Does having siblings really protect against childhood atopic diseases? A total population and within-family analysis.

The association between having older siblings and decreased risk for atopic symptoms is well-established. This has been interpreted as evidence for the microbiota hypothesis, i.e. that increased early-childhood microbial exposure caused by siblings protects from immune hypersensitivities. However, possible confounders of the association have received little attention. We used register data on Finnish cohorts born in 1995-2004 (N = 559,077) to assess medication purchases for atopic diseases: antihistamines, eczema medication, asthma medication and Epinephrine. We modelled the probability of atopic medication purchases at ages 0-15 by birth order controlling for important observed confounders and all unobserved genetic and environmental characteristics shared by siblings in a within-family fixed effects model. We further studied medication purchases among first-borns according to the age difference with younger siblings to assess whether having younger siblings in early childhood is beneficial. Having older siblings was associated with a lower probability of atopic medication purchases. Compared to first-borns, the probability was 10-20% lower among second-borns, 20-40% lower among third-borns, and 30-70% lower among subsequent children, depending on medication type. Confounding accounted for up to 75% of these differences, particularly for asthma and eczema medication, but significant differences by birth order remained across all medication types. Among first-borns, a smaller age difference with younger siblings was related to a lower likelihood of atopic medication use. Our results, based on designs that account for unobserved confounding, show that exposure to siblings in early childhood, protects from atopic diseases, and thus strongly support the microbiota hypothesis.

Atopy in chronic urticaria: an important yet overlooked issue.

Chronic urticaria (CU) is one of the most common dermatological diseases and has a significant impact on the quality of life of patients. However, the pathogenesis of this disease remains unclear. Autoimmunity in chronic spontaneous urticaria (CSU) has received considerable attention and has been studied previously. Atopy is an important characteristic of CU; however, it has not been fully recognized. Atopy predisposes individuals to immune responses to allergens, leading to type 2 inflammation and immunoglobulin E (IgE) overproduction. Compared with healthy individuals, patients with CU have a higher proportion of atopy, and an atopic background is correlated with the clinical characteristics of CU. The total IgE levels in patients with CU is significantly higher than those in healthy individuals. Although its level is not higher than that in classic allergic diseases, it is closely related to CU. Exogenous allergens, auto-allergens, and specific IgEs, which are closely related to atopy, have been reported, and their roles in CU pathogenesis are also being studied. Local and systemic atopic inflammation is present in patients with CU. This review summarizes the current knowledge regarding atopy and CU, speculating that there are CU subtypes, such as atopic CSU or atopic chronic inducible urticaria (CIndU) and that atopy may be involved in the pathogenesis of CU. These findings provide a new perspective for a comprehensive understanding of the clinical features of CU and further research regarding its pathogenesis.

Helicobacter pylori infection is associated with decreased odds for eosinophilic esophagitis in Mexican patients. / La infección por Helicobacter pylori se asocia con disminución del riesgo de esofagitis eosinofílica en pacientes mexicanos.

BACKGROUND: The incidence of eosinophilic esophagitis (EoE) is increasing in some regions of the world. Retrospective studies have found an inverse association with Helicobacter pylori infection (H. pylori). A recent prospective study has questioned this relationship. We aimed to evaluate this relationship in Mexican patients. PATIENTS AND METHODS: We evaluated adult patients without prior eradication of H. pylori. Cases were defined by the presence of esophageal symptoms and >15 eosinophils/high power field (HPF) in the esophageal biopsy. Controls were defined by the presence of <15 eosinophils/HPF in esophageal biopsy. H. pylori infection was defined by histology. Patients were matched by age and gender assigning four controls per case. RESULTS: We included 190 patients: 38 cases and 152 controls. Cases had higher frequency of atopy, dysphagia, food impaction, peripheral eosinophilia, and endoscopic EoE abnormalities. The overall prevalence of H. pylori was 63.6%. Cases had significantly lower prevalence of H. pylori than controls (36.8% vs. 70.4%, OR 0.21 95% CI 0.08-0.69, p = 0.001). Atopic patients had lower prevalence of H. pylori than non-atopic: 13.1% vs. 50.5% (OR 0.20, 95% CI 0.06-0.69, p < 0.001), particularly allergic rhinitis and food allergy. CONCLUSIONS: We observed an inverse relationship between H. pylori and EoE as well as atopy. Studies in experimental models of EoE that clarify the role of H. pylori in this interaction are required, as well as robust studies that include other factors (socioeconomic, cultural, microbiota, etc.) in order to clarify this relationship.

