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Background and Aim Hyper IgE syndromes (HIES) are rare primary immunodeficiency characterized by susceptibility to specific infections, eczema, and elevated IgE levels. Pathogenic mutations in STAT3, IL6R, IL6ST, ERBB2IP, PGM3, ZNF431, SPINK5, TGFBR1/2, and CARD11 have been identified as genetic factors contributing to phenotypes of HIES lead to hindered differentiation and activity, aberrant signaling cascades and disrupting immune regulation. HIES present a diverse clinical symptoms, challenging diagnosis and management; understanding its pathophysiology, genetics, and immunological abnormalities offer hope for improved outcomes. In this review we aim to provide a comprehensive understanding of the condition and also discuss latest updates on pathological features, clinical spectrum and its variability, immunological abnormalities, inheritance patterns, new candidate genes, challenges, management strategies, epidemiology and future directions of HIES. Methods This review conducted an extensive search of information from multiple databases, including PubMed, Scopus, WHO, and ClinVar to ensure comprehensive coverage. Preference was given to articles published recently to capture the latest research and developments. Endnote was employed as a reference manager. The relevant literature was meticulously reviewed to address the objectives of the study. Results Missense, nonsense, and frameshift variants are commonly observed in HIES. Understanding these genetic mutations is key to diagnosing and managing conditions such as Hyper‐IgE recurrent infection syndromes (linked to IL6R, STAT3, and ZNF341 mutations), Atopy associated with ERBIN mutations which links STAT3 and TGF‐β pathway, Immunodeficiency 23 (caused by PGM3 mutations), Netherton syndrome (resulting from SPINK5 mutations), and Loeys‐Dietz syndrome (related to TGFBR mutations). Each year, new genes and variants responsible for this type of immune deficiency are added to the list. Conclusion Although rare, HIES significantly impacts patients due to its complex medical manifestations and need for lifelong management. Identifying casual variants is essential for effective clinical management of these complex conditions. Summary Hyper IgE syndromes (HIES) is characterized with diverse clinical manifestations, caused by mutations in genes like STAT3, IL6R, PGM3, and others. Diagnosis is complex due to clinical variability and overlap with other disorders, requiring genetic analysis and standardized diagnostic criteria. Management includes antimicrobial prophylaxis, immunomodulators, biologics like dupilumab, and, in severe cases, hematopoietic stem cell transplantation (HSCT). Despite therapeutic advances, challenges remain in early diagnosis and personalized treatment. Emerging therapies like gene editing and targeted immunomodulation offer hope. Although rare, underdiagnosis and misdiagnosis contribute to challenges in understanding its true prevalence. Research priorities include identifying novel genetic causes, improving diagnostic tools, and developing advanced treatments like CRISPR‐based gene therapy.

Background: The relation between interleukin-33 (IL-33) and asthma is not precisely known yet. The present study set to compare the serum level of IL-33 in patients with asthma and controls and study the relation with the severity of disease. Methods: The serum level of IL-33 and total IgE in 89 asthmatic patients and 57 controls were analyzed. The association of levels of IL-33 with the severity of disease, levels of total IgE, measures of spirometry (forced expiratory volume in 1 s [FEV1]), age, sex, presence or absence of other allergic diseases, and the disease duration was evaluated. Results: Higher levels of IL-33 and total IgE were detected in asthmatic patients compared with controls (P = 0.0001 and P = 0.008, respectively). In the asthmatic group, a significant direct association of IL-33 with age (P = 0.02, R = 0.23) and with total IgE level (P = 0.003, R = 0.31) were observed, but there was no relationship between other variables. Comparison of mean level of IL-33 in different asthma groups concerning the disease severity showed the statistically significant difference between them and a significant increased serum level of total IgE was observed in more severe disease. The results showed a significant negative correlation between FEV1 and total IgE (P = 0.028, R = −0.23) and IL-33 level (P = 0.0001, R = −0.83). Conclusions: IL-33 is suggested as a new inflammatory marker of severe and refractory asthma. Therefore, it may be a unique therapeutic target in these patients.

