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Enteritis/terapia , Eosinofilia/terapia , Gastritis/terapia , Terapia Biológica , Biomarcadores , Ensayos Clínicos como Asunto , Terapia Combinada , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Enteritis/diagnóstico , Enteritis/etiología , Enteritis/metabolismo , Eosinofilia/diagnóstico , Eosinofilia/etiología , Eosinofilia/metabolismo , Gastritis/diagnóstico , Gastritis/etiología , Gastritis/metabolismo , Humanos , Terapia Molecular Dirigida , Nivel de Atención , Resultado del TratamientoRESUMEN
OBJECTIVES: The literature related to eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC) is limited. We aimed to characterize rates of diagnosis, clinical features, and initial treatments for patients with EG, EGE, and EC. METHODS: In this retrospective study, data were collected from 6 centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005 to 2016. We analyzed demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses. RESULTS: Of 373 subjects (317 children and 56 adults), 38% had EG, 33% EGE, and 29% EC. Rates of diagnosis of all diseases increased over time. There was no male predominance, and the majority of subjects had atopy. Presenting symptoms were similar between diseases with nausea/vomiting and abdominal pain, the most common. One hundred fifty-four subjects (41%) had eosinophilic inflammation outside of their primary disease location with the esophagus the second most common gastrointestinal (GI) segment involved. Multisite inflammation was more common in children than in adults (68% vs 37%; P < 0.001). Initial treatment patterns varied highly between centers. One hundred-nine subjects (29%) had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements. CONCLUSIONS: In this cohort, EG, EGE, and EC were diagnosed more frequently over time, and inflammation of GI segments outside the primary disease site co-occurrence of atopy was common with a lack of male predominance. Symptoms were similar between diseases, and initial treatment strategies were highly variable. Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.
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Antiinflamatorios/uso terapéutico , Colitis/epidemiología , Enteritis/epidemiología , Eosinofilia/epidemiología , Eosinófilos/patología , Gastritis/epidemiología , Gastroenteritis/epidemiología , Fármacos Gastrointestinales/uso terapéutico , Mucosa Intestinal/patología , Adolescente , Adulto , Niño , Preescolar , Colitis/diagnóstico , Colitis/tratamiento farmacológico , Comorbilidad/tendencias , Enteritis/diagnóstico , Enteritis/tratamiento farmacológico , Eosinofilia/diagnóstico , Eosinofilia/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Predicción , Gastritis/diagnóstico , Gastritis/tratamiento farmacológico , Gastroenteritis/diagnóstico , Gastroenteritis/tratamiento farmacológico , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenAsunto(s)
Acetazolamida/efectos adversos , Anafilaxia/prevención & control , Anticonvulsivantes/efectos adversos , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/terapia , Seudotumor Cerebral/tratamiento farmacológico , Acetazolamida/uso terapéutico , Adolescente , Anafilaxia/etiología , Anticonvulsivantes/uso terapéutico , Hipersensibilidad a las Drogas/complicaciones , Femenino , Humanos , Hipersensibilidad Inmediata , Tolerancia Inmunológica , Seudotumor Cerebral/complicaciones , Resultado del TratamientoRESUMEN
INTRODUCTION: Eosinophilic esophagitis (EoE) is rare but incidence and prevalence is increasing. EoE is characterized by eosinophilic inflammation of the esophagus causing gastrointestinal symptoms such as abdominal pain, vomiting, reflux, dysphagia, and food impactions. If untreated, remodeling and fibrosis of the esophagus can occur and stricture formation may result. Current treatment options are limited to food-restriction diets or medications including proton pump inhibitors (PPIs) or swallowed corticosteroids. Significant progress has been made in understanding the underlying mechanisms of EoE allowing for development of drugs that target specific points in EoE pathways. Investigation of these drugs is early with few controlled studies, but many show promise as future treatments. Areas covered: This review will provide an up to date discussion of current therapies and investigational drugs for EoE. Articles used in this review were retrieved from PubMed. Ongoing or completed clinical trials were obtained through clinicaltrials.gov and review of the PharmaProjects database. Expert Opinion: Multiple therapeutic targets have been identified and several have shown efficacy. Work is needed to define appropriate trial outcome measures. Collaboration between government agencies, patient advocacy groups, and investigator-led consortia is critical for completing new clinical trials which should pave the way for new therapies in clinical practice.
