Pub Date : 2026-03-03DOI: 10.1016/j.jaip.2026.02.026
Alicia Μ Johnston, Nicholas L Rider, Alexandra F Freeman, Steven M Holland, Jordan S Orange, Craig D Platt, Andrea Carlo Anglero, Michael Tsoulis, Daniel Zinn, Patrick Passarelli, Marcus Shaker
Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare group of immunodeficiencies with high mortality characterized by a failure of communication between phagocytic cells and their regulatory/support networks. The objective of this article is to review key aspects of MSMD management. A defective interleukin-12 (IL-12) / interferon-gamma (IFN-γ) circuit can result in overwhelming intracellular infection leading to lymphadenopathy, organomegaly, and sepsis. In the setting of unexplained lymphadenopathy, early tissue and blood culture, with special attention to mycobacteria, is essential. If MSMD is suspected, genetic testing to assess for pathogenic variants affecting the IFN-γ/IL-12 signaling pathway is available. To date, at least 19 genes with hundreds of unique mutations have been identified; thus, genetic testing is essential to determine the specific defect and direct therapy. Multiple antibiotics, cytokine therapy in selected cases, and bone marrow transplantation should be considered.
{"title":"What We Have Here Is a Failure to Communicate: Interleukin-12 / Interferon-gamma Axis Defects and Mendelian Susceptibility to Mycobacterial Disease.","authors":"Alicia Μ Johnston, Nicholas L Rider, Alexandra F Freeman, Steven M Holland, Jordan S Orange, Craig D Platt, Andrea Carlo Anglero, Michael Tsoulis, Daniel Zinn, Patrick Passarelli, Marcus Shaker","doi":"10.1016/j.jaip.2026.02.026","DOIUrl":"10.1016/j.jaip.2026.02.026","url":null,"abstract":"<p><p>Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare group of immunodeficiencies with high mortality characterized by a failure of communication between phagocytic cells and their regulatory/support networks. The objective of this article is to review key aspects of MSMD management. A defective interleukin-12 (IL-12) / interferon-gamma (IFN-γ) circuit can result in overwhelming intracellular infection leading to lymphadenopathy, organomegaly, and sepsis. In the setting of unexplained lymphadenopathy, early tissue and blood culture, with special attention to mycobacteria, is essential. If MSMD is suspected, genetic testing to assess for pathogenic variants affecting the IFN-γ/IL-12 signaling pathway is available. To date, at least 19 genes with hundreds of unique mutations have been identified; thus, genetic testing is essential to determine the specific defect and direct therapy. Multiple antibiotics, cytokine therapy in selected cases, and bone marrow transplantation should be considered.</p>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13001684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-04DOI: 10.1016/j.jaip.2026.02.003
{"title":"Early Diagnosis and Treatment in Patients With Eosinophilic Granulomatosis With Polyangiitis","authors":"","doi":"10.1016/j.jaip.2026.02.003","DOIUrl":"10.1016/j.jaip.2026.02.003","url":null,"abstract":"","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"14 3","pages":"Pages 611-612"},"PeriodicalIF":6.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147417234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-11-04DOI: 10.1016/j.jaip.2025.10.038
Grainne d’Ancona MSc , Faizan Haris MBBS , Jessica Gates MBBS , Niall Stewart-Kelcher BSc , Linda Green MSc , Jodie Lam BSc , Mariana Fernandes MSc , Louise Thomson MSc , Cris Roxas MSc , Zijing Yang PhD , Jaideep Dhariwal PhD , Alexandra M. Nanzer PhD , David J. Jackson PhD
Background
High-dose ICS are associated with adverse effects. Reductions in ICS use during treatment with anti-IL-5/5R therapies can lead to reduced clinical effectiveness in some patients.
Objective
This study explored whether the broader anti-type 2 (T2) effects of the anti-thymic stromal lymphopoietin therapy tezepelumab permitted a reduction in ICS use without deleterious clinical consequences.
Methods
We calculated adherence to ICS/LABA (long-acting β2-agonist) in the 12 months before and 12 months after commencing tezepelumab for severe asthma using the medication possession ratio methodology and classified results as poor (<0.5), suboptimal (0.51-0.74), or good (≥0.75). We compared clinical outcomes including the exacerbation rate, Asthma Control Questionnaire six-question version score, FEV1, and the ability to achieve clinical remission, as well as T2 biomarker levels at 1 year across ICS adherence subgroups.
Results
A total of 152 adults with severe asthma who commenced tezepelumab were included. At the end of 12 months’ treatment, there was a significant reduction in the median medication possession ratio from 1.0 (0.83-1.08) at baseline to 0.83 (0.58-1; p = .009). The ICS adherence was good in 69.1%, suboptimal in 12.5%, and poor in 18.4% of patients. At 1 year, improvements in all clinical outcome measures as well as rates of biological remission were similar across ICS adherence groups (all P > .05).
