Allergo Journal International最新文献

First-line therapy for a severe allergic reaction (anaphylaxis) is the administration of adrenaline, which, in an emergency, can be self-administered intramuscularly (i.m.) via an adrenaline autoinjector (AAI). Despite the known risk of anaphylaxis, AAIs are often not prescribed, not carried, not used, or used with delay in an emergency. Possible reasons for this include logistical issues (e.g., size and portability of the AAI), difficulties in recognizing symptoms that require the use of an AAI, lack of familiarity with the AAI application, and general fear of injections. Recently, an adrenaline nasal spray (ANS) for intranasal application of adrenaline has been authorized and introduced in Germany. Pharmacokinetic studies for ANS development in comparison with the i.m. injection using an AAI or manual injection (syringe and needle) resulted in comparable profiles. The simple use and small size of the ANS, the needle-free design, and the improved storage conditions can help reduce barriers to adrenaline administration for patients and other users. This may lead to an earlier administration of adrenaline in anaphylaxis treatment.

Mastocytosis, a clonal mast cell disorder, is strongly associated with severe insect venom allergy. This review summarizes the pathophysiologic mechanisms linking mastocytosis and Hymenoptera venom anaphylaxis and discusses diagnostic and therapeutic strategies. Patients with mastocytosis are at markedly increased risk for sting-induced anaphylaxis, often presenting with cardiovascular collapse and minimal cutaneous signs. Clonal mast cell expansion, usually driven by KIT D816V, lowers the threshold for mediator release. Baseline tryptase is typically elevated, but normal levels do not exclude disease, as occult mastocytosis may still be present. Hereditary alpha-tryptasemia (HαT), a genetic trait causing elevated tryptase, further increases risk and may coexist with mastocytosis. The diagnostic work-up in patients with venom allergy should include serum tryptase, venom-specific IgE (with component-resolved diagnostics), and KIT mutation analysis in patients with severe reactions. Bone marrow biopsy is indicated if suspicion remains high. Detection of KIT D816V is an independent predictor of severe sting reactions. Venom immunotherapy (VIT) is highly effective and lifesaving but associated with more frequent systemic reactions in mastocytosis (> 20%). Omalizumab may improve VIT safety in high-risk cases. Given the high relapse risk, lifelong VIT is recommended, along with epinephrine autoinjectors and rigorous emergency preparedness. Personalized management including risk stratification by KIT and HαT status, optimized VIT protocols, adjunctive therapy, and patient education is essential. Mastocytosis and venom allergy form a unique clinical constellation requiring proactive diagnosis and individualized long-term management to prevent fatal reactions.

Hymenoptera venom extracts for allergen-specific immunotherapy (AIT) are marketed with the attributes “purified” or “highly purified” or “non-purified.” However, all manufacturing processes include purification steps and are subject to the same requirements of the European Pharmacopoeia. European and national guidelines confirm that “purified” and “non-purified” Hymenoptera venom AIT (VIT) do not differ in their effectiveness and frequency of systemic adverse events (AE). Differences in preserving natural venom composition appear more relevant. Hymenoptera venom AIT is considered the success model for AIT. Protection rates of close to 100% can be achieved for both bees and wasps. However, with several years of administration of aluminum, depot VIT is also considered a role model for iatrogenic aluminum exposure through long-term subcutaneous immunotherapy (SCIT). Its relevant iatrogenic contribution to the accumulation of aluminum in the body is now widely recognized. Considering patient preferences improves adherence, among others. “Our own” surveys conducted by the author, comparing product characteristics of SCIT preparations, indicate that patients prefer products without aluminum.

Background

A reliable diagnosis of hymenoptera venom allergy is based on medical history, skin tests, and serological immunoglobulin E (IgE) determination. Over the past 10 years, component-resolved diagnostics (CRD) have gained in importance, and new strategies for interpreting serological double sensitization have been introduced with the bee/vespula venom-specific IgE ratio.

Objectives

The aim was to examine whether the bee/vespula venom-specific IgE ratio supplemented by CRD can be a reliable alternative to skin testing.

Methods

In a student project, the guideline algorithm for serological diagnostics was supplemented with the sIgE ratio (≥ 5:1) and tested in a simulation using anonymized data from a retrospective study (Fischer et al.). A partial data set of 375 cases with complete CRD and documented prick and intradermal test results was selected for the simulation. The performance of the algorithm was evaluated by a post hoc comparison of the algorithmic therapy recommendations with the allergen immunotherapies (AIT) actually implemented in the clinic.

Results

The simulation yielded 48.5% monosensitizations and 49.9% double sensitizations. In 56.3% of the double sensitizations, the ratio ≥ 5:1 indicated a dominant sensitization, which was classified as a mono-allergy. The therapies suggested by the algorithm corresponded to the clinically implemented AIT in 91% of cases; overall, the correspondence was 89.7%. While the algorithm predicted double AIT in 10% of cases, this was only clinically implemented in 2.7% of cases, with anamnestic details on sting circumstances and diagnostic certainty influencing the decision.