Retrospective evaluation of hypersensitivity reactions and anaphylaxis in dogs (2003-2014): 86 cases.

OBJECTIVE: To characterize anaphylactic reactions in dogs, including clinical signs, severity, treatments, prognosis, and estimated incidence. To determine whether glucocorticoids influence clinical recovery and survival. DESIGN: Retrospective study between January 1, 2003 and April 28, 2014. SETTING: University teaching hospital. ANIMALS: Eighty-six dogs treated for a type I hypersensitivity reaction. Nineteen dogs fulfilled the criteria for anaphylaxis, and 67 dogs had mild cutaneous reactions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The estimated incidence was 0.04% for anaphylaxis and 0.15% for mild hypersensitivity reactions. The female:male ratio (2.3:1) was significantly higher (P = 0.032) compared to our source population (ratio of 1:1.158). Vaccines were the most frequent trigger for anaphylaxis (57.9%) and mild hypersensitivity reactions (28.4%). Seventy-four (86%) dogs had cutaneous signs, and 11 (57.9%) dogs with anaphylaxis had no cutaneous signs reported. Forty-two (48.8%) dogs received both an H1 antagonist and a glucocorticoid, 34 (39.5%) dogs received an H1 antagonist only, and 6 (6.9%) dogs received a glucocorticoid only. The majority of the dogs survived, and 1 was euthanized due to complications. Clinical signs associated with nonsurvival included respiratory signs (P = 0.006), particularly respiratory distress (P < 0.00001) and cyanosis (P < 0.00001), and circulatory shock (P = 0.005). The analysis of the interaction between etiology, clinical signs, treatment, and outcome did not show any association between pairs of variables. CONCLUSIONS: In the current study, anaphylaxis had a relatively good prognosis, and cutaneous signs were not always present. Based on the present data, the use of glucocorticoids to treat mild type I hypersensitivity reactions and anaphylaxis in dogs was not associated with clinical improvement or survival.

Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. METHODS: Non-cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. RESULTS: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p < .001), defined by total and allergen-specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. CONCLUSION: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition.

Ocular surface inflammation and ectatic corneal disorders.

PURPOSE OF REVIEW: Inflammatory mediators are a focus of recent corneal ectasia (CE) research and are a profound, modifiable contributor to CE in general and keratoconus (KC) in particular, opening a path to explore new methods of control. As advanced imaging technology and expanded population screening allow for earlier detection, the possibility of early intervention can profoundly change the prognosis of CE. RECENT FINDINGS: Significant increases in the inflammatory mediators and immune components have been observed in the cornea, tear fluid, and blood of ectasia patients, while inflammation dampeners such as vitamin D and their receptors are reduced. Atopy and allergy have a strong association with KC, known to increase itch factors and stimulate eye rubbing, a risk factor in ectasia pathogenesis. Management of atopy or allergic conditions and topical anti-inflammatories has helped stabilize CE disease. SUMMARY: Strategies such as monitoring inflammatory factors and using immune or inflammatory modulators, including managing subclinical inflammation, may be clinically beneficial in stabilizing the disease and improving outcomes. The detected factors are biomarkers, but as yet unproven to be sensitive or specific enough to be considered biomarkers for early detection of CE. The establishment of such biomarkers could improve the therapeutic outcome.

