Patients with clonal mast cell disorders (cMCD); systemic mastocytosis (SM), and monoclonal mast cell activation syndrome (MMAS), represent an increased risk for hymenoptera venom anaphylaxis (HVA). Lifelong venom-immunotherapy (VIT) is recommended; however, its efficacy and safety is controversial. Hence, we sought to evaluate the efficacy and safety of VIT in HVA patients with cMCD.

A retrospective study was conducted among 46 patients with Vespula-venom allergy who had experienced severe HVA; 32 cMCD (22 with SM, 10 with MMAS) and 14 controls. There were no differences between cMCD patients and controls in age (58 vs 66) and duration of VIT (47 vs. 48 months), respectively.

During VIT, 11 (34%) cMCD patients experienced adverse reactions (ARs) (7% in controls), including 1 anaphylaxis. There were 23 re-stings in 17 (53%) patients during VIT. Of episodes, four (17%) presented with anaphylaxis, 14 (60%) with local reaction, and 5 (23%) were asymptomatic. In 11 episodes (48%), the patient did not take epinephrine, of these 8 (73%) presented with local reaction, and 3 (27%) were asymptomatic. Patient-based protection from anaphylaxis was 76% (4/17) in cMCD vs. 100% in controls during VIT. The venom-specific IgG4 levels increased during VIT (p <0.001); although tryptase and IgE levels were unaltered.

Both safety and efficacy of VIT in cMCD patients was slightly reduced than controls. Severe ARs were rare. The elevated IgG4 levels may be a biomarker for efficacy of VIT in cMCD patients, as it correlates with protection from re-stings.

Peanut oral immunotherapy (pOIT) has showed good short term outcomes, but allergic reactions may prevent effective up-dosing and is a major cause of stopping OIT. In placebo-controlled trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut.

We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD-sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab.

This is the 2nd part of a one-armed open phase-2 study where peanut allergic adolescents (n=23) started pOIT after an individualized omalizumab-treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step-wise withdrawal of omalizumab, based on clinical symptoms and CD-sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD-sens and allergen binding activity (ABA) and IgE-ab, IgG-ab and IgG4-ab to peanut and its components were measured during the study.

All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE-ab to peanut components Ara h 1-3 and CD-sens to peanut were significantly lower among successfully treated patients and IgG4-ab to peanut, Ara h 2 and 6 increased significantly more during treatment.

This study indicates that Omalizumab is an effective adjunctive therapy for initiation and rapid up-dosing of pOIT, however adverse events from pOIT become more frequent as omalizumab doses are decreased.

Asthma is a heterogeneous chronic syndrome which represents a relevant socioeconomic burden in both adults and children. Global asthma prevalence has been reported to be of approximately 300 million people, with an estimate of increasing figures up to 400 million by 20251 . Among the identified distinct phenotypes and endotypes2 , allergic asthma represents one of the most well-characterized and relevant nosologic entity, with atopy playing a key role in the disease risk, onset and progression.

Allergen-specific immunotherapy (AIT) is a potent and precise immune tolerance-inducing treatment towards specific proteins. AIT is a successful, but long-term treatment and therefore it is very demanding for the patients. Moreover, there are patients who do not respond to this therapy and others who develop allergic symptoms after initial success of the treatment. Therefore, novel approaches are urgently needed to potentiate its efficacy (i.e. new adjuvants), uncover unknown biological mechanisms, as well as discover the biomarkers of effective clinical response to AIT. If we do not fulfil these goals, we might face the deceleration of AIT development and significant decrease of its availability for the patients.

Allergic rhinitis is caused by sensitivity to environmental allergens that can significantly impact quality of life. The objective of this analysis was to estimate health state utilities and quality-adjusted life days (QALDs) for a tree allergy immunotherapy trial, TT-04 (EudraCT No.2015-004821-15). Health-state utilities are a measure of patient preference for health states and are necessary to derive QALDs for cost-utility analysis. Preference-based utilities were not collected in the TT-04 trial, so a mapping algorithm was developed based on a similar grass allergy immunotherapy trial, GT-08 (EudraCT No. 2004-000083-27) to estimate utilities.

A two-part model was developed to predict utilities for the GT-08 trial and applied to the TT-04 trial to estimate the difference in mean utility and QALDs between SQ® tree sublingual immunotherapy (SLIT)-tablet and placebo.

