Clinical characteristics and influence of postoperative Hirschsprung-associated enterocolitis: retrospective study at a tertiary children's hospital.

PURPOSE: To explore the influence of postoperative Hirschsprung-associated enterocolitis (post-HAEC) on long-term outcomes and to identify risk factors of post-HAEC. METHODS: The medical records of 304 eligible patients diagnosed with Hirschsprung's disease (HSCR) were reviewed. We analyzed the clinical characteristics of post-HAEC and its influence on long-term outcomes. Furthermore, risk factors for early and recurrent HAEC were identified separately. RESULTS: The overall incidence of post-HAEC was 29.9% (91/304). We categorized early HAEC as occurring within postoperative 3 months (n = 39) and recurrent HAEC as occurring ≥ 3 episodes within postoperative 6 months (n = 25). Patients with early HAEC were more likely to experience worse nutritional status, defecation function, and quality of life compared to those with late or no episodes (P < 0.05). Similarly, the adverse influences of recurrent HAEC on these outcomes were also significant (P < 0.05). The risk factors for early HAEC included preoperative undernutrition, long-segment HSCR, and postoperative Grade 3-4 complications within 30 days. For recurrent HAEC, risk factors were preoperative malnutrition, non-parental caregivers, long-segment HSCR, and postoperative Grade 3-4 complications within 30 days. CONCLUSION: Classification of post-HAEC based on the first episode time and frequency was necessary. The earlier or more frequent episodes of post-HAEC have detrimental influences on long-term outcomes. Furthermore, risk factors for early and recurrent HAEC were different.

Heterogeneity of food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with gastrointestinal symptoms such as vomiting and diarrhea. The development of international consensus guidelines for the diagnosis and management of FPIES in 2017 enabled us to compare patients worldwide, regardless of geographic variation in disease features. As a result, it has become clear that there is heterogeneity among patients with FPIES or that there are cases that partly fit the diagnostic criteria for FPIES but have different characteristics. This review highlights the heterogeneity in FPIES characteristics in terms of trigger foods, the age of onset, differences in geographic regions, and symptoms; it further proposes four disease entities, including acute FPIES in children, acute FPIES in adults, chronic FPIES, and early-onset neonatal FPIES, depending on the age of onset and presumed pathophysiology. The major symptoms at onset and trigger foods differ in acute FPIES in children, acute FPIES in adults, and chronic FPIES, whereas the disease entities may share a similar pathophysiology. Early-onset neonatal FPIES may have a different pathophysiology than acute or chronic FPIES, and may not necessarily fulfil the full diagnostic criteria for acute or chronic FPIES described in the international consensus guidelines. Due to the similarity in symptoms, early-onset neonatal FPIES may sometimes be misdiagnosed as necrotizing enterocolitis. We aim to increase awareness of FPIES among medical staff in pediatrics, neonatology, and internal medicine and promote research, to gain a better understanding of the heterogeneity and pathophysiology of FPIES.

Enterocolitis and other immunotherapy and targeted therapy-related gastrointestinal manifestations: A review for gastroenterologist.

New oncologic treatments, particularly immunotherapy (IT), have revolutionized the treatment of advanced-stage malignant tumors. Immune checkpoint inhibitors are the main form of IT and act by increasing T cell activity and the organism's immune response against neoplastic cells. Targeted therapy is another form of IT that acts by inhibiting oncogenes or inflammation signaling and tumor angiogenesis pathways. However, these mechanisms of tumor destruction can interfere with the host's immune self-tolerance or with the mechanisms of epithelial tissue repair and predispose to immune system-mediated adverse events that can affect multiple organs, including the digestive tract. The gastrointestinal manifestations of damage caused by IT can range from low-grade mucositis to ulceration, and in some cases, necrosis and perforation. Any part of the gastrointestinal tract can be affected, but there is greater involvement of the small bowel and colon, with a pattern similar to that seen in inflammatory bowel disease. The most common clinical manifestation is chronic diarrhea. The differential diagnosis includes enteropathogenic infections, especially those caused by opportunistic microorganisms; adverse drug reactions; and other inflammatory and malabsorption disorders. Treatment is guided by damage severity. Mild cases can be treated with antidiarrheals and rehydration in the outpatient setting; moderate cases with hospitalization, systemic steroids, and temporary suspension of IT; and severe cases with immunosuppressants or biologic agents and definitive suspension of IT.

