Noninfectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, noninfectious complications are a major challenge among CVID patients. METHODS: All CVID patients registered in the national database were included in this retrospective cohort study. Patients were divided into 2 groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, noninfectious organ involvement, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with noninfectious complications and 33.6% with isolated infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly more frequent among patients with B-cell lymphopenia. As for organ involvement, the dermatologic, endocrine, and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher than that of other types of autoimmunity not associated with B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were the most common type of malignancy. The mortality rate was 24.5%, and respiratory failure and malignancies were the most common causes of death, with no significant differences between the 2 groups. CONCLUSIONS: Considering that some of the noninfectious complications might be associated with B-cell lymphopenia, regular patient monitoring and follow-up with proper medication (in addition to immunoglobulin replacement therapy) are highly recommended to prevent sequelae and increase patient quality of life.

Non-Infectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND AND OBJECTIVE: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, non-infectious complications are also a major challenge among CVID patients. METHODS: All registered CVID patients in the national database were included in this retrospective cohort study. Patients were divided into two groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, non-infectious organ involvements, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with non-infectious complications; however, 33.6% had only infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly higher among patients with B-cell lymphopenia. Among organ involvement, dermatologic, endocrine and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher compared to other types of autoimmunity independent from the B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were slightly introduced as the most common type of malignancy. Meanwhile, the mortality rate was 24.5%, and respiratory failure and malignancies were reported as the most common cause of death in our patients without significant differences between the two groups. CONCLUSION: Considering that some of the non-infectious complications might be associated with B-cell lymphopenia, therefore, regular patient monitoring and follow-up along with proper medications (besides immunoglobulins replacement therapy) are highly recommended to prevent further sequels and increase the patients' quality of life.

Sustained unresponsiveness development in wheat oral immunotherapy: predictive factors and flexible regimen in the maintenance phase.

Summary: Background. Immunotherapy may induce sustained unresponsiveness (SU )in which the patient can tolerate the allergen without any severe symptoms after discontinuing immunotherapy. The present study evaluated serum and cutaneous markers for predicting SU in patients with wheat anaphylaxiswho underwent oral immunotherapy. We investigated the effectiveness of a flexible regimen of 5 to 10 g wheat protein (WP) in the maintenance phase of oral immunotherapy (OIT). Methods.This study was conducted on 19 patients with wheat anaphylaxis who underwent OIT. The results of the skin prick test (SPT), besides specific serum IgE (sIgE) and IgG4 (sIgG4) to WP, were evaluated before the desensitization. The maintenance dose started from the preferred dose of 5 to 10 g WP after the build-up phase, if the patient could tolerate it. All patients were recruited 7 to 9 months after undergoing this flexible regimen, and the results of SPT and sIgE, and sIgG4l evels were obtained once more. The patients underwent oral food challenge (OFC) after a 3-4-week avoidance to evaluate SU. Results. There was anassociation between mean IgE reduction and SU (p < 0.0006), while no association was observed between the mean increase in specific IgG4 (p = 0.1), and the mean wheal diameter decrease (p = 0.29). A 50% reductionin sIgE was associated with SU. Thirteen patients were considered to havea SU. There was no association between the flexible regimen and the desensitization rate. Conclusions.The reduction of 50% sIgE is a predictive factor for SU in patients with IgE-mediated wheat allergy.

Can concurrent lower gastrointestinal manifestations help the timely diagnosis of small intestinal bacterial overgrowth in CVID patients?.

