Allergic conjunctivitis (AC) is a common chronic condition, especially in children. Ocular symptoms are often overlooked during treatment of allergic rhinoconjunctivitis (ARC). Pediatric ARC can be effectively treated using sublingual immunotherapy (SLIT), which is a guideline-recommended safe treatment approach. However, the therapeutic efficacy of SLIT in terms of ameliorating eye symptoms has not been effectively evaluated.

We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the use of SLIT for infants, children, and adolescents (aged from 3 to 18 years) with AC or ARC. We searched the Cochrane Library database, EMBASE, and Medline from November 1990 to 2017 to find papers dealing with the effects of SLIT on pediatric AC or ARC. We used standardized mean differences (SMDs) to assess therapeutic effects, employing a random effects model. Subgroup and sensitivity analyses were also conducted. The I2 metric was used to evaluate heterogeneity

In total, 13 clinical RCTs were included in our meta-analysis. SLIT reduced ocular symptoms to a level below that of controls (SMD = -0.21; 95% confidence interval [CI], -0.41 to -0.01; p = 0.04; I2 = 55%). Notably, on subgroup analysis, SLIT clearly reduced pollen-induced pediatric AC (SMD = -0.36; 95% CI, -0.53 to -0.19; p < 0.0001; I2 = 25%) but not mite-induced AC (SMD = 0.20; 95% CI, -0.20 to 0.60; p = 0.34; I2 = 46%).

SLIT relieved ocular symptoms in children with ARC or AC. To confirm these results, future meta-analyses should evaluate high-quality, large-scale population-based trials.

In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods.

We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT.

The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5kU/l. A doubleblind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26g and 0.55g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045kU/l differentiated those patients that tolerated cooked egg white.

OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045kU/l differentiates those patients that tolerate cooked egg white.

Allergy immunotherapy (AIT) is a treatment option for respiratory allergy that is complementary to pharmacotherapy, with a distinct mechanism of action. Alternative methods to subcutaneous administration of AIT that enable patients to safely self-administer AIT is considered an unmet clinical need. The sublingual immunotherapy tablet (SLIT-tablet) is an orally disintegrating pharmaceutical formulation (oral lyophilisate) containing standardized allergens. SLIT-tablets have been developed for sublingual immunotherapy (SLIT) of cedar-pollen, grass-pollen, ragweed-pollen, tree-pollen, and house dust mite allergies. It is a once-daily tablet treatment to be self-administered after the first dose has been provided under the supervision of a physician with experience in the diagnosis and treatment of allergic diseases. Once the first dose is adequately tolerated, subsequent doses may be self-administered. SLIT-tablets have proven efficacy for allergic rhinitis (AR) with and without conjunctivitis (C) and allergic asthma (AA) in adults, children, and polysensitized allergic patients. Meta-analyses indicate that SLIT-tablets have superior or similar efficacy compared with anti-allergic pharmacotherapies for seasonal AR and superior efficacy for perennial AR. SLIT-tablets have also demonstrated clinically relevant improvements of asthma, with significant reductions in the following: daily inhaled corticosteroid use, risk of asthma exacerbations, and asthma symptoms. SLIT-tablets are generally well tolerated, with a low risk of systemic allergic reactions. The most common treatment-related adverse events are mild-moderate oral reactions. Current evidence supports SLIT-tablets to be considered as an alternative or add-on treatment to pharmacotherapy for AR/C and asthma. Future SLIT developments may include early intervention to prevent the development or progression of allergic disease in children.

Ambrosia artemisiifolia, also known as common or short ragweed, is an invasive annual flowering herbaceous plant that has its origin in North America. Nowadays, ragweed can be found in many areas worldwide. Ragweed pollen is known for its high potential to cause type I allergic reactions in late summer and autumn and represents a major health problem in America and several countries in Europe. Climate change and urbanization, as well as long distance transport capacity, enhance the spread of ragweed pollen. Therefore ragweed is becoming domestic in non-invaded areas which in turn will increase the sensitization rate. So far 11 ragweed allergens have been described and, according to IgE reactivity, Amb a 1 and Amb a 11 seem to be major allergens. Sensitization rates of the other allergens vary between 10 and 50%. Most of the allergens have already been recombinantly produced, but most of them have not been characterized regarding their allergenic activity, therefore no conclusion on the clinical relevance of all the allergens can be made, which is important and necessary for an accurate diagnosis. Pharmacotherapy is the most common treatment for ragweed pollen allergy but fails to impact on the course of allergy. Allergen-specific immunotherapy (AIT) is the only causative and disease-modifying treatment of allergy with long-lasting effects, but currently it is based on the administration of ragweed pollen extract or Amb a 1 only. In order to improve ragweed pollen AIT, new strategies are required with higher efficacy and safety.