New Dominant-Negative IL6ST Variants Expand the Immunological and Clinical Spectrum of GP130-Dependent Hyper-IgE Syndrome.

Patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) suffer from a constellation of manifestations including recurrent bacterial and fungal infections, severe atopy, and skeletal abnormalities. This condition is typically caused by monoallelic dominant-negative (DN) STAT3 variants. In 2020, we described 12 patients from eight kindreds with DN IL6ST variants resulting in a new form of AD HIES. These variants encoded truncated GP130 receptors, with intact extracellular and transmembrane domains, but lacking the intracellular recycling motif and the four STAT3-binding residues, resulting in an inability to recycle and activate STAT3. We report here two new DN variants of IL6ST in three unrelated families with HIES-AD. The biochemical and clinical impacts of these variants are different from those of the previously reported variants. The p.(Ser731Valfs*8) variant, identified in seven patients from two families, lacks the recycling motif and all the STAT3-binding residues, but its levels on the cell surface are only slightly increased and it underlies mild biological phenotypes with variable clinical expressivity. The p.(Arg768*) variant, identified in a single patient, lacks the recycling motif and the three most distal STAT3-binding residues. This variant accumulates at the cell surface and underlies severe biological and clinical phenotypes. The p.(Ser731Valfs*8) variant shows that a DN GP130 expressed at near normal levels on the cell surface can underlie heterogeneous clinical presentations, ranging from mild to severe. The p.(Arg768*) variant demonstrates that a truncated GP130 protein retaining one STAT3-binding residue can underlie severe HIES.

Comparison of adult food protein-induced enterocolitis syndrome to crustaceans and immediate-type food allergy.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is increasingly found in adults. FPIES requires different treatment from immediate-type food allergy (FA) in emergency medicine. However, no comparison of the clinical presentations of these diseases has been reported. OBJECTIVE: To compare the clinical presentations and causative crustaceans of adult FPIES and FA using a standardized questionnaire and to thereby lay the groundwork for establishing an algorithm that distinguishes those diseases. METHODS: We conducted a retrospective cohort study of crustacean-avoidant adults by telephone interview based on the previously reported diagnostic criteria for adult FPIES to compare the clinical features and crustacean intake status between FPIES and FA. RESULTS: Of 73 adult patients with crustacean allergy, 8 (11%) were diagnosed with having FPIES and 53 (73%) FA. Compared with the patients with FA, those with FPIES had a longer latency period (P < .01), more episodes (P = .02), longer duration of symptoms (P = .04), more frequent abdominal distention (P = .02), and severe colic pain (P = .02). Half of the patients with FPIES experienced fear of death during an episode. Panulirus japonicus (Japanese spiny lobster) and Homarus weber (lobster) were significantly common FPIES-causing foods. A statistically significant 62.5% of patients with FPIES were able to ingest some type of crustacean. CONCLUSION: FPIES and FA can be clearly differentiated by the abdominal symptoms, latency period, and duration of episodes. Furthermore, some patients with FPIES do not necessarily need to avoid all crustaceans. Our findings lay the groundwork for establishing an algorithm that distinguishes FPIES from FA in adults.

Genetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers.

Advances in next generation sequencing technologies, as well as their expanded accessibility and clinical use over the past 2 decades, have led to an exponential increase in the number of identified single gene disorders. Among these are primary atopic disorders-inborn errors of immunity resulting in severe allergic phenotypes as a primary presenting feature. Two cardinal aspects of type I immediate hypersensitivity allergic reactions are hives and angioedema. Mast cells (MCs) are frequent primary drivers of these symptoms, but other cells have also been implicated. Even where MC degranulation is believed to be the cause, mediator-induced symptoms may greatly vary among individuals. Angioedema-particularly in the absence of hives-may also be caused by hereditary angioedema conditions resulting from aberrant regulation of contact system activation and excessive bradykinin generation or impairment of vascular integrity. In these patients, swelling can affect unpredictable locations and fail to respond to MC-directed therapies. Genetic variants have helped delineate key pathways in the etiology of urticaria and nonatopic angioedema and led to the development of targeted therapies. Herein, we describe the currently known inherited and acquired genetic causes for these conditions, highlight specific features in their clinical presentations, and discuss the benefits and limitations of biomarkers that can help distinguish them.

