Search

Background: Primary immunodeficiency diseases (inborn errors of immunity) with partial albinism are a group of autosomal recessive syndromes including Chediak Higashi Syndrome (CHS), Griscelli Syndrome type 2 (GS2), Hermansky‐Pudlak Syndromes type 2 and 10 (HPS2, HPS10), Vici syndrome and P14/LAMTOR2 deficiency. Methods: Twenty‐five patients including 10 CHS, 10 GS2, and 5 HPS2 were evaluated in this study within the last 10 years. Five cases with oculocutaneous albinism (OCA) and 5 healthy subjects without albinism were used as two control groups. Genetic analyses were performed by whole exome or panel sequencing or targeted Sanger sequencing. Subsequently, leukocyte granules in peripheral blood smear and hair shaft were examined as screening tests. Results: Giant granules were only presented in the leukocytes cytoplasm of 10/10 CHS patients. The uneven cluster of pigments and giant melanin granules in hair samples were observed in 10/10 GS2 and 10/10 CHS patients, respectively. In both 5/5 OCA and 5/5 HPS2 patients, there were regular pigments in the middle of hair shafts. Genetic analyses were performed for all patients, revealing 7 novel variants in LYST gene for CHS patients and 4 novel variants in AP3B1 for HPS2 patients. Conclusion: Receiving hematopoietic stem cell transplantation (HSCT) in a timely manner is crucial in CHS and GS2 patients; therefore, screening tests may provide a vital clue for early diagnosis in these patients. However, the final confirmation of CHS, GS2, and HPS2 disorders is done by genetic assay. [ABSTRACT FROM AUTHOR]

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon–intron boundaries. Two patients in this study were subjected to whole‐exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: An increasing interest in the field of molecular diagnosis of allergy has been developed in recent years and it goes to be as the routine in vitro protocol in allergy diagnosis. friendly allergen nano-bead array (FABER) is a new multiplex assay for the evaluation of specific IgE against 244 allergens including whole extracts and allergenic molecules. The research intended to assess the pattern of IgE sensitization to allergenic components of allergens in allergic adults using FABER 244. Methods: Sixty patients with allergic diseases entered this cross-sectional study. Specific IgE to 122 whole allergens extracts and 122 allergenic components were assessed using an allergen nano-bead array (FABER) for all patients. This test includes inhalant and food allergens. Results: Thirty-seven patients were male (61.7%). The mean (SD) age of patients was 30.73(±6.87) years. As the allergen nano-bead array results showed, Lolium perenne (63.3%), Phleum pratense (60%) and Platanus acerifolia (51.7%) were considered as the most common IgE sensitizations to the aeroallergen extracts. Moreover, Lol p 1, Phl p 1.0102 and Cup a 1 were found as the most frequent allergenic components in our allergic patients. Among protein families, CCD-bearing proteins, expansin, cysteine protease and profilin families illustrated the highest allergic sensitization. Conclusions: The results of the present study demonstrated that despite the higher prevalence of sensitization to Salsola kali (47.2%) using extract-based assays in the previous phase of this research, allergenic components of grasses (Lol p 1, Phl p 1.0102), Cup a 1 as well as Sal k1 as the major components of Cupressuss arizonica and Salsola kali showed the higher sensitization, respectively, in adults' allergic patients using FABER test. [ABSTRACT FROM AUTHOR]

