Dan Atkins

Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report

Autism spectrum disorders (ASDs) are common and clinically heterogeneous neurodevelopmental disorders. Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs, but key issues such as the prevalence and best treatment of these conditions are incompletely understood. A central difficulty in recognizing and characterizing gastrointestinal dysfunction with ASDs is the communication difficulties experienced by many affected individuals. A multidisciplinary panel reviewed the medical literature with the aim of generating evidence-based recommendations for diagnostic evaluation and management of gastrointestinal problems in this patient population. The panel concluded that evidence-based recommendations are not yet available. The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs. Care providers should be aware that problem behavior in patients with ASDs may be the primary or sole symptom of the underlying medical condition, including some gastrointestinal disorders. For these patients, integration of behavioral and medical care may be most beneficial. Priorities for future research are identified to advance our understanding and management of gastrointestinal disorders in persons with ASDs.

Allergic reactions to foods in preschool-aged children in a prospective observational food allergy study.

OBJECTIVE: To examine circumstances of allergic reactions to foods in a cohort of preschool-aged children. METHODS: We conducted a prospective, 5-site observational study of 512 infants aged 3 to 15 months with documented or likely allergy to milk or egg, and collected data prospectively examining allergic reactions. RESULTS: Over a median follow-up of 36 months (range: 0–48.4), the annualized reaction rate was 0.81 per year (367/512 subjects reporting 1171 reactions [95% confidence interval: 0.76–0.85]). Overall, 269/512 (52.5%) reported >1 reaction. The majority of reactions (71.2%) were triggered by milk (495 [42.3%]), egg (246 [21.0%]), and peanut (93 [7.9%]), with accidental exposures attributed to unintentional ingestion, label-reading errors, and cross-contact. Foods were provided by persons other than parents in 50.6% of reactions. Of 834 reactions to milk, egg, or peanut, 93 (11.2%) were attributed to purposeful exposures to these avoided foods. A higher number of food allergies (P < .0001) and higher food-specific immunoglobulin E (P < .0001) were associated with reactions. Of the 11.4% of reactions (n = 134) that were severe, 29.9% were treated with epinephrine. Factors resulting in undertreatment included lack of recognition of severity, epinephrine being unavailable, and fears about epinephrine administration. CONCLUSIONS: There was a high frequency of reactions caused by accidental and nonaccidental exposures. Undertreatment of severe reactions with epinephrine was a substantial problem. Areas for improved education include the need for constant vigilance, accurate label reading, avoidance of nonaccidental exposure, prevention of cross-contamination, appropriate epinephrine administration, and education of all caretakers.

The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis

Objective Eosinophil predominant inflammation characterises histological features of eosinophilic oesophagitis (EoE). Endoscopy with biopsy is currently the only method to assess oesophageal mucosal inflammation in EoE. We hypothesised that measurements of luminal eosinophil-derived proteins would correlate with oesophageal mucosal inflammation in children with EoE. Design The Enterotest diagnostic device was used to develop an oesophageal string test (EST) as a minimally invasive clinical device. EST samples and oesophageal mucosal biopsies were obtained from children undergoing upper endoscopy for clinically defined indications. Eosinophil-derived proteins including eosinophil secondary granule proteins (major basic protein-1, eosinophil-derived neurotoxin, eosinophil cationic protein, eosinophil peroxidase) and Charcot–Leyden crystal protein/galectin-10 were measured by ELISA in luminal effluents eluted from ESTs and extracts of mucosal biopsies. Results ESTs were performed in 41 children with active EoE (n=14), EoE in remission (n=8), gastro-oesophageal reflux disease (n=4) and controls with normal oesophagus (n=15). EST measurement of eosinophil-derived protein biomarkers significantly distinguished between children with active EoE, treated EoE in remission, gastro-oesophageal reflux disease and normal oesophagus. Levels of luminal eosinophil-derived proteins in EST samples significantly correlated with peak and mean oesophageal eosinophils/high power field (HPF), eosinophil peroxidase indices and levels of the same eosinophil-derived proteins in extracts of oesophageal biopsies. Conclusions The presence of eosinophil-derived proteins in luminal secretions is reflective of mucosal inflammation in children with EoE. The EST is a novel, minimally invasive device for measuring oesophageal eosinophilic inflammation in children with EoE.

Oral Food Challenges in Children with a Diagnosis of Food Allergy

OBJECTIVE To assess the outcome of oral food challenges in patients placed on elimination diets based primarily on positive serum immunoglobulin E (IgE) immunoassay results. STUDY DESIGN This is a retrospective chart review of 125 children aged 1-19 years (median age, 4 years) evaluated between January 2007 and August 2008 for IgE-mediated food allergy at National Jewish Health and who underwent an oral food challenge. Clinical history, prick skin test results, and serum allergen-specific IgE test results were obtained. RESULTS The data were summarized for food avoidance and oral food challenge results. Depending on the reason for avoidance, 84%-93% of the foods being avoided were returned to the diet after an oral food challenge, indicating that the vast majority of foods that had been restricted could be tolerated at discharge. CONCLUSIONS In the absence of anaphylaxis, the primary reliance on serum food-specific IgE testing to determine the need for a food elimination diet is not sufficient, especially in children with atopic dermatitis. In those circumstances, oral food challenges may be indicated to confirm food allergy status.