Conclusion

Standardized serological diagnostics with bee/vespula venom-specific IgE ratio and CRD provide high diagnostic precision and comprehensively demonstrate the progress made over the last 10 years. Skin tests remain a medically useful and valuable part of diagnostics, especially in cases of double sensitization.

Hereditary angioedema (HAE) is a rare genetic disorder that can cause sudden and repeated swelling in various parts of the body. In the respiratory tract, these attacks are potentially life-threatening. Since neither the timing of the attacks nor their location or severity can be predicted, the quality of life of affected patients is often severely impaired. Important therapeutic advances have been made in recent years and decades. For example, the possibility of self-administering medication has enabled those affected to respond quickly to HAE attacks. Another milestone was the establishment of long-term prophylaxis, which can guarantee freedom from attacks over a long period of time for some patients. Despite these advances, all affected individuals are required to always carry medication for acute treatment. The patient population is very heterogeneous and always requires individualized therapy planning in each case. It is important to adapt the management options to the respective life situations, which can be done at any time. In practice, the implementation of the therapy concept can be associated with various challenges. These will be discussed in this publication based on available data and our own experience to highlight the problems faced by patients and practitioners and how these barriers can potentially be removed or overcome.

Background

Molecular technologies have paved the way to improved understanding of allergic diseases in many ways, ranging from molecular allergens to tailor-made tools for analytic, diagnostic, and therapeutic purposes. In particular, the progress in molecular targeting opens a variety of opportunities for improving protection and treatment of allergies and anaphylaxis.

Methods

This review summarizes the state-of-the-art and the feasibility of applying molecular tools for exemplary applications within insect venom allergy and anaphylaxis.

Results

In recent years, novel technologies have been established and applied in the development of antibodies offering advantages compared to current approaches. These antibodies might overcome current limitations and provide novel opportunities for treatment of Hymenoptera venom allergy. Hence, novel targets, molecular architectures, and forms of application of antibodies may provide a benefit for the allergic patient.

Conclusion

Recent approaches give a first glimpse of the future possibilities of targeting approaches in a complex system such as allergic diseases. It has become clear that the simplicity of state-of-the-art antibody technologies will both broaden and deepen the scope of applications in allergology.

Background

Domestic mites, i.e. house dust mites (HDM) and storage mites (SM), which cause an IgE-mediated reaction, are a major cause of indoor allergies. For a long time, SM were thought to be restricted to rural areas; however, they can also be found in urban dwellings. Given that SM exhibit minimal cross-reactivity with HDM and among different SM species, these mite species should be diagnosed and treated separately. To date, there is no overview of which mite species occur in which areas of Germany. The aim of this study was therefore to investigate the indoor acarofauna in Germany, especially allergologically relevant HDM and SM.

Methods

Between 2006 and 2009, 2554 dust samples were collected from volunteers in all German federal states at different times of the year. Samples from mattresses were microscopically analysed for various species of HDM and SM to provide an overview of the prevalence of allergologically relevant species for each federal state.

Results

The HDM species Dermatophagoides pteronyssinus and Dermatophagoides farinae were most common throughout Germany, whereas the abundance of SM species such as Lepidoglyphus destructor and Tyrophagus putrescentiae varied regionally. Little or no seasonal variation in mite populations was observed.

Conclusion

In addition to the ubiquitous HDM, some allergologically relevant SM were found in house dust from all federal states. To our knowledge, this is the first study to analyse house dust samples for mite populations throughout Germany. The results help to specify the diagnosis of mite allergy and can be used as a reference for future analyses.

Background

Determining total allergenic potency is key in standardization of active substances being a prerequisite in achieving acceptable batch-to-batch consistency of allergen products. Currently, a human serum pool collected from allergic individuals serves as allergen-, recognizing antibodies for determining the total allergenic activity. Human serum presents disadvantages, including variability, ethical dilemmas, and limited availability. These drawbacks can be addressed by developing monoclonal antibody (mAb) IgE (immunoglobulin E) pools, providing a more standardized approach for determining the potency of allergen immunotherapy products.

Methods

Human IgE mAbs targeting individual Apis mellifera allergens were generated by performing single-cell RNA sequencing on honeybee venom specific memory B‑cells from beekeepers. MAbs were expressed in Expi293 HEK293 cells, with epitope binning and affinity assessment ensuring selection of functionally relevant antibodies for potency testing.

Results

Initial results indicate that the recombinant antibody pool mirrors the allergen specificity of human serum pools.

Conclusion

Recombinant antibody pools presenting a viable alternative for allergen potency testing and ensuring consistent product quality.