Background Inborn errors of immunity (IEI) are inherited defects of innate or adaptive immune system. Thrombocytopenia is a significant multifactorial complication in IEI patients leading to severe clinical consequences including coagulative disorders and vasculopathies. Methods In the present study, we assessed frequency of thrombocytopenia in the most common IEI including combined immunodeficiency (CID), common variable immunodeficiency (CVID), selective immunoglobulin A deficiency (SIgAD), agammaglobulinemia (AGA), hyper immunoglobulin M (HIGM) syndrome, chronic granulomatous disease (CGD) and congenital neutropenia (CN). Also, we compared demographic, clinical and laboratory data between IEI patients with and without thrombocytopenia. Results A total of 890 patients (37% female) were included in this study. The frequency of thrombocytopenia in total IEI was 26.6%. Patients with CID and SIgAD had the highest and lowest frequency of thrombocytopenia (50.9% and 8.7%), respectively. Although rare, thrombocytopenia was more severe (< 50000/ul) among patients with AGA compared to other IEI entities. Notably hepatosplenomegaly and autoimmunity were significantly associated with thrombocytopenia and higher mortality in patients with humoral immunodeficiencies. Conclusion The significant association between thrombocytopenia with lymphoproliferation and autoimmunity emphasizes the importance of paying attention to these clinical features for suspecting IEI disorders. Understanding the pathophysiology of thrombocytopenia in various genetic defects associated with IEI is required for the development of proper diagnostic and therapeutic techniques as well as improved quality of life of these patients.

Objective Whilst the prevalence and severity of asthma influenced by environmental factors, the effect of parental smoking on asthma status of their children was examined. Patients and Methods Ninety asthmatic children, 32 with smoker and 58 with non‐smoker parents (baseline age, 8.5 ± 3.5 and 8.2 ± 3.3 respectively) were studies in two sessions 3 years apart by evaluating respiratory symptoms (RS) prevalence and severity, various drugs used, and pulmonary function tests (PFT) including forced vital capacity; forced volume in the first second, peak expiratory flow; and maximum expiratory low at 75, 50 and 25% of vital capacity (FVC, FEV1, PEF, MEF75, MEF50 and MEF25, respectively). Results The prevalence and severity of all RS were significantly increased in asthmatic children with smoking parents after 3 years except prevalence and severity of night wheeze and the prevalence of chest wheeze (p < 0.05 to p < 0.001), but the PFT values were non‐significantly reduced. In asthmatic children with non‐smoking parents, the prevalence and severity of RS were decreased after 3 years, which was significant for night and chest wheeze for prevalence and night cough and chest wheeze for severity (all, p < 0.05), and the PFT values were increased, which were statistically significant for FVC, FEV1, MEF50 and MEF25 (p < 0.05 to p < 0.01). Drugs used by the group with smoking parents were increased and were significantly higher than their reduction in the groups with non‐smoking parents at the end of the study (p < 0.05 for fluticasone propionate 125/salmeterol and budesonide160/formoterol). Conclusion Long‐term parental smoking increased prevalence and severity of RS and drug used but decreased PFT values of their asthmatic children. The effect of 3‐year parental smoking on asthma status of their children was examined. The prevalence and severity of respiratory were significantly higher, but the PFT values were lower in asthmatic children with smoking parents compared to those of non‐smoking parents at the end of the study. Long‐term parental smoking affects their asthmatic children status.

Cetuximab can be used for the treatment of advanced basal cell carcinoma, especially when the patient cannot tolerate routine chemotherapy. Future studies are needed to confirm it. Cetuximab can be used for the treatment of advanced basal cell carcinoma, especially when the patient cannot tolerate routine chemotherapy. Future studies are needed to confirm it.

Although presentation of COVID‐19 in patients with immunodeficiency could be mild, it should not be missed, while early diagnosis and appropriate treatment can survive infected patients. Because even severe infections in PID patients may be presented with few symptoms and signs, this diagnosis should be considered in those immunocompromised patients who have exacerbating preexisting symptoms. Although presentation of COVID‐19 in patients with immunodeficiency could be mild, it should not be missed, while early diagnosis and appropriate treatment can survive infected patients. Because even severe infections in PID patients may be presented with few symptoms and signs, this diagnosis should be considered in those immunocompromised patients who have exacerbating preexisting symptoms.

