{"title":"Angioedema without urticaria: Diagnosis and management.","authors":"Marielle C Young, Aleena Banerji","doi":"10.2500/aap.2025.46.250013","DOIUrl":"10.2500/aap.2025.46.250013","url":null,"abstract":"<p><p>Angioedema is nonpitting swelling that involves the deeper subcutaneous and submucosal layers of tissue. Angioedema can be classified as histaminergic, bradykinin mediated, or idiopathic in etiology. Bradykinin-mediated angioedema presents without urticaria, whereas histaminergic angioedema is usually associated with urticaria (i.e., chronic spontaneous urticaria and angioedema) but manifests with isolated angioedema in ∼20% of patients and clinically overlaps with idiopathic angioedema. Bradykinin-mediated angioedema most commonly occurs in hereditary angioedema (HAE) with or without C1-esterase inhibitor (C1-INH) (HAE-C1INH) deficiency, acquired C1-INH deficiency, and angiotensin-converting enzyme (ACE) inhibitor angioedema. HAE is a life-threatening genetic autosomal dominant disorder most commonly due to a mutation in the serpin family G member 1 (SERPING1) gene, which leads to a deficiency in C1-INH, although multiple new genetic mutations have also been described in HAE with normal C1-INH (HAE-nl-C1INH) level. Clinically, patients have edema that can lead to life-threatening laryngeal edema and asphyxiation. HAE-nl-C1INH describes patients with similar symptoms to those with HAE-C1INH deficiency but have normal C1-INH function and are distinguished by various genetic mutations and a family history of angioedema. Acquired C1-INH deficiency also mimics HAE with symptoms but is due to circulating anti-idiotypic antibodies, leading to either C1-INH consumption or inactivation. Patients are often diagnosed with underlying malignant, lymphoproliferative, or autoimmune disorders. ACE-inhibitor angioedema classically presents with facial, tongue, and oral cavity swelling not associated with pruritus accompanied by normal laboratory studies. Treatment involves stopping the ACE inhibitor though recurrence can occur for a few weeks to months after discontinuation. Idiopathic angioedema is the largest category and is diagnosed when patients experience angioedema without an identifiable etiology with nl-C1INH function and no family history of angioedema. Idiopathic angioedema is further characterized into histaminergic or nonhistaminergic angioedema, depending on the response to high-dose antihistamines. Given the considerable impact of angioedema, physicians and patients must collaborate to craft personalized management strategies. For those with HAE, short- and long-term prophylaxis and on-demand therapy must be considered.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"185-191"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cankat Genis, Fatma Nur Kuzucu, Ahmet Selmanoglu, Kezban Ipek Demir, Zeynep Sengul Emeksiz, Emine Dibek Misirlioglu
{"title":"Antibiotic allergy in children: Can the severity and characteristics of the index reaction predict drug provocation test results?","authors":"Cankat Genis, Fatma Nur Kuzucu, Ahmet Selmanoglu, Kezban Ipek Demir, Zeynep Sengul Emeksiz, Emine Dibek Misirlioglu","doi":"10.2500/aap.2025.46.250010","DOIUrl":"10.2500/aap.2025.46.250010","url":null,"abstract":"<p><p><b>Background:</b> Antibiotic allergy in children is often misdiagnosed. The criterion standard for confirming drug allergy is the drug provocation test (DPT) based on the patient's history and clinical findings. <b>Objective:</b> This study aimed to assess whether the characteristics and the severity grades of the index reaction can accurately predict DPT outcomes in children with suspected antibiotic allergy. <b>Methods:</b> A retrospective study was conducted from 2014 to 2024, which included children with immediate-type index and provocation reactions. Data included age, type, duration, severity grades of reactions, and suspected antibiotic. Reactions were graded by using the Brown scoring system. Statistical analyses included the Spearman correlation and kappa coefficient. <b>Results:</b> Seventy-three children with negative skin test results underwent DPT in this study. Urticaria was the most common reaction, which occurred in 46.6% of index and 57.5% of provocation