Dairy intake in association with asthma symptoms among a large sample of children and adolescents: a cross-sectional study.

Background and objective: Dairy products may be associated with an increased risk of asthma, although there is little scientific evidence to support this association. The goal of this study was to explore the association between dairy consumption and asthma symptoms. Materials and methods: This cross-sectional study was conducted on children and adolescents aged 6-8 and 13-14 years living in central Iran. Dietary food consumption was assessed using a multiple-choice questionnaire. Logistic regression was used to obtain odds ratios for the association between milk, other dairy products, and total dairy consumption with the risk of asthma symptoms. Results: In total, 7,667 participants (3,414 boys and 4,253 girls) were included in the current study. Milk intake and total dairy consumption were not associated with the likelihood of wheezing, asthma confirmed by a doctor, current asthma, and asthma medication use. In addition, there was no association between other dairy product intake and the odds of wheezing in the past 12 months in the crude model. However, after adjusting for several confounders, those in the top category had lower odds of wheezing in the past 12 months than those in the bottom category (OR: 0.58; 95% CI: 0.40-0.85). Conclusion: The consumption of dairy products other than milk, including cheese and yogurt, might reduce the likelihood of wheezing in children and adolescents.

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.

Which Groups of Children Are at More Risk of Fatality during COVID-19 Pandemic? A Case-Control Study in Yazd, Iran.

Introduction: The study aims to investigate the characteristics, comorbidities, laboratory findings, and clinical manifestations of under 18-year-old patients who died with the diagnosis of COVID-19 and determination of the most prevalent risk factors. Method: This case-control study was performed at a referral hospital in Yazd from March 2020 to August 2021. All patients under 18 years who were diagnosed through real-time RT-PCR, chest computed tomography, and the World Health Organization definition were divided into deceased and survived groups. The characteristics (age and sex), disease severity, comorbidities, laboratory findings, and clinical manifestations of the two groups were compared and analyzed using SPSS, version 18 (SPSS Inc., Chicago, III., USA). Results: A total of 24 patients in the deceased group and 167 patients in the survived group were compared. The highest mortality rate was observed in the age group of 1 month to 5 years, although no statistically significant relationship was found between age groups and the risk of mortality. Disease severity, dyspnea, low oxygen saturation on admission, length of hospital stays, and hospitalization history before the last admission were significantly correlated with mortality (P < 0.05). Lymphopenia increased the probability of mortality by more than two times (OR: 2.568; 95% CI (0.962-6.852)), but this was not the case for D-dimer and C-reactive protein. Furthermore, 27.5% of survived patients had normal chest CT scans, which was a statistically significant difference compared to the deceased patients (P: 0.031). Conclusion: Based on the findings of this study, dyspnea, low oxygen saturation, and lymphopenia are critical indicators for identifying high-risk children with COVID-19 and triaging them for better care and treatment.

Association between Butter, Margarine, and Olive Oil Intake and Asthma Symptoms among School Children: Result from a Large-Scale Cross-Sectional Study.

Background: There are conflicting results about the association between dietary fat intake and asthma symptoms. Since few studies in the Middle East have been explored the relation between dietary fat consumption and risk of asthma, the present study was conducted to investigate the association between the consumption of butter, margarine, and olive oil and asthma risk in school children living in central Iran. Method: In this cross-sectional study, out of 10,240 participants, asthma and its symptoms and dietary intake of butter, margarine, and olive oil of 7,667 children and adolescents were assessed using a validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The relationship between fat subtypes and asthma was assessed using logistic regression. Results: The prevalence of asthma confirmed by a doctor in the study population was 4.22%. An inverse association was found between butter and margarine consumption once or twice a week and odds of current asthma and wheezing in the past 12 months (OR = 0.52, 95% CI: 0.28-0.96; OR = 0.7, 95% CI: 0.55-0.88, respectively); however, those with higher consumption did not have a higher chance for developing wheezing or asthma. Conclusion: We found that margarine and butter intake one or two times a week might have an inverse association with asthma and its symptoms among children. Prospective cohort studies are recommended to confirm these findings.

Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population.

PURPOSE: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy. METHODS: We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency. RESULTS: Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range 7 days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were also documented in about one-third of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died. CONCLUSION: MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of CID at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We are better determined to study the c.162delG RFXANK heterozygous mutation frequency in the Iranian population.

