Efficacy and safety of food allergy oral immunotherapy in adults.

BACKGROUND: Oral immunotherapy (OIT) is an emerging method for treating food allergy in children. However, data regarding adults undergoing this process are lacking. METHODS: We retrospectively analyzed the medical records of patients with food allergy aged ≥17 years who completed OIT treatment between April 2010 and December 2020 at Shamir Medical Center. Data were compared with that of children aged 4 to <11 years and adolescents aged ≥11 to 17 treated during the same time period. RESULTS: A total of 96 adults at a median age of 22.3 years who underwent OIT for milk (n = 53), peanut (n = 18), sesame (n = 7), egg (n = 5), and tree nuts (n = 13) were analyzed and compared with 1299 children and 309 adolescents. Adults experienced more adverse reactions requiring injectable epinephrine, both during in-clinic up-dosing (49% vs. 15.9% and 26.5% for children and adolescents, respectively, p < 0.0001) and during home treatment (22.9% vs. 12.4%, p = 0.007 for children, and 17.5%, p = 0.23 for adolescents). Most adults (61.5%) were fully desensitized, but the rates of full desensitization were significantly lower than children (73.4%, p = 0.013). Significantly more adults (28.3%) undergoing milk OIT failed treatment than children (14.3%, p = 0.015) and adolescents (14.1%, p = 0.022), while failure rates in adults undergoing OIT for other foods were low (9.3%) and comparable with children and adolescents. CONCLUSIONS: OIT is successful in desensitizing most adults with IgE-mediated food allergy. Adults undergoing milk OIT are at increased risk for severe reactions and for OIT failure while failure rates in adults undergoing OIT for other foods are low.

Proton pump inhibitors in eosinophilic esophagitis (EoE) related to oral immunotherapy: is it as effective as in other EoE?

Oral immunotherapy (OIT) may induce eosinophilic esophagitis (EoE). Proton pump inhibitors (PPIs) are an effective treatment for EoE. However, the effect of PPI treatment is not well established in patients with EoE induced by OIT. Our primary aim was to compare the clinical, endoscopic, and histological response rates to PPIs in children with EoE induced by OIT (EoE+OIT) versus EoE patients without OIT (EoE-OIT). The secondary aims are to describe the clinical and histological features of EoE+OIT. Demographic, clinical, endoscopic, and histological findings of patients with EoE in the gastroenterology clinic at Shamir Medical Center between March 2015 and December 2022 were collected. Comparisons were performed between EoE+OIT and EoE-OIT patients. The study included 42 children (74% male, mean age 11.2), of whom 31 had EoE-OIT and 11 had EoE+OIT. There were no significant differences between groups regarding sex, comorbidities, symptoms, or endoscopic and histological characteristics at diagnosis. All 42 children were treated with PPIs after diagnosis with or without diet changes. The rates of any clinical response were 83.9% and 90.1% in the EoE-OIT group and EoE+OIT group, respectively (p = 1.0). The rate of any endoscopic response was 74.2% for EoE-OIT and 81.8% for EoE+OIT (p = 0.54). Histologically, PPIs were even more effective in the EoE+OIT group, where only 18.2% had no histological response at all compared to 51.6% in the EoE-OIT group (p = 0.1). CONCLUSION: PPI treatment is as effective in EoE with OIT as it is in EoE due to other etiologies. WHAT IS KNOWN: • Proton pump inhibitor (PPI) treatment is effective for achieving clinical response and histologic remission in some patients with eosinophilic esophagitis (EoE). • EoE has also been reported to be triggered by oral immunotherapy (OIT). WHAT IS NEW: • PPI treatment in EoE with OIT is as effective as treatment for EoE due to other etiologies.

Quality of life of children aged 8-12 years undergoing food allergy oral immunotherapy: Child and parent perspective.

BACKGROUND: Oral immunotherapy (OIT) for food allergy improves the quality of life (QOL) of children from parental perspective but little is known about the child perception. METHODS: The Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF) was administered to children aged 8-12 years, and the FAQLQ-Parent Form (FAQLQ-PF) was administered to their parents at the start of OIT for milk, egg, peanut, sesame, or tree nuts, at the end of up-dosing, and after 6 months of follow-up. Food-allergic children not undergoing OIT served as controls. Children QOL scores were compared to their parents. RESULTS: The total FAQLQ-CF score of 103 children undergoing OIT improved significantly from start of OIT (median (IQR); 4.8, 3.8-5.7) to end of up-dosing (3.9, 3-5.2) (P < .001). A greater improvement was noted in the 56 children who reached a follow-up visit, from 5.0 (3.7-5.8) at OIT start to 3.1 (1.8-5.0) on follow-up, (P < .001). In contrast, FAQLQ-CF scores of control patients improved mildly and nonsignificantly between the two time points from 5.3 (4.3-5.7) to 4.8 (3.6-6.0), (P = .13). The improvement in the total FAQLQ-CF scores from OIT start to follow-up was significantly greater compared to the change in control patients during observation (P = .015). Parents reported better QOL scores compared to their children at all stages of OIT (start 4.0, 3.2-5, P = .004; end of up-dosing 2.9, 1.9-4.7, P = .04; follow-up 2.2, 1.6-3.6, P = .003). CONCLUSIONS: QOL of food-allergic children undergoing OIT improves significantly compared to controls. Parents perceive QOL to be better than the perception of the children.