reactions. Brown's grading showed 64 grade 1, 5 grade 2, 3 grade 3, and 1 ungraded index reactions. The Brown grading showed 64 grade 1, 5 grade 2, and 3 grade 3 reactions, and 1 ungraded index reaction. For provocation, 64 grade 1, 6 grade 2, 1 grade 3, and 2 were ungraded. There was moderate agreement between the index and provocation reaction types (kappa = 0.348; p < 0.001). A significant agreement was found between urticaria in the index reaction and anaphylaxis during the DPT (kappa = 0.173; p = 0.009). Moderate agreement was also observed for index and provocation anaphylaxis (kappa = 0.480; p < 0.001). In addition, a positive correlation was noted between the severity of the index and provocation reactions (Spearman = 0.460; p < 0.001). <b>Conclusion:</b> The severity and characteristics of index reactions provide valuable insight into the outcome of DPT. The Brown grading system is a valuable tool for predicting DPT outcomes, including severe reactions. Urticaria and anaphylaxis during the index reaction may be predictors of severe outcomes in DPT and should be closely monitored. Understanding the characteristics and severity of the index reaction and incorporating them into clinical practice may facilitate the prediction of DPT outcomes, guide clinical decision-making, improve diagnostic accuracy, and enhance patient safety.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"227-234"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early-life risk factors for recurrent wheezing in preschool children: A meta-analysis of 15 cohort studies.","authors":"Kaiwen Zheng, Xiang Wang","doi":"10.2500/aap.2025.46.250020","DOIUrl":"10.2500/aap.2025.46.250020","url":null,"abstract":"<p><p><b>Background:</b> Recurrent wheezing (RW) is particularly prevalent in preschool-age children and is strongly associated with the future development of asthma. <b>Objective:</b> Because no meta-analysis of risk factors for RW comprehensively assess is needful. <b>Methods:</b> The research was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of English-language studies was performed across four medical literature data bases. Subgroup analyses, sensitivity analyses, and evaluations of publication bias were carried out. Multiple cohort studies were included. Stata software and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used for data analysis; risk factors associated with positive results were discussed qualitatively. <b>Results:</b> A total of 15 cohort studies that covered 128,065 children were included. Some risk factors, including allergic rhinitis (odds ratio [OR] 4.16 [95% confidence interval {CI}, 1.06-16.33]), family history of asthma (OR 2.14 [95% CI, 1.24-3.69]), food allergy (OR 2.25 [95% CI, 1.73-2.93]), preterm (OR 1.87 [95% CI, 1.36-2.58]), male (OR 1.47 [95% CI, 1.17-1.84]), cesarean section (OR 1.36 [95% CI, 1.08-1.71]), environmental tobacco smoke (OR 2.15 [95% CI, 1.55-2.99]), got positive results. <b>Conclusion:</b> Risk factors for RW in preschool children were sought. This meta-analysis provides a new perspective theoretical basis for preventing childhood asthma.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"e98-e109"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the frequency of allergic diseases in pediatric patients with juvenile idiopathic arthritis.","authors":"Ozge Yilmaz Topal, Nilufer Tekgoz, Melike Mehves Kaplan, Metin Yigit, Azize Pinar Metbulut, Elif Celikel, Ilknur Kulhas Celik, Banu Celikel Acar, Emine Dibek Misirlioglu","doi":"10.2500/aap.2025.46.250022","DOIUrl":"10.2500/aap.2025.46.250022","url":null,"abstract":"<p><p><b>Objective:</b> Allergic diseases are characterized by a T-helper type 2 (Th2) dominant immune response, whereas juvenile idiopathic arthritis (JIA) is an autoimmune condition attributed to the Th1 pathway of CD4<sup>+</sup> T cells. Reciprocal inhibition between the Th1 and Th2 responses is proposed to result in mutual exclusion of their polarized immune responses and associated diseases. This study aimed to ascertain the frequency of allergic diseases among children with JIA. <b>Methods:</b> The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to assess symptoms of allergic diseases in children with JIA and a