Clinical heterogeneity in families with multiple cases of inborn errors of immunity.

BACKGROUND: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation. METHODS: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities. RESULTS: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family. CONCLUSION: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve.

Adverse reactions in a large cohort of patients with inborn errors of immunity receiving intravenous immunoglobulin.

BACKGROUND: Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions. METHODS: Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity. RESULTS: 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg. CONCLUSION: The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg.

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency.

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran.

BACKGROUND: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM. METHODS: Clinical and immunological data were collected from the 75 patients' medical records diagnosed in Children's Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing. RESULTS: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients. CONCLUSION: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.

Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency.

BACKGROUND: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. OBJECTIVES: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. METHODS: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. RESULTS: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. CONCLUSIONS: This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.

Investigation of the relationship between atopy and psoriasis.

INTRODUCTION: The relationship between allergic and autoimmune diseases is an important issue, which has recently attracted the researchers' interest. AIM: To determine the relationship between atopy and psoriasis. MATERIAL AND METHODS: This case-control study was conducted on 102 patients referred to the Ghaem Hospital, Mashhad, Iran, in 2016. The participants were assigned into two groups: experimental and control groups, including the patients suffering from psoriasis and those with no history of cutaneous or other systemic diseases, respectively. Both groups filled in the ISAAC questionnaire and had skin prick tests. In addition, the serum levels of immunoglobulin E (IgE) and blood eosinophil cell count were measured. The data were analysed using the regression test through SPSS version 16. RESULTS: According to the results of the ISAAC questionnaire, there was a significant difference between the control and experimental groups in terms of asthma (p = 0.04). The mean serum concentrations of IgE and eosinophil cell count were not significantly different between the experimental (153.93 IU/ml and 187.77 cells/µl, respectively) and control groups (152.19 IU/ml and 187.68 cells/µl, respectively) (p = 0.057 and p = 0.886, respectively). In addition, there was an indirect correlation between the eosinophil cell count and psoriasis severity (p = 0.032, r = -0.297). Furthermore, the comparison of the skin prick test results revealed no significant difference between the two groups regarding the number of positive and negative cases (p = 0.436). CONCLUSIONS: The findings suggested that atopy was not common in the patients with psoriasis and supported the concept that atopy protects against such autoimmune diseases such as psoriasis.

A significant decrease in the gene expression of interleukin-17 following the administration of synbiotic in patients with allergic rhinitis who underwent immunotherapy: A placebo-controlled clinical trial.

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-ß), 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-ß, 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.

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

BACKGROUND: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. METHOD: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry.

BACKGROUND: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers. METHODS: This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006. RESULTS: A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %). CONCLUSIONS: Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases.

Synbiotic in the management of infantile colic: a randomised controlled trial.

AIM: Infant colic is a frequent problem affecting up to 10-30% of infants in first 3 months of life. Results from previous trials have shown that manipulation of gut microbiota can lead to symptomatic improvements. In a randomised clinical trial, we aimed to determine efficacy of synbiotic in reducing average infant crying time at day 7 and day 30 after starting intervention. METHODS: Fifty breastfed infants aged 15-120 days with infantile colic randomly assigned to receive either the synbiotic sachet containing 1 billion CFU of: Lactobacillus casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, B. infantis, L. bulgaricus and fructooligosacharide (Protexin Healthcare, Somerset, UK), or placebo daily for 30 days. Parents were asked to record details of crying times in a symptoms diary. The primary outcome measure was the treatment success (reduction in the daily crying time >50%) and the secondary outcome measure was symptom resolution (reduction in the daily crying time >90%). RESULTS: The treatment success was significantly higher in synbiotic group (82.6%) compared with placebo (35.7%) at day 7 (P < 0.005). At day30, treatment success was 87% and 46% in synbiotic and placebo group, respectively (P < 0.01). Symptom resolution was also higher in synbiotic group (39%) compared with placebo (7%) at day 7 (P < 0.03) but not at day 30 (56% vs.36%, P = 0.24). We encountered no complication related to synbiotic use. CONCLUSION: This synbiotic (a mixture of seven probiotic strains plus FOS) significantly improved colic symptoms in comparison with placebo.

The clinical relationship between histamine-1 receptor antagonists and risk of cancer: a systematic review and meta-analysis.

BACKGROUND: A systematic research was performed to review the relationship between use of histamine-1 receptor antagonists and cancer risk. METHOD: Databases were searched up to December 2021. Case-control and cohort studies evaluating the relationship between use of histamine-1 receptor antagonists and risk of cancer were selected. The major outcome was cancer risk. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated. Subgroup, cumulative, and sensitivity analysis and Egger test were performed. RESULTS: Five case-controls and one cohort study were included. According to cohort study, use of antihistamines were not associated with cancer risk (RR = 0.92, 95% CI = (0.78-1.07). In case-controls, the frequency of antihistamine use in cases and controls was 11.28% and 14.82% respectively which was associated with decreased cancer risk (p value = 0.02, OR = 0.93, 95%CI = (0.87, 0.99)). Sensitivity analysis showed a change in direction of pooled OR by omitting some studies. Sub-group analysis according to type of cancer showed a decrease in cancer risk in antihistamine users in glioma (p value = 0.03). CONCLUSION: Antihistamines might reduce the risk of certain cancers. More studies with defined background of allergy are needed which can clarify the relevancy of different types of cancer with anti-H1 receptors.

Respiratory viral infections in children with asthma: do they matter and can we prevent them?

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.

The Potential of Probiotics for Treating Skin Disorders: A Concise Review.

Probiotics are defined as "live microorganisms that confer a health benefit on the host when administered adequately." In recent years, the cosmetic industry has tried to develop many products classified as probiotics. They can exert their benefits at the skin level because of their favorite properties, and they could prevent and treat skin diseases and represent an emerging area for skin health. The antibacterial and immunomodulatory properties make them promising candidates to target skin disorders including acne, psoriasis, and atopic dermatitis and aid wound healing. The scientific reports show that specific probiotic strains can modulate cutaneous microflora, skin immune system, lipid barrier, and skin health preservation. This review summarizes the most relevant evidence from scientific literature concerning potential topical applications of probiotics in dermatology. Altogether, the evidence reported here affords the possibility of designing new strategies based on a topical approach to prevent and treat cutaneous disorders.

The effect of 3-year parental smoking on asthma status of their children.

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.

Diversity of malignancies in patients with different types of inborn errors of immunity.

Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin's lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin's lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

Epidermal growth factor receptor inhibitor in advanced basal cell carcinoma.

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.

Prevalence of IgE-Mediated Food Hypersensitivity to Cereals and Beans Based on Skin Prick Test in Children with Celiac Disease.

BACKGROUND Celiac disease is a non-IgE mediated food allergy, which can cause extensive villus atrophy. Because of increased food allergen absorption, there are elevated IgA and IgG antibodies in these patients, so there is a concern about IgE antibody production against wheat and other cereals. METHODS In this study, we evaluated IgE-mediated hypersensitivity to wheat, rice, and other cereals in children with celiac disease. RESULTS 22 patients (50%) had at least one positive skin prick test to food allergens. The most frequent food allergen was peanut (31.8%), followed by wheat (18.2%), corn (9.1%), and rice (4.5%). The results revealed no significant correlation between age, sex, and the results of the skin prick test (p >0.05). The correlation between diagnosis time of celiac disease and results of skin prick test was also not significant statistically (p >0.05). CONCLUSION Because of the high prevalence of IgE mediated hypersensitivity to cereals and beans in children with celiac disease, a skin prick test might be considered in these patients, especially in refractory cases.