Mean utility difference between SQ® tree SLIT-tablet and placebo was 0.030 [95% CI 0.015-0.046] during the birch pollen season (BPS), 0.019 [95% CI 0.007-0.030] during the tree pollen season (TPS) and 0.018 [95% CI 0.007-0.030] during the full trial. The treatment showed a QALD benefit of 1.26 [95% CI 0.619-1.917] during the BPS, 1.90 [95% CI 0.692-3.047] during the TPS, and 2.47 [95% CI 0.930-4.101] during the full trial.

The generalizability of this algorithm is limited to allergy trials containing the same covariates as those present in the model. The analysis also assumes that grass and tree pollen allergy have the same relationship with EQ5D utilities, which is supported by the fact that both grass and tree pollen induce similar symptoms.

Application of the mapping function enabled the calculation of QALDs associated with the treatment, with the caveat that data were extrapolated from grass seasonal allergy to tree seasonal allergy. The results showed a significant QALD benefit of the treatment over placebo in treatment of tree pollen-induced rhinoconjunctivitis.

To explore the efficacy and safety of sublingual house dust mite (HDM) drops in children with mono- or polysensitized allergic rhinitis.

We conducted a retrospective cohort study of 65 children with monosensitized AR and 118 children with polysensitized AR who were scheduled for sublingual administration of HDM drops from January 2015 to June 2016. Interleukin (IL)-2, IL-4, and IL-17α, transforming growth factor-β1 (TGF-β1), specific immunoglobulin E (IgE), and specific IgG4 were detected by ELISA. The efficacies were assessed using symptoms score and medication score. All the outcomes were measured 1 month before the study and 1 month after the end of the 2-year treatment.

The total nasal symptoms score (TNSS) decreased significantly from 11.27 (9.81 ± 12.73) at baseline to 3.48(1.98 ± 4.98) at the end of sublingual treatment for the monosensitized AP group (t = 30.00, P < 0.01), and from 11.54(10.04 ± 13.04) to 3.56 (2.00 ± 5.16) for the polysensitized AR group (t = 40.05, P < 0.01), respectively. IL-2 and TGF-β1 increased significantly after treatment in contrast with before treatment in both the monosensitized group and the polysensitized group (both P < 0.01). In contrast, IL-4 and IL-17α decreased significantly after treatment compared with the baseline in both groups (both P < 0.01). Sublingual HDM drops were generally safe and well tolerant in both groups.

This study confirmed the efficacy and safety of sublingual AIT in both monosensitized and polysensitized AR patients (Chinese children).

Several studies have demonstrated the efficacy of house dust mite (HDM) immunotherapy in allergic rhinitis (AR). We aimed to compare the efficacy and safety of 2 commercial HDM extracts in a Chinese AR population.

This was an open-label study. HDM-associated AR patients were randomized into Dermatophagoides pteronyssinus (Dp) extracts (Alutard SQ; ALK, Hørsholm, Denmark) and Dp/Dermatophagoides farinae (Df) extracts (NovoHelisen Depot [NHD]; Allergopharma, Reinbek, Germany) groups. All patients received subcutaneous injections for 1 year, and were followed every 3 months during that 1-year period. Symptom score, medication score, and adverse reactions were recorded. The primary endpoint was the total combined symptom and medication score (CSMS) during the efficacy evaluation period. Blood samples were taken for specific immunoglobulin E (IgE), IgG4, and IgE-blocking factor tests at baseline and after the 1-year treatment.

A total of 230 AR patients were randomized; 29 patients dropped out. Analysis of the primary endpoint demonstrated significant reductions in CSMS of 1.8 vs 3.1 (p < 0.001) in the Alutard group and 1.8 vs 3.3 (p 0.05). The treatment was well tolerated in both groups; 17 (14.8%) patients experienced systemic reactions (SRs) in the Alutard group and 13 (11.3%) in the NHD group. The rates of SRs showed no difference in the 2 groups (p > 0.05), and no anaphylaxis occurred. IgG4 and IgE-blocking factor to Dp and Df were increased significantly in both groups after the 1-year treatment.

Our study confirmed the equal efficacy and safety profile of both commercial extracts in HDM-associated AR patients.