control group of children with no known autoimmune diseases. The presence of current wheezing, allergic rhinitis and/or rhinoconjunctivitis symptoms, eczema symptoms, and food allergy symptoms were assessed based on affirmative answers. <b>Results:</b> The ISAAC questionnaire was administered to 101 children with JIA and 99 healthy controls. The median (interquartile range [IQR]) age was 12.64 years (8.83-15.83 years) in the JIA group and 11.99 years (6.65-14.90 years) in the control group. Children with JIA had lower rates of current wheezing (p = 0.003), current allergic rhinitis (p < 0.001), current rhinoconjunctivitis (p = 0.006), current atopic dermatitis (p < 0.001), and current food allergy (p = 0.005) symptoms. In addition, ever having had allergic rhinitis, wheezing, and atopic dermatitis were less common in the JIA group. In the multivariate logistic regression model, the absence of autoimmune disease in the patient and the presence of any allergic disease in the mother emerged as independent risk factors for current wheezing symptoms and current rhinoconjunctivitis and/or rhinitis. <b>Conclusion:</b> The results of this study demonstrated that the frequency of allergic diseases was lower in the presence of JIA, an autoimmune disease. This offers further evidence of mutual opposition between diseases that involve the Th1 and Th2 pathways, but there remains no consensus on this matter. More comprehensive studies that delve into the molecular foundations of these diseases are still needed to reach more definitive conclusions.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"e110-e116"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hatice Serpil Akten, Emel Dilek, Mehmet Orman, Emine Nihal Mete Gokmen
{"title":"Can depression and anxiety be predicted in hereditary angioedema? A comprehensive assessment.","authors":"Hatice Serpil Akten, Emel Dilek, Mehmet Orman, Emine Nihal Mete Gokmen","doi":"10.2500/aap.2025.46.250017","DOIUrl":"10.2500/aap.2025.46.250017","url":null,"abstract":"<p><p><b>Background:</b> Hereditary angioedema (HAE) is a rare genetic disorder marked by unpredictable episodes of recurrent swelling. This unpredictability, combined with the risk of death and its impact on daily life, leads to significant psychological distress, which profoundly affects patients' quality of life. <b>Objective:</b> This study assessed the levels of depression, general anxiety, and death anxiety in patients with HAE, along with the factors that influence them. <b>Methods:</b> This single-center cohort study included patients ages ≥18 years and with HAE type 1 or 2, who were followed up at the Allergy and Clinical Immunology Department, Medical Faculty, Ege University, between December 2023 and September 2024. Participants completed questionnaires with regard to their demographics, general health, and disease characteristics. In addition, their psychological conditions were assessed by using the Hospital Anxiety and Depression Scale (HADS) and Templer Death Anxiety Scale, a tool that has not been previously applied to this group. <b>Results:</b> One hundred patients participated in the study, with a mean ± standard deviation age of 40.5 ± 14.5 years; 66% (n = 66) were women. Among the participants, 30% (n = 30) had a family history of death related to HAE, and 74% (n = 74) reported experiencing oropharyngeal/laryngeal edema. Anxiety was observed in 54% of the patients (n = 54), whereas 36% (n = 36) experienced depression. Women had higher levels of anxiety than men (p = 0.048), and younger patients (ages <65 years) exhibited greater anxiety levels (p = 0.022). Mild-to-moderate depression was more prevalent among patients who had experienced a recent laryngeal attack (p = 0.031). Seventy-seven percent of the patients (n = 77) reported experiencing death anxiety, which was notably higher in those who had recent laryngeal attacks (p = 0.004) and moderate-to-severe attacks (p = 0.003). <b>Conclusion:</b> Patients with HAE, especially those who experienced frequent severe attacks or recent laryngeal episodes, face a higher risk of psychological distress.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"e71-e81"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehmet Emin Gerek, Fatih Colkesen, Tugba Onalan, Fatma Arzu Akkus, Mehmet Kilinc, Recep Evcen, Selim Kahraman, Sevket Arslan
