Drug-induced anaphylaxis—elicitors, mechanisms and diagnosis

Abstract

Drugs are one of the major causes of anaphylaxis. For example 2346 cases of drug-induced anaphylaxis were reported to the anaphylaxis register as of March 2019. The most common triggers of drug-induced anaphylaxis were nonsteroidal anti-inflammatory drugs (NSAIDs; n = 902) and antibiotics (n = 721). Drug-induced anaphylaxis can be caused by IgE-dependent (e.g., penicillins) and IgE-independent mechanisms. Recently MRG-PX2 has been identified as a receptor for non-IgE-dependent mechanisms. Drug-induced anaphylaxis results more frequently in lethal reactions and is more commonly associated with cardiovascular symptoms. Also therapy refractory anaphylaxis is more frequently triggered by drugs. For the diagnosis of drug-induced anaphylaxis current national and international guidelines should be followed including provocation tests to avoid future reactions.

What we learned from TAO – 10 years of German therapy allergen ordinance

Abstract

Purpose

The Therapy Allergen Ordinance (TAO) came into force in Germany in 2008 in order to ensure proven and tested quality, efficacy and safety of therapy allergens for the treatment of allergies to frequent allergen sources (birch, alder, hazel, sweet grasses (without maize), bee-, yellow jacket-venom). It excludes exemptions from marketing authorizations (MA) for AIT-products containing these allergens. Due to the particular nature of the therapeutic allergens, rather long transitional periods are legally defined to resolve deficient clinical data. The aim was to analyze the status quo of AIT products developed according to TAO.

Methods

Quality data and clinical trials of AIT products subjected to TAO (obtained until 2019) were analyzed and findings were clustered.

Results

The first two AIT products (for tree-pollen allergy) received a national MA in 2018. Of the 123 initial MA applications submitted, 65 are still active (26 for grass-, 17 for tree-, 5 for grass-/tree-pollen-mix and 17 for house dust mite allergy). Quality issues frequently identified were: Lack of comparability of the drug due to extensive changes in the manufacturing process, insufficient/missing stability data or process validation, insufficiently validated analytical methods, unsuitable in-house reference preparations, inadequate specifications and/or in-process controls. Dose-finding and phase III studies are required for MA. Doses of best benefit/risk balance were recommended for phase III studies. PEI takes measures to ensure that products of presumptive lacking efficacy based on study results do not gain access to the market.

Conclusions

In Germany, TAO ensures that all previously untested named patient products for the treatment of frequent allergies are subjected to an assessment of their risk/benefit ratio according to the current state of science.

Severe skin reactions: clinical picture, epidemiology, etiology, pathogenesis, and treatment

Abstract

Background

Severe skin reactions, mostly following medication use, are rare and can be associated with high mortality. A suitable treatment approach that is able to reduce mortality is needed.

Methods

Recent publications on this topic were reviewed and evaluated.

Results

In the case of the self-limiting diseases acute generalized exanthematous pustulosis (AGEP) and generalized bullous fixed drug eruption (GBFDE), there is no clear indication for systemic immunomodulating treatment, and supportive care remains the gold standard. The situation is less clear in the case of drug reaction with eosinophilia and systemic symptoms (DRESS); nevertheless, primarily in the case of severe organ involvement, systemic glucocorticosteroids are recommended. This is associated with complications and often also with virus reactivation, which may delay healing. The evidence on various immunomodulating therapies in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is controversial. Recent publications favor steroid pulse treatment, the tumor necrosis factor (TNF)-α inhibitor etanercept, as well as the calcineurin inhibitor cyclosporine A, with the latter representing the most promising approach.

Conclusion

The rarity and unpredictability of the reactions make a randomized double-blind therapeutic trial extremely difficult. Using meta-analyses, it is possible to trace a trend in the use of systemic treatment options. Supportive care remains the most important treatment strategy for all clinical entities.

Correction to: Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics

Correction to:

Allergo J Int 2019

https://doi.org/10.1007/s40629-019-0100-8

In the “Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics” Figs. 5 and 6 (allergy passports) are in German. Here you will find the allergy passports in …

Ash pollen allergy and aerobiology

Abstract

Background

Allergy to ash pollen is common in some parts of Europe. Sensitization is overlooked if Oleaceae pollen allergens are not included in screening tests.

Methods

Between 1983 and 2007, sensitization to aeroallergens was systematically investigated using serological methods in 15-year-old school children (Immuno-CAP [carrier polymer] test). Samples from 1986 and 2006 were also tested using the immuno-solid-phase allergen chip (ISAC) assay. School children with sensitizations in 1986 were retested in 2010. Airborne pollen concentrations were determined by the Swiss pollen measuring network.

Results

Sensitization (>0.7 kU/l) to ash pollen (Fraxinus americana t15)—16.3% (102/627)—was more frequent than to birch pollen (Betula verrucosa t3): 15.3% (96/627). ISAC assays performed in children in 1986 and 2006 revealed higher molecular seroprevalence for nOle e 1 (15%; 15/100) compared to rBet v 1 (12%; 12/100). Followed-up subjects (age, 39) showed an increase in sensitizations to ash pollen. IgE levels to pollen from indigenous ash (Fraxinus excelsior t25) were higher than to pollen from American ash (Fraxinus americana t15). Low ash pollen emission levels were recorded at all measuring sites in Switzerland every 2–4 years. The infection of ashes by Chalara fraxinea resulted in increased emission of ash pollen.

