Allergo Journal International最新文献

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.

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

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.

Background

Cutaneous adverse drug reactions cover a broad clinical and immunological spectrum—from common, mild maculopapular drug exanthema to potentially lethal forms such as Stevens–Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Due to the increasing life expectancy, rising multimorbidity, and growing polypharmacy, there is an increase not only in incidence, but also in diagnostic and therapeutic complexity. Cutaneous adverse drug reactions (CADRs) are highly relevant from a clinical and health economic perspective and require differentiated, guideline-based management.

Objective

The aim of this study is to provide a comprehensive overview of the pathophysiological mechanisms, clinical manifestations, and current diagnostic and therapeutic strategies for cutaneous drug reactions.

Results

Analyses of the current literature show that early and differentiated diagnosis is essential for the effective treatment of cutaneous drug reactions. Immunologically, CADRs can be classified predominantly as type IV hypersensitivity reactions. In addition to T‑cell-mediated mechanisms, genetic risk factors and viral reactivations are becoming increasingly important. Advances in biomarker research could further improve early and accurate diagnosis. Depending on the severity, topical or systemic corticosteroids, immunoglobulins, immunomodulatory agents such as ciclosporin or Janus kinase inhibitors are available for treatment.

Conclusion

Differentiating between cutaneous drug reactions based on their clinical presentation and underlying immunological mechanisms is crucial for choosing an appropriate therapy. Given the increasing prevalence and growing complexity of cutaneous drug reactions, a thorough understanding of pathophysiological relationships is essential. Current research approaches, in particular pharmacogenetic screening and validated biomarkers, offer promising opportunities to individualize diagnosis and therapy, thereby significantly expanding the range of treatment options in the future.

Chlorhexidine (1:6-di-4’-chlorophenyldiguanidohexane) has been a widely used antiseptic since its introduction in 1954. Alongside alexidine, it belongs to the group of cationic bisbiguanides with a broad spectrum of activity. Due to its diverse applications—such as in skin and mucous membrane disinfection, with use in mouthwashes, wound antiseptics, or catheterization—chlorhexidine has been an integral part of healthcare and beyond as an antiseptic for decades. Despite its generally good tolerability, chlorhexidine is also a potent allergen that can trigger both type I and type IV hypersensitivity reactions. In the following article, we provide an overview of anaphylactic reactions caused by chlorhexidine.

Background

Adverse drug reactions (ADR) associated with local anesthetics (LA) like lidocaine are often interpreted as allergy. This assumption leads to a large number of allergological investigations. There are numerous studies that investigate the frequency of type I allergies to LA, and they all agree that a real type I allergy as the culprit of ADR to LA is extraordinarily rare. Other mechanisms are more likely. Specifically, the unequal sex distribution of patients with ADR is rarely discussed and hardly any studies address this topic.

Aim

The aim of this paper is to examine sex disparities in ADR to LA. Differences in symptoms, causes and pathomechanisms between men and women are analyzed.

Methods

This study integrates our own clinical data with a comprehensive literature review. Our data are based on an analysis of 140 patients with suspected allergy to LA. Patient anamnesis, clinical data and skin test results performed with different LA are analyzed in relation to the sex. A PubMed search provides comparative data.

Results

Our data and literature research show that women are significantly more likely than men to present to allergy centers with suspected allergies to LA. True type I allergies are exceedingly rare in both sexes. Symptoms of ADR can be diverse and there is no pathognomonic symptom and not even a symptom complex that reliably indicates a real type I allergy. Pharmacophysical differences, such as different drug distribution and metabolism, and psychological differences in females could account for a part of the symptoms.

Conclusion

The reason for the unbalanced sex distribution is still unknown, but probably multifactoral. A research focus on this subject is needed to better understand gender specific aspects, in order to provide more efficient workup in allergological diagnostics.

Graphical Abstract