{"title":"Selective immunoglobulin E deficiency and its association with autoimmune and autoinflammatory diseases.","authors":"Mehmet Emin Gerek, Fatih Colkesen, Tugba Onalan, Fatma Arzu Akkus, Mehmet Kilinc, Recep Evcen, Selim Kahraman, Sevket Arslan","doi":"10.2500/aap.2025.46.250016","DOIUrl":"10.2500/aap.2025.46.250016","url":null,"abstract":"<p><p><b>Background:</b> Selective immunoglobulin E deficiency (sIgED) is a rare condition characterized by low serum IgE levels with normal levels of other immunoglobulin classes. The prevalence of sIgED varies considerably across populations, with a higher prevalence observed in clinical settings. Studies report sIgED prevalence that ranges up to 9.7% in patients attending rheumatology clinics, 8.1% in allergy/immunology clinics, and 2.6% in healthy blood donors. Its role in immune regulation and association with autoimmune and autoinflammatory disorders remains poorly understood. <b>Objective:</b> This study aimed to investigate the relationship between sIgED and immune-mediated diseases by hypothesizing that sIgED may predispose individuals to an increased prevalence of these conditions. <b>Methods:</b> This retrospective cohort study analyzed data from 3692 patients at a tertiary care center between November 2018 and December 2023. Patients with IgE levels ≤2.5 IU/mL and normal levels of other immunoglobulin classes were classified as having sIgED, whereas those with IgE levels >2.5 IU/mL served as controls. Autoimmune and autoinflammatory diseases were identified by using medical records and International Classification of Diseases codes. Statistical analyses were performed to compare the prevalence of these conditions between the groups. <b>Results:</b> The prevalence of autoimmune and autoinflammatory diseases was significantly higher in the sIgED group versus controls (25.2% versus 15.6%; p < 0.001). Conditions such as Hashimoto thyroiditis, vitiligo, familial Mediterranean fever, and Behçet disease were disproportionately observed in patients with sIgED. Demographic characteristics, including age and gender, were not significantly different between the groups (p = 0.171 and p = 0.257, respectively). <b>Conclusion:</b> The sIgED is associated with a higher prevalence of autoimmune and autoinflammatory diseases, which underscores its potential role in immune dysregulation. This finding highlights the need for further prospective, multicenter studies to validate these associations, elucidate underlying mechanisms, and explore potential clinical implications of IgE deficiency in immune-mediated pathologies.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"e91-e97"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehmet Halil Celiksoy, Ilke Yildirim, Kubra Yirgin, Zeynep Haziroglu Okmen
{"title":"Risk factors predisposing children to transient hypogammaglobulinemia of infancy.","authors":"Mehmet Halil Celiksoy, Ilke Yildirim, Kubra Yirgin, Zeynep Haziroglu Okmen","doi":"10.2500/aap.2025.46.250019","DOIUrl":"10.2500/aap.2025.46.250019","url":null,"abstract":"<p><p><b>Introduction:</b> Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder characterized by reduced serum immunoglobulin G (IgG) levels in early infancy. <b>Objective:</b> This study aimed to identify potential risk factors associated with THI. <b>Methods:</b> Children with THI and normoglobulinemic healthy children were compared by using a questionnaire that addressed possible risk factors. <b>Results:</b> In total, 108 participants were enrolled, 54 patients with THI and 54 healthy controls. The median age at diagnosis of the patients with THI was 17 months (range, 4-38 months), and 40 (74.1%) were boys. In the control group, the median age was 22 months (range, 16-61 months), and 27 (50.0%) were boys. Male sex (p = 0.004), cesarean section birth (p = 0.003), low maternal education (p = 0.001), low paternal education (p = 0.004), analgesic use during pregnancy (p = 0.001), antibiotic use during pregnancy (p = 0.001), multivitamin use during pregnancy (p = 0.001), gestational diabetes or preeclampsia (p = 0.039), smoking exposure (p = 0.001), atopic disease (p = 0.001), and familial atopy (p = 0.001) were associated with THI, whereas low socioeconomic level (p = 0.001) and breast-feeding for > 6 months (p = 0.032) were less likely in the THI group. <b>Conclusion:</b> There are several features of pregnancy history and family demographics that are associated with THI.