Efficacy of omalizumab treatment for pediatric chronic spontaneous urticaria: A multi-center retrospective case series.

BACKGROUND: Chronic urticaria is defined by the presence of itchy wheals, sometimes accompanied by angioedema, lasting for at least 6 weeks. In children, most cases occur without an eliciting factor and are defined as chronic spontaneous urticaria (CSU). CSU affects up to 0.75% of children with a negative impact on quality of life and school performance. CSU is treated in adults with second-generation antihistamines, increased up to four times normal doses for second-line treatment. Omalizumab (a monoclonal antibody to IgE) may be recommended as third-line therapy. A similar protocol is used in children, yet little is known of its efficacy and safety. OBJECTIVES: To summarize our multi-center experience in treating children with recalcitrant CSU with omalizumab. METHODS: A retrospective multi-center case series conducted in 5 tertiary care centers in Israel. Patients included were children <18 years old diagnosed with recalcitrant CSU who were treated with omalizumab. Patients were followed up throughout the duration of omalizumab therapy/symptom remission. Patients' electronic medical records were used to gather data. RESULTS: Nineteen participants (11 F; 8 M) presented with CSU between ages 6 and 16.9 years. Sixteen (84%) responded to omalizumab, including children <12 years old, although two became non-responsive after 6-12 months of therapy. Another three patients (16%) were resistant to treatment, achieving remission through fourth-line (Cyclosporine A) or other therapies. CONCLUSION: Children with recalcitrant CSU, even those <12 years old, respond well to standard-dose, third-line omalizumab therapy at rates similar to adults. Yet, some cases may become non-responsive with ongoing treatment.

Patient quality of life following induction of oral immunotherapy for food allergy.

BACKGROUND: Patient quality of life improves following successful completion of oral immunotherapy (OIT), but the process itself might have undesirable effects. We aimed to evaluate patient quality of life following OIT initial induction. METHODS: The Hebrew version of the Food Allergy Quality of Life Questionnaire-Parental Form (FAQLQ-PF) was validated and administered to the parents of children following the first week of OIT for food allergy (n = 119). Patient demographics and clinical history as well as the course of initial induction week were reviewed. RESULTS: Pre-OIT severity of food allergy, defined as severity of reactions due to accidental exposure to the allergenic food (anaphylactic reactions, p = 0.017; epinephrine use, p = 0.049; emergency room referrals p = 0.003; and hospital admissions, p = 0.015) and a lower number of tolerated doses during initial induction, reflective of a lower maximal tolerated dose for the different allergens (p = 0.011) were associated with worse total FAQLQ-PF scores. The number of tolerated doses during induction and pre-OIT emergency room referrals remained significantly associated with worse total score of the FAQLQ-PF on multivariate analysis (p = 0.016 and p = 0.005, respectively). The correlation between the number of tolerated doses and quality of life scores was moderate-strong primarily in children aged 6-12 years (Total score, r = -0.41, p = 0.001; Emotional Impact r = -0.42, p = 0.001; Food Anxiety, r = -0.38, p = 0.002; Social and Dietary Limitations, r = -0.33, p = 0.009). CONCLUSIONS: Pre-OIT reaction severity affects quality of life in both preschool and school-aged food-allergic children. In contrast, a lower maximal tolerated dose during OIT induction is associated with worse indices of quality of life primarily in children aged 6-12 years.

Minor Clinical Impact of COVID-19 Pandemic on Patients With Primary Immunodeficiency in Israel.

In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. While human immunity against COVID-19 is not fully understood, it is, so far, well documented, that both adaptive and innate cells have a critical role in protection against SARS-CoV-2. Here, we aimed to summarize the clinical and laboratory data on primary immunodeficiency (PID) patients in Israel, who were tested positive for SARS-CoV-2, in order to estimate the impact of COVID-19 on such patients. Data was collected from mid-February to end-September. During this time Israel experienced two "waves" of COVID-19 diseases; the first, from mid-February to mid-May and the second from mid-June and still ongoing at the end of data collection. A total of 20 PID patients, aged 4 months to 60 years, were tested positive for SARS-CoV-2, all but one, were detected during the second wave. Fourteen of the patients were on routine monthly IVIG replacement therapy at the time of virus detection. None of the patients displayed severe illness and none required hospitalization; moreover, 7/20 patients were completely asymptomatic. Possible explanations for the minimal clinical impact of COVID-19 pandemic observed in our PID patients include high level of awareness, extra-precautions, and even self-isolation. It is also possible that only specific immune pathways (e.g. type I interferon signaling), may increase the risk for a more severe course of disease and these are not affected in many of the PID patients. In some cases, lack of an immune response actually may be a protective measure against the development of COVID-19 sequelae.

