Allergo Journal International最新文献

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

Background

Over the last 8 years, the treatment of atopic dermatitis (AD) has been revolutionized by the development and approval of novel systemic therapies. In addition to the biologics dupilumab, tralokinumab, lebrikizumab, and nemolizumab, the three Janus kinase inhibitors (JAKi) baricitinib, abrocitinib, and upadacitinib are now also available.

Methods and results

A selection of the most important publications on the approved JAKi for the systemic treatment of AD and their statements were used as the basis for this review.

Conclusion

Systemic JAKi have become established as a promising therapeutic option in the guidelines for the treatment of AD. They specifically block the JAK signaling pathways involved in the inflammatory response and provide rapid and effective relief of the inflammatory reaction as well as the symptoms such as itching and pain. Compared to the class of biologics, they have a broader effect on various cytokines. Despite very good efficacy, there are some safety concerns, which is why a careful risk–benefit assessment is required in accordance with European Medicines Agency recommendations.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and requires therapy that is individualized, yet also based on the current guidelines. This narrative review gives an update on the conventional therapy of AD depending on severity according to the German S3 guideline on AD. AD severity is graded as mild, moderate, and severe AD. Consequent topical basic therapy and avoidance of potential trigger factor is recommended for all patients. Basic therapy should be applied not only during a flare, but also to clear skin to prevent worsening; furthermore, mild/moderate eczema should receive anti-inflammatory therapy with topical corticosteroids/calcineurin inhibitors. Systemic therapy is indicated in moderate-to-severe AD with insufficient response to other measures, if applicable, also ultraviolet therapy. Systemic therapies are grouped into conventional and targeted therapies (biologics and Janus kinase inhibitors). Systemic corticosteroids should only be used as rescue therapy for 3 weeks maximum. Targeted therapies in AD have the highest recommendation grade for long-term therapy. Cyclosporin A (CsA), azathioprine (AZT), methotrexate (MTX), and mycophenolate mofetil (MMF) belong to the conventional steroid-sparing therapies. However, only CsA is licensed for AD. MTX should be and MMF might be considered for AD according to the German S3 guideline, while AZT may be considered in adults.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in industrialized countries and is characterized by heterogeneous (endo)phenotypes and a high disease burden. In Europe, four biologics and three oral Janus kinase (JAK) inhibitors are currently approved by the European Medicines Agency (EMA) for the treatment of moderate to severe AD in adolescents (≥ 12 years) and adults: dupilumab (anti-interleukin [IL]-4Rα; 2017), tralokinumab (anti-IL-13; 2021), lebrikizumab (anti-IL-13; 2023) and nemolizumab (anti-IL-31Rα; 2024) as well as the JAK inhibitors baricitinib (JAK 1/2; 2020), upadacitinib (JAK 1; 2021) and abrocitinib (JAK 1; 2022). Among the abovementioned therapies, baricitinib for moderate and severe AD from the second year of life and dupilumab for severe AD from the sixth month of life are already two approved systemic therapies for early childhood. This narrative review provides an update on the biologics currently approved for treatment of moderate and severe AD. It also provides a brief overview of monoclonal antibodies currently in phase III clinical trials and future issues and opportunities for immunomodulatory systemic therapies for AD.