Current and future perspectives on the consensus guideline for food protein-induced enterocolitis syndrome (FPIES).

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.

Clinical relevance of inflammation on rectal biopsy for Hirschsprung disease: An outcomes analysis.

OBJECTIVES: Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing. METHODS: A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull-through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30-days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6-months of ERPT. RESULTS: Forty-nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT. CONCLUSIONS: Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull-through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy.

The Effect of the Ganglionic Segment Inflammatory Response to Postoperative Enterocolitis in Hirschsprung Disease.

INTRODUCTION: We examined the relationship between proinflammatory cytokines that occur in the inflammatory reaction in the intestine in Hirschsprung disease (HD) and Hirschsprung-associated enterocolitis (HAEC). METHODS: Thirty cases (M:27, F:3) operated on due to HD. The cases were divided into three groups: group 1 with pre and post operative EC, group 2 with post-operative, and group 3 with pre-operative EC. The intestinal segments were evaluated by immunohistochemistry for interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). RESULTS: IL-1ß staining was significantly higher in the ganglionic zone of groups with enterocolitis compared to the control group (p = 0.012). TNF-α staining in the transitional zone of Group 3 and IL-1ß staining in the ganglionic zone of Group 1 was significantly higher than the control group (p = 0.030, p = 0.020). CONCLUSION: In our study, older age at diagnosis and more than 20% IL-1ß staining in the ganglionic segment were found to be risk factors for HAEC. It is noteworthy that the increase in IL-1ß can be associated with HAEC.

Discrepancy between Caregivers' Reports and Physicians' Evaluation of Causative Foods in Food Protein-Induced Enterocolitis Syndrome in Japan: The Japan Environment and Children's Study.

INTRODUCTION: Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE-mediated gastrointestinal food allergy. FPIES is considered a rare food allergy disorder and is often under-recognized. Therefore, clinicians should have a better understanding of its manifestations and maintain a high index of suspicion for a correct diagnosis. To this end, information about differences in the characteristics of caregiver-reported and physician-diagnosed FPIES is important. METHODS: The present, national, multicentric, prospective birth cohort study, called the Japan Environment and Children's Study (JECS), enrolled a general population of 104,062 fetal records. The characteristics of FPIES in 1.5-year-old children were categorized as cases reported by caregivers or as those diagnosed by a physician using questionnaire data. RESULTS: The prevalence of caregiver-reported and physician-diagnosed FPIES cases was 0.69% and 0.06%, respectively. Among the former, the most common causative food was hen's egg (HE), and the second most common causative food was cow's milk (CM) (51.0% and 17.1% of patients responded to HE and CM, which accounted for 46% and 15% of all the causative foods, respectively). Conversely, among the physician-diagnosed cases, the most common causative food was CM followed by HE (57.7% and 36.5% of patients responded to CM and HE, which accounted for 46% and 29% of all the causative foods, respectively). CM accounted for a significantly higher proportion of causative foods in physician-diagnosed FPIES while HE accounted for a significantly higher proportion of caregiver-reported FPIES (p < 0.05). CONCLUSION: A discrepancy was found in reports of the most common causative food between caregiver-reported and physician-diagnosed cases of FPIES.

Late Diagnosis of Hirschsprung Disease: Clinical Presentation and Long-Term Functional Outcomes.