Clinical and immunological characteristics of 69 leukocyte adhesion deficiency-I patients.

BACKGROUND: In order to support the comprehensive classification of Leukocyte Adhesion Deficiency-I (LAD-I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD-I patients during the last 15 years. METHODS: Sixty-nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD-I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study. RESULTS: The diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min-max: 0-82 months). Forty-six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%-30%). During the follow-ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively. CONCLUSION: Physicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I.

Dietary approaches to stop hypertension (DASH)-style diet in association with gastroesophageal reflux disease in adolescents.

BACKGROUND: Dietary patterns and food items have been associated with gastroesophageal reflux disease (GERD) risk and they have led to conflicting findings. The aim of this study was to determine the association between a dietary approach to stop hypertension (DASH)-style diet with the risk of GERD and its symptoms in adolescents. STUDY DESIGN: Cross-sectional. METHODS: This study was performed on 5,141 adolescents aged between 13 and 14 years. Dietary intake was evaluated using a food frequency method. The diagnosis of GERD was done by using a six-item GERD questionnaire that asked about GERD symptoms. A binary logistic regression was used to assess the association between the DASH-style diet score and GERD and its symptoms in crude and multivariable-adjusted models. RESULTS: Our findings revealed that after adjustment for all confounding variables, the adolescents with the highest adherence to the DASH-style diet had a lower chance of developing GERD [odds ratio (OR) = 0.50; 95%CI 0.33-0.75, Ptrend< 0.001)], reflux (OR = 0.42; 95%CI 0.25-0.71, Ptrend=0.001), nausea (OR = 0.59; 95% CI:0.32-1.08, Ptrend=0.05) and stomach pain (OR = 0.69; 95%CI 0.49-0.98, P trend=0.03) compared to those with the lowest adherence. Similar results were found for odds of GERD among boys, and the total population (OR = 0.37; 95%CI: 0.18-0.73, Ptrend=0.002, OR = 0.51; 95%CI: 0.34-0.77, P trend<0.0, respectively). CONCLUSION: The current study revealed that adherence to a DASH-style diet might protect against GERD and its symptoms including, reflux, nausea, and stomach pain in adolescents. Further prospective research is needed to confirm these findings.

Association Between Pet Keeping and Current Asthma Among Adolescents Living in Yazd; Evidence from Global Asthma Network (GAN) 2020 Cross-sectional Study.

BACKGROUND: The relationship between current pet keeping and allergic diseases, including bronchial asthma in adolescents, is controversial. This study was conducted to evaluate these associations among children aged 13-14 years in Yazd. METHODS: This study is part of a multicenter cross-sectional study of the Global Asthma Network (GAN) in Yazd, Iran, in 2020, in which 5141adolescents enrolled. Information on respiratory symptoms and pet-keeping (dog/cat/birds) was obtained by a questionnaire derived from the GAN standard questionnaire. RESULTS: Of 5141 participants who completed the study, 1800 (35%) children kept pets during the last year. Birds were the most common pet kept by adolescents (88%). Severe asthma was more common in bird and cat keepers (P=0.003 and P=0.034, respectively) than dog keepers. Furthermore, there was a statistically significant association between study-defined current asthma and cat keeping, but not bird or dog ownership (P=0.02). Moreover, we found that current any pet-keeping (birds, cats, dogs) was associated with a higher prevalence of asthma-related symptoms, including wheezing, night dry cough, and exercise-induced wheezing in the past year (P=0.002, P=0.000 and P=0.000 respectively). CONCLUSION: Current any pet-keeping is associated with asthma-related symptoms. Additionally, cat keeping had a significant association with study-defined current asthma. The current keeping of birds, as the most common pet in our area, or cat keeping increases the risk of severe asthma in adolescents. Therefore, as an important health tip, this needs to be reminded to families by health care providers.

Protein Kinase C-Delta Defect in Autoimmune Lymphoproliferative Syndrome-Like Disease: First Case from the National Iranian Registry and Review of the Literature.