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Diseño de Fármacos , Esofagitis Eosinofílica/tratamiento farmacológico , Terapia Molecular Dirigida , Esofagitis Eosinofílica/fisiopatología , Glucocorticoides/uso terapéutico , Humanos , Inhibidores de la Bomba de Protones/uso terapéuticoAsunto(s)
Citometría de Flujo/métodos , Proteína del Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Tamizaje Masivo/métodos , Sensibilidad y Especificidad , Proteína del Síndrome de Wiskott-Aldrich/análisisRESUMEN
OBJECTIVES/HYPOTHESIS: To delineate clinical characteristics and treatment outcomes of eosinophilic esophagitis (EoE) in the youngest of children. STUDY DESIGN: Retrospective chart review. METHODS: A 7-year retrospective chart review of children with clinicopathologic diagnosis of EoE was performed with specific analysis of patients under 5 years old. EoE was defined as the presence of symptoms of esophageal dysfunction with pathologically proven eosinophilic inflammation (≥15 eosinophils per high-power field [EOS/HPF]) unresponsive to reflux therapy. Patient parameters and clinical results were systematically reviewed. RESULTS: Of 558 children diagnosed with EoE, 127 (22.8%) were younger than 5 years old (mean age 2.5 years). This subgroup presented with reflux symptoms (90.1%), vomiting (86.2%), diarrhea (55.3%), liquid dysphagia (52.0%), and constipation (50.0%), whereas food impaction (1.6%) was rare. Liquid dysphagia was present at all ages but significantly more common in younger children (P = .0101). The most common food and environmental allergens were egg whites (39.7%), cow's milk (36.5%), peanuts (34.9%), animal dander (15.1%), and weed pollen (11.1%). Patients were managed with antireflux medication (100%), elimination diet (83.5%), and steroid medication (68.5%). After treatment, 86% of parents reported symptom improvement. Mean reduction of EOS in pos-treatment biopsy was 33.5 EOS/HPF (P < .0001), and 67 patients showed histologic resolution of EoE (56.8%, P < .0001). CONCLUSIONS: Approximately one-quarter of children with EoE present under 5 years of age with multiple esophageal symptoms, comorbidities, and allergen-sensitization profiles. These patients demonstrate substantial clinicohistologic improvement following therapy. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:798-805, 2018.
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Trastornos de Deglución/etiología , Esofagitis Eosinofílica/patología , Reflujo Gastroesofágico/etiología , Preescolar , Estreñimiento/etiología , Diarrea/etiología , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/inmunología , Esófago/patología , Femenino , Hipersensibilidad a los Alimentos/inmunología , Humanos , Masculino , Estudios Retrospectivos , Vómitos/etiologíaRESUMEN
BACKGROUND: In children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits. OBJECTIVE: To determine the effects of environmental allergen sensitization on response to treatment in children with EoE in the southeastern United States. METHODS: Patients 2 to 18 years old who were referred to the Arkansas Children's Hospital Eosinophilic Gastrointestinal Disorders Clinic from January 2012 to January 2016 were enrolled in a prospective, longitudinal cohort study with collection of demographics, clinical symptoms, medical history, allergy sensitization profiles, and response to treatment over time. Comparisons were made between complete responders (peak esophageal eosinophil count <15 per high-power field [HPF]) and nonresponders (>25 eosinophils per HPF) after treatment with diet elimination alone, swallowed corticosteroids alone, or diet elimination and swallowed corticosteroids. Sensitization patterns to environmental allergens found in the southeastern United States were analyzed for the effect on treatment response. RESULTS: A total of 223 individuals were enrolled. Of these, 182 had environmental allergy profiling and at least one endoscopy while receiving proton pump inhibitor (PPI) therapy. Twenty-nine individuals had PPI-responsive EoE and were excluded from further analysis, leaving 123 individuals with non-PPI-responsive EoE who were further analyzed; 72 (58.5%) were complete responders and 33 (26.8%) were nonresponders. Seventeen individuals (13.8%) were partial responders (≥1 but ≤25 eosinophils per HPF) and excluded from further analysis. Nonresponders were more likely to be sensitized to perennial allergens (P = .02). There was no significant difference in response based on seasonal allergen sensitization. Individuals with mold or cockroach sensitization were more likely to fail combination diet and swallowed corticosteroid treatment (P = .02 and P = .002). CONCLUSION: Perennial allergen and mold sensitization may lead to nonresponse to EoE treatment in some patients. Additional studies are needed to further understand the effect of environmental allergens on EoE. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01779154.