The skin prick test (SPT) could be applied as a useful in vivo method for the detection of sensitization in epidemiological and diagnostic studies if the wheal size is ideally evaluated. We focused on SPT wheal size to identify sensitization pattern to common inhalant and food allergens. In this cross‐sectional study, SPT results were obtained from a total of 972 allergic patients. Common allergen extracts for SPT were selected according to the type of allergic diseases, and the geographical pattern. SPT with food allergens was performed for patients with atopic dermatitis (AD) and chronic urticaria (CU). A total of 461 male (47.4%) and 511 female (52.6%) participated in this study (median age: 31 years). The majority of individuals were affected with allergic rhinitis (AR) (n = 624) and asthma (n = 224); while 129 and 67 patients suffered from AD and CU, respectively. The most common aeroallergens were Russian thistle (52.1%) and lamb's quarter (50.7%) with the largest wheal diameter. The wheal size of lamb's quarter was significantly different between patients with asthma and AR (P<.001). In addition, a significant difference was detected in wheal diameter in response to the Russian thistle between patients with AR and AD (P =.001). Shrimp (23.6%) and Peanut (22.5%) caused the most common food sensitization in patients with AD and CU. Having in mind the most common weed pollens including the Russian thistle and lamb's quarter, preventive strategies, such as, removing unwanted weeds or preventing them from growing, avoidance, and specific immunotherapy may be crucial for better disease control. [ABSTRACT FROM AUTHOR]

Background: The actual prevalence of paediatric asthma as a worldwide chronic disease has been surveyed in developed countries. However, no sufficient survey has been conducted in most of the eastern developing countries. Herein, we took measures to evaluate the prevalence of paediatric asthma in Iran. Methods: In this national cross‐sectional study, the prevalence of asthma symptoms was estimated throughout the country using a randomized multistage stratified cluster sampling method in 16 410 and 16 850 individuals aged 6‐7 and 13‐14 years, respectively. A validated questionnaire including core questions of the International Study of Asthma and Allergies in Childhood (ISAAC) was applied between November 2015 and February 2016. Results: The total prevalence of asthma was 10.9% (n = 3624) (95% confidence interval [CI]: 10.6%‐11.2%) which was significantly higher among 13‐ to 14‐year olds compared to a younger age group (12.4% vs. 9.4%, P < 0.001), males versus females (12.1% vs. 9.8%, P < 0.001) and residents of urban compared to rural areas (P = 0.003). The prevalence of severe asthma was 3.9%, being significantly more prevalent in higher age groups and male individuals (P < 0.001). A significant relationship was found between asthma and passive smoking in both 6‐ to 7‐ and 13‐ to 14‐year olds (P < 0.001). Conclusions: The prevalence of asthma and severe asthma in the paediatric population of Iran was similar to other developing countries. It is recommended to pay special attention to urban regions, male individuals and higher age groups for better controlling of asthma. Nevertheless, further national surveys are necessary to determine the trend of paediatric asthma in Iran. [ABSTRACT FROM AUTHOR]