BACKGROUND: Protein kinase C is a family of serine/threonine kinases that play a key role in the adaptive immune cell signaling, as well as regulation of growth, apoptosis, and differentiation of a variety of cell types. Patients homozygous for a null mutation of the Protein Kinase C Delta (PRKCD) gene, present clinical feature of immune dysregulation with susceptibility to Epstein-Barr virus infection. However, a minority of patients present the autoimmune lymphoproliferative syndrome (ALPS). METHODS: The data were collected by direct interview and examining the patient's clinical record. Whole-exome sequencing was performed to detect the underlying genetic mutation in the patient. We also conducted electronic searches for ALPS-like reported patients in PubMed, Web of Science, and Scopus databases. RESULTS: In this study, we reported a 13-year-old boy who presented with autoimmunity, lymphoproliferation, recurrent pneumonia, cardiomyopathy, and dermatological manifestations. An elevation of double-negative T cells, CD8+ T cells, serum IgG level, as well as a reduction in NK cells, was observed in the patient. A homozygous frameshift mutation (c.1293_1294insA) in exon 13 of the PRKCD gene was confirmed. The literature search showed 39 ALPS-like patients with monogenic defects which only six (15.3%) of them were due to PRKCD genes. CONCLUSION: PRKCD should be considered in the context of ALPS clinical manifestations with prominent dermatological involvements.

New onset of diabetes in a child infected with COVID-19: a case report.

BACKGROUND: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes. A few studies have reported that COVID-19 is associated with the development of new-onset diabetes. Here, we present an infected child with new onset diabetes leading to DKA. CASE PRESENTATION: A 10-year-old patient with respiratory distress admitted to the Emergency Department of our center. The patient's COVID-19 Polymerase Chain Reaction (PCR) test was positive and also biochemical analyses confirmed that he had DKA. Despite standard initial treatments, ketoacidosis remained resistant; hence we prescribed oral bicarbonate (40 cc every 8 h) to treat the patient's refractory acidosis. Due to the patient's improvement, he was discharged after 10 days (7 days in the PICU), receiving outpatient enoxaparin (for a week) and ongoing subcutaneous insulin. CONCLUSION: We report an interesting case of a child with COVID-19 infection precipitating presentation with new onset diabetes. Due to refractory acidosis, starting oral bicarbonate treatment after 2 days improved acidosis and tachypnea in the patient. The patient's medical team suggest close biochemical monitoring, prescribing enoxaparin for high level of D-dimer, and ordering oral bicarbonate acidosis persists.

Prevalence of Allergic Rhinitis and Eczema in Adolescents Living in Yazd City: Part of Global Asthma Network Survey.

Allergic rhinitis and eczema are two common global diseases that can lead to impaired quality of life. Determining the prevalence of these allergic disorders can be useful in planning prevention and treatment. This study aimed to investigate the prevalence and severity of allergic rhinitis and eczema in adolescents living in Yazd city. Using an electronic questionnaire based on the Global Asthma Network (GAN) core questionnaire, 5141 adolescents aged 13-14 years were cross-sectionally surveyed. The prevalence of current symptoms of rhinitis turned out to be 36.3%, proving significantly higher in boys (p=0.009). Moreover, the prevalence of allergic rhinitis and rhinoconjunctivitis in the past year leveled at 12.4% and 10.5%, respectively; however, the former was significantly higher in females (p=0.014). Additionally, severe rhinoconjunctivitis was observed in 0.2% of the participants with no gender preference (p=0.09). Confirmed hay fever by a doctor was reported in 13.2% of adolescents, significantly higher in males (p<0.001). The prevalence of current itchy rash and current eczema was found to be 5.5%, and 2.9%, respectively, with no difference in terms of gender. Severe atopic eczema and eczema confirmed by a doctor were seen in 0.4% and 5% of the participants, no gender preference was identified. Concurrent prevalence of current rhinoconjunctivitis and eczema was detected in 1% of the participants. Despite the increasing trend of allergic diseases in most parts of the world, the prevalence of rhinoconjunctivitis and eczema in adolescents has not increased in Yazd in the last two decades, and this city is located in a low to moderate prevalence area.

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.

Prevalence and Severity of Adolescent Asthma in Yazd, Iran: Based on the 2020 Global Asthma Network (GAN) Survey.