Delayed Severe Gingivitis After Placement of Orthodontic Braces in an Atopic Teenager: A Case Report and Literature Review.

We report a case of a 15-year-old atopic patient presenting with delayed, severe ulcerative hypertrophic gingivitis after placement of orthodontic braces, which required removal of braces and restorative laser surgical procedures. Patch testing to multiple metals and chemicals showed weak positive reactions to steel bands and formaldehyde. The patient experienced urticarial, gingivitis, and other intraoral symptoms after patch testing and re-exposure to nickel-containing products. In contrast, nickel, cobalt, and cobalt-chromium (Co-Cr) bracket patch testing sites were negative. Nickel-caused contact dermatitis is Type IV delayed hypersensitivity reaction occurring at least 24 h after exposure. This reaction can result in intraoral blisters, ulcerations, eczematous and urticarial reactions of the face and more distant skin areas. This case illustrates the intraoral delayed response, symptom resolution after removing the braces, and brackets and local reactions upon subsequent nickel exposure, despite negative patch testing and lymphocyte stimulation test to nickel. This case further illustrates the difficulty associated with diagnosing nickel allergy.

Immediate hypersensitivity reactions to antineoplastic agents - A practical guide for the oncologist.

Immediate hypersensitivity reactions (IHRs) to antineoplastic agents occur frequently, and every oncologist will encounter these reactions in their clinical practice at some point. The clinical signature of IHRs can range from mild to life-threatening, and their occurrence can substantially impede the treatment course of patients with cancer. Yet, clear guidelines regarding the diagnosis and management are scarce, especially from an oncologic point of view. Therefore, herein, we review the definition, pathophysiology, epidemiology, diagnosis and management of IHRs to chemotherapeutic agents and monoclonal antibodies. First, we focus on defining the specific entities that comprise IHRs and discuss their underlying mechanisms. Then, we summarize the epidemiology for the antineoplastic agents that represent the most common causes of IHRs, i.e., platinum compounds, taxanes and monoclonal antibodies (mAbs). Next, we describe the possible clinical pictures and the comprehensive diagnostic work-up that should be executed to identify the culprit and safe alternatives for the future. Finally, we finish with reviewing the treatment options in both the acute phase and after recovery, with the aim to improve the oncologic care of patients with cancer.

Incidence of urticaria, angioedema, and type I hypersensitivity reactions associated with fibrinolytic agents in Thailand using the database of the health product vigilance center.

BACKGROUND: Besides hemorrhage, allergic reactions have also been observed in several clinical trials of fibrinolytic agents. These reactions might negatively affect patient outcomes, especially life-threatening type I hypersensitivity reactions such as anaphylaxis. However, there are limited data on the incidence of these reactions. OBJECTIVE: The aim of study was to analyze the incidence of urticaria, angioedema, and type I hypersensitivity reactions from fibrinolytic agents for various indications. METHODS: A retrospective analysis of data from the Thai Vigibase database was conducted. All reports of adverse drug reactions from fibrinolytic agents from 1984 to 2017 were identified using the World Health Organization adverse reaction terminology. The proportion of each suspected adverse drug reaction and the cumulative incidence were calculated. RESULTS: A total of 284 reports were identified in the Thai Vigibase database. The overall incidence of urticaria, angioedema, and type I hypersensitivity reactions for the streptokinase group was 52.64/10,000 persons, with individual incidence rates of 9.64/10,000 persons for urticaria, 8.90/10,000 persons for angioedema, and 34.11/10,000 persons for type I hypersensitivity reactions. In the alteplase group, the overall incidence for all suspected reactions was 18.90/10,000 persons, with individual incidence rates of 3.29/10,000 persons for urticaria, 5.75/10,000 persons for angioedema, and 9.86/10,000 persons for type I hypersensitivity reactions. CONCLUSIONS: Type I hypersensitivity reactions were the most common allergic reactions from fibrinolytic agents. It is necessary to take these reactions into consideration when using fibrinolytic therapy.