Conclusions
A fall in ICS adherence after initiation of tezepelumab for severe asthma was not associated with evidence of reduced clinical effectiveness of tezepelumab, including the ability to achieve remission. Similar rates of biological remission further suggest that the broad anti-T2 effect of anti-thymic stromal lymphopoietin may be sufficient to permit a safe reduction in ICS exposure.
{"title":"Adherence to Inhaled Corticosteroids and Clinical Outcomes Following a Year of Tezepelumab Therapy for Severe Asthma","authors":"Grainne d’Ancona MSc , Faizan Haris MBBS , Jessica Gates MBBS , Niall Stewart-Kelcher BSc , Linda Green MSc , Jodie Lam BSc , Mariana Fernandes MSc , Louise Thomson MSc , Cris Roxas MSc , Zijing Yang PhD , Jaideep Dhariwal PhD , Alexandra M. Nanzer PhD , David J. Jackson PhD","doi":"10.1016/j.jaip.2025.10.038","DOIUrl":"10.1016/j.jaip.2025.10.038","url":null,"abstract":"<div><h3>Background</h3><div>High-dose ICS are associated with adverse effects. Reductions in ICS use during treatment with anti-IL-5/5R therapies can lead to reduced clinical effectiveness in some patients.</div></div><div><h3>Objective</h3><div>This study explored whether the broader anti-type 2 (T2) effects of the anti-thymic stromal lymphopoietin therapy tezepelumab permitted a reduction in ICS use without deleterious clinical consequences.</div></div><div><h3>Methods</h3><div>We calculated adherence to ICS/LABA (long-acting β<sub>2</sub>-agonist) in the 12 months before and 12 months after commencing tezepelumab for severe asthma using the medication possession ratio methodology and classified results as poor (<0.5), suboptimal (0.51-0.74), or good (≥0.75). We compared clinical outcomes including the exacerbation rate, Asthma Control Questionnaire six-question version score, FEV<sub>1</sub>, and the ability to achieve clinical remission, as well as T2 biomarker levels at 1 year across ICS adherence subgroups.</div></div><div><h3>Results</h3><div>A total of 152 adults with severe asthma who commenced tezepelumab were included. At the end of 12 months’ treatment, there was a significant reduction in the median medication possession ratio from 1.0 (0.83-1.08) at baseline to 0.83 (0.58-1; p = .009). The ICS adherence was good in 69.1%, suboptimal in 12.5%, and poor in 18.4% of patients. At 1 year, improvements in all clinical outcome measures as well as rates of biological remission were similar across ICS adherence groups (all <em>P</em> > .05).</div></div><div><h3>Conclusions</h3><div>A fall in ICS adherence after initiation of tezepelumab for severe asthma was not associated with evidence of reduced clinical effectiveness of tezepelumab, including the ability to achieve remission. Similar rates of biological remission further suggest that the broad anti-T2 effect of anti-thymic stromal lymphopoietin may be sufficient to permit a safe reduction in ICS exposure.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"14 3","pages":"Pages 637-643.e2"},"PeriodicalIF":6.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-09DOI: 10.1016/j.jaip.2025.12.002
Tejas S. Athni MS , Lingxiao Zhang MPH , Baijun Zhou MHS , Stella E. Lee MD , Sara Barmettler MD, MPH
{"title":"Acute rhinosinusitis in patients with primary and secondary hypogammaglobulinemia due to B-cell targeted therapy and CAR T-cell therapy","authors":"Tejas S. Athni MS , Lingxiao Zhang MPH , Baijun Zhou MHS , Stella E. Lee MD , Sara Barmettler MD, MPH","doi":"10.1016/j.jaip.2025.12.002","DOIUrl":"10.1016/j.jaip.2025.12.002","url":null,"abstract":"","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"14 3","pages":"Pages 718-721.e2"},"PeriodicalIF":6.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poppy seed (Papaver somniferum) allergy is an uncommon but potentially severe form of seed hypersensitivity. Despite the increasing consumption of seeds worldwide, data on poppy seed (PS) allergy remain limited, mostly derived from case reports.
Objective
This study aimed to describe the clinical and laboratory characteristics of PS-allergic children and evaluate the diagnostic performance of conventional and molecular assays.
Methods
A retrospective review was conducted on children evaluated for suspected PS allergy at a tertiary pediatric allergy center between 2020 and 2024. Clinical reactivity was confirmed by an oral food challenge or a consistent reaction history with documented sensitization. Diagnostic tools included prick-to-prick (PtP) testing, serum specific IgE (sIgE), and multiplex microarray Allergy Xplorer (ALEX2) for PS allergens, including α-hairpinin.