Allergen-specific immunotherapy for house dust mite allergy is effective, but there are no validated biomarkers reflecting or predicting the clinical efficacy. We aimed to investigate the relationship between clinical outcomes and functional responses of allergen-specific IgG4 (sIgG4) and specific IgE (sIgE) during Dermatophagoides pteronyssinus s.c. allergen immunotherapy (SCIT) in allergic rhinitis and/or asthma patients. Combined symptom medication scores (SMS), D. pteronyssinus-sIgG4 levels, D. pteronyssinus-sIgE levels, and the serum inhibitory capacity against D. pteronyssinus-sIgE facilitated allergen binding to B cells (IgE-FAB) were determined during the updosing (week 0, 4, 12, and 16) and maintenance (week 52, 104, and 156) phase of SCIT. We found that SCIT patients had a significant improvement in SMS from week 52 to 156 compared with medication-treated control subjects (p < 0.05). Levels of D. pteronyssinus-sIgG4 in SCIT patients showed a significant increase from week 12 to 156 (p < 0.05). Serum obtained from SCIT patients significantly inhibited D. pteronyssinus-sIgE binding to B cells after 16 wk (p < 0.01). Significantly lower levels of D. pteronyssinus-sIgE were observed in SCIT patients after 52 wk (p < 0.05). A significant relationship was demonstrated between SMS and IgE-FAB or D. pteronyssinus-sIgG4 during the maintenance phase according to linear regression analysis. In conclusion, D. pteronyssinus-sIgG4 level and D. pteronyssinus IgE-FAB are associated with clinical efficacy in the maintenance phase rather than the updosing phase of SCIT. Immunologic tolerance can be induced with SCIT when maintenance phase is achieved.

Timothy grass pollen allergen extract tablets (Grastek) are standardized sublingual immunotherapy tablets (SLIT-T) approved for the treatment of grass pollen-induced allergic rhinitis (AR) and conjunctivitis. Many grass allergic patients are also cosensitized to birch pollen. Whether Timothy grass SLIT-T can confer symptomatic benefits for birch pollen-induced AR symptoms is unknown.

To evaluate the treatment effect of Timothy grass SLIT-T for birch pollen-induced AR in participants sensitized to both grass and birch pollen using an environmental exposure unit (EEU).

This study was a phase 4, randomized, double-blind, placebo-controlled, parallel-group study that enrolled participants aged 18 to 65 years allergic to both timothy grass and birch pollen. After a baseline EEU birch pollen challenge, in which a minimum total nasal symptom score (TNSS) of 6 of 12 was required for enrollment, participants were randomized to receive Timothy grass SLIT-T or placebo taken once daily for 4 months. No confirmatory grass pollen challenge was performed. The primary end point was the change in TNSS averaged from assessments from hours 2 to 5 during the post treatment birch pollen challenge compared with baseline. The secondary and exploratory end points included temporally identical changes in total ocular symptom score (TOSS), total rhinoconjunctivitis symptom score (TRSS), and individual symptom scores.

The difference in TNSS reduction after 4 months of therapy between the Timothy grass SLIT-T and placebo group was not significant (P = .83). Reductions in TOSS (P = .19) and TRSS (P = .67) were also comparable between groups. Findings between groups for individual symptom scores were similar (all P > .40), except for watery eyes, in which symptom reduction was slightly better in the placebo arm (P = .01). Timothy grass SLIT-T was well tolerated, and no serious adverse effects occurred.

A bystander effect of grass SLIT-T on birch pollen-induced AR symptoms was not detected. Symptomatic benefits of grass SLIT-T are likely allergen specific.

The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed two phase II studies to determine its optimal cumulative dose.

The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction of Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modelling analysis was used to test for the dose-response, shape of the curve, and estimation of the median effective dose (ED50 ), a measure of potency.

Statistically significant dose-responses (p<0.01 & 0.001) were seen respectively. The highest cumulative dose in PQBirch204 (27300 standardised units [SU]) approached a plateau. Potency of the PQ Birch was demonstrated by an ED50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups.

Increasing the cumulative dose of PQ Birch 5.5-fold from 5100 to 27300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase of efficacy of 50%, without compromising safety. The cumulative dose-response was confirmed to be curvilinear in shape.