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"e117-e124"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-bag rapid drug desensitization for chemotherapeutic hypersensitivity reactions: A single-center experience.","authors":"Ozcan Gul, Makbule Seda Bayrak Durmaz, Reyhan Yıldız, Fuat Aytekin, Nazan Beyhan, Orhun Efe, Sevim Bavbek","doi":"10.2500/aap.2025.46.250014","DOIUrl":"10.2500/aap.2025.46.250014","url":null,"abstract":"<p><p><b>Background:</b> Rapid drug desensitization (RDD) is a procedure that provides temporary tolerance to chemotherapeutics for appropriate patients who experience hypersensitivity reactions (HSR), which allow them to continue their treatments. Due to the labor-intensive and time-consuming nature of the commonly used multiple-bag RDD procedure, there is a need to develop an alternative protocol. We aimed to share our experiences with single-bag RDD in patients experiencing HSRs with chemotherapeutics. <b>Methods:</b> The study was conducted by retrospectively reviewing the files of patients who experienced immediate-type HSRs to chemotherapeutics and underwent single-bag RDD. The severity of HSRs was classified according to the Brown grading system. Prick and/or intradermal skin tests were performed with the relevant agents. The protocols were applied as a single-bag, 12-step process. <b>Results:</b> The study comprised 46 patients (women/men, 35/11; mean ± standard deviation age, 55.9 ± 11.9 years; 27 HSRs to platinums; 16 HSRs to taxanes; and 3 HSRs to biologic agents). Nine patients (19.6%) had an initial HSR of grade 1, 26 patients (56.5%) had an initial HSR of grade 2, and 11 patients (23.9%) had an initial HSR of grade 3. The skin testing result with the responsible drug was positive in 15 of 42 (35.7%), and the rate of positive responses in patients with grade 1, 2, and 3 initial HSRs was 37.5%, 33.3%, and 40%, respectively. A total of 163 single-bag RDDs procedures were performed, and 17 breakthrough reactions (BTR) occurred during the procedure (five of these reactions [29.5%] were grade 1; nine [53.9%] were grade 2; three [17.6%] were grade 3). Of these BTRs, 16 occurred with platinums and one with rituximab; no BTRs were observed with taxanes. In conclusion, 99.3% of the total 163 single-bag RDD procedures were successfully completed. <b>Conclusion:</b> Our experience indicates that single-bag RDD can be a safe and effective alternative that saves time and labor in appropriate patients.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 3","pages":"240-246"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eli Magen, Eugene Merzon, Ilan Green, Israel Magen, Avivit Golan-Cohen, Shlomo Vinker, Ariel Israel
{"title":"Allergic comorbidities in fibromyalgia.","authors":"Eli Magen, Eugene Merzon, Ilan Green, Israel Magen, Avivit Golan-Cohen, Shlomo Vinker, Ariel Israel","doi":"10.2500/aap.2025.46.240080","DOIUrl":"10.2500/aap.2025.46.240080","url":null,"abstract":"<p><p><b>Background:</b> The relationship between fibromyalgia (FM) and allergic diseases remains poorly understood, despite emerging evidence that suggests a possible association. <b>Objective:</b> This study aimed to evaluate the prevalence of allergic comorbidities in patients with FM compared with a matched control group. <b>Methods:</b> We conducted a retrospective, population-based case-control study within Leumit Health Services, which caters to ∼750,000 members. Patients meeting the evolving criteria of the American College of Rheumatology from January 2002 to December 2023 were included. Control subjects were selected from the same population base but did not have a diagnosis of FM, were matched 5:1 on sex, age, and year of first membership. All diagnoses were identified by using International Classification of Diseases, Ninth Revision (ICD-9) codes up to March 2024. <b>Results:</b> The analysis included 15,869 patients diagnosed with FM and 79,345 matched