Characteristics of immediate hypersensitivity reaction to paclitaxel-based chemotherapy in gynecologic cancer patients.

BACKGROUND: Immediate hypersensitivity reactions (IHRs) are commonly found in patients receiving paclitaxel. Effects of paclitaxel vary because of variable co-therapy or re-challenge with paclitaxel. OBJECTIVE: Our objective was to investigate the incidence, patterns, and risk factors for paclitaxel-related IHRs and management of IHRs in gynecologic malignancy patients. METHODS: This retrospective study was performed in gynecologic cancer patients receiving paclitaxel-based regimens at Siriraj hospital from January 2012 to December 2017. RESULTS: 416 subjects were included and received ranitidine 50 mg, dexamethasone 20 mg, ondansetron 16 mg intravenously and diphenhydramine 50 mg orally 30 minutes before starting chemotherapy. The incidence of IHRs was 17.79%. IHRs occurring on first exposure to paclitaxel was 81.1% and occurred within 30 minutes after starting paclitaxel. The most commonly found presentation of IHRs were skin reactions (86.5%). In multivariate analysis, age < 54.5 years, stage of cancer < 2, and leukocyte cell count < 7.735 × 109/L were significantly associated with IHRs. Seventy-two out of 74 patients that recovered from IHRs were reintroduced paclitaxel. Forty-seven patients (97.92%) of 48 patients with mild reactions were successfully reintroduced to paclitaxel after treatment with chlorpheniramine or other interventions. CONCLUSIONS: The incidence of paclitaxel-related IHRs was about one in five. Skin reactions were the most commonly occurring reactions. Younger age, stage of cancer < 2, and leukocytes < 7.735 × 109/L were significant risk factors for IHRs. Patients with IHRs recovered without the use of dexamethasone and antihistamines before the reintroduction of paclitaxel.

Is mold sensitization associated with severe asthma exacerbation in children?

BACKGROUND: Mold sensitization has been reported as a factor associated with severe asthma exacerbation (SAE). OBJECTIVE: To identify the factors associated with SAE in asthmatic children, particularly mold sensitization. METHODS: The asthmatic children recruited into this case-control study were classified into an SAE and an outpatient (OPD) group, based on their histories of asthma exacerbation with hospitalization in the preceding year. A skin prick test to common aeroallergens was performed. Possible SAE risk factors were analyzed. RESULTS: A total of 102 patients were enrolled. The 51 patients in the SAE group were significantly younger than the 51 in the OPD group (mean ages of 6.8 ± 3.3 vs 8.7 ±3.2 years, p = 0.005). Higher proportions of patients with partly controlled or uncontrolled asthma were found in the SAE group (41.2% vs 17.6%, p = 0.009). The incidences of a paternal history of atopy, an emergency department visit, and a history of systemic corticosteroid administration in the preceding year were significantly higher for the SAE group (35.3% vs 15.7%, p = 0.023; 100% vs 43.5%, p < 0.001; and 100% vs 31.4%, p < 0.001; respectively). The multivariate logistic regression analysis showed that risk factors for SAE were Alternaria sensitization (adjusted odds ratio [AOR] 3.00; 95% CI 1.09-8.3; p = 0.033), patients who were younger than 6 years (AOR 3.28; 95% CI 1.17-9.18; p = 0.024), and a paternal history of atopy (AOR 2.94; 95% CI 1.05-8.25; p = 0.040). CONCLUSIONS: Alternaria sensitization, an age younger than 6 years, and a paternal history of atopy were associated with SAE in asthmatic children.