Substance P (SP) is a neurotransmitter emitted from neurons that plays a role in the pathogenesis of itching conditions including chronic urticarial (CU). The present research aims to investigate the serum level of S.P among CU patients and compare them with healthy subjects and explore how it correlates with the severity of urticaria. The present research was conducted on 87 CU patients who visited the allergy clinic of Ghaem Hospital, Mashhad, Iran from October 2017 to June 2018. Besides, 86 healthy subjects were recruited as the control group. Background information of patient was collected including age, sex, duration of the disease and the co-occurrence of angioedema. S.P serum level was measured in two groups by ELISA method. In the patients group, the autologous serum skin test (ASST) was performed along with the urticaria evaluation questionnaire include Urticaria Activity Score 7 (UAS7), Urticaria Control Test (UCT) and Chronic Urticaria Quality of Life (CU-Q2OL). Among the patients, the SP serum level showed to be about two times higher than the healthy subjects (p˂0.001). SP showed to be increased as patients’ age grew (p=0.010). In patients with a positive ASST, SP level was higher (p=0.012). No correlation was found between SP and the presence of angioedema among patients. There was no correlation between the SP serum level and the scores obtained from urticaria evaluation questionnaires. SP among CU patients was higher than healthy subjects. SP was also higher among female, older and positive ASST patients. The SP value was not correlated with the severity of urticaria, angioedema. In conclusion, Using SP antagonist drugs could be a potential treatment for chronic urticaria.

Background: Allergic Rhinitis (AR) is the most common allergic disease worldwide. The present study, evaluated effects of synbiotic on gene expression of interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-17 (IL-17), transforming growth factor beta (TGF-β), and forkhead box P3 (FoxP3) in AR patients who received concomitant immunotherapy in a placebo-controlled clinical trial. Materials and Methods: Twenty AR patients were randomized in synbiotic and placebo groups and received cluster immunotherapy for 2 months. RNA was extracted from peripheral PBMCs, then the cDNA synthesized. Subsequently, SYBR Green real-time Reverse transcription polymerase chain reaction technique was employed for studying the expression of mentioned genes. In addition, SNOT-22 and mini-Rhinoconjunctivitis Quality of Life Questionnaire questionnaires were completed by patients. Data were analyzed before and also 2 and 6 months after intervention. Results: Clinical symptoms and quality of life were improved with immunotherapy, but there was no significant difference between the placebo and synbiotic groups. Gene expression of IFN-γ, TGF-β, and FoxP3 was increased whereas the gene expression of IL-4 and IL-10 decreased, but not significant. Interestingly, the gene expression of IL-17 in the synbiotic group was significantly decreased versus placebo after 2 months (P = 0.001) and also at the end of intervention (P = 0.0001) comparing with the time zero. Conclusion: Significant reduction in the IL-17 gene expression following administration of synbiotic versus placebo shows the importance of synbiotic in control of the immunopathogenesis of AR. Further studies with more samples are recommended. In addition, evaluating the effects of synbiotic in patients who do not undergo immunotherapy is suggested to get a better conclusion.

Background Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. Discussion While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. Summary Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children.

Identifying the causes of anaphylaxis which is an acute, potentially fatal systemic reaction is very important in every community. Treatment strategies and pitfalls should also be determined. We sought to determine the most common triggers of anaphylaxis, clinical manifestations and treatment strategies in Mashhad, northeast of Iran. An observational cross-sectional study was conducted to evaluate all patients with a history of anaphylactic reaction who were referred to University Allergy Clinics between 2006 and 2016 in Mashhad Iran. We used a combination of patient's clinical history and allergy diagnostic testing including radioallergosorbant test and skin prick test in order to determine the etiology of anaphylaxis. We identified 172 anaphylactic reactions in 70 patients. Median age was 15 years with a range from 6 months to 48 years. The triggers included: foods, 61.4%; drugs, 15.7%; hymenoptera venom, 8.6%; idiopathic, 5.7%; immunotherapy, 4.3% and other etiologies: 5.7%. Nuts and seeds were the most important triggers of food induced anaphylaxis, especially in school children, adolescents and young adults, followed by fruits. However, Cow's milk and hen's egg were the main triggers of anaphylaxis in children aged under 2 years. The most common symptoms were cutaneous and cardiovascular. Corticosteroids (94.3%) and/or antihistamines (85.7%) were used most frequently for treatment followed by intravenous fluids (54.3%), whereas epinephrine was only used in 17.1% of the cases. Food related anaphylaxis and other typical triggers of anaphylaxis are age dependent and the risks and triggers change with age. Epinephrine injection should be increased by improving the awareness of physician and medical teams. The study was approved by the Ethics Committee of the Faculty of Medicine of Mashhad University of Medical Sciences (approved number: IR.MUMS.REC.1393.960).