T-cell receptor excision circles (TRECs) and κ -deleting recombination excision circles (KRECs) are recently used for detection of T or B cell lymphopenia in neonates based on region -specific cutoff levels. Here, we report cutoffs for TREC and KREC copies useful for newborn screening and/or diagnosis of primary immunodeficiency diseases (PID) in Iran. DNA was extracted from a single 3.2 mm punch of dried blood spots collected from 2160 anonymized newborns referred to two major referral health centres between 2014 and 2016. For refinement of the cutoffs, 51 patients with a definite diagnosis of severe combined immunodeficiency, X -linked agammaglobulinaemia and combined immunodeficiency, including ataxia telangiectasia, human phosphoglucomutase 3 and Janus kinase -3 deficiency, as well as 47 healthy controls were included. Samples from patients with an X -linked hyper -IgM -syndrome, Wiskott -Aldrich syndrome and DNA ligase 4 deficiency were considered as disease controls. Triplex -quantitative real -time PCR was used. Cutoffs were calculated as TRECs < 11 and KRECs < 6 copies with an ACTB > 700 copies with sensitivity of 100% for TREC and 97% for KREC. Among thirty anonymized newborn samples (1.5%) with abnormal results for TREC and/or KREC, only twenty -one available cases were retested and shown to be in the normal range except for three samples (0.15%). All of the patients with a definitive diagnosis were correctly identified based on our established TREC/KREC copy numbers. Determining cutoffs for TREC/ KREC is essential for correctly identifying children with PID in newborn screening. Early diagnosis of PID patients enables appropriate measures and therapies like stem cell transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Background and objective: Asthma and chronic obstructive pulmonary disease (COPD) could be considered as a major health problem in industrialized and developing countries. This study was designed to analyze the trends of mortality from asthma and COPD at national and subnational levels in Iran based on National Death Registry, from 2001 to 2015. Materials and methods: We used Death Registration System (DRS) as the basic source of data. Death Registration System data were available from 1995 to 2010 in Iran's Ministry of Health. Although, Tehran and Isfahan, 2 most populated cities in Iran, had independent death registry systems in their cemeteries, by combining their data we achieved more comprehensive and representative data on death among Iranian people. We addressed incompleteness and misclassification of death registry system using demographic and statistical methods. We also employed spatio‐temporal and Gaussian process regression to extrapolate and interpolate mortality rates for the missing data. Results: Age‐standardized asthma mortality rate was 7.2 (5.6‐9.2) in females and 8.8 (6.9‐11.1) in males at the national level in 2015. Age‐standardized COPD mortality rates in females and males, respectively, were 8.46 (6.6‐10.9) and 12.38 (9.8‐15.6) during the studied years. A reduction in age‐standardized asthma mortality was observed during the period of study. In addition, the trend of COPD mortality was increasing. Conclusions: It seems that mortality rate attributable to COPD has risen during the past 15 years in Iran. It could have increased because of increased exposure of people to related risk factors such as air pollution which is a common problem in larger cities and border provinces. [ABSTRACT FROM AUTHOR]

Background: The worldwide increase in the prevalence of asthma has made it a major public-health concern. We aimed to identify the prevalence of asthma and asthma symptoms in adults living in urban and rural areas of Iran as a populated country with about 80 millions of residents. Methods: This cross-sectional study was conducted to estimate the prevalence of asthma in adults between 20 and 44 years old in all provinces of Iran. Data were collected by personal interview via a standardized questionnaire [European Community Respiratory Health Survey (ECRHS)] between November 2015 and February 2016. Results: A total of 24 344 individuals were enrolled. The prevalence of asthma was 8.9% [95% confidence interval (CI): 8.5-9.3]. The most common asthma symptoms were wheezing (14.2%, n = 3465), nocturnal cough (13.3%, n = 3234) and chest tightness (11.3%, n = 2760). Additionally, the prevalence of current asthma (taking asthma medications or asthma attack) was estimated to be 4.7% (n = 1155). Asthma was significantly more prevalent in males compared to females (P = .002), while no significant relationship was detected between gender and asthma after adjusted analysis with other variables. The prevalence of asthma was significantly higher in older participants (P < .001) and individuals with low educational level (P < .001). Interestingly, there was no significant relationship between asthma and area of residency (P = .8). Conclusions: The prevalence of asthma in Iran was similar to other Asian and European countries. However, repeated national surveys are required to determine the trend of asthma prevalence in Iran in comparison to other countries. [ABSTRACT FROM AUTHOR]

Introduction Despite reports of response to steroid inhaler in some clinically suspected asthma patients with negative methacholine challenge test (CSA/MCT−), treatment in these patients has not been prospectively studied. Objective We studied the role of a 12 week high dose inhaled fluticasone trial in CSA/MCT− patients. Methods After a 2 week run-in period, CSA/MCT−patients were treated with 12 weeks of Fluticasone propionate 1000 µg/day. The Asthma Control Test (ACT), numeric cough score (NCS) and bronchodilator use were compared with their pretreatment values. Results Thirty-four of 42 CSA/MCT−patients completed the study. Mean pretreatment ACT score (pACT) was significantly increased after treatment (14.7 ± 3.37 to 20.9 ± 3.1, P < 0.001). Posttreatment values of daytime (1.0 ± 1.0) and night-time (0.6 ± 0.9) NCS decreased compared to their pretreatment values (2.8 ± 1.1 and 1.9 ± 1.3, respectively; P < 0.001). ACT score change (ΔACT) were significantly greater in those with pACT < 15 than in those ≥15 ( P < 0.001) . Fifteen of 21 patients with ΔACT > 5 did not need to use bronchodilator for their symptom relief. Wheeze disappeared in all six patients with ΔACT > 5 after the trial. Six months after the study, steroid inhaler continued to be used by 72.2% of patients. Conclusion A significant portion of CSA/MCT− (especially those with pretreatment ACT score <15) respond to high dose fluticasone inhaler in terms of symptoms relief, disappearance of wheeze and need to bronchodilator use. ΔACT could not be predicted with any individual symptoms or signs before MCT, % FEV1 decline or symptoms during MCT and exhaled nitric oxide. [ABSTRACT FROM AUTHOR]

Key Clinical Message DOCK8 deficiency is a rare autosomal recessive combined immunodeficiency with high IgE level, eosinophilia, severe eczema, extensive cutaneous viral, and respiratory bacterial infections, mostly in populations with higher prevalence of consanguinity. Molecular diagnosis of this gene is a useful approach for early diagnosis and timely HSCT due to deleterious consequences. [ABSTRACT FROM AUTHOR]

Objective Primary hemophagocytic lymphohistiocytosis ( HLH) is a life-threatening condition that clinically characterized by fever, hepatosplenomegaly, and cytopenia. Hematopoietic stem cell transplantation ( HSCT) is the only curative treatment option for patients diagnosed with primary HLH. Methods In this prospective study, we analyzed the outcome of 10 pediatric patients with primary HLH who had received HSCT, using reduced-intensity conditioning ( RIC) regimen from 2007 to 2012. The median age at transplantation was 22.6 months (range: 6-60). All of the patients received the same RIC regimen based on the use of fludarabine in combination with melphalan and horse antithymocyte globulin ( ATG). Cyclosporine and methylprednisolone were used as graft-vs.-host disease ( Gv HD) prophylaxis. Results Hematopoietic engraftment occurred in all patients. At the present time, 8 patients with a median follow-up of 39 months are still alive and all of them are disease free. Acute and chronic Gv HD developed in 6 and 2 patients, retrospectively. Two patients died of sepsis and chronic Gv HD during the study. Conclusion Because of pretransplant infections caused by underlying immunodeficiency in patients with primary HLH, the use of less toxic regimen with RIC seems to be highly effective in this regard. Recipients of RIC transplant, with either full or mixed chimerism, had a long-term survival rate with no manifestation of primary HLH symptoms. [ABSTRACT FROM AUTHOR]

Partial albinism with variable immunodeficiency are the two major characteristics of Griscelli syndrome type 2 ( GS-2). This syndrome is usually associated with a high mortality rate and commonly results in early childhood death. Patients suffer from different infections and experience crisis of HLH. HSCT remains the sole curative treatment for GS-2. We prospectively analyzed the outcomes of transplantation with RIC regimen in five patients. The median age at transplantation was 21.6 months (range: 12-30). All of the patients underwent HSCT from HLA-matched related donors. Currently, four patients are cured, and symptoms of recurrent infections and HLH crisis are not seen in them. The only patient who died had undergone HSCT in the accelerated phase of HLH. One patient who developed acute GvHD had a favorable response to therapy. No chronic GvHD occurred in patients. It seems that the use of RIC regimen as a method of transplant preparation is effective and tolerable in this group of patients with various comorbidities. It is recommended to carry out HSCT in these patients at lower ages, before presentations of different infections and HLH crisis. [ABSTRACT FROM AUTHOR]

