Effects of Sex and Gender in Immediate Beta-Lactam Antibiotic Allergy: A Systematic Review and Meta-analysis.

BACKGROUND: Beta-lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of beta-lactam antibiotics. OBJECTIVE: This systematic review and meta-analysis aimed to identify sex and gender-based differences in the prevalence of immediate beta-lactam allergy. METHODS: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013-2023. Patients with a documented beta-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in beta-lactam allergy with meta-analysis. RESULTS: We included 69 primary studies, assessing 53,989 participants from outpatient and inpatient cohorts. 7,558 patients had a confirmed beta-lactam allergy. There was no difference in the prevalence of positive beta-lactam allergy test between males and females. Sub-group analysis of studies that performed oral challenges did show a higher risk of beta-lactam allergy in females than males (RR 1.40, 95% CI 1.18-1.66, p < 0.001, I2 =77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in beta-lactam allergy studies. CONCLUSIONS: Our findings suggest both sex-based and gender-based differences in the prevalence of immediate beta-lactam allergy. Both biological factors, such as sex hormones, and gender-based behaviors, including increased healthcare utilization, may contribute to higher rates of beta-lactam allergy diagnosis in females.

An Unusual Transition from Cutaneous to Systemic Mastocytosis in a Pediatric Patient.

Background: Cutaneous mastocytosis (CM) occurs when abnormal mast cells accumulate in the skin, whereas in systemic mastocytosis (SM), accumulation also occurs in other tissues. A transition from CM to SM is an atypical occurrence in pediatric patients. Case Presentation: An 8-month-old female presented with a 3-month history of whole body hyperpigmented macules with a normal serum tryptase level, consistent with a diagnosis of CM. At age 2.5 years, cutaneous lesions increased and repeat serum tryptase levels were elevated. Subsequent positive peripheral blood KIT D816V mutation testing furthered concern for a monoclonal mast cell disorder; therefore, prompting a bone marrow biopsy which was consistent with a diagnosis of SM. Conclusion: Our case depicts the possible transition from CM to SM in a pediatric patient. Despite an initial presentation consistent with a diagnosis of CM, watchful monitoring for signs and symptoms indicative of systemic involvement may be warranted in some pediatric patients.

Clinical Presentation of Schnitzler's Syndrome: A Rare Autoimmune Disease.

Schnitzler's Syndrome (SS) is a rare late-onset acquired autoinflammatory disorder which consists of chronic urticaria associated with a monoclonal IgM-kappa gammopathy, arthralgias, skeletal hyperostosis, lymphadenopathy, and recurrent constitutional symptoms. The average age of diagnosis is 51 years with a slight male predominance with a male to female ratio of 1.6. Diagnosis of SS requires the presence of 2 major criteria including chronic urticaria and monoclonal IgM along with at least two of the following minor criteria: recurrent intermittent fevers, bone pain, arthralgias, elevated erythrocyte sedimentation rate (ESR), neutrophilic dermal infiltrate on skin biopsy, and leukocytosis or elevated C-reactive protein (CRP). Early diagnosis and clinical awareness are paramount in SS as it is associated with a 15-20% risk of lymphoproliferative malignancy. The median overall survival is 12.8 years. We present a case of a 39-year-old female with new onset urticaria associated with recurrent fevers and joint pain. Symptoms were refractory to steroids, and high dose antihistamines. Multi-disciplinary evaluation resulted in the ultimate diagnosis of Schnitzler's Syndrome. The patient was ultimately treated with canakinumab (Il-1 inhibitor), with near resolution of symptoms. This case demonstrates the importance of a broad differential diagnosis and maintaining a high clinical suspicion for rare diseases when presented with a complex form of an otherwise common condition.

Global disparities in availability of epinephrine auto-injectors.

Background: Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis - both acute and preventative - varies by region. Methods: The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. Results: Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. Conclusion: This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.

Sex differences in a murine model of asthma are time and tissue compartment dependent.

CONCLUSION: Sexual dimorphism in lung inflammation is both time and tissue compartment dependent. Spatiotemporal variability in sex differences in a murine model of asthma must be accounted for when planning experiments to model the sex bias in allergic inflammation.

Prevention of Recurrent Attacks of Hereditary Angioedema (HAE): Berotralstat and Its Oral Bioavailability.