Conclusion

Symptoms in individuals sensitized to ash pollen vary according to the pollen count and may be masked by pollen from other trees that flower at the same time of year. Sensitization to ash/Ole e 1 can be higher than to birch/Bet v 1. The determination of IgE to common ash (Fraxinus excelsior) is more sensitive than to American ash (Fraxinus americana). Ash dieback due to Chalara appears to increase pollen emission. Allergies to ash pollen can be significantly underestimated due to a failure to (correctly) identify them; they can also be masked by other pollen families (birch). Harmful organisms such as Chalara can intensify pollen emissions at least temporarily.

Atopic eczema score of emotional consequences—a questionnaire to assess emotional consequences of atopic eczema

Abstract

Purpose

Atopic eczema (AE, atopic dermatitis), one of the most common chronic skin diseases worldwide, can dramatically influence the lives of affected patients as well as the lives of their families. Despite the availability of several questionnaires for assessing the impairment of quality of life, so far the emotional consequences of AE have received limited attention. The purpose therefore was to develop an instrument to assess the emotional consequences of AE in affected adults.

Methods

The Atopic Eczema Score of Emotional Consequences (AESEC) was developed based on a review of available instruments and by consulting individuals with AE about the emotional consequences of AE through social media. Validation was performed in a test-sample, followed by a large cross-sectional study in patients with AE across nine European countries. AESEC results were compared with the Patient Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI) and the Hospital Anxiety and Depression Scale (HADS).

Results

A 28-item questionnaire on emotional consequences of having AE was developed. Applied to 1189 participants, AESEC showed high reliability and correlated well with DLQI, HADS and POEM. More than half (57%) of the respondents were emotionally burdened. Large to very large emotional consequences were reported by 43.8% of those with currently moderate AE, 62.2% with severe AE and 66.7% with very severe AE-symptoms.

Conclusion

AESEC is a questionnaire for assessing the emotional consequences of living with AE. It may prove useful in evaluating the burden of disease, beyond skin symptoms and time-specific quality of life.

Effectiveness of a portable air filtration device in reducing allergen exposure during household chores

Abstract

Background

Exposure to airborne allergens is an important risk factor for sensitization, allergic rhinitis and asthma. The aim of this study is to verify whether the use of an air filtration device, called “air purifier” (AP) is able to reduce indoor allergen exposure.

Methods

In three rooms of one household with pets (a cat and a dog), inhalable dust was sampled with transportable pumps for 1–2 h during typical household chores on 15 days—either in the morning without the AP or in the afternoon using an AP. In addition to sampling inhalable dust both with a stationary and a personally carried pump with Teflon filters, nasal filters were used. Inhalable dust on the Teflon filters was quantified gravimetrically, and allergen content was measured on all filters (n = 90) using fluorescence enzyme immunoassays for domestic mites (DM), the cat allergen Fel d 1, and the dog allergen Can f 1.

Results

The use of the AP significantly reduced inhalable dust in both personal and stationary samples by 40 or 20%, respectively. In most cases, allergen exposure was also reduced; the median allergen concentrations in the air were up to 60% lower with the AP than without. Allergen exposure varied greatly, and with the exception of Can f 1 sampled with the personally carried pump, and DM allergens in the nasal samples, there was no significant difference with or without an AP.

Discussion

Typical household chores can result in high levels of exposure to indoor dust and allergens. The use of an AP however can reduce the inhalable dust concentrations, but the effect on allergen exposure was in most cases not large enough to achieve statistical significance.

ARIA guideline 2019: treatment of allergic rhinitis in the German health system

Abstract

Background

The number of patients affected by allergies is increasing worldwide. The resulting allergic diseases are leading to significant costs for health care and social systems. Integrated care pathways are needed to enable comprehensive care within the national health systems. The ARIA (Allergic Rhinitis and its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases.

Methods

ARIA serves to improve the care of patients with allergies and chronic respiratory diseases. In collaboration with other international initiatives, national associations and patient organizations in the field of allergies and respiratory diseases, real-life integrated care pathways have been developed for a digitally assisted, integrative, individualized treatment of allergic rhinitis (AR) with comorbid asthma. In the present work, these integrated care pathways have been adapted to the German situation and health system.

Results

The present ICP (integrated care pathways) guideline covers key areas of the care of AR patients with and without asthma. It includes the views of patients and other healthcare providers.

Discussion

A comprehensive ICP guideline can reflect real-life care better than traditional guideline models.

Characterization of a cohort of storage mite sensitized subjects

Abstract

Purpose

Storage mites (SM) are ubiquitously found close to human habitation and are a source of allergic reactions ranging from allergic rhinitis and asthma to anaphylactic reactions.

Methods

Data on 3997 patients with suspected allergic rhinitis were included. We performed correlation of intradermal testing and specific IgE-test results using Cohen’s kappa and univariate logistic regression to evaluate the probability of symptoms and the point of time symptoms were reported. In some patients nasal provocation was performed to prove allergic rhinitis.

Results

Patients with storage mite sensitization show a high degree of cross reactivity between different storage mite species. Cross reactivity of storage mite species with house dust mites (HDM) was found in 56% and is only slightly higher than that of other common allergens such as grasses (45%) or birch (42%). A correlation of intradermal testing and specific IgE testing could not be found. The most common symptoms of sensitized subjects were nasal obstruction and hyposmia and symptoms were dependent on presence of chronic sinusitis. Nasal provocation was positive in 16 to 33% of subjects tested.

Conclusions

SM are a common sensitization in the study population and should be included in standard skin prick test arrays. Cross sensitization to house dust mites is limited and nasal symptoms are most frequent. Nasal provocation testing is necessary to secure clinical diagnosis of allergy and further research is needed to evaluate the clinical relevance of the high sensitization rates found for intradermal testing.