Primary Atopic Disorders.

Primary atopic disorders describes a series of monogenic diseases that have allergy- or atopic effector-related symptoms as a substantial feature. The underlying pathogenic genetic lesions help illustrate fundamental pathways in atopy, opening up diagnostic and therapeutic options for further study in those patients, but ultimately for common allergic diseases as well. Key pathways affected in these disorders include T cell receptor and B cell receptor signaling, cytokine signaling, skin barrier function, and mast cell function, as well as pathways that have not yet been elucidated. While comorbidities such as classically syndromic presentation or immune deficiency are often present, in some cases allergy alone is the presenting symptom, suggesting that commonly encountered allergic diseases exist on a spectrum of monogenic and complex genetic etiologies that are impacted by environmental risk factors.

Organ-specific allergen challenges in airway allergy: Current utilities and future directions.

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic respiratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial allergen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy.

Atopy and allergy following solid organ transplantation: A 15-year experience.

AIM: There are increasing reports of atopy/allergy following solid organ transplantation, especially paediatric liver transplantation (LT) with minimal New Zealand (NZ) data. We describe the prevalence of transplant-acquired atopy and allergy (TAA) in NZ paediatric liver transplant recipients, compared to paediatric kidney and adult liver transplants. METHODS: TAA focussed health questionnaires were sent to patients selected from the NZ transplant registry (transplanted between January 2003 and December 2017). Demographic and clinical data were also obtained from electronic health records and follow-up phone calls. RESULTS: A total of 232 patients (62% male) participated (111 adult liver, 82 paediatric liver, 39 paediatric kidney transplant recipients). Tacrolimus was primary immunosuppression for all LT patients; with combined tacrolimus, mycophenolate and corticosteroids for kidney transplants. The number of patients who developed TAA was significantly higher (P < 0.001) in the paediatric LT group (36/82, 44%) compared to adult liver (12/111, 11%) and paediatric kidney transplants (4/39, 10%). Eczema was most common (73%), then IgE-mediated food allergy (FA, 33%), allergic rhinitis (19%) and asthma (17%). Six paediatric LT recipients developed eosinophilic oesophagitis (EoE). Egg was the most common allergen in the IgE-mediated FA group. TAAs were severe enough to warrant a switch from tacrolimus to another agent in seven paediatric LT patients. For paediatric LT patients, female gender and younger age at transplant were risk factors for developing TAA. CONCLUSIONS: TAA is common in paediatric liver transplant recipients, with female gender and younger age at transplant being risk factors identified. This highlights the need for detailed atopic and allergy history to be incorporated in all pre-transplant assessments.

Non-immediate hypersensitivity reactions to iomeprol: Diagnostic value of skin tests and cross-reactivity with other iodinated contrast media.

BACKGROUND: Iodinated contrast media produce non-immediate hypersensitivity reactions (NIHR). The goal of this prospective study was to determine the utility of skin tests and the subsequent tolerance to negative skin-tested iodinated contrasts in patients with NIHR caused by iomeprol. METHODS: Prick and intradermal tests with iomeprol, iopamidol, iopromide, and iobitridol were performed in all patients. IV challenge with the causative contrast (iomeprol in 90%) was made if skin tests were negative. In case of a positive skin test with the causal contrast, or a positive challenge test with it, IV challenge test with an alternative, negative skin-tested contrast was performed in all patients. RESULTS: Skin tests were positive in 47.6% (20/42) of patients with NIHR induced by iomeprol. Of the 66 challenge tests performed with negative skin-tested iodinated contrasts, tolerance was confirmed in 35 (53%): 32 iomeron, 2 iobitridol, 1 iopamidol. Cross-reactivity between iomeprol and iopamidol was 22% (4/20 in patients with positive skin tests and 5/21 in patients with negative skin tests). CONCLUSIONS: Sensitivity of the skin tests was less than 50% NIHRs due to iomeprol, while the negative predictive value of skin tests in patients who tolerated challenges with alternative contrasts (mainly iopamidol) was 53% (35 tolerated out of 66 performed). The cross-reactivity between iomeprol and iopamidol is high.

Prenatal antibiotic exposure, asthma, and the atopic march: A systematic review and meta-analysis.