Hereditary angioedema (HAE) is a condition characterized by episodes of cutaneous and submucosal edema. Angioedema of the extremities and abdominal attacks are the most common manifestations of the disease. It can also affect the upper airways with the potential of becoming life-threatening. The two most common causes of HAE are a deficiency of C1 inhibitor (classified as type 1 HAE) or a dysfunction of C1 inhibitor (type 2 HAE). A malfunction or deficiency of C1 inhibitor leads to an overactivated plasma kallikrein (an inflammatory vasoactive peptide), that increases bradykinin, mediating the angioedema episodes in patients with HAE. To minimize the difficulties of this pathology and to improve patients' quality of life, prevention of this condition is essential. Berotralstat is a unique option for oral administration for routine prophylaxis. This drug acts by binding to kallikrein and reducing its plasma activity, lowering bradykinin levels. Open-label studies have demonstrated the effectiveness of a single daily dose of berotralstat 150 mg in preventing HAE attacks. This review aims to examine studies performed to elucidate the efficacy, safety, and tolerability of berotralstat.

Dupilumab-Associated Head and Neck Dermatitis With Ocular Involvement in a Ten-Year-Old With Atopic Dermatitis: A Case Report and Review of the Literature.

Facial and neck erythema secondary to dupilumab use is a side effect not reported in clinical trials; however, it has been reported aftermarket initially in adults and most recently in adolescents. We report the youngest known case of head and neck dermatitis (HND) secondary to Malassezia furfur accompanied by ocular involvement. Treatment with oral fluconazole 150 mg weekly was initiated with subsequent cutaneous improvement. Additionally, his conjunctivitis improved with fluorometholone 0.1% eye drops. As dupilumab becomes more accessible to children, understanding the pathophysiology of HND, characterizing the clinical course, and developing diagnostic and treatment guidelines for this age group will be imperative.

Digital tools in allergy and respiratory care.

Patient care in the allergy and respiratory fields is advancing rapidly, offering the possibility of the inclusion of a variety of digital tools that aim to improve outcomes of care. Impaired access to several health care facilities during the COVID-19 pandemic has considerably increased the appetite and need for the inclusion of e-health tools amongst end-users. Consequently, a multitude of different e-health tools have been launched worldwide with various registration and access options, and with a wide range of offered benefits. From the perspective of both patients and healthcare providers (HCPs), as well as from a legal and device-related perspective, several features are important for the acceptance, effectiveness,and long-term use of e-health tools. Patients and physicians have different needs and expectations of how digital tools might be of help in the care pathway. There is a need for standardization by defining quality assurance criteria. Therefore, the Upper Airway Diseases Committee of the World Allergy Organization (WAO) has taken the initiative to define and propose criteria for quality, appeal, and applicability of e-health tools in the allergy and respiratory care fields from a patient, clinician, and academic perspective with the ultimate aim to improve patient health and outcomes of care.

Clinical and Phenotypic Characterization of Common Variable Immunodeficiency Diagnosed in Younger and Older Adults.

PURPOSE: Common variable immunodeficiency (CVID) is the most prevalent symptomatic immunodeficiency in adults. Little is known about the manifestations of CVID presenting in older adults. Herein, we performed a phenotypic characterization of patients diagnosed older than age 40. METHODS: A retrospective chart review of 79 patients seen at UF Health between 2006 and 2020 with a verified diagnosis of CVID per the ICON 2016 criteria was conducted. Patients were classified according to four phenotypes: no-disease-related complications, autoimmune cytopenias, polyclonal lymphoproliferation, and unexplained enteropathy. Patients diagnosed with CVID from age 2 to 40 (n = 41, "younger cohort") were compared to patients diagnosed with CVID age 41 and older (n = 38, "older cohort"). RESULTS: Among the younger cohort, pathologic genetic variants, positive family history for immunodeficiency, autoimmunity (49% vs 24%, p = 0.03), and splenomegaly (46% vs 16%, p = 0.004) were more common, as was the "autoimmune cytopenias" phenotype (24% vs 3%, p = 0.007). Among the older cohort, lymphoma (11% vs 0%, p = 0.049) and the "no disease-related complications" phenotype (79% vs 57%, p = 0.03) were more commonly seen. Comorbidities such as bronchiectasis (27% vs 21%, p = 0.61), GI involvement (34% vs 24%, p = 0.33), and GLILD (5% vs 8%, p = 0.67) were equally present among both the younger and older cohorts, respectively. CONCLUSION: The lower incidence of autoimmunity and splenomegaly, as well as overlapping clinical features with immunosenescence, may make diagnosing CVID in older patients more challenging; however, the disease is not more indolent as the risks for lymphoma, bronchiectasis, and GLILD are similar to those of younger patients.