Summary: Introduction and objective. Gastrointestinal complications are considered as one of the most common manifestations in patients with Common Variable Immunodeficiency (CVID). These complications can result from Small Intestinal Bacterial Overgrowth (SIBO). Hydrogen breath test is extensively used to diagnose SIBO. The objective of this study was to evaluate the prevalence of SIBO using the Hydrogen Breath Test (HBT) in patients with CVID. Materials and methods. Twenty-seven patients with CVID entered this cross-sectional study. Demographic and lower gastrointestinal symptoms were recorded in a check list. Hemoglobin level was measured in all patients. The concentration of IgA and IgG was assessed using nephelometry. Moreover, SIBO was detected by means of Glucose hydrogen breath test. Results. The mean (plus-minus SD) age of the patients was 35.25 (plus-minus 11.69) years. Twenty patients (74.1%) manifested at least one lower gastrointestinal symptom. The most frequent lower gastrointestinal manifestations were bloating (66.7%) and chronic diarrhea (40.7%), respectively. IgA level less than 10 mg/dl and IgG level less than 600 mg/dl were determined in 77.8% and 25.9% of patients, respectively. Positive HBT was detected in 40.7% (n = 11) of the patients. In the positive HBT group, bloating, chronic diarrhea and abdominal pain were the most common lower GI manifestations. There was no significant difference in terms of age, BMI, IgA level, and duration of CVID between the positive and negative HBT groups. The significant association of co-occurrence of anemia and abdominal pain with positive HBT (positive predictive value: 100%) might be considered as a clue to SIBO diagnosis. Conclusions. Regarding the high prevalence and non-specific manifestation of SIBO, it is suggested to consider concurrent symptoms in patients with CVID to manage the timely and precise diagnosis of SIBO.

Assessment of IgE- and cell-mediated immunity in pediatric patients with eosinophilic esophagitis.

Summary: Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease leading to esophageal dysfunction. Food allergens play critical roles in the pathogenesis and treatment of EoE via different mechanisms. This study aimed to present the characteristics and evaluate the ability of skin prick test (SPT), skin prick to prick test (SPP) (IgE-mediated), and atopic patch test (APT) (cell-mediated) individually or simultaneously to diagnose food allergy in patients suffering from EoE. This prospective study was conducted on 58 patients with EoE. Seven patients (12.1%) were positive to only one, 3 (5.2%) were simultaneously positive to two, and 32 (55.2%) were simultaneously positive to three tests. Single and double sensitizations were totally 10.4% in IgE-mediated reactions, while 36.5% in cell-mediated reactions. In contrast, poly sensitization (> 2 allergens) was 51.7% in IgE-mediated tests and 20.7% in the cell-mediated test. Multiple sensitization findings showed egg white, milk, yolk, and soy were the most frequent allergens. Our findings indicate that EoE is early onset and associated with multiple food sensitizations, particularly via IgE-mediated mechanisms. These immune-mediated responses encompass both IgE-mediated (SPT and SPP) and cell-mediated (APT) reactions simultaneously not individually. Therefore, employing multiple assays may strengthen the diagnosis of food sensitization.

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade´s Experience.

BACKGROUND: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. METHODS: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. RESULTS: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, one-third experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. CONCLUSIONS: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients' families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process.

Work ability index among healthcare personnel in a university hospital in Tehran, Iran.

BACKGOUND: Work ability is an important issue from a social point of view, as it is essential for workers health and welfare. OBJECTIVE: This study aimed to determine work ability among healthcare personnel and to investigate its relationship with demographic and lifestyle-related factors. METHODS: Data were collected using the Work Ability Index (WAI) questionnaire among 517 personnel of a hospital in Tehran, Iran. RSULTS: Findings showed a mean WAI of 40.3 (±5.2) for the study population. Work ability was significantly lower in the older personnel and higher for men. A significant correlation was observed between BMI and exercise activity and WAI score. Moreover, employees with experience of less than five years had significant higher work ability than those with 16-20 years of service. CONCLUSIONS: Considering the young study population, it seems the mean WAI is not as desirable. The use of lifestyle promoting programs, besides workplace interventions, can be an effective strategy to increase work ability among healthcare workers.

Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre.

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients.

First report of asthma prevalence in Afghanistan using international standardized methods.