Antibiotic use during pregnancy may increase the risk for asthma in children. We performed a meta-analysis assessing prenatal antibiotic exposure and the risk for childhood wheeze or asthma, as well as for diseases associated with the atopic march. A systematic literature search protocol (PROSPERO-ID: CRD42020191940) was registered and searches were completed using Medline, Proquest, Embase, and the Cochrane central register of controlled trials. Screening for inclusion criteria: published in English, German, French, Dutch, or Arabic, intervention (use of any antibiotic at any time point during pregnancy), and disease (reporting atopic disease incidence in children with a primary outcome of asthma or wheeze), and exclusion criteria: reviews, preclinical data, and descriptive studies, yielded 27 studies. Study quality was assessed using the Newcastle-Ottawa Assessment Scale. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Our meta-analysis demonstrates that antibiotic use during pregnancy is associated with an increased relative risk (RR) of developing wheeze RR 1.51 (95% CI: 1.17-1.94) or asthma RR 1.28 (95% CI 1.22-1.34) during childhood. Assessment of the atopic march in association with asthma or wheeze revealed that antibiotic use during pregnancy also increases the risk for eczema/dermatitis RR 1.28 (95% CI: 1.06-1.53) and allergic rhinitis RR 1.13 (95% CI: 1.02-1.25). One study found an increase in food allergy RR 1.81 (95% CI: 1.11-2.95). Maternal antibiotic use during pregnancy is associated with an increased risk for wheeze or asthma development in children, as well as for diseases involved in the atopic march. There was high heterogeneity in the data, and the certainty of the evidence was determined to be low quality, highlighting the need for more high-quality studies on this topic. These results have importance for antibiotic stewardship throughout the prenatal period. This work was supported by the Deutsche Forschungsgemeinschaft and the Konrad Adenauer Foundation.

Delivery mode and the incidence of atopic sensitization and food allergy in a Finnish child population.

BACKGROUND: Caesarean section (CS) has been associated with an increased risk of subsequent atopic diseases, particularly asthma and respiratory allergies, but controversial findings have also been reported. Our aim was to clarify the association between the delivery mode and longitudinal (atopic) outcomes. METHODS: The target population was identified from the population register and comprised all children born between 2001 and 2006 and living in the province of South Karelia, Finland (N = 5564). The information on the delivery mode was available for 5552 children from the Finnish Medical Birth Register. Results of allergy tests (skin prick tests, specific IgE and open food challenges, OFCs) were collected from patient records of all healthcare units in the area. RESULTS: By 12 years of age, the cumulative incidence of atopic sensitization was 15% for those born by normal vaginal delivery (VD), 20% (adjusted RR 1.28; 95% CI 0.99-1.65) by assisted VD, 20% (adjusted RR 1.28; 95% CI 1.02-1.61) by elective CS and 20% (adjusted RR 1.24; 95% CI 0.99-1.56) by others, for example emergency CS. Among the offspring of mothers without atopic diseases, the incidence of food allergy (positive OFC) was 6% for those born by elective CS and 2% for those born by normal VD (adjusted RR 2.41; 95% CI 1.19-4.88), while the respective incidences were 5% and 6% (adjusted RR 0.82; 95% CI 0.33-2.06) among the offspring of mothers with atopic diseases. CONCLUSION: By adolescence, the cumulative incidences of atopic sensitization was highest among those born by assisted VD or CS. The incidence of food allergy was highest among those born by elective CS among the offspring of mothers without atopic diseases.

Atopy manifestations in pediatric patients with acute lymphoblastic leukemia: correlation assessment with interleukin-4 (IL-4) and IgE level.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in the age range of under 15 years old and accounts for 25-30% of all childhood cancers. Although conventional chemotherapy regimens are used to improve the overall survival rate, it has been associated with some complications, amongst which allergic manifestations with unknown mechanisms are more common. METHODS: Our study compared serum IgE and IL-4 concentration, as a hallmark of allergic responses in pediatric ALL patients before and after 6 months of intensive (high-dose) chemotherapy, to show whether changes in the level of these markers may be associated with atopy. Serum level of IL-4 and IgE was measured using enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The results showed that the level of IgE and IL-4 increased following chemotherapy in both ALL patients with and without atopy. In addition, post-chemotherapy treatment IgE and IL-4 levels were significantly elevated in patients with atopy compared to those without it. The difference between baseline and post-chemotherapy level of IgE and IL-4 was significantly higher in patients with atopy compared to those without it. CONCLUSIONS: To the best of our knowledge, this is the first study that showed a connection between post-chemotherapy allergic manifestations in pediatric ALL patients and IL-4 and IgE level. Flow cytometry analysis of the T-helper 2 (Th2) lymphocytes and other allergy-related T cell subsets like Tc2 and Th9 as well as the study of the genetic variations in atopy-related genes like IL-4/IL-4R, IL-5, IL-9, IL-13, and high affinity FcεRI IgE receptor and also HLA genes is necessary to clearly define the underlying mechanism responsible for post-chemotherapy hypersensitivity reaction in pediatric ALL patients.