PURPOSE: Hirschsprung Disease (HD) is typically diagnosed in the neonatal period. A small subset of patients have a prolonged course of abdominal distention and constipation prior to diagnosis. Late HD is defined as having been diagnosed at greater than or equal to one year of age. The literature is limited and offers conflicting data on the implications of a late diagnosis. We aim to investigate the presentation, operative approach, and functional outcomes of a large cohort of patients with a late HD diagnosis. METHODS: All patients with a late diagnosis of HD (after 1 year of age) at our institution between 1997 and 2021 were included. RESULTS: Twenty-eight patients were diagnosed with HD at a median age of 3.4 years. Chronic constipation, failure to thrive, and enterocolitis occurred in 100 %, 31 %, and 14 %, respectively. All patients underwent contrast enema and biopsies during their workup, identifying primarily rectosigmoid disease (n = 27) and total colonic aganglionosis (n = 1). Surgical intervention was performed in 27 patients, with 4 patients (15 %) needing a stoma (3 with plan for staged pull-through, 1 long-term stoma) and 23 patients (85 %) undergoing a single-stage pull-through. Postoperative complications included Hirschsprung-associated enterocolitis (n = 5), ostomy prolapse and revision (n = 2), abdominal distention requiring ileostomy creation (n = 2), redo pull-through (n = 2), retroperitoneal hematoma (n = 1), and cecostomy tube placement (n = 1). At a median follow-up of 5.4 years, 83 % of eligible patients achieved fecal continence with 43 % needing laxatives for persistent constipation. CONCLUSION: Recognizing a late presentation of HD requires a high index of suspicion. Patients with a late diagnosis did not experience an increased rate of permanent stoma, complications, or redo surgery compared to rates reported for the larger HD population. Similar long-term functional outcomes were achieved compared to the larger HD population. LEVEL OF EVIDENCE: IV.

Food protein-induced enterocolitis syndrome is an important differential diagnosis of vomiting in pediatric emergency.

BACKGROUND: The aim of this study was to clarify the clinical characteristics and management of infants with suspected acute food protein-induced enterocolitis syndrome (FPIES) who presented to the pediatric emergency department (ED) before and after the guidelines were published. METHODS: This was a retrospective cohort study. We classified the infants as "acute FPIES-like symptoms" who were younger than 12 months of age and visited the pediatric ED of the National Center for Child Health and Development due to vomiting 1-4 h after food ingestion without any causative disease, such as infection. The medical records of those infants in 2015 and 2021 were reviewed. We used the nonparametric Mann-Whitney U test to compare two groups for continuous variables, whereas chi-squared or Fisher's exact tests were used for nominal variables. RESULTS: The number of infants with acute FPIES-like symptoms was 15 (13%) in 2015 and 14 (15%) in 2021. The trigger foods were cow's milk or dairy products in half of the infants, and five as a result of ingestion of hen's eggs in 2021, compared to zero cases in 2015. Five in 2015 and 12 in 2021 required examination at the ED. Three in 2015 and six in 2021 met the diagnostic criteria for acute FPIES in the international consensus guidelines. The emergency physicians did not record at least four minor criteria for acute FPIES in seven in 2015 and five in 2021. No infants (0%) in 2015 and two (14%) in 2021 were referred to the allergy department by an emergency physician. CONCLUSIONS: Acute FPIES should be considered one of the differential diagnoses of vomiting, and pediatric medical staff should be aware of FPIES diagnostic criteria and appropriately refer suspected cases to a specialist.

Histological transitional zone pull-through in Hirschsprung disease. Postoperative functional results and current recommendations.