No data on the prevalence of asthma in Afghanistan have been published before. In a school-based survey in 2010-2011 the wheezing section of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was completed by a random sample of 1500 children aged 6-7 years and 1500 adolescents aged 13-14 years old. The prevalence of physician-diagnosed asthma was 12.5% in 6-7-year-olds and 17.3% in 13-14-year-olds (P = 0.002). The prevalence of wheeze in the last 12 months was similar in children and adolescents (19.2% and 21.7% respectively). The prevalence of ever wheezing, night attacks, speech-limiting wheeze and exercise-induced wheeze was 23.1%, 4.8%, 12.2% and 9.6% respectively in children and 30.5%, 4.4%, 13.0% and 13.6% respectively in adolescents. These rates are higher than those in neighbouring countries. This first epidemiological survey of asthma in Afghanistan shows that asthma and wheezing are common in Kabul students.

AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency.

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed.

Increased level of interleukin-13, but not interleukin-4 and interferon-γ in chronic rhinosinusitis with nasal polyps.

BACKGROUND: This study was performed to investigate the serum level of interleukin (IL)-13, IL-4, and interferon (IFN)-γ in chronic rhinosinusitis with nasal polyps (CRSwNP) and subsequent inflammation pattern and comorbidities including asthma and aspirin intolerance. METHODS: A case-control study was conducted on 60 adult patients with CRSwNP with mean age of 37.7±12.7 (ranging from 18 to 70) years, and on 20 healthy controls. Serum levels of IL-13, IL-4, and IFN-γ were assessed, using enzyme-linked immunosorbent assay to be compared between case and control groups. Serum level of total immunoglobulin (Ig) E was also assessed in the patients with CRSwNP. RESULTS: Serum level of IL-13 in the patients with CRSwNP was significantly higher than the controls (0.98±1.56 vs. 0.34±0.16 pg/ml, respectively, p=0.002). IL-4 and IFN-γ did not differ significantly between the two groups. Total IgE level was significantly increased in the patients with CRSwNP, compared to the normal values (301.43±516.54 IU/ml, p=0.033). Among the patients with CRSwNP, 12/60 (20%) had aspirin intolerance and 44/60 (73.3%) had asthma. IgE was also higher in asthmatics than non-asthmatics patients (364.9±586.6 vs. 126.7±135.7, respectively, p=0.015). Patients with aspirin intolerance had higher levels of IFN-γ (4.7±1.4 vs. 4.1±0.6, respectively, p=0.022). CONCLUSIONS: IL-13 with high level of total IgE was observed in the patients with CRSwNP, which predisposes them to have concomitant asthma. IFN-γ seems to be down-regulated in the patients with CRSwNP, but could be over-expressed in the presence of aspirin intolerance.

Clinical effectiveness of knee rehabilitation techniques and implications for a self-care treatment model.

BACKGROUND: Physiotherapy is a complex intervention frequently recommended for knee conditions. The International Classification of Functioning and Disability (ICF) can be used as a framework to evaluate evidence to develop care models and clinical guidelines. OBJECTIVE: To evaluate the clinical effectiveness of knee rehabilitation modalities categorised according to the ICF domains. DATA SOURCES: A keyword search of Medline, Cinahl, Amed, Embase and Cochrane databases from 1996 to 2010 using terms related to the knee joint and physiotherapeutic interventions. STUDY SELECTION: Reviewer assessment using inclusion/exclusion criteria and a quality assessment tool compiled from the Critical Appraisal Skills Programme Tool, Consort and Cochrane Bone Joint and Muscle Trauma Groups. DATA EXTRACTION: Information about the research design, intervention and subjects was extracted. Outcome measures and findings were categorised according to ICF domains. DATA SYNTHESIS: The majority of studies evaluated exercise. Findings were supportive but specific recommendations were limited due to variations in content and application. There was limited quality research to support the theory that manual therapy, electrotherapy or taping in isolation contributes to recovery. Multimodality physiotherapy programmes were found to be beneficial and to reflect clinical practice, but the effectiveness of each component is unknown. Outcome measures from the participation domain of the ICF were used least frequently and were not generally true measures of participation. CONCLUSION: Development of participation outcome measures is required to evaluate the long-term benefits of interventions. Rehabilitation should be based around delivery of effective exercise programmes incorporating participation outcomes to provide feedback and complement self-care for knee conditions.

Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism.