Asthma, as the most common chronic disease in children, encompasses substantial health and socioeconomic burden worldwide. This study aimed to evaluate the prevalence, severity, and management of asthma in adolescents aged 13-14 years. This cross-sectional study, which was part of the Global Asthma Network (GAN) 2020 survey, was conducted in early 2020 in Yazd, Iran. A total of 48 schools in Yazd city were selected by cluster sampling. In this study, 5141 students, including 3069 (59.7%) females and 2072 (40.3%) males participated. Prevalence of ever and current wheezing was 19% and 9% respectively. The former was significantly higher in males than females (p<0.001). About 2% of the participants, which was 22.1% of students with current wheezing, had severe asthma. The prevalence of severe asthma was significantly higher in males (p=0.026). Our results showed that 4.8% of students had confirmed asthma by a doctor, significantly predominant in males (p<0.001). The prevalence of using inhaled medicines in the past 12 months was 3.8%, which was significantly higher in males than females (p<0.001). The prevalence of using short-acting ß-agonists (SABA) and long-acting ß-agonists (LABA) was 2.3% and 1.4% among the students, respectively, with a male predominance (p=0.019). About 1.2% and 0.8% of participants were using inhaled corticosteroids (ICS) and the combination of ICS and LABA, respectively, which was significantly higher in male participants (p<0.001). According to our findings and in comparison to the previous ISAAC study in Yazd, the prevalence of severe asthma has decreased which indicates better management of asthma during the past two decades.

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.

The Effect of Gelfoam Impregnated With Botulinum Toxin on Allergic Rhinitis.

INTRODUCTION: This study evaluated the effect of gelfoam impregnated with botulinum toxin on the symptoms induced by allergic rhinitis. MATERIALS AND METHODS: In total, 30 patients with allergic rhinitis who did not respond to common therapies were included in this clinical trial study. All patients were treated with intranasal gelfoam impregnated with botulinum toxin type a (40 unit in each side) placed in the middle meatus of each nostril. The main symptoms of allergic rhinitis were scored from zero to three by the patients. Symptoms recorded and compared before and two months after the treatment. RESULT: The mean age of patients was 31.03±6.9 years. The mean score for sneezing was 2.23 before the treatment which significantly decreased to 1.06 after the treatment (P<0.05). The mean scores of rhinorrhea, nasal congestion, and nasal itching were 2.53, 2.03, and 1.93, respectively, before the treatment which significantly decreased to 0.93, 1, and 0.8 after the treatment (P<0.05). No reported side effects was observed in this study. CONCLUSION: According to the results, treatment with gelfoam impregnated with botulinum toxin is an effective and safe method in patients who have not responded to common therapies for allergic rhinitis. Accordingly, it is recommended to relieve symptoms in patients with seasonal allergic rhinitis in order to maintain the effectiveness of this treatment at least 8 weeks.

Candidiasis associated with very early onset inflammatory bowel disease: First IL10RB deficient case from the National Iranian Registry and review of the literature.

Defects in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) are closely related to very early onset (infantile) inflammatory bowel disease (VEO-IBD). In the present study, we report a novel homozygous null mutation within interleukin-10 receptor B (IL10RB) gene in a child presenting with severe VEO-IBD. In accordance with previous reports, our patient manifested with chronic diarrhea, failure to thrive, intermittent fever and multiple anal ulcers associated with Candidiasis. Homozygous null mutation within IL10RB gene (c.92C > T, p.S31P) affecting the extracellular domain of protein was discovered in this patient. In conclusion, the diagnosis of IL-10R gene mutations should always be considered as a possible cause of refractory diarrhea and failure to thrive. Mutation analysis could help detect the genetic defects associated with these clinical manifestations and to determine the most appropriate treatment option for patients affected by this disease.

Antiepileptic Hypersensitivity Syndrome to Phenobarbital: A Case Report.

Phenobarbital is still one of the most commonly used medical treatments for different types of seizures. It has numerous different side-effects. Antiepileptic hypersensitivity syndrome (AHS) is a rare and potentially life-threatening adverse reaction to aromatic anticonvulsants such as phenobarbital. Its characteristic features are fever, rash, and lymphadenopathy with different severity of hematologic abnormalities. This case report presents a 26-month-old girl that developed fever, disseminated maculopapular rash, petechiae and thrombocytopenia two weeks after the initiation of phenobarbital prescribed for febrile seizure prophylaxis. The patient was admitted in our center with the impression of hypersensitivity syndrome, so phenobarbital was discontinued and her treatment was resumed with methylprednisolone and intravenous immunoglobulin. After a few days, all symptoms improved and the platelet count was normalized. Thrombocytopenia is a rare complication of hypersensitivity syndrome to phenobarbital in children. Paying attention to this point can prevent the life-threatening adverse effects of this highly consumed medicine.

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 µ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with µ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with µ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

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.

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.