Sensitization to house dust mites (HDM) is frequent in patients with atopic dermatitis (AD).

To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus(Dpt) extract in patients with AD sensitized to HDM.

In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients aged ≥3 years, with SCORing Atopic Dermatitis (SCORAD) ≥15 and positive skin test and/or IgE to Dpt. Patients were stratified according to age (15-point decrease in SCORAD. Secondary outcomes were decreases in SCORAD and objective SCORAD (O-SCORAD), Eczema Area and Severity Index (EASI), visual analog scale (VAS) for symptoms, pruritus scale; Investigator's Global Assessment (IGA) 0/1; and decrease ≥4 points in Dermatology Life Quality Index (DLQI). Background therapy was maintained.

A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% patients in HDM SLIT and placebo groups, respectively, showed >15-point decrease in SCORAD (relative risk[RR]1.28, 95% confidence interval[CI] 0.89-1.83). Significant SCORAD decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference 20.4;95%CI 3.89-37.3); significant O-SCORAD decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference 21.3;95%CI 0.66-41.81); and more patients with IGA 0/1 in HDM SLIT group as compared to placebo group (14/35 vs 5/31;RR 2.63, 95%CI 1.09-6.39), were observed at 18 months.

Our results suggest that HDM SLIT may be effective in HDM sensitized patients as an add-on treatment for AD.

Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-μg peanut protein (Viaskin™ Peanut 250 μg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children.

To examine the safety of VP250 in children, using a study design approximating potential real-world use.

REALISE is a phase 3 multicenter study consisting of a 6 month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported.

Three hundred ninety-three children were randomized 3:1 to receive VP250 (n=294) or placebo (n=99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued due to adverse events. Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall adverse event rates were similar among participants with and without history of peanut anaphylaxis.

In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions.

We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in baked milk allergic children.

Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated.

11/15 (73%) of the BMOIT participants reached the primary endpoint, tolerating 4044 mg of baked milk protein after 12 months of OIT, compared to 0/15 (0%) on placebo. The median maximal tolerated dose (MTD) and median change from baseline was significantly higher in the BMOIT group compared to placebo (median MTD 4044mg vs 144mg; p=0.001; median change in MTD of 3900mg vs 0mg, p=0.0001). Dose-related reactions were common but >95% in both groups were mild. There was no significant change in CM- or beta lactoglobulin-IgE from baseline for either group. CM-sIgG4 did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only with more improving while on placebo compared BMOIT. The majority of children and adolescents in the BMOIT group directly reported improvement in at least one domain.

BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.

Food desensitization via oral immunotherapy (OIT) is gaining higher acceptance in clinical practice. Due to adverse reactions, the duration of the buildup phase until a maintenance dose is achieved may be prolonged, and in a minority of cases, OIT is stopped.

We aimed to assess factors associated with the probability of reaching the maintenance dose in cow's milk (CM) OIT.

Data was collected from patients undergoing CM OIT at the Montreal Children's Hospital, BC Children's Hospital, and Hospital for Sick Children. We compared uni- and multivariable Cox regressions to evaluate sociodemographic factors, co-morbidities, clinical characteristics and biomarkers at study entry associated with the likelihood of reaching a maintenance dose of 200 mL of CM.

Among 69 children who reached 4 mL of milk, the median age was 12 years (Interquartile Range [IQR] 9-15) and 59% were male. The median duration of build-up phase from 4 mL to 200 mL was 24.0 weeks (IQR 17.7-33.4). After adjusting for age and sex, higher baseline levels of specific IgE (sIgE) antibodies for αlactalbumin (ALA, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.67-0.95), β-lactoglobulin (BLG, HR 0.86, 95% CI 0.76-0.98), casein (HR 0.82, 95% CI 0.72-0.94), and total CM (HR 0.79, 95% CI 0.65-0.97), were associated with a decreased probability of reaching maintenance. Additionally, for every increase of 10 mL CM tolerated at entry challenge, the probability of reaching maintenance increased by 10%.

The data suggest that higher levels of CM-sIgE decreased the likelihood of reaching maintenance, while an increased cumulative CM dose at entry challenge increased the likelihood. Assessing these factors prior to therapy may assist in predicting the success of CM OIT.

There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated.

The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT).

Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022).

To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision.

To compare the efficacy of single- and double-species mite allergen immunotherapy.

An open, pseudo-randomized, controlled study was conducted (n = 125 allergic rhinitis patients). The primary end point involved the visual analogue scale. Secondary end points included a basophil activation test and serum specific IgE and IgG4 assays.

Visual analogue scale analysis indicated considerable reductions in both groups. Both treatments improved quality of life and induced sIgG4 antibody production. Basophil activation and serum IgE inhibition were not evident in either treatment. Neither treatment displayed an early stage immune synergistic effect on cross-allergens.

Both treatments were effective against allergic rhinitis, and statistical differences were not observed. Future studies may require long-term, large-scale research.

