Allergen-specific immunotherapy

Allergen-specific immunotherapy remains the only causal treatment of allergic disease to date. Its efficacy in symptom reduction was demonstrated in double blind, placebo-controlled studies of allergic rhinoconjunctivitis, allergic asthma, and Hymenoptera venom hypersensitivity, including long-term effects after discontinuation of treatment. In addition, immunotherapy decreases the risk of developing new sensitisations to aeroallergens in monosensitised patients and allergic asthma in patients with mere allergic rhinitis. The mechanism of immunotherapy entails redirection of the T lymphocyte response from a T helper cell Type 2 phenotype in favour of induction of regulatory T cells and/or immune deviation toward a T helper cell Type 1 phenotype, with resulting inhibition of downstream effector pathways and induction of immunoglobulin G-associated blocking antibodies. Two main application forms are used in clinical practice: subcutaneous immunotherapy and sublingual immunotherapy. The advantage of subcutaneous immunotherapy is its proven efficacy over a broad range of indications. Disadvantages are systemic allergic reactions and inconvenience for the patient due to frequent doctor visits. Sublingual immunotherapy has been shown to result in less systemic allergic reactions and may be more convenient due to home application; however, efficacy has only been proven for allergic rhinitis. For clinicians, the adherence to practice guidelines and thorough knowledge of allergen products, application routes, indications, immunomodulatory mechanisms, efficacy, safety, and cost-effectiveness is important for successful treatment and will be addressed in this review article

Structured diagnostic assessment of hand eczema in cleaning workers

Hand dermatitis is a widespread problem among cleaners. In most cases, it is caused by a combination of wet work and contact with irritants, which can result in irritant (toxic) contact dermatitis. In some cases, the irritant contact eczema then evolves into allergic contact dermatitis, although not all cases of allergic contact dermatitis are preceded by irritant contact dermatitis. This mini-review proposes a two-step diagnostic algorithm based on patch testing, which can be used if allergic contact dermatitis is suspected in cleaning workers. As a first step, we recommend performing the DKG standard series (German Contact allergy research group, DKG), the DKG rubber series, both DKG "further fragrances" series as well as the DKG preservative and disinfectant series. If there are clear hints of an occupational contact dermatitis, the first step can also involve testing patients' own products alongside the standardized tests. In a second step (at the latest), if standardized tests do not suffice to identify the culprit allergen and there is well-founded suspicion, we recommend testing the patients' own products. If necessary, the second step can also include testing the individual contact allergens contained in the screening mixes that are part of the standard series

Contact dermatitis to hair cosmetics: current diagnostic recommendations

Hair cosmetics such as shampoos, hair dyes, bleaching agents or hair straightening creams contain frequent contact allergens. These can lead to allergic contact dermatitis especially in hairdressers, but also in their customers and in others who use hair products at home. While hairdressers suffer mainly from hand dermatitis, in customers and home-users, dermatitis primarily affects the head, neck and face. In this mini-review, we propose a diagnostic algorithm in two steps, based on patch testing, that can be used for the assessment of suspected hair product-induced contact dermatitis. In a first step, we recommend testing the German Contact Allergy Group (DKG) standard series, DKG ointment series, DKG preservative series, DKG hairdresser series, DKG fragrance series as well as (especially in hairdressers) the DKG rubber series. In a second step, if the culprit allergen cannot be identified with the help of the standardized test series and there is a well-founded suspicion, testing the patient's own products, such as shampoos, hair sprays and hair dyes, is recommended

Management of hypersensitivity reactions to nondextran iron products: new insights into predisposing risk factors

Hypersensitivity reactions (HSRs) to nondextran iron products (NDIPs) are rare, but can manifest with severe signs and symptoms. Predisposing risk factors are not well understood.; To characterize patients with HSRs to NDIPs, with a special focus on possible risk factors.; We analyzed clinical characteristics of patients with HSRs to NDIPs referred to our allergy division between 2007 and 2019 compared with tolerant controls, including the type of the eliciting NDIP, severity and characteristics of the HSR, atopy status, history of allergies and urticaria, laboratory and skin test results, and outcome of reexposure with NDIPs.; We evaluated the data of 59 patients and 21 controls. Sixteen patients and 4 controls received the NDIP iron sucrose and 41 patients and 15 controls received ferric carboxymaltose. In 2 patients and in 2 controls, the culprit NDIP was not known. Twenty-seven patients (46%) experienced an anaphylactic reaction grade I, 15 (25%) a grade II reaction, and 17 (29%) a grade III reaction according to Ring and Messmer. On analyzing the history, we found that 22 patients (37%) and 3 controls (14%) reported previous HSRs to other medications. Interestingly, more than half the patients (n = 35 [59%]) compared with only 7 controls (33%) reported an episode of any type of urticaria in their previous history. Most patients (n = 15 [79%]) tolerated reexposure of an NDIP using a low-reactogenic administration protocol.; A history of drug hypersensitivity and urticaria represent potential risk factors for HSRs to NDIPs. On the basis of our findings, we propose an algorithm for practical management of patients receiving NDIPs aiming to prevent HSRs