Serum 25-hydroxyvitamin D deficiency is associated with atopy, and sex may be an effect modifier of its association with asthma in teenagers from northeast Brazil.

OBJECTIVE: Sufficient vitamin D (25-hydroxyvitamin D [25(OH)D]) serum levels are associated with decreased asthma symptoms. Our aim was to investigate associations between vitamin D and atopy, asthma, asthma severity, and asthma phenotypes in Brazilian teenagers. METHODS: This cross-sectional study involved 942 individuals (11-19 years old) engaged in an asthma cohort. The ISAAC questionnaire was employed to diagnosis asthma and asthma severity. Serum allergen-specific immunoglobulin E (sIgE) was measured by ImmunoCap and serum 25(OH)D was measured by ELISA. We calculated the correlation between sIgE and 25(OH)D. We used multivariate logistic regression analysis to assess associations of interest. RESULTS: We found that 25(OH)D deficiency was positively associated with atopy (OR 1.45, confidence interval [CI] 1.05-2.00) and high levels of this vitamin negatively correlated with sIgE to Dermatophagoides pteronyssinus (r = -0.11, p = 0.019). The average 25(OH)D serum level was 27.0 ± 9.5 ng/ml; 366 individuals (38.8%) had a sufficient level. There was no association between 25(OH)D and asthma, asthma severity or asthma phenotypes in the population. However, sex was a possible effect modifier of the association between vitamin D and asthma: insufficiency in asthmatic women (86%) was higher than in asthmatic men (42%), and there was an association between insufficient vitamin D levels and greater asthma risk only in women (OR = 3.06, 95% CI 1.16-8.07). CONCLUSION: We have shown that vitamin D deficiency was associated with greater risk of atopy in both sexes and vitamin D insufficiency was associated with asthma only in women. There was no association between vitamin D levels and asthma phenotypes or asthma severity.

Basophil activation test for allergic and febrile non-haemolytic transfusion reactions among paediatric patients with haematological or oncological disease.

BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are common, although their mechanisms remain unclear. Immunoglobulin E (IgE)-mediated type I hypersensitivity may be involved in the pathogenesis of ATR. A basophil activation test (BAT) may help elucidate this process. MATERIALS AND METHODS: The BAT was based on peripheral blood samples from paediatric patients with a haematological or oncological disease and on samples of residual blood products transfused in each case. Dasatinib was used to evaluate whether basophil activation was mediated by an IgE-dependent pathway. RESULTS: Twenty-seven patients with and 19 patients without ATR/FNHTR were included in this study, respectively. The median BAT values associated with ATR- (n = 41) and FNHTR-causing (n = 5) blood products were 22.1% (range = 6.1%-77.0%) and 27.8% (range = 15.2%-47.8%), respectively, which were higher than the median value of 8.5% (range = 1.1%-40.9%) observed in blood products without a transfusion reaction. Dasatinib suppressed basophil activity. BAT values were comparable in patients with ATR regardless of severity. Meanwhile, BAT values analysed with blood products non-causal for ATR/FNHTR were higher in patients with ATR/FNHTR than in those without. CONCLUSION: The IgE-mediated type I hypersensitivity may be involved in the pathogenesis of ATR and FNHTR. BAT analyses may help elucidate the underlying mechanisms and identify patients at risk.

Chronic Rhinosinusitis in Patients with Primary Immunodeficiency.