Results
Of 191 PS-sensitized patients, 38 (19.9%) were clinically allergic. Anaphylaxis occurred in 10 cases (26.3%). Median PtP wheal size, PS-sIgE, and α-hairpinin levels were significantly higher in allergic patients than in tolerant ones (8.0 mm vs 3.0 mm, P < .001; 3.62 vs 0.79 kU/L, P = .001; and 7.20 vs 0.00 kUA/L, P < .001, respectively). PtP wheal size and α-hairpinin levels showed the best diagnostic performance (area under the curve [AUC] = 0.937, positive likelihood ratio [LR+] = 4.86 and AUC = 0.932, LR+ = 5.88, both P < .001). Many children had multiple food allergies, most commonly to sesame and tree nuts.
Conclusion
Although rare, PS allergy can induce severe reactions and should be considered in children with multiple seed or nut allergies. PtP and α-hairpinin testing demonstrated strong diagnostic performance, with α-hairpinin emerging as a promising molecular marker for distinguishing true PS allergy from cross-reactivity.
背景：罂粟籽（Papaver somniferum）过敏是一种罕见但潜在严重的种子过敏形式。尽管全世界对罂粟籽的消费量不断增加，但关于罂粟籽（PS）过敏的数据仍然有限，主要来自病例报告。目的：本研究旨在描述ps过敏儿童的临床和实验室特征，并评价常规和分子检测的诊断效果。方法：对某三级儿科过敏中心2020 - 2024年疑似PS过敏的患儿进行回顾性分析。临床反应性由口腔食物刺激（OFC）或一致的过敏史证实。诊断工具包括刺对刺（PtP）检测、血清特异性IgE （sIgE）和多重芯片（ALEX2）检测PS过敏原，包括α-发夹蛋白。结果：191例ps致敏患者中，临床过敏38例（19.9%）。发生过敏反应10例（26.3%）。过敏患者PtP轮大小、PS-sIgE和α-发夹蛋白水平中位数明显高于耐受患者（8.0 mm vs 3.0 mm）。结论：罂粟籽过敏虽罕见，但可引起严重反应，应考虑多发种子或坚果过敏患儿。PtP和α-发夹蛋白检测显示出较强的诊断能力，其中α-发夹蛋白有望作为区分PS过敏和交叉反应的分子标志物。
{"title":"Alpha-Hairpinin (Pap s 1.0101) Sensitization and Optimized Prick-to-Prick Testing Define Clinical Poppy Seed Allergy in Children","authors":"Canan Caka MD, Melike Ocak MD, Ozge Soyer MD, Bulent Enis Sekerel MD","doi":"10.1016/j.jaip.2025.12.001","DOIUrl":"10.1016/j.jaip.2025.12.001","url":null,"abstract":"<div><h3>Background</h3><div>Poppy seed (<em>Papaver somniferum</em>) allergy is an uncommon but potentially severe form of seed hypersensitivity. Despite the increasing consumption of seeds worldwide, data on poppy seed (PS) allergy remain limited, mostly derived from case reports.</div></div><div><h3>Objective</h3><div>This study aimed to describe the clinical and laboratory characteristics of PS-allergic children and evaluate the diagnostic performance of conventional and molecular assays.</div></div><div><h3>Methods</h3><div>A retrospective review was conducted on children evaluated for suspected PS allergy at a tertiary pediatric allergy center between 2020 and 2024. Clinical reactivity was confirmed by an oral food challenge or a consistent reaction history with documented sensitization. Diagnostic tools included prick-to-prick (PtP) testing, serum specific IgE (sIgE), and multiplex microarray Allergy Xplorer (ALEX<span><span><sup>2</sup></span></span>) for PS allergens, including α-hairpinin.</div></div><div><h3>Results</h3><div>Of 191 PS-sensitized patients, 38 (19.9%) were clinically allergic. Anaphylaxis occurred in 10 cases (26.3%). Median PtP wheal size, PS-sIgE, and α-hairpinin levels were significantly higher in allergic patients than in tolerant ones (8.0 mm vs 3.0 mm, <em>P <</em> .001; 3.62 vs 0.79 kU/L, <em>P</em> = .001; and 7.20 vs 0.00 kUA/L, <em>P <</em> .001, respectively). PtP wheal size and α-hairpinin levels showed the best diagnostic performance (area under the curve [AUC] = 0.937, positive likelihood ratio [LR+] = 4.86 and AUC = 0.932, LR+ = 5.88, both <em>P</em> < .001). Many children had multiple food allergies, most commonly to sesame and tree nuts.</div></div><div><h3>Conclusion</h3><div>Although rare, PS allergy can induce severe reactions and should be considered in children with multiple seed or nut allergies. PtP and α-hairpinin testing demonstrated strong diagnostic performance, with α-hairpinin emerging as a promising molecular marker for distinguishing true PS allergy from cross-reactivity.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"14 3","pages":"Pages 676-684.e2"},"PeriodicalIF":6.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-09DOI: 10.1016/j.jaip.2025.12.003
Yutong Chen PhD , Joohan Kim BA , Timothy G. Chow MD , Arthur S. Hong MD, MPH , Joshua M. Liao MD, MSc , Luyu Xie PharmD, PhD
{"title":"Association between asthma and dementia across age groups","authors":"Yutong Chen PhD , Joohan Kim BA , Timothy G. Chow MD , Arthur S. Hong MD, MPH , Joshua M. Liao MD, MSc , Luyu Xie PharmD, PhD","doi":"10.1016/j.jaip.2025.12.003","DOIUrl":"10.1016/j.jaip.2025.12.003","url":null,"abstract":"","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"14 3","pages":"Pages 715-717.e1"},"PeriodicalIF":6.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-04DOI: 10.1016/j.jaip.2026.01.010
Vanessa L. Clark PhD , Mark Hew MBBS, PhD
{"title":"Dupilumab for Functional Impairment—Severe Asthma’s Final Frontier","authors":"Vanessa L. Clark PhD , Mark Hew MBBS, PhD","doi":"10.1016/j.jaip.2026.01.010","DOIUrl":"10.1016/j.jaip.2026.01.010","url":null,"abstract":"","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"14 3","pages":"Pages 666-667"},"PeriodicalIF":6.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-11-22DOI: 10.1016/j.jaip.2025.10.051
Salman H. Siddiqui MD, PhD , Harold Wilson-Morkeh MD , Sara Monti MD, PhD , Bernhard Hellmich MD, PhD
Eosinophilic granulomatosis with polyangiitis (EGPA), originally termed Churg–Strauss syndrome, represents the rarest form of antineutrophil cytoplasmic antibody-associated vasculitis. It is characterized by the presence of asthma, rhinosinusitis with or without nasal polyps, eosinophilic inflammation of the blood, and tissues and necrotizing vasculitis of small to medium-sized blood vessels. Owing to its rare, multisystemic nature with diverse symptom presentation, diagnosis is complex, requiring a multidisciplinary approach and a careful array of diagnostic and clinical assessments. Conventional therapy is composed of the use of oral glucocorticoids, which are associated with long-term adverse effects, and other immunomodulatory drugs. However, earlier diagnosis and prompt tailored treatment can improve clinical outcomes and reduce drug-related toxicity. The initiation of biologic therapies, such as those blocking IL-5 or its receptor, which have recently been approved for the treatment of non-severe relapsing EGPA, has emerged as a paradigm shift in management. An illustrative case is used to present a comprehensive representation of the diagnosis, pathophysiology, and management of EGPA.
{"title":"Early Diagnosis and Treatment in Patients With Eosinophilic Granulomatosis With Polyangiitis","authors":"Salman H. Siddiqui MD, PhD , Harold Wilson-Morkeh MD , Sara Monti MD, PhD , Bernhard Hellmich MD, PhD","doi":"10.1016/j.jaip.2025.10.051","DOIUrl":"10.1016/j.jaip.2025.10.051","url":null,"abstract":"<div><div>Eosinophilic granulomatosis with polyangiitis (EGPA), originally termed Churg–Strauss syndrome, represents the rarest form of antineutrophil cytoplasmic antibody-associated vasculitis. It is characterized by the presence of asthma, rhinosinusitis with or without nasal polyps, eosinophilic inflammation of the blood, and tissues and necrotizing vasculitis of small to medium-sized blood vessels. Owing to its rare, multisystemic nature with diverse symptom presentation, diagnosis is complex, requiring a multidisciplinary approach and a careful array of diagnostic and clinical assessments. Conventional therapy is composed of the use of oral glucocorticoids, which are associated with long-term adverse effects, and other immunomodulatory drugs. However, earlier diagnosis and prompt tailored treatment can improve clinical outcomes and reduce drug-related toxicity. The initiation of biologic therapies, such as those blocking IL-5 or its receptor, which have recently been approved for the treatment of non-severe relapsing EGPA, has emerged as a paradigm shift in management. An illustrative case is used to present a comprehensive representation of the diagnosis, pathophysiology, and management of EGPA.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"14 3","pages":"Pages 599-610"},"PeriodicalIF":6.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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