A meta-analysis on allergen-specific immunotherapy using MCT(R) (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis

Background The World Allergy Organization and the European Academy of Allergy and Clinical Immunology recommend to perform product-specific meta-analyses for allergen-specific immunotherapies because of the high degree of heterogeneity between individual products. This meta-analysis evaluates the efficacy and safety of Glutaraldehyde-modified and MCT(R) (MicroCrystalline Tyrosine)-adsorbed allergoids (MATA). Methods The databases MEDLINE, LILACS, embase, LIVIVO, Web of Science and Google (Scholar) were searched for publications on MATA up to June 2019. Primary endpoint was the combined symptom and medication score (CSMS). Secondary endpoints were single scores, immunogenicity and improvement of allergic condition. Secondary safety endpoints were the occurrence of side effects. A random effects model was applied with (standardized) mean differences ([S]MDs) including confidence intervals (CI). Heterogeneity was analyzed using the I-2 index and publication bias using Egger's test and Funnel plots. Subgroups were analyzed regarding age and asthma status. Results Eight randomized double-blind placebo-controlled trials were selected for efficacy and 43 publications for safety analysis. In total, 4531 patients were included in this analysis including eight studies containing data on children and adolescents. AIT with MATA significantly reduced allergic symptoms and medication use with a SMD for CSMS of -0.8 (CI: -1.24, -0.36) in comparison to placebo. Heterogeneity was moderate between the studies. The total symptom score (-1.2 [CI: -2.11, -0.29]) and the total medication score (-2.2 [CI: -3.65, -0.74]) were also significantly reduced after MATA treatment. Patient's condition improved significantly after treatment with MATA, with an odds ratio of 3.05 (CI: 1.90, 4.90) when compared to placebo. The proportion of patients, who developed side effects was 38% (CI: 19%, 57%). No serious side effects occurred. Safety in the subgroups of asthmatic patients, children and adolescents did not differ from the overall patient population. Conclusions This meta-analysis reveals a large body of evidence from publications investigating MATA. MATA significantly improved allergic symptoms and reduced the use of anti-allergic medication in comparison to placebo, with an excellent safety profile. Especially for children and asthmatic patients, the use of MATAs can be considered as safe, because the safety profiles in these groups did not differ from the total patient population

Predictors of increased daytime sleepiness in patients with chronic obstructive pulmonary disease: a cross-sectional study

Background; . Patients with Chronic Obstructive Pulmonary Disease (COPD) suffer from increased daytime sleepiness. The aim of this study was to identify potential predictors of subjective daytime sleepiness with special regard to sleep-related breathing disorder and nocturnal activity.; Methods; . COPD patients were recruited at the University Hospital Basel, Switzerland. COPD risk groups A-D were determined according to spirometry and COPD Assessment Test (CAT). Breathing disorder evaluation was performed with the ApneaLink device. Nocturnal energy expenditure was measured with the SenseWear Mini Armband. Subjective daytime sleepiness was recorded using the Epworth Sleepiness Scale (ESS).; Results; . Twenty-two patients (36%) were in COPD risk group A, 28 patients (45%) in risk group B, and 12 patients (19%) in risk groups C + D (; n; = 62). Eleven patients (18%) had a pathological ESS ≥ 10/24. ESS correlated positively with CAT (; r; = 0.386,; p; < 0.01) and inversely with age (; r; = -0.347,; p; < 0.01). In multiple linear regression age (; β; = -0.254,; p; < 0.05), AHI (; β; = 0.287,; p; < 0.05) and CAT score (; β; = 0.380,; p; < 0.01) were independent predictors of ESS, while nocturnal energy expenditure showed no significant association (; p; = 0.619).; Conclusion; . These findings provide evidence that daytime sleepiness in COPD patients may partly be attributable to nocturnal respiratory disturbances and it seems to mostly affect younger patients with more severe COPD symptoms

Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1– ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy