Human papilloma virus and nasopharyngeal carcinoma: pathology, prognosis, recurrence and mortality of the disease

Background: One of the malignant tumors among head and neck cancers is nasopharyngeal carcinoma. Many studies consider human papilloma virus (HPV) as a cause for nasopharyngeal carcinoma. Methods: 41 paraffin-wax-embedded block samples were examined to detect HPV DNA and its subtype’s presence by polymerase chain reaction. The recurrence, prognosis and survival were evaluated for an average of 48 months. Results: HPV DNA was positive in 9 patients (22%). The overall recurrence rate was 75% in HPV negative patients and 11% in HPV positive ones. The mortality rate in HPV negative and positive patients was 37.5% and 0%, respectively. Conclusion: HPV type 18 and 16 were the most common subtypes. Also, it can be implied that patients which are HPV positive had better prognosis and also less recurrence. Key Words: human papilloma virus, nasopharyngeal cancer, polymerase chain reaction, prognosis, recurrence

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

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. © 2020 Georg Thieme Verlag. All rights reserved

Impact of IgE-mediated Food Allergy on Parental Quality of Life in Iranian Patients

Food allergy is a common disorder especially in the first years of life. Strict avoidance of the responsible food is the most effective therapeutic measure so far. But this continuous vigilance could be stressful for the patient and family and decreases their quality of life (QOL). This survey was designed to evaluate the impact of IgE-mediated food allergy on parental QOL in Iranian patients and to develop a valid Persian version of "Food Allergy Quality Of Life-Parental Burden (FAQL-PB) questionnaire". 90 patients (28 females, 62 males) and their parents who were referred to the clinic of Allergy in Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran were enrolled. The questionnaire was translated with scientific method and its reliability was approved in a pilot study (ICC=0.75, cronbach-alpha=0.90). Among all patients the most common allergens were wheat (60) and cow's milk (42). The patient's age (p=0.02), parent's gender (p=0.004), mother's age (p=0.02), duration of the disease (p=0.048), and allergen multiplicity (p=0.004) were found to have the most significant correlation with family and social activity (FSA) domain. The most meaningful associations were achieved between parent's gender (p<0.001) and emotional issues (EM); as well as meal preparation (MP) with patient's age (p=0.02), parent's gender (p<0.0001) and also allergen multiplicity (p=0.003); likewise nutrition and health concern (NH) domain with parent's gender (p<0.001). Anaphylaxis's history did not place any burden on each domain. It was concluded that presence of food allergic patients in families could considerably affect all domains of QOL

Effect of topical furosemide on intraoperative bleeding during functional endoscopic sinus surgery

Intraoperative bleeding reduction during functional endoscopic sinus surgery is a key factor in preventing surgery complications. That is implemented through prescribing systemic corticostroid before surgery. This study aimed to explore an efficient nasal Furosemide versus systematic corticosteroids to reduce intraoperative bleeding. Study Design: This study was conducted on 40 patients with bilateral nasal polyps who undergone functional endoscopic sinus surgery. The patients were randomly divided into 2 groups of furosemide and corticosteroids. Methods: The first group was treated with prednisolone for a week before surgery (1 mg/kg daily) and twice-daily spray by saline as placebo. The second group was treated a week before surgery by topical furosemide nasal spray and placebo pill. The surgeons' opinions about the surgery field and intraoperative blood loss were recorded in both groups. Results: Regarding intraoperative bleeding loss, the difference between furosemide group (262.1545.57 cc) and corticosteroid (232.7556.08) was not statistically significant (P value0.077). Time operation in the furosemide group was 112.812.46 minutes and in the corticosteroids was 105.7512.59 minutes that was not significant (P value0.83). No statistically significant difference was found between the median of both groups in terms of the surgery field (P value0.17). Conclusion: According to this results, when there is a restriction for the use of corticosteroids, 1 week before functional endoscopic sinus surgery the use of topical nasal furosemide can be as effective as the use of oral prednisone to reduce intraoperative bleeding. Copyright © 2016 Mutaz B. Habal, MD

Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-β1 in Iranian children with atopic dermatitis

Background: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. Objective: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-β1 gene polymorphisms. Methods: The allele and genotype frequencies of genes encoding for IL-10 and TGF-β1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. Results: A significant increase was found in the frequency of the TGF-β1 codon 10/C allele among patients (p < 0.001, OR = 6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p < 0.001, OR = 0.14). The frequency of the TGF-β1 codon 25/G allele in the control group was significantly higher than among patients (p < 0.001, OR = 0.08). A significant positive correlation was seen between CC (p < 0.001, OR = 15.10) and CG (p < 0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-β1 CG which was significantly higher than in the control subjects (50 in patients vs. 39.9 in controls, p = 0.042). A significant increase was found in the frequency of TGF-β CC (36 in patients vs. 7.6 in controls, p < 0.001) and TC (14 in patients vs. 0 in controls, p < 0.001) haplotypes among patients compared to controls. By contrast, the TGF-β1 TG haplotype was significantly lower in patients than controls (0 in patients vs. 52.5 in controls, p < 0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. Conclusions: We found a strong association between the polymorphisms of the TGF-β1 gene at codon 10 and codon 25 positions and atopic dermatitis. © 2017 SEICA

Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-β1 in Iranian children with atopic dermatitis

Background: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. Objective: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-β1 gene polymorphisms. Methods: The allele and genotype frequencies of genes encoding for IL-10 and TGF-β1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. Results: A significant increase was found in the frequency of the TGF-β1 codon 10/C allele among patients (p < 0.001, OR = 6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p < 0.001, OR = 0.14). The frequency of the TGF-β1 codon 25/G allele in the control group was significantly higher than among patients (p < 0.001, OR = 0.08). A significant positive correlation was seen between CC (p < 0.001, OR = 15.10) and CG (p < 0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-β1 CG which was significantly higher than in the control subjects (50 in patients vs. 39.9 in controls, p = 0.042). A significant increase was found in the frequency of TGF-β CC (36 in patients vs. 7.6 in controls, p < 0.001) and TC (14 in patients vs. 0 in controls, p < 0.001) haplotypes among patients compared to controls. By contrast, the TGF-β1 TG haplotype was significantly lower in patients than controls (0 in patients vs. 52.5 in controls, p < 0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. Conclusions: We found a strong association between the polymorphisms of the TGF-β1 gene at codon 10 and codon 25 positions and atopic dermatitis. © 2017 SEICA

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

PurposeMajor 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.MethodsWe describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency.ResultsConsanguinity 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.ConclusionMHC-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

Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients

Objectives: Common variable immune deficiency (CVID) is the most frequent form of symptomatic primary immunodeficiency disease, characterized by hypogammaglobulinemia, recurrent infections and increased predisposition to autoimmunity and malignancies. The aim of this study was to reconsider important points of previously performed studies on Iranian CVID patients diagnosed and followed from 1984 to 2013. Methods: Diagnosis was made using approved criteria including reductions of serum levels of immunoglobulins and exclusion of well-known single gene defects in individuals with an age &gt;4 years and evidence of specific antibody deficiency. Results: Detailed information on demographic data, survival rates, clinical phenotypes, immunologic and genetic data and treatment of 173 patients are provided. The early onset presentation (74.5) and rate of consanguineous marriage (61.2) were considerably higher in our cohort. Our study revealed clinically related correlations regarding consanguinity, the population of naïve CD4+T cells and switched-memory B cells, cytokine levels and special genetic factors (including HLA and AID genes). Conclusion: Despite current efforts, more comprehensive studies are needed, especially for classification and investigation of the genetic background and prognostic factors for patients with CVID in order to better managment and followup of patinets. © 2014 Informa UK, Ltd