BACKGROUND: Surgeons create a neorectum to repair patients with Hirschsprung's disease (HD), which should be formed from a normoganglionic bowel. However, the neorectum is occasionally created with a transition zone (TZ) bowel. A neorectum created with a TZ has been postulated as a cause of postoperative enterocolitis or constipation. This study compares the incidence of enterocolitis and constipation in patients with TZ neorectum and normoganglionic bowel. METHODS: We conducted a retrospective review of patients with rectosigmoid HD who underwent primary pull-through. Patients were divided into normoganglionic neorectum (NNR) and TZ neorectum. The diagnosis was based on the final histopathologic report of the proximal margin. The incidence of enterocolitis and constipation was compared between these two groups. RESULTS: A total of 98 HD patients were analyzed. Seventy-one patients fulfilled the inclusion criteria. 65 (92%) had a NNR, and six patients (8%) had a TZ neorectum. From these patients, 42 (59%) presented with enterocolitis or constipation. However, there was no significant difference between both groups. CONCLUSION: The present study showed no difference in the incidence of enterocolitis or postoperative constipation in HD patients with normoganglionic or TZ neorectum. These results suggest that TZ neorectum does not cause postoperative obstructive symptoms.

INTRODUCCIÓN: Los cirujanos crean un neo-recto para tratar a los pacientes con enfermedad de Hirschsprung (EH), que debe formarse con intestino normogangliónico; sin embargo, en ocasiones el neo-recto se forma con intestino de la zona de transición. Se ha postulado que un neo-recto en zona de transición causa enterocolitis o estreñimiento postoperatorio. El objetivo de este estudio fue comparar la frecuencia de enterocolitis y estreñimiento en pacientes con neo-recto en zona de transición y con neo-recto normogangliónico. MÉTODOS: Se llevó a cabo una revisión retrospectiva de pacientes con EH recto sigmoideo que se sometieron a descenso primario. Los pacientes se dividieron en el grupo neo-recto normogangliónico y el grupo con neo-recto en zona de transición. El diagnóstico del neo-recto se estableció con el informe histopatológico definitivo del margen proximal. Se comparó la frecuencia de enterocolitis y estreñimiento entre estos dos grupos. RESULTADOS: Se analizó un total de 98 pacientes con EH, de los cuales 71 pacientes cumplieron los criterios de inclusión; 65 (92%) con neo-recto normogangliónico y seis (8%) con neo-recto en zona de transición. Posteriormente, 42 (59%) pacientes presentaron enterocolitis asociada a Hirschsprung (HAEC) o estreñimiento; sin embargo, no hubo diferencia significativa entre ambos grupos. CONCLUSIONES: El presente estudio no demostró una diferencia en la frecuencia de HAEC o estreñimiento postoperatorio en pacientes con EH con neo-recto normogangliónico o en zona de transición. Estos resultados sugieren que un neo-recto en zona de transición no causa síntomas obstructivos postoperatorios.

Comparation of robotic-assisted surgery and laparoscopic­assisted surgery in children with Hirschsprung's disease: a single-centered retrospective study.

BACKGROUND: There are few studies comparing robotic-assisted surgery (RAS) and laparoscopic-assisted surgery (LAS) in Hirschsprung's disease (HSCR). This study aimed to compare intraoperative and postoperative outcomes between RAS and LAS performed during the same period. METHODS: All consecutive 75 patients with pathologically diagnosed as HSCR who underwent Swenson pull-through surgery from April 2020 to Nov 2022, were included. Patients were divided into RAS group and LAS group and a retrospective analysis was performed based on clinical indexes and prognosis. RESULTS: A total of 75 patients were included, among which, 31 patients received RAS and 44 received LAS. The RAS and LAS groups had similar ages, sex, weight, postoperative hospital stays, and fasting times. Compared with LAS, blood loss (p = 0.002) and the incidence of Hirschsprung-associated enterocolitis (p = 0.046) were significantly lower in the RAS group. The first onset of Hirschsprung-associated enterocolitis in patients younger than 3 months occurred significantly earlier (p = 0.043). Two patients experienced anastomotic leakage in the LAS group and one patient experienced incisional hernia in the RAS group. The cost of RAS was significantly higher than that of LAS (p < 0.0001). CONCLUSIONS: RAS is a safe and effective alternative for HSCR children, and a delaying primary surgery until later in infancy (> 3 months) may improve outcomes.