Pentoxifylline in the Treatment of Cutaneous Leishmaniasis: A Randomized Clinical Trial in Colombia.

Addition of the immunomodulator pentoxifylline (PTX) to antimonial treatment of mucosal leishmaniasis has shown increased efficacy. This randomized, double-blind, placebo-controlled trial evaluated whether addition of pentoxifylline to meglumine antimoniate (MA) treatment improves therapeutic response in cutaneous leishmaniasis (CL) patients. Seventy-three patients aged 18−65 years, having multiple lesions or a single lesion ≥ 3 cm were randomized to receive: intramuscular MA (20 mg/kg/day × 20 days) plus oral PTX 400 mg thrice daily (intervention arm, n = 36) or MA plus placebo (control arm, n = 37), between 2012 and 2015. Inflammatory gene expression was evaluated by RT-qPCR in peripheral blood mononuclear cells from trial patients, before and after treatment. Intention-to-treat failure rate was 35% for intervention vs. 25% for control (OR: 0.61, 95% CI: 0.21−1.71). Per-protocol failure rate was 32% for PTX, and 24% for placebo (OR: 0.50, 95% CI: 0.13−1.97). No differences in frequency or severity of adverse events were found (PTX = 142 vs. placebo = 140). Expression of inflammatory mediators was unaltered by addition of PTX to MA. However, therapeutic failure was associated with significant overexpression of il1ß and ptgs2 (p < 0.05), irrespective of study group. No clinical benefit of addition of PTX to standard treatment was detected in early mild to moderate CL caused by Leishmania (V.) panamensis.

Myocarditis following mRNA vaccination against SARS-CoV-2, a case series.

INTRODUCTION: mRNA COVID-19 vaccines have emerged as a new form of vaccination that has proven to be highly safe and effective against COVID-19 vaccination. Rare adverse events including myocarditis have been reported in the literature. METHODS: Data were gathered from the electronic medical record of four patients personally treated by the authors. RESULTS: Four patients, ages 20 to 30, presented with myocarditis characterized by chest pain, elevations in troponin-I and C-reactive protein, and negative viral serologies two to four days following mRNA vaccine administration. One had a cardiac MRI showing delayed gadolinium enhancement in a subpericardial pattern. All experienced symptom resolution by the following day, and the two who have returned for follow-up had normal troponin-I and CRP values. DISCUSSION: Along with previously reported instances, these cases raise suspicion for a possible link between mRNA vaccines and myocarditis.

Metabolism of Epithelial Cells in Health and Allergic Disease: Collegium Internationale Allergologicum Update 2021.

Concomitant dramatic increase in prevalence of allergic and metabolic diseases is part of a modern epidemic afflicting technologically advanced societies. While clinical evidence points to clear associations between various metabolic factors and atopic disease, there is still a very limited understanding of the mechanisms that link the two. Dysregulation of central metabolism in metabolic syndrome, obesity, diabetes, and dyslipidemia has a systemic impact on multiple tissues and organs, including cells of the epithelial barrier. While much of epithelial research in allergy has focused on the immune-driven processes, a growing number of recent studies have begun to elucidate the role of metabolic components of disease. This review will revisit clinical evidence for the relationship between metabolic and allergic diseases, as well as discuss potential mechanisms driving metabolic dysfunction of the epithelial barrier. Among them, novel studies highlight links between dysregulation of the insulin pathway, glucose metabolism, and loss of epithelial differentiation in asthma. Studies of mitochondrial structure and bioenergetics in lean and obese asthmatic phenotypes recently came to light to provide a novel framework linking changes in tricarboxylic acid cycle and oxidative phosphorylation with arginine metabolism and nitric oxide bioavailability. New research established connections between arachidonate metabolism, autophagy, and airway disease, as well as systemic dyslipidemia in atopic dermatitis and ceramide changes in the epidermis. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease.

Risk for Anaphylactic Reaction from Cardiac Catheterization in Patients Receiving ß-Adrenergic Blockers or Angiotensin-Converting Enzyme-Inhibitors.