Hamidieh AA, Pourpak Z, Alimoghaddam K, Movahedi M, Bahoush G, Behmanesh F, Moin M, Ghavamzadeh A. Successful allogeneic stem cell transplantation with a reduced-intensity conditioning in a leukocyte adhesion deficiency type I patient. Pediatr Transplantation 2011: 15:E30-E33. © 2009 John Wiley & Sons A/S. LAD-I is a rare, autosomal recessive, primary immunodeficiency in which phagocyte adhesion and chemotaxis are impaired. Multiple infections in the absence of pus accumulation and persistent elevated peripheral blood neutrophil counts are the hallmark of LAD-I. Allogeneic HSCT is the only treatment proved to be potentially curative for phagocyte adhesion impairment in LAD-I. Here, we report on a case of a 30-month-old girl with LAD-I, in whom peripheral blood stem cell from a genotypically identical sibling resulted in mixed chimerism. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of asthma among pregnant women with dyspnea.Methods: Pregnant women referred for prenatal care visits who had complaints of dyspnea were included. All pregnant women were evaluated by a respiratory specialist. Spirometry was performed by a single trained physician.Results: Asthma was diagnosed in 38.8% of participants. Dyspnea was diagnosed as being physiologic in 36.4% of cases, but 24.8% of cases were of probable asthma (spirometric values were within normal range but symptoms and signs were suggestive of asthma). Cough, wheezing, and post-exercise symptoms were significantly more prevalent in asthmatic and probable-asthmatic women than in women without asthma.Conclusion: Dyspnea in pregnancy can be physiologic, but when it is accompanied by other symptoms such as cough or wheezing it is likely to be caused by asthma. Because of the high prevalence of asthma during pregnancy, it seems logical to evaluate dyspnea via physical examination and response to bronchodilators. [ABSTRACT FROM AUTHOR]

Background The severe adverse cutaneous reactions of erythema multiforme (EM), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare mucocutaneous diseases associated with significant morbidity and mortality. The most common cause is antiepileptic drugs, particularly carbamazepine and lamotrigine, as well as the barbiturates group (phenobarbital and phenytoin). In this article, we present seven children with severe adverse cutaneous reactions caused by barbiturates. Case Reports The age of the affected children was between 2 and 11 years and they all had a history of taking barbiturates. Their symptoms started 1–3 weeks after the initiation of barbiturates, including a prodrome characterized by 2–3 days of malaise, fever, cough and anorexia, after which the skin and mucosal lesions appeared and worsened. The skin lesions varied from rash to large bullae, plus different forms of mucous membrane involvement. The offending drugs (barbiturates) were stopped immediately and care was largely supportive. Conclusion As a result of the morbidity and/or mortality associated with EM, SJS and TEN, physicians should keep in mind their differential diagnosis when cutaneous reactions are observed in patients undergoing barbiturate therapy. Furthermore, although TEN and SJS are life-threatening diseases, early detection and appropriate care can lead to a decrease in the incidence of death. The strategies described here seem to be successful and safe because, despite the serious conditions, our patients responded well. All survived. [ABSTRACT FROM AUTHOR]