With rising prevalence of food allergy (FA), allergen-specific immunotherapy (AIT) for FA has become an active area of research in recent years. In AIT, incrementally increasing doses of inciting allergen are given with the goal to increase tolerance, initially through desensitization, which relies on regular exposure to allergen. With prolonged therapy in some subjects, AIT may induce sustained unresponsiveness, in which tolerance is retained after a period of allergen avoidance. Methods of AIT currently under study in humans include oral, sublingual, epicutaneous, and subcutaneous delivery of modified allergenic protein, as well as via DNA-based vaccines encoding allergen with lysosomal-associated membrane protein I. The balance of safety and efficacy varies by type of AIT, as well as by targeted allergen. Age, degree of sensitization, and other comorbidities may affect this balance within an individual patient. More recently, AIT with modified proteins or combined with immunomodulatory therapies has shown promise in making AIT safer and/or more effective. Though methods of AIT are neither currently advised by experts (oral immunotherapy [OIT]) nor widely available, AIT is likely to become a part of recommended management of FA in the coming years. Here, we review and compare methods of AIT currently under study in humans to prepare the practitioner for an exciting new phase in the care of food allergic patients in which improved tolerance to inciting foods will be a real possibility.

Allergic conjunctivitis (AC) is a common chronic condition, especially in children. Ocular symptoms are often overlooked during treatment of allergic rhinoconjunctivitis (ARC). Pediatric ARC can be effectively treated using sublingual immunotherapy (SLIT), which is a guideline-recommended safe treatment approach. However, the therapeutic efficacy of SLIT in terms of ameliorating eye symptoms has not been effectively evaluated.

We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the use of SLIT for infants, children, and adolescents (aged from 3 to 18 years) with AC or ARC. We searched the Cochrane Library database, EMBASE, and Medline from November 1990 to 2017 to find papers dealing with the effects of SLIT on pediatric AC or ARC. We used standardized mean differences (SMDs) to assess therapeutic effects, employing a random effects model. Subgroup and sensitivity analyses were also conducted. The I2 metric was used to evaluate heterogeneity.

In total, 13 clinical RCTs were included in our meta-analysis. SLIT reduced ocular symptoms to a level below that of controls (SMD = -0.21; 95% confidence interval [CI], -0.41 to -0.01; p = 0.04; I2 = 55%). Notably, on subgroup analysis, SLIT clearly reduced pollen-induced pediatric AC (SMD = -0.36; 95% CI, -0.53 to -0.19; p < 0.0001; I2 = 25%) but not mite-induced AC (SMD = 0.20; 95% CI, -0.20 to 0.60; p = 0.34; I2 = 46%).

SLIT relieved ocular symptoms in children with ARC or AC. To confirm these results, future meta-analyses should evaluate high-quality, large-scale population-based trials.

Life-threatening anaphylactic shock is a rare (1 in 1 million) but documented occurrence in response to subcutaneous immunotherapy. Immediate administration of Epinephrine (Epi) is critical to save lives in these situations. The current protocol for systemic reactions in immunotherapy is for the prescribing physician to reassess the dosing and schedule as well as the risk: benefit assessment for the therapy and determine whether or not to proceed.

The patient revealed concerns regarding the neurologic sequela sustained after undergoinig life-threatening anaphylactic shock.

The patient was diagnosed with anaphylactic shock and treated appropriately.

The patient experienced shortness of breath and was promptly administered 2 shots of 0.3mg Epi followed by a loss of consciousness (LOC) and a series of 4 consecutive seizures accompanied with LOC and urinary incontinence. Seizures as a manifestation of anaphylaxis are rare with 1 study claiming 13% of cases of anaphylaxis having LOC and only 1.5% cases with loss of bladder or bowel control.

This case is one of continued subcutaneous immunotherapy after the patient had an initial systemic reaction suspicious for anaphylaxis 6 months before the life-threatening anaphylaxis, both induced by immunotherapy. In both instances, there was a significant amount of neurologic involvement. Neurologic sequela included a transient tremor and permanent deficits in vision, fine motor coordination evidenced by a change in handwriting.

The current protocol was followed in this patient but still ended up almost ending her life. This protocol seems to be inadequate with regards to potential fatality. Even though a very small number, some patients face life-threatening adverse effects after apparently very low-risk immunotherapies. Therefore, reevaluating the treatment protocol with addition of a longer post-shot observation step and discontinuing treatment in the case of adverse events may help minimize the overall risk of any fatal outcome.