BACKGROUND: ß-Adrenergic blockers (BBs) have been associated with increased risk for severe anaphylactic reaction (AR) from contrast media; however, this was shown with intravenous contrast media, before widespread use of low osmolar contrast media, angiotensin-converting enzyme-inhibitors (ACE-Is), and cardioselective BBs. OBJECTIVE: To assess the risk for AR during cardiac catheterization (CC) associated with BB or ACE-I exposure. METHODS: Patients who experienced adverse reactions during CC from January 2004 to December 2013 were identified; 1 to 2 matched controls were assigned for each case. We analyzed AR rates in association with demographic variables, medication exposures (BBs, ACE-Is, angiotensin-receptor blockers, aspirin), and comorbidities: cardiovascular disorders, asthma, and atopy. RESULTS: We analyzed 71,782 CCs. Of these, severe 70 reactors were identified-46 (0.06%) fulfilled AR criteria. There were 35 cases of mild to moderate AR and 11 cases of severe AR (0.015%). There were no significant differences in age (61.3% vs 61.5%), sex (63% vs 64% males), cardiovascular disorder rate (78% vs 93%), and exposure to BBs (46% vs 51%; cardioselective: 77% vs 80%) and ACE-Is (37.0% vs 37.2%) in cases versus controls. Via multivariate logistic regression, BB exposure was not associated with greater AR frequency (P = .35) or severity (P = .40). Neither cardioselective BBs (P = 0.2) nor noncardioselective BBs (P = .5) influenced AR severity. ACE-Is had no effect on AR frequency (P = .35) or severity (P = .14). Lower AR frequency was associated with cardiovascular disorder (P = .01). CONCLUSIONS: In this case-control study, severe AR was rarely observed. Exposure to BBs or ACE-Is did not significantly influence AR frequency or severity; however, most BBs were cardioselective. Our findings imply that cardioselective BB or ACE-I suspension is not warranted in association with CC.

Gene expression of TMEM178, which encodes a negative regulator of NFATc1, decreases with the progression of asthma severity.

In two independent microarray studies involving primary airway epithelial cells, the relative gene expression of TMEM178 decreases with the progression of asthma severity. Our manuscript creates a paradigm for future studies dissecting the role of Tmem178 in the pathogenesis of severe asthma.

YouTube and food allergy: An appraisal of the educational quality of information.

BACKGROUND: Food allergy affects an estimated 8% of children and 3% of adults in the United States. Food-allergic individuals increasingly use the web for medical information. We sought to determine the educational quality of food allergy YouTube videos. METHODS: We performed a YouTube search using keywords "food allergy" and "food allergies". The 300 most viewed videos were included and analyzed for characteristics, source, and content. Source was further classified as healthcare provider, alternative medicine provider, patient, company, media, and professional society. A scoring system (FA-DQS) was created to evaluate quality (-10 to +34 points). Negative points were assigned for misleading information. Eight reviewers scored each video independently. RESULTS: Three hundred videos were analyzed, with a median of 6351.50 views, 19 likes, and 1 dislike. More video presenters were female (54.3%). The most common type of video source was alternative medicine provider (26.3%). Alternative treatments included the following: water fast, juicing, Ayurveda, apple cider, yoga, visualization, and sea moss. Controversial diagnostics included kinesiology, IgG testing, and pulse test. Almost half of the videos depicted a non-IgE-mediated reaction (49.0%).Videos by professional societies had the highest FA-DQS (7.27). Scores for videos by professional societies were significantly different from other sources (P < .001). There was a high degree of agreement among reviewers (ICC = 0.820; P < .001). CONCLUSION: YouTube videos on food allergy frequently recommend controversial diagnostics and commonly depict non-IgE-mediated reactions. There is a need for high-quality, evidence-based, educational videos on food allergy.

Diagnostic utility of challenge procedures for physical urticaria/angioedema syndromes: a systematic review.

PURPOSE OF REVIEW: Physical urticaria/angioedema syndromes (PUAs) are commonly encountered. They are identified by a history of physical factors provoking cutaneous symptoms, and confirmed by provocation testing. Recent guidelines have recommended use of challenge procedures for diagnosis; however, their positive/negative likelihood ratios have not been established. RECENT FINDINGS: We conducted a systematic review to determine the diagnostic utility of recommended office procedures for three common PUAs: dermatographia (DERMATO), cholinergic urticaria (CHOL), and delayed pressure urticaria/angioedema (DPUA). In this study, we were unable to identify studies of sufficient methodologic quality to calculate positive/negative likelihood ratios for recommended diagnostic challenges for PUAs. SUMMARY: The study highlights the need for well designed studies to aid the clinician in interpretation of diagnostic challenges for patients with DERMATO, CHOL, and DPUA. There are limited high-quality data available to support the diagnostic utility of office challenges for PUAs. There is a low sensitivity associated with methacholine intradermal challenge for confirming a diagnosis of CHOL.