Quality of Life of Food-Allergic Patients Before, During, and After Oral Immunotherapy.

BACKGROUND: Oral immunotherapy (OIT) for food allergy is demanding but data on patients' quality of life (QOL) throughout the process are limited. OBJECTIVE: To characterize changes in QOL of food-allergic patients during and after OIT. METHODS: In a prospective cohort study, the Food Allergy Quality of Life Questionnaire-Parental Form (FAQLQ-PF) was administered to parents of 191 consecutive children aged 4 to 12 years undergoing OIT for food allergy. Questionnaires were administered at OIT initiation, mid up-dosing, upon reaching maintenance, and after 6 months of follow-up. Age- and sex-matched food-allergic children (n = 48) not undergoing OIT served as controls. RESULTS: FAQLQ-PF scores had significantly improved (decreased) from OIT initiation to reaching full maintenance (emotional impact [EI], 3.66-3.32, P = .001; food anxiety [FA], 3.90-3.32, P < .001; social and dietary limitation [SDL], 3.50-2.94, P < .001; and total score, 3.69-3.19, P < .001) and partial maintenance, whereas no change was noted in control patients. Worse baseline QOL, single food allergy, and a younger age predicted greater QOL improvement. Of the 85 (88.5%) patients who completed the FAQLQ-PF at mid up-dosing and for whom QOL deteriorated, a significant improvement was noted upon reaching maintenance. Additional significant improvement in QOL was observed in the 95 (88.8%) patients who completed the FAQLQ-PF 6 months after reaching maintenance (EI, 3.414-2.993, P = 0.049; FA, 3.37-2.593, P = .001; SDL, 2.989-2.264, P = .001; and total score, 3.266-2.614, P = .001). CONCLUSION: The QOL of food-allergic children improves significantly upon reaching OIT maintenance, with additional improvement 6 months later. The detrimental effect of OIT on some patients' QOL during up-dosing is reversed upon reaching maintenance.

Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study.

BACKGROUND: The safety and efficacy of oral immunotherapy for tree nut allergy has not been demonstrated to date, and its effectiveness is complicated by the high prevalence of co-allergies to several nuts. This study aimed to investigate the use of walnut oral immunotherapy in the desensitisation of walnut and additional tree nuts in patients who are co-allergic to several nuts. METHODS: In a single-centre, prospective cohort study (the Nut Co-Reactivity ACquiring Knowledge for Elimination Recommendations study) at the Institute of Allergy, Immunology, and Paediatric Pulmonology at the Yitzhak Shamir Medical Centre, we recruited patients aged 4 years or older who were allergic to walnut, with or without co-allergy to pecan, hazelnut, and cashew. The diagnosis of each food allergy was based on a positive skin prick test or specific serum IgE (≥0·35 kUA/L) to the corresponding nut together with a positive oral food challenge, unless an immediate (within 2 h of exposure) reaction in the past year had been documented. Patients with uncontrolled asthma or a medical contraindication to receive adrenaline were excluded. Patients were assigned to walnut oral immunotherapy or the control group (observation and strict dietary exclusion) on the basis of the order of presentation to the clinic. Oral immunotherapy began with a 4-day dose-escalation phase to establish the single highest tolerated dose, which was consumed daily at home for 24 days; subsequent monthly dose escalations were repeated until 4000 mg walnut protein was achieved. Patients who were desensitised to walnut continued to consume 1200 mg walnut protein daily for 6 months as maintenance. The primary outcome was walnut desensitisation (passing an oral food challenge with 4000 mg of walnut protein) at the end of the study, analysed by intention to treat. In patients who were co-allergic to pecan, hazelnut, and cashew, the proportion who achieved cross-desensitisation to these nuts in addition to walnut desensitisation was examined. FINDINGS: 73 patients with a walnut allergy were enrolled between May 15, 2016, and Jan 14, 2018. 49 (89%) of 55 patients in the oral immunotherapy group were desensitised to walnut compared with none of 18 patients in the control group (odds ratio 9·2, 95% CI 4·3-19·5; p<0·0001). Following walnut desensitisation, all patients who were co-allergic to pecan (n=46) were also desensitised to pecan. Additionally, 18 (60%) of 30 patients who were co-allergic to hazelnut or cashew, and 14 (93%) of 15 patients who were co-allergic to hazelnut alone, were either fully desensitised or responded to treatment. 47 (85%) of 55 patients had an adverse reaction (mostly grade 1 or 2) during up-dosing in the clinic; eight patients required intramuscular epinephrine in response to a dose at home. Of 45 patients who had follow-up data for the maintenance phase, all maintained walnut desensitisation and one patient required epinephrine during this period. INTERPRETATION: Walnut oral immunotherapy can induce desensitisation to walnut as well as cross-desensitisation to pecan and hazelnut in patients who have tree nut co-allergies, with a reasonable safety profile. A low daily dose of the allergen maintains desensitisation. FUNDING: None.