INTRODUCTION: Primary immunodeficiencies are a heterogeneous group of diseases associated with an increased incidence of infections, autoimmunity, autoinflammatory diseases, allergies, and cancer. Rhinosinusitis is one of the most common infections in these patients. In our study, we aimed to determine the presence of chronic rhinosinusitis in our patients with primary immunodeficiency and to investigate the etiology of chronic rhinosinusitis. METHODS: Forty-four patients (age range: 4-26 years) diagnosed with primary immunodeficiency were enrolled in our study. Patients were interviewed about the symptoms of chronic rhinosinusitis, and nasal endoscopic examinations were performed prospectively. The results of laboratory tests, medications, skin allergy tests, and the patients' lung computed tomography were retrospectively recorded from patient files. RESULTS: The distribution of patients' diagnoses included 38.6% (n = 17) primary antibody deficiencies, 6.6% (n = 3) combined immunodeficiencies, 27.3% (n = 12) combined immunodeficiencies with syndromic features, 6.8% (n = 3) phagocytic disorders, and 20.5% (n = 9) immune dysregulation disorders. There was no significant difference in the frequency of chronic rhinosinusitis among the different immunodeficiency groups. There were no significant differences between chronic rhinosinusitis and conditions such as atopy, hypogammaglobulinemia, and treatments with immunoglobulin and/or azithromycin. The incidence of chronic rhinosinusitis was 77.8% (n = 7) in patients with a history of acute sinusitis and 20% (n = 7) in patients without a history of sinusitis, with a statistically significant difference between them (p = 0.002). CONCLUSION: Chronic rhinosinusitis is more common in patients with primary immunodeficiencies than in the normal population. For effective treatment, it is necessary to identify the factors that cause chronic rhinosinusitis. Further studies involving larger patient populations are needed to explain the mechanisms of chronic rhinosinusitis.

Prevalence of eosinophilic, atopic, and overlap phenotypes among patients with severe asthma in Saudi Arabia: a cross-sectional study.

BACKGROUND: Eosinophilia is a significant factor in asthma severity; however, the prevalence of severe eosinophilic asthma in Saudi Arabia is largely unknown. We aimed to determine the prevalence of the eosinophilic (defined in this study as ≥ 300 cells/mm3 in blood), atopic (atopic phenotype 1, defined in this study as > 100 IU/mL total serum IgE; atopic phenotype 2, defined in this study as > 150 IU/mL), and overlap phenotypes among patients with severe asthma in Saudi Arabia. METHODS: A cross-sectional study was conducted in centers specialized in severe asthma management. Patients aged ≥ 12 years with severe asthma were enrolled. Study patients responded to the Global Initiative for Asthma 2018 assessment of asthma control questionnaire and provided study investigators with current information related to the study objectives. Additional medical record data and a blood sample for total serum IgE and complete blood count were collected. RESULTS: A total of 101 patients were enrolled; 83% were female and the mean (standard deviation) age was 48.7 (13.2) years. Forty-five (45%) patients had the eosinophilic phenotype, 50 (50%) had atopic phenotype 1, and 25 (25%) had phenotypic overlap (eosinophilic and atopic 1). Forty-one (41%) patients had atopic phenotype 2 and 23 (23%) had phenotypic overlap (eosinophilic and atopic 2). Asthma control and oral corticosteroid use patterns were similar and there were no significant differences in number of asthma exacerbations across phenotypes. CONCLUSIONS: In Saudi Arabia, 45% of patients with severe asthma had the eosinophilic phenotype, which is most likely an underestimation as no clinical features of eosinophilia were taken into account in the definition of eosinophilia. Approximately half of them had phenotypic overlap with the atopic phenotype. Trial registration NCT03931954; ClinicalTrials.gov, April 30, 2019.

Road Less Traveled: Drug Hypersensitivity to Fluoroquinolones, Vancomycin, Tetracyclines, and Macrolides.