controls. There was a predominant female representation (82.1%) in both groups. The prevalence of bronchial asthma was higher in patients with FM compared with the controls, with an odds ratio (OR) of 1.91. The patients with FM also exhibited higher rates of both nonseasonal and seasonal allergic rhinitis, with ORs of 1.60 and 1.30, respectively, and chronic rhinosinusitis without nasal polyps demonstrated an OR of 2.46. Acute allergic conjunctivitis had an OR of 2.05. Skin-related allergies such as contact dermatitis and atopic dermatitis showed ORs of 1.48 and 1.41, respectively. Furthermore, the patients with FM displayed elevated rates of various forms of urticaria and chronic pruritus, alongside higher incidences of food allergies and specific drug allergies. Anaphylactic reactions to food were notably more common in patients with FM, who presented an OR of 2.50. <b>Conclusion:</b> FM is associated with a higher prevalence of allergic diseases compared with the controls. Analysis of these findings suggests the need for allergological assessments in FM management.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 2","pages":"e33-e42"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dongmei Li, Idalia Cruz, Sharareh Sorkhabi, Patricia L Foley, Julie Wagner, Joseph A Bellanti
{"title":"Dose-response studies of methylated and nonmethylated CpG ODNs from <i>Bifidobacterium</i> longum subsp. <i>infantis</i> for optimizing Treg cell stimulation.","authors":"Dongmei Li, Idalia Cruz, Sharareh Sorkhabi, Patricia L Foley, Julie Wagner, Joseph A Bellanti","doi":"10.2500/aap.2025.46.250001","DOIUrl":"10.2500/aap.2025.46.250001","url":null,"abstract":"<p><p><b>Background:</b> Allergen immunotherapy (AIT) is the most effective treatment for atopic allergic diseases, aiming to induce regulatory T cells (Treg) that modify the immune response to specific allergens, which leads to long-term tolerance and reduced symptoms. Enhancing Treg activity is crucial for improving immunotherapy outcomes. In a previous murine model study, we examined the effects of a synthetic methylated DNA oligodeoxynucleotide (ODN) from the Bl-T2 m5C motif of <i>Bifidobacterium longum</i> subsp. <i>infantis</i>. The ODN that contains the methylated BI-T2 m5C motif (methylated ODNA) sequence conjugated with ovalbumin induced Treg production, whereas ODN that contains the unmethylated BI-T2 m5C motif (unmethylated ODNB) induced proinflammatory responses, which demonstrated the potential of methylated ODNs for AIT. <b>Objective:</b> In building on these results, this study explored the effects of methylated and nonmethylated DNA motifs from <i>B. longum</i> subsp. <i>infantis</i> on inflammation and Treg induction, while investigating the dose-response relationships of methylated Cytosine-phosphate-Guanine (CpG) ODNs for optimal Treg stimulation in clinical applications. <b>Methods:</b> Serum levels of IL-17A, IL-4, IL-10, and transforming growth factor beta (TGF-β) were measured by enzyme linked immunosorbent assay (ELISA), and flow cytometry assessed splenic Treg populations in BALB/c mice receiving graded doses of methylated or unmethylated ODNs. Mice were immunized intraperitoneally with a single 100-μg dose (plan A) or multiple 25 μg (plan B) or 100 μg (plan C) doses. Calf thymic DNA served as a positive control, with phosphate-buffered saline solution and alum as negative controls. <b>Results:</b> Methylated ODNs significantly increased CD25<sup>+</sup>FOXP3<sup>+</sup> Tregs compared with unmethylated ODNs and controls. Plan A (100 μg) elevated serum IL-10, which indicated effective Treg induction, whereas plan B (four 25 μg doses) did not activate Tregs. Plan C (multiple 100 μg doses) reduced Treg responses, which highlighted a critical dosing threshold for optimal Treg induction. <b>Conclusion:</b> This study demonstrated the potential of methylated DNA motifs as therapeutic agents in AIT. The dose-response relationships of methylated CpG ODNs from <i>B. longum</i> pave the way for clinical applications that target Treg activity in allergic diseases.</p>","PeriodicalId":7646,"journal":{"name":"Allergy and asthma proceedings","volume":"46 2","pages":"98-104"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}