Inborn errors of immunity manifesting as atopic disorders.

Inborn errors of immunity are traditionally best known for enhancing susceptibility to infections. However, allergic inflammation, among other types of immune dysregulation, occurs frequently in patients with inborn errors of immunity. As such, the term primary atopic disorders (PADs) was recently coined to describe the group of heritable monogenic allergic disorders. It is becoming increasingly important for clinicians to recognize that allergic diseases such as food allergy, atopic dermatitis, and allergic asthma are expressions of misdirected immunity, and in patients who present with severe, early-onset, or coexisting allergic conditions, these can be indications of an underlying PAD. Identifying monogenic allergic disease through next-generation sequencing can dramatically improve outcomes by allowing the use of precision-based therapy targeting the patient's underlying molecular defect. It is therefore imperative that clinicians recognize PADs to be able to provide informed therapeutic options and improve patient outcomes. Here, we summarize the clinical features commonly seen with each of the currently known PADs, identify clinical warning signs that warrant assessment for PADs, and lastly, discuss the benefits of timely diagnosis and management of these conditions.

Maternal stress and depression are associated with respiratory phenotypes in urban children.

BACKGROUND: Prenatal and early-life exposure to maternal stress and depression is linked to development of recurrent wheezing in young children. OBJECTIVE: We sought to determine whether maternal stress and depression in early life are associated with nonatopic wheezing phenotype in urban children. METHODS: The Urban Environment and Childhood Asthma Study examined a birth cohort of children at high risk for asthma in low-income neighborhoods. Prenatal and postnatal (through age 3 years) maternal stress and depression scores were compared with respiratory phenotypes through age 10 years (multinomial regression), self-reported colds (linear regression), and detection of respiratory viruses (Poisson regression). RESULTS: Scores for maternal depression, and, to a lesser extent, maternal perceived stress, were positively related to multiple wheezing phenotypes. In particular, cumulative measures of maternal depression in the first 3 years were related to the moderate-wheeze-low-atopy phenotype (odds ratio, 1.13; [1.05, 1.21]; P < .01). Considering indicators of respiratory health that were used to identify the phenotypes, there were multiple positive associations between early-life scores for maternal stress and depression and increased wheezing illnesses, but no consistent relationships with lung function and some inverse relationships with allergic sensitization. Cumulative maternal stress and depression scores were associated with cumulative number of respiratory illnesses through age 3 years. CONCLUSIONS: Among high-risk, urban children, maternal stress and depression in early life were positively associated with respiratory illnesses and a moderate-wheeze-low-atopy phenotype. These results suggest that treating stress and depression in expectant and new mothers could reduce viral respiratory illnesses and recurrent wheeze during the preschool years and some forms of childhood asthma.

Think Twice before Interpreting the Skin Prick Test as Age, Body Mass Index, and Atopy Affect Reaction Time and Size.

INTRODUCTION: The skin prick test (SPT) is a reliable method to confirm sensitization in IgE-mediated allergic diseases; however, it has been reported to be affected by several personal and environmental factors. Our objective was to determine the factors affecting the skin reactivity to histamine and allergens and investigate whether it differs according to age in terms of reading time. METHODS: A total of 500 patients, aged 4 months-18 years, were enrolled in the study. Wheal and flare reaction sizes were documented as the mean of the longest and the midpoint perpendicular diameter in the 5th, 10th, 15th, and 20th min. Skin reactivity was compared between children >24 and ≤24 months of age. RESULTS: We found larger histamine and allergen wheal sizes in children >24 months than the ones ≤24 months of age (p < 0.001 and p = 0.007, respectively). The duration of maximum histamine reactivity was 15 min for children >24 months whereas 10 min for children ≤24 months of age. The number of children losing their histamine reactivity after 15 and 20 min was significantly higher in the smaller age-group. Multiple regression analysis revealed a larger histamine reactivity in children >24 months of age, having obesity, and having allergen sensitization (p = 0.002, p = 0.003, and p = 0.018, respectively). CONCLUSION: It seems more accurate to evaluate SPT after 10 min in children ≤24 months of age. Cutoff values and ideal measurement time according to individual factors such as age, body mass index, or atopy are needed.