Feeding Dysfunction in Children With Eosinophilic Gastrointestinal Diseases

OBJECTIVES: Feeding dysfunction (FD) seen in younger children with eosinophilic gastrointestinal disease (EGID) has not been well described. Thus, our aim was to further characterize FD in children with EGIDs. METHODS: A retrospective medical record analysis of 200 children seen over 12 months in a multidisciplinary Gastrointestinal Eosinophilic Diseases Program was performed. The clinical data of 33 children identified as also having FD were examined, including information obtained by history, physical examination, feeding evaluation, review of nutritional data, allergy testing and histologic assessment of mucosal biopsies. RESULTS: Of 200 children with EGIDs, 16.5% had significant FD. The median age of this group was 34 months (range: 14–113 months). A variety of learned maladaptive feeding behaviors were reported in 93.9%. Frequent gagging or vomiting occurred in 84.8%. Food sensitivity was documented in 88% while 52% had other allergic disease. Twenty one percent were diagnosed with failure to thrive and 69.7% required individual or group feeding therapy. Forty-two percent had residual eosinophilia of >15 per HPF on esophageal biopsies performed at the time of symptoms. CONCLUSIONS: FD is prevalent in children with EGIDs often presenting as maladaptive learned feeding behaviors with altered mealtime dynamics and physical difficulties in eating mechanics. FD can persist even after eosinophilic inflammation is successfully treated. Awareness of the increased prevalence of FD in children with EGIDs with enable earlier recognition of this problem, resulting in a comprehensive, individualized treatment plan with the desired outcome of improving the development, feeding, and nutrition of these children.

International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology.

&NA; Food protein–induced enterocolitis (FPIES) is a non‐IgE cell‐ mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high‐quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence‐based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.

Eosinophilic esophagitis: the newest esophageal inflammatory disease

Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory disease of undetermined pathophysiology that results in dense mucosal eosinophilia and esophageal dysfunction. In childhood, vague symptoms associated with GERD and feeding difficulties are the first manifestations of EoE. Adults typically present with dysphagia and food impaction. No pathognomonic features have been identified for EoE and, therefore, its diagnosis must be made on both clinical and histological grounds. Effective treatments rely on steroids and dietary exclusions.

Evaluation of the patient with suspected eosinophilic gastrointestinal disease.

This article focuses on the evaluation and management of eosinophilic gastrointestinal diseases other than eosinophilic esophagitis. Those diseases include eosinophilic gastritis, gastroenteritis, enteritis, and colitis. The diagnosis of eosinophilic gastrointestinal disease is primarily dependent on the clinical history and histopathology of multiple biopsy specimens after ruling out other causes of intestinal eosinophilia. The diagnosis of eosinophilic gastrointestinal diseases other than eosinophilic esophagitis is complicated by the lack of uniformly accepted diagnostic criteria. Treatment involves evaluation for food sensitivity, elimination diets, and the use of anti-allergy and anti-inflammatory medications with varying degrees of success. Little is known about the natural history of eosinophilic gastrointestinal diseases, underscoring the need for long-term follow-up studies of patients with these disorders.

Health-Related Quality of Life Over Time in Children With Eosinophilic Esophagitis and Their Families

Objectives: Existing treatments for pediatric eosinophilic esophagitis (EoE) effectively reduce inflammation. The impact of treatment on health-related quality of life (HRQoL) over time for pediatric patients with EoE and their families, however, has not been systematically assessed. We hypothesized that individualized multidisciplinary treatment would improve both child and family HRQoL over time, with improvements associated with decreased symptom severity. Methods: Children with EoE treated in 4 tertiary care centers were enrolled. Baseline assessments occurred at the time of patients’ first evaluation; follow-up assessments occurred at 2 and 6 months after baseline. Presence and severity of 8 EoE symptoms were measured. HRQoL was measured with the Pediatric Quality of Life Inventory parent proxy report, child self-report (CR), and Family Impact Module (FIM). Statistical analyses used mixed-effects modeling to test changes over time for child and family HRQoL. Results: Ninety-seven children were enrolled (ages 2–18 years, mean age 7.7 years ± 4.8, 78% boys, 80% white). Baseline mean symptom number was 3.5 (standard deviation 2.3), and symptom severity was 5.5 (standard deviation, 4.5). HRQoL scores were significantly related to symptom scores (P < 0.001). EoE symptom severity decreased during the study (P = 0.03). Pediatric Quality of Life Inventory parent proxy Total and FIM Total scores improved from baseline to 6 months (respectively, adjusted means 78.4 vs 81.0, P = 0.0006; 68.9 vs 70.1, P = 0.03). Interactions with baseline symptom severity revealed that subjects with lowest symptom severity showed the most improved HRQoL scores (P = 0.0013). Conclusions: HRQoL improved during the course of evaluation and treatment, with positive changes being strongest for patients with less symptom severity at baseline.

Peanut-allergic subjects and their peanut-tolerant siblings have large differences in peanut-specific IgG that are independent of HLA class II.

We enrolled 53 peanut-allergic subjects and 64 peanut-tolerant full siblings, measured peanut-specific IgG and IgE, determined HLA class II at high resolution, and analyzed DRB1 alleles by supertypes. Peanut-specific IgG and IgE were elevated in the peanut-allergic subjects (p<0.0001) but did not stratify with HLA alleles, haplotypes, or supertypes. There were no significant differences in HLA class II between the peanut-allergic and peanut-tolerant siblings but there was an increased frequency of DRB1*0803 in both sets of siblings compared to unrelated controls (p(c)=4.5×10⁻⁹). Furthermore, we identified 14 sibling pairs in which the peanut-allergic and the peanut-tolerant siblings have identical HLA class II and again found an elevation of anti-peanut IgG in the peanut-allergic subjects (p<0.0001). In conclusion, although DRB1*0803 may identify a subset of families with increased risk of peanut allergy, differences in peanut-specific immunoglobulin production between peanut-allergic subjects and their peanut-tolerant siblings are independent of HLA class II.