Although the precise mechanisms underlying the efficacy of allergen-specific immunotherapy (AIT) are not clear, some evidence suggests that this may be linked to polymorphisms in HLA-II gene. We aimed to investigate the correlation between HLA-II gene polymorphisms and house dust mite (HDM)-specific immunotherapy efficacy, and evaluate specific polymorphisms as potential biomarkers in allergic rhinitis (AR) patients who would benefit most from AIT.

Fifty-one Han Chinese patients with AR receiving HDM AIT were recruited. Genomic DNA was extracted from venous blood samples and genotyped for HLA-DRB1 and HAL-DQB1 alleles using the polymerase chain reaction sequence-based genotyping method. Nasal and eye symptoms were investigated based on visual analogue scale and rhinoconjunctivitis quality of life.

Allele DRB1*04:06; DRB1*14:05 showed a positive correlation with improvements in nasal blockage, nasal itching, eye itching, and activities. Similarly, DQB1*03:02:01; DQB1*05:03: 01 was positively correlated with improvements in nose blocking, nasal itching, eye itching, behavioral problems, and nasal symptoms scores; and DRB1*03:01; DRB1*04:06 positively correlated with nasal symptoms scores. In contrast, DRB1*07:01:01; DRB1*11:01 was negatively correlated with non-pollen symptoms, behavioral problems, and nasal symptoms.

HLA-DRB1 and HLA-DQB1 gene polymorphism are associated with AIT efficacy in HDM-sensitive Chinese patients with AR, of which DRB1*03:01; DRB1*04:06 and DQB1*03:02:01; DQB1*05:03:01 may be useful biomarkers of AR patient candidacy for effective AIT.

Chronic rhinitis is a very common disease that can be divided in various phenotypes. Historically, the condition has been classified into the allergic rhinitis (AR) and non-allergic non-infectious rhinitis (NAR) forms, based on the results of the classical biomarkers of atopy: skin prick test and serum allergen-specific IgE However, this classification does not reflect the complexity of the rhinitis syndrome, as illustrated by the existence of non-atopic rhinitis patients who display a nasal reactivity to environmental allergens. This new phenotype has been termed local allergic rhinitis (LAR) and can be only recognized if an additional test such as the nasal allergen challenge (NAC) is integrated in the diagnostic algorithm for chronic rhinitis. Recent data shows that the NAC is a very safe and reliable technique ready for the clinical practice. LAR is a differentiated rhinitis phenotype which often commences during childhood and quickly progresses towards a clinical worsening and the association of comorbidities in other mucosal organs. Recent evidence supports the existence of a bronchial counterpart of LAR (local allergic asthma), which highlights the pathophysiological links between the upper and lower airways and reinforces the united airways concept. Importantly, several controlled studies have demonstrated the ability of allergen immunotherapy to control LAR symptoms while the therapy is being administered. This review emphasizes the need to implement the NAC in the clinical practice in order to facilitate the recognition of LAR patients, allowing for an early prescription of specific therapies with disease-modifying potential.

Guidelines on insect sting allergy and venom immunotherapy (VIT) have been updated. This review describes the evolution of these guidelines and their similarities and differences.

The US and European guidelines show the evolution of guideline development in the grading of recommendations and the transparency of the evaluation of evidence. The US and European guidelines on VIT are similar in most areas and complimentary in others. The European guidelines are limited to VIT and are based on a published systematic review; the US practice parameters cover all areas of the diagnosis and management of insect sting allergy and do not use the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. There is general agreement that both children and adults with cutaneous systemic reactions do not require VIT, and that there is minimal risk associated with β-blockers and angiotensin-converting enzyme inhibitors during VIT. There are minor differences in the details of VIT dose, regimen, and choice of venom, but agreement on the duration and risk factors for relapse after VIT. The US and European guidelines are complementary in their discussion of the relation of mastocystosis and insect sting anaphylaxis and the value of measuring basal serum tryptase.

The updated guidelines on insect sting allergy from the US and European groups differ in scope, with a somewhat different focus in specific areas but are complementary overall. Where they overlap, there are relatively few differences in recommendations, and these are subtle. The US practice parameter offers an annotated algorithm for the evaluation and treatment of patients with reactions to insect stings.