Risk factors for fatal and nonfatal reactions to immunotherapy (2008-2018): postinjection monitoring and severe asthma.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is highly effective but risks exist. OBJECTIVE: To identify practices that influence systemic allergic reactions (SRs) to SCIT and SCIT-associated infections. METHODS: Members of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology completed an annual survey of SCIT-related SRs of varying severity (2008-2018). Injection-related infections were queried (2014-2018). Strategies to enforce postinjection waiting times and to reduce risks from asthma/severe asthma were queried (2016-2018). RESULTS: Data were gathered on 64.5 million injection visits. Ten confirmed fatalities occurred since 2008, including 3 new fatalities since 2017. One fatal reaction occurred per 7.2 million injection visits (2008-2018). No infections occurred. Practices that tracked the time after injections, and required checking out with office personnel, had significantly lower total (P < .001), grade 3 (severe) (P < .001), and grade 4 (very severe) SRs (P < .001). Having more individuals with asthma on SCIT was associated with more grade 3 SRs (P < .02). Not prescribing SCIT in individuals with uncontrolled asthma was associated with fewer grade 3 SRs (P = .02). Having individuals with more severe asthma on SCIT was associated with more total, grade 1, and grade 2 SRs (P < .001); 50% of grade 3 and 4 SRs occurred in individuals with severe asthma. CONCLUSION: SCIT-related fatalities have declined since 2008, with a slight increase in recent years. SCIT is not associated with an increased risk of infections. Tracking the time after injections and checking out with office staff confer significantly lower risks of severe SRs. Asthma, especially severe asthma, is a major risk factor for severe and fatal SRs. Strategies that reduce risks for individuals with asthma, such as not prescribing SCIT to patients with uncontrolled asthma, may lower the risks.

The roles of lipid mediators in type I hypersensitivity.

Type I hypersensitivity is an immediate immune reaction that involves IgE-mediated activation of mast cells. Activated mast cells release chemical mediators, such as histamine and lipid mediators, which cause allergic reactions. Recent developments in detection devices have revealed that mast cells simultaneously release a wide variety of lipid mediators. Mounting evidence has revealed that mast cell-derived mediators exert both pro- and anti-inflammatory functions and positively and negatively regulate the development of allergic inflammation. This review presents the roles of major lipid mediators released from mast cells. Author believes this review will be helpful for a better understanding of the pathogenesis of allergic diseases and provide a new strategy for the diagnosis and treatment of allergic reactions.

Immediate local anesthetic reactions and diagnostic test results in pediatric patients.

BACKGROUND/OBJECTIVES: Adverse reactions to local anesthetics are relatively common, but proven IgE-mediated allergy is extremely rare. We aimed to determine the frequency of local anesthetic allergy in pediatric patients. PATIENTS AND METHODS: The medical records of 73 patients who presented to our clinic with a history of suspected allergic reaction to local anesthetics and underwent diagnostic testing between 2012 and 2020 were retrospectively analyzed. Diagnoses were based on case histories, skin tests, and subcutaneous challenge tests. RESULTS: A total of 75 test series were carried out on the 73 patients (43 boys; median [IQR] age 9.25 [7.26-14.25] years, range 3-17.8 years). The most commonly tested drugs were lidocaine (n = 38; 50.6%) and prilocaine (n = 15; 20%). Local anesthetic allergy was confirmed in one (1.3%) of the 73 patients by positive subcutaneous challenge test with mepivacaine. CONCLUSION: There are limited data in the current literature regarding local anesthetic allergies and diagnosis test results in pediatric patients. Proven local anesthetic allergy is less common than expected by society and physicians, and therefore diagnostic tests are needed for patients with no contra-indications such as severe or life-threatening reactions.

Reduction in mouse allergen exposure is associated with greater lung function growth.