Allergen-specific sublingual immunotherapy (SLIT), a safe and efficient route for treating type I hypersensitivity disorders, requires high doses of allergens. SLIT is generally performed without adjuvants and delivery systems. Therefore, allergen formulation with appropriate presentation platforms results in improved allergen availability, targeting the immune cells, inducing regulatory immune responses, and enhancing immunotherapy's efficacy while decreasing the dose of the allergen. In this review, we discuss the adjuvants and delivery systems that have been applied as allergen-presentation platforms for SLIT. These adjuvants include TLRs ligands, 1α, 25-dihydroxy vitamin D3, galectin-9, probiotic and bacterial components that provoke allergen-specific helper type-1 T lymphocytes (TH1), and regulatory T cells (Tregs). Another approach is encapsulation or adsorption of the allergens into a particulate vector system to facilitate allergen capture by tolerogenic dendritic cells. Also, we proposed strategies to increasing the efficacy of SLIT via new immunopotentiators and carrier systems in the future.

People with allergic rhinitis (AR) who are not controlled on conventional therapy can be treated using allergy immunotherapy (AIT) administered as tablets, injections or drops. In the US, the use of sublingual immunotherapy as tablets (SLIT-tablets) is limited in comparison to subcutaneous immunotherapy (SCIT).

This study investigated patients' preference for SLIT-tablets vs monthly or weekly SCIT from a US patient perspective.

We carried out a discrete choice experiment (DCE) consisting of two blocks with eight choice sets. Adults and caregivers of children with moderate tosevere AR were included if they had not previously or were not currently receiving AIT. Three attributes were included in the design: the mode and frequency of administration, the risk of systemic reactions and the co-payment.

A total of 724 adults with AR and 665 caregivers of children with AR were included in the study. Both adults and caregivers had a significant preference for SLIT-tablets compared with both weekly and monthly injections and for less risk of anaphylactic shock. Caregivers were more risk-averse than adults when choosing their treatment, and the younger the child, the more risk averse the caregiver. The preference for SLIT-tablets was found for both monoallergic and polyallergic adults and caregivers of monoallergic and polyallergic children. Respondents not wanting AIT for free were more risk-averse than those indicating that they wanted AIT for free.

Our findings suggest that SLIT-tablets is the preferred route of administration for AIT among adults and caregivers of children with AR.

The Food Allergy Quality of Life Questionnaire Parent Form (FAQLQ-PF) is the most widely used quality of life questionnaire in food allergy. The objective of this study was to develop a mapping algorithm to convert FAQLQ-PF scores into health state utilities.

The Short-Form Six-Dimensions version 2 (SF-6Dv2) and FAQLQ-PF questionnaires were collected from an academic center oral immunotherapy referral cohort. Utility estimates were derived from the SF-6Dv2 using the food allergy preference set. Candidate mapping algorithm models were developed using seven regression methods starting from either the total average score, the average scores of each of the three domains or the individual item scores of FAQLQ-PF. The process was repeated twice, including only section A, common to all age groups, or including all age-applicable sections of the FAQLQ-PF. The mean absolute error (MAE) and root mean squared error (RMSE) were used to select the best fitting model. An independent cohort from a previous national online survey was used for external validation.

In the index cohort, 1000 of 1257 respondents had completed both questionnaires. The lowest MAE (0.0791) and RMSE (0.1020) were recorded when entering individual item scores in a categorical regression model. The model including only FAQLQ-PF section A was found to be most consistent when tested in the external validation cohort (n=248) (MAE of 0.0898).

The FAQLQ-PF was mapped onto SF-6Dv2 utilities with good predictive accuracy in two independent cohorts. This will enable calculation of health utility for cost-effectiveness analyses in food allergy.

In recent years, landmark clinical trials investigating the role of early oral exposure to food antigens for food allergy (FA) prevention have highlighted the importance of immunoregulatory pathways in the ‘gut– skin axis’. This review highlights recent literature on the mechanisms of the immune system and microbiome involved in the gut–skin axis, contributing to the development of atopic dermatitis (AD), FA, allergic rhinitis (AR) and asthma. Therapeutic interventions harnessing the gut–skin axis are also discussed.

Epicutaneous sensitization in the presence of AD is capable of inducing Th2 allergic inflammation in the intestinal tract and lower respiratory airways, predisposing one to the development of AR and asthma. Probiotics have demonstrated positive effects in preventing and treating AD, though there is no evident relationship of its beneficial effects on other allergic diseases. Prophylactic skin emollients use has not shown consistent protection against AD, whereas there is some evidence for the role of dietary changes in alleviating AD and airway inflammation. More randomized controlled trials are needed to clarify the potential of epicutaneous immunotherapy as a therapeutic strategy for patients with FA.

The growing understanding of the gut–skin interactions on allergic disease pathogenesis presents novel avenues for therapeutic interventions which target modulation of the gut and/or skin.