Purpose Adverse drug reactions (ADRs) are a major cause of hospital admission and inpatient morbidity. The department of internal medicine is not an exception to this issue. This study was performed to determine the nature and frequency of ADRs in an internal medicine ward in Iran. Methods This survey was a prospective observational study based on admissions of 400 patients to the internal medicine ward over a 15-week period. Patients were intensively followed in order to assess any ADR as a cause of admission or occurring during hospitalization. Any suspicious ADR was confirmed by a pharmacist/pharmacologist. Results There were 47 patients of 400 patients (11.75%) that experienced at least one ADR. ADR leading to the admission was seen in seven cases (1.75%) and in 40 (10%) it occurred during hospitalization. ADRs were identified as preventable reactions in 50% of cases and as predictable in 94.3%. The severity of 18.6% of the ADRs was identified as mild, 62.9% as moderate, 14.3% as severe and 4.3% as lethal. Gastrointestinal system disorders (44.3%) represented the most frequent ADRs. The therapeutic groups that most commonly associated with suspected ADRs were antineoplastic, immunosuppressive and medicines used in palliative care (54.8%). Conclusions ADRs are common among hospitalized patients in department of internal medicine and can be severe and even lethal. Since most ADRs occurred during hospitalization in studied patients and half of them were preventable, prevention strategies should be considered in hospitals. Also, our findings confirmed the role of hospital pharmacists in the reducing ADRs. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Severe Combined Immunodeficiency (SCID) consists of a heterogeneous group of genetic disorders characterized by an arrest in T lymphocyte development which is variably associated with an abnormal differentiation of B and NK cells. In order to depict the clinical state of Iranian patients with SCID, records of forty patients were reviewed. Patients were classified based on the flow cytometry data in two groups of B− and B+. In thirty two families (80%) parents were consanguine and in 17 families (50%) there were affected members other than proband. We showed that autosomal forms of SCID might be more frequent due to higher rate of consanguineous marriages. Alongside several infective complications, complicated Bacillus Calmette-Guérin (BCG) vaccination was documented in 18 cases (45%) following the routine vaccination at birth. BCG immunization is still a part of standard vaccination for newborns in developing countries; whereas in communities with a better health condition it could be held for a few months and performed for kids whose immune system sounds intact. We discuss where consanguine mating is common, a test of screening should be run timely. A complete blood count of cord blood could reveal lymphocytopenia at birth; this helps early diagnosis. Genetic consultation would help the families with affected members preventing new SCID offspring. [ABSTRACT FROM AUTHOR]

Introduction: Selenium is one of the essential trace elements which is more notified in children in recent years. Reliable age-specific reference values for selenium in children in Iran are not clear and are important for the identification of selenium deficiency and some other researches that is the aim of this study. Methods: Serum samples of 216 healthy children were analyzed by using hydride generation and flame atomic absorption spectroscopy to measured selenium level. Results: The mean and standard deviation of serum selenium level in children 0–16 years old (mean: 39.83 months) was 72.14 ± 16.80 μg/l. There was significant difference in serum selenium concentration between two sexes which was 76.78 ± 15.24 μg/l and 69.56 ± 17.09 μg/l in girls and boys respectively (P value = 0.002). There was also a positive correlation between higher selenium serum concentration and age in both sexes. Conclusion: Essential trace element's normal ranges are fundamental data which could use in many studies. Serum selenium concentration in healthy Iranian children that found in this study is very close to serum concentration of European children. Our findings may reveal nutritional culture's similarity. [ABSTRACT FROM AUTHOR]

Problem: Primary Immunodeficiency Disorders (PiD) are a heterogeneous group of genetic disorders, with different modes of inheritance. This study was accomplished in order to determine the frequency of consanguineous marriages in the families of patients with PiD., Method: In this study, the records 515 Iranian PiD patients were reviewed during a 25-year period., Results: The mean proportion of consanguineous marriages was 65.6% among PiD patients, while the overall rate was 38.6% in the country. The rate of consanguinity was 77.8% in cellular immunodeficiencies, 75.8% in combined immunodeficiencies, 72.5% in defects of phagocytic function, 58.6% in other immunodefiiencies, 54.1% in predominantly antibody deficiencies, and 50% in complement deficiencies. Moreover all patients with immunodeficiency associated with other diseases had consanguineous parents. Such marriages were most common in the parents of patients with Chediak-Higashi syndrome, severe combined immunodeficiencies, primary CD4 deficiency, ataxia-telangiectasia, selective IgG class deficiencies, chronic granulomatous disease, and Schwachman syndrome., Conclusions: It is important to inform the general population about the dangers of consanguinity, which is very common in some areas such as Iran. Premarital examination to avoid genetic diseases could be suggested, especially in a community where the rate of consanguineous marriage is high.