BACKGROUND: Current childhood asthma therapies have little effect on lung function trajectory. OBJECTIVE: We sought to determine whether mouse allergen exposure reduction is associated with lung function growth in mouse-sensitized/exposed asthmatic children. METHODS: Three hundred fifty mouse-sensitized/exposed asthmatic children (5-17 years old) were enrolled in a 1-year randomized trial of integrated pest management plus education versus education alone. Prebronchodilator/postbronchodilator spirometry was performed at baseline and 6 and 12 months, and bedroom floor mouse allergen levels were measured every 3 months. Mouse allergen reduction was defined as a 75% or greater decrease in mouse allergen levels from baseline. Treatment groups were combined for analyses because there were no differences in outcomes between groups. Changes in lung function over time were modeled, adjusting for age, sex, race, atopy, group, and bronchodilator reversibility and including an interaction term (allergen reduction*time). RESULTS: The study population was predominantly black (79.4%) and low income (66.3% [<$30,000]). At baseline, the median mouse allergen level was 5.7 µg/g (interquartile range, 1.5-22.8 µg/g), and the mean (SD) prebronchodilator FEV1/forced vital capacity ratio was 80.2% (9.0%). Ninety-two (26.3%) participants had 75% or greater reduction in mouse allergen levels. For a 10-year-old black boy, 75% or greater allergen reduction was associated with an increase in prebronchodilator FEV1 of 238 mL/y (95% CI, 177-299 mL/y), whereas less than 75% allergen reduction was associated with an increase in prebronchodilator FEV1 of 131 mL/y (95% CI, 97-166 mL/y). Estimated differences in prebronchodilator and postbronchodilator FEV1 growth were as follows: 107 mL/y (95% CI, 37-177 mL/y; Pint = .003) and 48 mL/y (95% CI, -17 to 113 mL/y; Pint = .15), respectively. Estimated differences in prebronchodilator and postbronchodilator forced expiratory flow at 25% to 75% of vital capacity growth were as follows: 182 mL/y (95% CI, 61-304 mL/y; Pint = .003) and 181 mL/y (95% CI, 48-314 mL/y; Pint = .008), respectively. CONCLUSION: Mouse allergen reduction is associated with greater increases in prebronchodilator FEV1 and prebronchodilator/postbronchodilator forced expiratory flow at 25% to 75% of vital capacity over 1 year among sensitized/exposed asthmatic children.

COMMD8 changes expression during initial phase of wasp venom immunotherapy.

BACKGROUND: Hymenoptera venom allergy (HVA) is of great concern because of the possibility of anaphylaxis, which may be fatal. Venom immunotherapy (VIT) is the only disease-modifying treatment in HVA and, although efficient, its mechanism remains partially unknown. Gene expression analysis may be helpful for establishing a proper model of tolerance induction during the build-up phase of VIT. The present study aimed to analyze how the start of VIT changes the expression of 15 selected genes. METHODS: Forty-five patients starting VIT with a wasp venom allergy were enrolled. The diagnosis was established based on anaphylaxis history (third or fourth grade on the Mueller scale) and positive soluble immunoglobulin E and/or skin tests. Two blood collections were performed in the patient group: before and after 3 months of VIT. One sample was taken in the control group. Gene expression analysis was performed using a reverse transcriptase-polymerase chain reaction with microfluidic cards and normalized to the 18S housekeeping gene. RESULTS: Commd8 was the only gene that changed expression significantly after the start of VIT (p = 0.012). Its expression decreased towards the levels observed in the healthy controls. Twelve out of 15 genes (commd8, cldn1, cngb3, fads1, hes6, hla-drb5, htr3b, prlr, slc16a4, snx33, socs3 and twist2) revealed a significantly different expression compared to the healthy controls. CONCLUSIONS: The present study shows that commd8 changes significantly its expression during initial phase of VIT. This gene might be a candidate for VIT biomarker in future studies.

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis.

Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are limited data regarding nephrogenic systemic fibrosis (NSF) risk, but there are few if any unconfounded cases of NSF. Purpose To perform a systematic review and meta-analysis of gadoxetic acid adverse events, including immediate hypersensitivity reactions, NSF, and intracranial gadolinium retention. Materials and Methods Original research studies, case series, and case reports that reported adverse events in patients undergoing gadoxetic acid-enhanced MRI were searched in MEDLINE (1946-2019), Embase (1947-2019), CENTRAL (March 2019), and Scopus (1946-2019). The study protocol was registered at Prospero (number 162811). Risk of bias was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2, or QUADAS-2. Meta-analysis of proportions was performed by using random-effects modeling. Upper bound of 95% confidence interval (CI) for risk of NSF was determined. Results Seventy-one studies underwent full-text review. From 17 studies reporting 14 850 administrations, hypersensitivity reactions occurred in 0.3% (31 of 14 850; 95% CI: 0.2%, 0.4%) with zero deaths. From four studies reporting 106 administrations in patients with stage 4 or 5 chronic kidney disease or undergoing dialysis, the upper bound 95% CI for the risk of NSF was 2.8%. Five studies evaluating intracranial retention of gadolinium after gadoxetic acid administration were at high risk of bias. Conclusion Gadoxetic acid had a similar safety profile to American College of Radiology group 2 gadolinium-based contrast agents for hypersensitivity reactions and nephrogenic systemic fibrosis (NSF) but had lower confidence for risk of NSF because of fewer administrations in patients with severe kidney impairment. There is incomplete information documenting intracranial gadolinium retention in patients administered gadoxetic acid. © RSNA, 2020 Online supplemental material is available for this article.

The role of gut microbiota in atopic asthma and allergy, implications in the understanding of disease pathogenesis.

Asthma is a clinical syndrome characterized by chronic airway inflammation. There is mounting evidence on the role of microbiota in the development of asthma. This review focuses on the role of microbiota in maintaining the integrity of the epithelia and their role in regulating the immune response. The review compiles data from multiple studies on the role of microbiota in the innate immune response and the development and differentiation of CD4+ T cells, a major component of the adaptive arm of the immune response. As a result of dysbiosis, invariant natural killer T cells may induce T helper 2 cell differentiation and immunoglobulin E isotype switching through the release of interleukin-4 and interleukin-13. Furthermore, degradation of immunoglobulin A antibodies, increased circulating mast cells and basophils, and inflammation are among other mechanisms by which dysbiosis can induce or exacerbate asthma. After explaining the underlying mechanisms, the review derives conclusions from studies that investigate dysbiosis in infancy and the development of asthma later in life. The review also includes studies that investigate asthmatic mothers and the development of asthma in children and the role of dysbiosis in that regard. Finally, the review explains the statistical relationship between eczema and asthma through multiple studies that investigate the role of dysbiosis in both atopic states. This review provides insight into the role of dysbiosis in asthma, and an understanding that is required to establish clinical trials which aim to modulate the gut microbiota as a means of preventing and treating asthma.

Drug hypersensitivity in the fast lane: What clinicians should know about phenotypes, endotypes, and biomarkers.

OBJECTIVE: To review novel concepts in drug hypersensitivity and the management of immediate hypersensitivity reactions. DATA SOURCES: English language literature on MEDLINE and Embase surrounding drug hypersensitivity and desensitization. STUDY SELECTIONS: References were selected based on relevance, date of publication, and originality. RESULTS: There are numerous citations looking at categorizing drug reactions, pathogenesis, biomarkers, and desensitization. Current understanding supports the use of a phenotype-endotype-biomarker model for categorizing immediate hypersensitivity reactions. Drug desensitization is a powerful therapeutic strategy that enables temporary induction of tolerance to medications that triggered immediate reactions. CONCLUSION: Immediate hypersensitivity reactions are diverse in presentation and pathogenesis. Drug desensitization is an effective intervention with sufficient evidence to support its more widespread availability.

Treating COVID-19: Review of Drug Hypersensitivity Reactions.

The disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ie, coronavirus disease 2019 (COVID-19), has become a global pandemic since it was first reported in Wuhan, China in December 2019. Its severe clinical manifestations, which often necessitate admission to intensive care units, and high mortality rate represent a therapeutic challenge for the medical community. To date, no drugs have been approved for its treatment, and various therapeutic options are being assayed to address the pathophysiological processes underlying the clinical manifestations experienced by patients. New and old drugs administered as monotherapy or in combination to immunologically compromised patients may favor the development of adverse drug reactions, including drug hypersensitivity reactions, which must be identified and managed accordingly. Given the lack of herd immunity and the high rate of viral contagion, new cases are expected to emerge in the coming months. Thus, the probability of more adverse reactions or even new clinical manifestations may increase in parallel. Allergists must receive updated information on these treatments, as well as on the management of possible drug hypersensitivity reactions.