Current Opinion in Allergy and Clinical Immunology最新文献

Purpose of review: To provide an accessible, comprehensive overview of past, present, imminent, and future therapies for systemic mastocytosis.

Recent findings: Based on recent trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved two drugs for treating advanced systemic mastocytosis: avapritinib and midostaurin. The FDA also approved imatinib for selected cases of aggressive systemic mastocytosis without the D816V c-Kit mutation. Moreover, for the first time, a cytoreductive molecule, avapritinib, has been approved for patients with indolent systemic mastocytosis.

Summary: Despite the considerable therapeutic progress in recent years, systemic mastocytosis is an incurable disease. In the last 20 years, the management of systemic mastocytosis has transformed from a one-size-fits-all approach, characterized by nonspecific cytoreductive drugs, to a tailored strategy focused on increasingly precise molecular targets, with the most notable example being the KIT inhibitors. Recently, the FDA and EMA have approved two drugs for treating systemic mastocytosis: avapritinib and midostaurin. Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results.

Purpose of review: This review addresses the clinical and biological complexities of hypereosinophilia (HE) and hypereosinophilic syndrome (HES), highlighting the need for improved diagnostic frameworks and therapeutic strategies. Due to the increasing recognition of HE and its potential for severe multiorgan involvement, a structured, multidisciplinary approach to diagnosis and management is essential for optimizing patient outcomes.

Recent findings: Recent literature categorizes HE into hereditary, reactive, and neoplastic forms, with significant advancements in defining associated conditions and their pathophysiological mechanisms. Clinical manifestations range from asymptomatic eosinophilia to life-threatening complications involving the skin, lungs, gastrointestinal tract, heart, and nervous system. Corticosteroids remain the first-line treatment across most subtypes. Imatinib has shown high efficacy, particularly in patients with FIP1L1::PDGFRA fusion. However, therapeutic resistance and relapse still occur. Biologic therapies targeting interleukin (IL)-5 or its receptor, such as mepolizumab and benralizumab, have demonstrated promise in reducing eosinophils counts and preventing flare-ups. Additional agents under investigation include dupilumab and lirentelimab.

Summary: The findings highlight the importance of accurate classification and tailored management of HE and HES, which are crucial for preventing organ damage and improving quality of life. Ongoing clinical trials and research will expand therapeutic options, clarify underlying mechanisms, and address current unmet needs.

Purpose of review: Advances in understanding the molecular pathways underlying nasal epithelial inflammation have ushered in the era of personalized medicine for chronic rhinosinusitis with nasal polyps (CRSwNP). Research progress has led to the approval of several monoclonal antibodies (mAbs) for severe CRSwNP, demonstrating promising outcomes in both clinical trials and real-world settings. Similarly, evolution in surgical techniques has enhanced progression-free survival due to the development of novel approaches. This narrative review summarizes current evidence comparing medical and surgical options for CRSwNP.

Recent findings: There is general consensus that surgery is most effective in reducing nasal polyp size (NPS), while mAbs appears to provide greater benefits in terms of quality-of-life measures and olfactory function. Overall, surgery has shown higher long-term cost-effectiveness, although this could change with the upcoming patent expirations of mAbs. Additionally, head-to-head trials will allow for a direct comparison of the effectiveness of different mAbs in disease-specific outcomes.

Summary: The high heterogeneity among studies has limited the ability to draw definitive conclusions through meta-analyses. To date, endoscopic sinus surgery remains the preferred option for surgery-naive patients, while individuals with recalcitrant CRSwNP and confirmed type-2 inflammation should be considered for mAb treatment.

Purpose of review: Asthma is a heterogeneous disease encompassing distinct phenotypes and endotypes. Advances in elucidating the pathogenic role of type 2 (T2) cytokines and epithelial-derived alarmins have profoundly reshaped our understanding of airway inflammation in asthma. This review provides an updated perspective on how these mediators contribute to asthma pathobiology and examines their integration into emerging precision medicine strategies.

Recent findings: Biologic agents targeting T2 cytokines (IL-4, IL-5, and IL-13) and alarmins (TSLP and IL-33) have demonstrated efficacy across a broad spectrum of severe asthma phenotypes. Recent evidence underscores the central role of alarmins in orchestrating both innate and adaptive immune responses within the airways. In parallel, the development of alarmin-associated molecular and clinical biomarkers is expanding patient stratification beyond traditional eosinophilic and allergic profiles.

Summary: Advancing our understanding of alarmins and T2 cytokines offers new opportunities to refine asthma endotyping, personalize therapeutic decisions, and pursue sustained disease remission. Future directions include the integration of multiomics, real-world evidence, and novel biomarker platforms to consolidate the next phase of precision medicine in asthma and optimize long-term disease modification strategies.

Purpose of review: Beta-lactam allergy is frequently reported, but only a minority of cases correspond to true allergies. Tools to stratify the risk of a real allergic reaction can possibly help delabeling patients. We aimed to retrieve evidence on algorithms for risk stratification of patients with a beta-lactam allergy label.