Pediatric patients with leukocyte adhesion deficiency type-I (LAD-I) experience severe and recurrent life-threatening bacterial infections with failure of pus formation and delayed wound healing. LAD-I is a rare inherited disease caused by mutation in the leukocyte CD18 integrin expression, resulting in defective adherence and migration of leukocytes, in particular neutrophilic granulocytes through the intravascular space. Hematopoietic SCT is the only curative treatment option available to patients with LAD-I. Since 2007, in a prospective trial, reduced-intensity conditioning regimen have been developed for 10 consecutive patients with LAD-I who were referred to our center. Based upon available data, it is the first time that such a number of patients affected by LAD-I have been treated with this regimen. This study attempts to show that reduced-intensity regimen leads to a favorable result in LAD-I patients even in those who have experienced comorbid complications. Following transplantation, some patients develop mixed chimerism, however, in our study mixed chimerism was not followed by transplant rejection.

Anopheline species composition in borderline of Iran-Azerbaijan.

Malaria is still one of the most important health-problems in the world and is endemic in Iran. Since 1994, after collapse of former Soviet Union, a new threat of malaria importation emerged from those countries into the northern Iran. This work was carried out to provide further evidence on the status of anopheline species composition, the malaria parasite species, and natural infectivity of mosquitoes distributed in Pars-Abad district, on the borderline of Azerbaijan in northwestern Iran. Mosquitoes were collected from May to December 2008 in anopheline seasonal activity and were identified at the species level. The genus- and species-specific primers against Plasmodium ssrDNA gene were used for specific amplification on female mosquito head+thorax. Members of the Anoheles maculipennis complex were identified by sequence analysis of the ribosomal internal transcribed spacer II (ITS2-rDNA). Morphological character-based identification showed that out of 1455 anopheline female specimens, 1121 (77%) were of A. maculipennis s.l. and 334 (23%) were of Anoheles hyrcanus. Molecular analysis of the species complex indicated the presence of Anoheles sacharovi 984 (67.6%) and A. maculipennis 137 (9.4%) in the region. None of themosquito's head-thorax was found to be naturally infected by malaria parasite. Results of this study, particularly high dominance of A. sacharovi, suggest a potential risk of malaria epidemic in the region, and the need for a continuous epidemiological surveillance.

Prevention-oriented epidemiology of burns in Ardabil provincial burn centre, Iran.

In preventing burns, it is essential to know how they occur and which population groups, environments and heating appliances can be targeted for prevention work. The aim of this study was to determine the epidemiological characteristics of burns leading to hospitalisation in the northwest of Iran with a focus on the pre-event phase of injury. Between 2007 and 2008, 237 burn victims hospitalised in Ardabil provincial burn centre were enrolled into a descriptive study. A questionnaire was filled in during hospital stay for all patients, with a focus on obtaining information necessary for prevention purposes. Males constituted 56% of victims. Mean age was 22 years. The most severe burns occurred between the ages of 18 and 32 years, and were mainly flame related. Both in case of flame and non-flame burns, women suffered more severe burns and mortality than men. However, with respect to non-flame burns of which most were scalds, the majority of the severe cases involved children under the age of 5 years. More than 80% of burns occurred at home. The kitchen was the main place of injury in 47% of cases, followed by living rooms in 28%. Nearly 45% of burns were scalds and 47% were flame burns. The main container was the samovar in 37%, followed by kettles in 32% and pots in 22%. The overturning of a container was the major mechanism of contact with hot liquids in 86%. Bumping into a container was the main scenario of a scald injury, constituting nearly 70% of the cases. The difference between flame and non-flame burns in the distribution of burns in extremities was not statistically significant, but head and neck burns were 3.7 times more likely to be caused by flame. The two most important injury patterns, more common among women, were getting burned while using a camping gas stove or while refilling the chamber of kerosene-burning appliances without first extinguishing them. Domestic burns among children and young women are a priority in injury-prevention programmes. Camping gas stoves, valors (traditional dual-purpose heating and cooking appliances) and samovars can be considered as target appliances for burn-specific home-safety-promotion efforts in this area or in similar settings.