Pearls and pitfalls in food protein-induced enterocolitis syndrome (FPIES).

Background: Food protein-induced enterocolitis syndrome (FPIES) is a rare, non-immunoglobulin E (IgE) mediated gastrointestinal food hypersensitivity. It is a clinical diagnosis commonly characterized by profuse vomiting 1 to 4 hours after ingestion of the triggering food(s). Objective: The objective was to increase awareness of FPIES and review the epidemiology, clinical presentation, pathogenesis, diagnosis, and management of FPIES. The lack of availability of a definite biomarker or diagnostic tool often leads to a delay in diagnosis. Methods: A literature search of salient articles that described case reports and case series of FPIES and their management were analyzed. Results: A case of FPIES with a literature review is presented with emphasis on clinical pearls and pitfalls. FPIES is a diagnosis of exclusion and the mainstay of treatment is avoidance of the trigger food(s) for at least 12-18 months from the last exposure. Conclusion: As FPIES is a non-IgE-mediated reaction, allergy testing via skin-prick test or blood tests to measure food IgE antibodies is not routinely recommended. Many children outgrow FPIES by 3-4 years of age. Supervised oral food challenge is recommended to assess acquisition of tolerance.

Food Protein-induced Enterocolitis Syndrome Due to Cuttlefish in a Child with Anaphylaxis to Crustaceans.

Shellfish is defined as any edible marine invertebrate and refers to crustaceans and mollusks. Crustaceans belong to the phylum Arthropods. Mollusks belong to the phylum Mollusca. This report illustrates a rare case of a 6-year-old girl with challenge-proven acute food protein-induced enterocolitis syndrome (FPIES) to cuttlefish (phylum Mollusca, class Cephalopoda), anaphylaxis to crustaceans (phylum Arthropoda), and tolerance to other mollusks, including clams and mussels (phylum Mollusca, class Bivalvia). The association of IgE-mediated food allergy and acute FPIES seen in this case is rare. To our knowledge, this is the first case of FPIES to cuttlefish reported in a child. This challenge highlights the need for further research into the allergens and mechanisms underpinning FPIES at a molecular level, enabling a better understanding of cross-reactivity patterns and the development of diagnostic and predictive tests to assist in clinical practice.

Comparison of adult food protein-induced enterocolitis syndrome to crustaceans and immediate-type food allergy.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is increasingly found in adults. FPIES requires different treatment from immediate-type food allergy (FA) in emergency medicine. However, no comparison of the clinical presentations of these diseases has been reported. OBJECTIVE: To compare the clinical presentations and causative crustaceans of adult FPIES and FA using a standardized questionnaire and to thereby lay the groundwork for establishing an algorithm that distinguishes those diseases. METHODS: We conducted a retrospective cohort study of crustacean-avoidant adults by telephone interview based on the previously reported diagnostic criteria for adult FPIES to compare the clinical features and crustacean intake status between FPIES and FA. RESULTS: Of 73 adult patients with crustacean allergy, 8 (11%) were diagnosed with having FPIES and 53 (73%) FA. Compared with the patients with FA, those with FPIES had a longer latency period (P < .01), more episodes (P = .02), longer duration of symptoms (P = .04), more frequent abdominal distention (P = .02), and severe colic pain (P = .02). Half of the patients with FPIES experienced fear of death during an episode. Panulirus japonicus (Japanese spiny lobster) and Homarus weber (lobster) were significantly common FPIES-causing foods. A statistically significant 62.5% of patients with FPIES were able to ingest some type of crustacean. CONCLUSION: FPIES and FA can be clearly differentiated by the abdominal symptoms, latency period, and duration of episodes. Furthermore, some patients with FPIES do not necessarily need to avoid all crustaceans. Our findings lay the groundwork for establishing an algorithm that distinguishes FPIES from FA in adults.