Recent findings: We performed a systematic review, searching three databases and included 28 studies. Most of the applied tools involved the assessment of the presence of rash/hives/other exanthemas ( n  = 24), angioedema/localized swelling ( n  = 23), bronchospasm/wheezing/dyspnea ( n  = 22) and gastrointestinal symptoms ( n  = 21). Seventeen studies classified participants into different categories according to their risk of having a penicillin allergy; three studies presented algorithms indicating management approaches to be followed; six studies applied predictive models. Most studies had a high risk of bias, particularly concerning the reference standard and lack of external validation.

Summary: Existing algorithms for beta-lactam allergy risk stratification are very heterogeneous and most of them lack validation.

Purpose of review: Tuberculosis (TB) incidence is rising globally, and TB medication-associated drug reaction with eosinophilia and systemic symptoms (DRESS) presents a significant clinical challenge, particularly in people living with HIV (PLH). Treatment interruption during active TB, especially with comorbid immunosuppression can be detrimental. This review highlights global variations in management practices and emphasizes the need for a more personalized approach to care.

Recent findings: Timely cessation of the suspected medication, supportive care, and topical corticosteroids remain central to DRESS management. However, the routine use of systemic corticosteroids remains debated, as good outcomes from topical steroids alone have been observed, especially in TB/HIV co-infected patients. Efforts to reduce TB treatment interruption have driven interest in the use of shortened TB regimens, sequential additive drug challenge (SADC) with stat dose intravenous corticosteroids to limit positive drug challenge morbidity, and even desensitization protocols. Although not yet widely adopted, these strategies show promise in reintroducing first-line TB drugs, limiting treatment interruptions. Management remains complex, with prolonged hospital stays and high healthcare costs continuing to drive innovation.

Summary: The findings support a move towards personalized approaches to TB-DRESS management, with future efforts focused on integrating clinical, genomic, and in-vitro tools to guide risk-stratified reintroduction of TB medications.

Purpose of review: T-cell-mediated drug hypersensitivity reactions represent a major impediment to the drug discovery process whilst presenting a significant burden to the healthcare sector. These reactions are predominantly facilitated by the adaptive immune system, yet the equilibrium of immune tolerance appears to be a significant determinant in whether an individual will experience a hypersensitivity reaction to a therapeutic.

Recent findings: Indeed, regulatory T cells (Tregs) play a significant part in diminishing an immune response by CD4+ and CD8+ T cells and preventing autoimmunity by keeping an immune response in check. These cell subsets have been observed to be upregulated in times of immune activation, and unsurprisingly, their impairment has been associated in tandem with dysregulated immune responses contributing to the sliding scale of drug hypersensitivity.

Summary: It is becoming increasingly evident that the fine balance of immune regulation significantly impacts on drug hypersensitivity reactions. As the area progresses, it will be interesting to assess whether therapies targeting Tregs hold the key to maintaining the synergy required to prevent the onset of drug hypersensitivity reactions.

Purpose of review: This review gives an overview on the current knowledge of the physiological and pathophysiological features of enolases and how these features might contribute to the enzymes' allergenic properties. It summarizes the most recent literature on allergenic enolases and raises questions that need to be answered in the future to gain a better understanding of the role of enolases in allergic diseases.

Recent findings: The recent identification of two novel allergenic enolases, from London plane tree and whiff, further supports the uniqueness of this allergen family: the occurrence of enolases in the three major kingdoms of life and the capability to induce allergic symptoms via inhalation, ingestion, and skin contact.

Summary: The importance and uniqueness of enolases as allergenic molecules is widely accepted. However, studies linking the biochemical and physiological features of enolases with their potential to induce allergies are still needed. This would contribute to a better understanding about the role of enolases in the induction of allergic diseases, to improve specificity and sensitivity of allergy diagnosis and to further enable the development of patient-tailored prophylactic and therapeutic approaches.

Purpose of review: This review explores the clinical outcomes used in immunoglobulin E (IgE)-mediated food allergy (FA) intervention studies, emphasizing unmet need for patient-centred outcomes. Standardizing outcome measurement is critical as research into FA treatments, particularly food immunotherapy, expands. Here we discuss how outcomes should reflect the multidimensional impact of FA on people's lives.

Recent findings: Current evidence reveals a discrepancy between clinical trial outcomes and those most valued by patients and carers. While trials often prioritize changes in reactivity thresholds or immunological markers, patients and carers emphasize need in reducing severe reactions, improving quality of life, and enhancing confidence in disease management. This disparity highlights importance of harmonization efforts to guide FA research.The Core Outcome Measures for Food Allergy (COMFA) initiative recently identified two core outcomes - 'allergic symptoms' and 'quality of life' - through an international consensus process involving patients, caregivers, clinicians, and researchers. Outcomes like 'desensitization' and 'remission/sustained unresponsiveness' were considered important but were not seen as the most critical.

Summary: Developing and implementing a COS for FA intervention studies is essential to align research with patient priorities, ensuring meaningful improvements in routine clinical care. Standardized outcome measurement will generate robust evidence, inform clinical practice, and empower patients and caregivers in decision-making about FA management.