While fluoroquinolones, vancomycin, macrolides, and tetracyclines are generally safe antibiotics, they can induce both immediate and delayed hypersensitivity reactions (HSRs). Historically, less has been published on allergies to these antibiotics compared to beta lactams, but the prevalence of non-beta lactam HSRs is increasing. To fluoroquinolones, immediate HSRs are more common than delayed reactions. Both IgE and non-IgE mechanisms, such as the mast cell receptor Mas-related G protein-coupled receptor X2 (MRGPRX2), have been implicated in fluoroquinolone-induced anaphylaxis. Skin testing for fluoroquinolones is controversial, and the gold standard for diagnosis is a graded dose challenge. To vancomycin, the most common reaction is vancomycin infusion reaction (previously called "red man syndrome"), which is caused by infusion rate-dependent direct mast cell degranulation. Severity can range from flushing and pruritis to angioedema, bronchospasm, and hypotension that mimic type I HSRs. MRGPRX2 has been implicated in vancomycin infusion reactions. IgE-mediated HSRs to vancomycin are rare. Vancomycin skin testing yields high false positive rates. Thus, direct provocation challenge with slower infusion rate and/or antihistamine pre-treatment is preferred if symptoms are mild to moderate, and desensitization can be considered if symptoms are severe. To tetracyclines, non-IgE-mediated and delayed HSRs predominate with cutaneous reactions being the most common. There is no standardized skin testing for tetracyclines, and avoidance is generally recommended after a severe reaction because of the paucity of data for testing. Graded dose challenges and desensitizations can be considered for alternative or index tetracyclines if there are no alternatives. With macrolides, urticaria/angioedema is the most common immediate HSR, and rash is the most common delayed HSR. The predictive value for skin testing to macrolides is similarly poorly defined. In general, HSRs to fluroquinolones, vancomycin, macrolides, and tetracyclines are challenging to diagnose given the lack of validated skin testing and in vitro testing. Direct provocation challenge remains the gold standard for diagnosis, but the benefits of confirming an allergy may not outweigh the risk of a severe reaction. Skin testing, direct provocation challenge, and/or desensitization to the index non-beta lactam antibiotic or alternatives in its class may be reasonable approaches depending on the clinical context and patient preferences.

Risk of Chronic Rhinosinusitis With Nasal Polyps in Endotypes of Dermatophagoides pteronyssinus-Induced Rhinitis.

BACKGROUND: Observation of the natural history of two emerging endotypes of allergic rhinitis, local-sensitization rhinitis (LAR) and dual-allergic rhinitis (DAR), compared with systemic-sensitization rhinitis (AR), could improve knowledge of the role of allergy in chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: To test the hypothesis that endotypes of Dermatophagoides pteronyssinus (DP)-induced rhinitis were risk factors for CRSwNP and adult-onset asthma and to investigate whether delayed hypersensitivity to DP, assessed by atopy patch test, could be a contributing factor. METHODS: We conducted a prospective observational study over 15 years on a cohort of 999 patients: 468 with AR, 333 with LAR, and 198 with DAR. The latter endotype was characterized by the coexistence of seasonal disease caused by systemic sensitization to pollen in patients with DP-induced LAR. The study design included a physical visit; ear, nose, and throat examination with anterior rhinoscopy; skin prick test; serum-specific IgE; DP-atopy patch test; nasal allergen provocation test with DP; paranasal sinuses computed tomography scan; nasal endoscopy; and spirometry. RESULTS: During 15 years of follow-up, 194 patients developed CRSwNP with a higher rate of LAR (28.2%) and DAR (22.2%) than AR (12%). For LAR and DAR, 7.5% and 10.6% of patients developed adult-onset asthma temporally linked to CRSwNP in 68% and 71.4% of cases, respectively. A total of 858 patients with rhinitis had delayed hypersensitivity to DP. Moreover, DP-ATP was an independent predictive factor for CRSwNP and had elevated positive and negative predictive values for localized allergic disease of the nasal mucosa. CONCLUSIONS: Endotypes of DP-induced allergic rhinitis represent risk factors for CRSwNP. Patients with local-sensitization rhinitis and DAR are more at risk than those with AR. In these emerging endotypes, progression toward CRSwNP is often associated with the development of adult-onset asthma. Chronic rhinosinusitis with nasal polyps shows several possible indicators for type 2 endotype. Delayed hypersensitivity to DP is an independent predictive factor for CRSwNP.