Risk factors for Hirschsprung disease-associated enterocolitis: a systematic review and meta-analysis.

BACKGROUND: The incidence of Hirschsprung disease (HSCR) is nearly 1/5000 and patients with HSCR are usually treated through surgical intervention. Hirschsprung disease-associated enterocolitis (HAEC) is a complication of HSCR with the highest morbidity and mortality in patients. The evidence on the risk factors for HAEC remains inconclusive to date. METHODS: Four English databases and four Chinese databases were searched for relevant studies published until May 2022. The search retrieved 53 relevant studies. The retrieved studies were scored on the Newcastle-Ottawa Scale by three researchers. Revman 5.4 software was employed for data synthesis and analysis. Stata 16 software was employed for sensitivity analysis and bias analysis. RESULTS: A total of 53 articles were retrieved from the database search, which included 10 012 cases of HSCR and 2310 cases of HAEC. The systematic analysis revealed anastomotic stenosis or fistula [ I2 =66%, risk ratio (RR)=1.90, 95% CI 1.34-2.68, P <0.001], preoperative enterocolitis ( I2 =55%, RR=2.07, 95% CI 1.71-2.51, P <0.001), preoperative malnutrition ( I2 =0%, RR=1.96, 95% CI 1.52-2.53, P <0.001), preoperative respiratory infection or pneumonia ( I2 =0%, RR=2.37, 95% CI 1.91-2.93, P <0.001), postoperative ileus ( I2 =17%, RR=2.41, 95% CI 2.02-2.87, P <0.001), length of ganglionless segment greater than 30 cm ( I2 =0%, RR=3.64, 95% CI 2.43-5.48, P <0.001), preoperative hypoproteinemia ( I2 =0%, RR=1.91, 95% CI 1.44-2.54, P <0.001), and Down syndrome ( I2 =29%, RR=1.65, 95% CI 1.32-2.07, P <0.001) as the risk factors for postoperative HAEC. Short-segment HSCR ( I2 =46%, RR=0.62, 95% CI 0.54-0.71, P <0.001) and transanal operation ( I2 =78%, RR=0.56, 95% CI 0.33-0.96, P =0.03) were revealed as the protective factors against postoperative HAEC. Preoperative malnutrition ( I2 =35 % , RR=5.33, 95% CI 2.68-10.60, P <0.001), preoperative hypoproteinemia ( I2 =20%, RR=4.17, 95% CI 1.91-9.12, P <0.001), preoperative enterocolitis ( I2 =45%, RR=3.51, 95% CI 2.54-4.84, P <0.001), and preoperative respiratory infection or pneumonia ( I2 =0%, RR=7.20, 95% CI 4.00-12.94, P <0.001) were revealed as the risk factors for recurrent HAEC, while short-segment HSCR ( I2 =0%, RR=0.40, 95% CI 0.21-0.76, P =0.005) was revealed as a protective factor against recurrent HAEC. CONCLUSION: The present review delineated the multiple risk factors for HAEC, which could assist in preventing the development of HAEC.

Neuroimmune regulation in Hirschsprung's disease associated enterocolitis.

Neuroimmune pathways are important part of the regulation of inflammatory response. Nerve cells regulate the functions of various immune cells through neurotransmitters, and then participate in the inflammatory immune response. Hirschsprung's disease (HD) is a congenital abnormal development of intestinal neurons, and Hirschsprung-associated enterocolitis (HAEC) is a common complication, which seriously affects the quality of life and even endangers the lives of children. Neuroimmune regulation mediates the occurrence and development of enteritis, which is an important mechanism. However, there is a lack of review on the role of Neuroimmune regulation in enterocolitis associated with Hirschsprung's disease. Therefore, this paper summarizes the characteristics of the interaction between intestinal nerve cells and immune cells, reviews the neuroimmune regulation mechanism of Hirschsprung's disease associated enterocolitis (HAEC), and looks forward to the potential clinical application value.