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.

Introduction: Primary immunodeficiency disorders (PID) are rare and heterogeneous group of disease. In attempts to ad- dress and to provide an estimate of the precise prevalence of these disorders in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was established in 1999. The Registry is currently being expanded and is a part of IAARI (Immunolo- gy, Asthma & Allergy Research Institute). Method: During (2006-2013), 1857 patients who were re- ferred to IAARI with possible diagnosis of PID were enrolled in this study.Primary and advanced screening tests were done and after confirmation of diagnosis all patients registered in IPIDR (Ipidr.tums.ac.ir) Results: fifty hundred and sixty-five patients (354 M/211F) had definite or probable diagnosis of PID; Consanguinity rate and family history of previous child with PID were 58% and 24.6%, respectively. Genetic studies were done in 50.8% of patients and in 37.3% of them specific mutation was found. The most com- mon form of immunodeficiency was congenital defects of phagocyte number, function, or both. (43.5%), mainly chronic granulomatous disease, followed by Well-defined syndromes with immunodeficiency (32.6%), predominantly antibody disor- ders (16%), combined immunodeficiencies (9.7%), Comple- ment deficiencies (8.8%), Diseases of immune dysregulation (7.2%) and defects of innate immunity (2.1%) Conclusion: Recent development in molecular diagnosis can help in early and definite diagnosis of PID. Accurate diagnosis of these conditions are essential for eval uation of PID burden , better decision in prevention and treatment strategies and research studies A Report from Iranian Primary Immunodeficiency Registry (IPIDR), New Trend in Diagnosis of PID (PDF Download Available). Available from: https://www.researchgate.net/publication/268280484_A_Report_from_Iranian_Primary_Immunodeficiency_Registry_IPIDR_New_Trend_in_Diagnosis_of_PID [accessed Jun 20, 2017].

Objective: Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia, defective specific antibody responses to pathogens and increased Susceptibility to recurrent bacterial infections. Delay in diagnosis and inadequate treatment can lead to irreversible complications and mortality. In order to determine infectious complications among undiagnosed CVID patients, 47 patients diagnosed in the Children's Medical Center Hospital during a period of 25 years (1984-2009) were enrolled in this study.Methods: Patients were divided into two groups including Group 1 (G1) with long diagnostic delay of more than 6 years (24 patients) and Group 2 (G2) with early diagnosis (23 patients). The clinical manifestations were recorded in a period prior to diagnosis in G1 and duration follow Lip in G2. The number of infections, non infectious complications, hospitalizations, and mortality rate was compared between the two groups.Findings: The patients in G1 group had 500 episodes of infections before diagnosis in 256 patient-years (0.08 per patient per year) and 203 times of hospitalization (0.03 per patient per year), which were significantly higher than in G2 patients, who had 75 episodes of infections (0.015 per patient per year) and 88 hospital admissions (0.018 per patient per year) during 207 patient follow-Lip years. Frequency of enteropathies and liver diseases in G1 were also significantly higher than in G2. Lack of awareness about nature of disease, especially among rural and suburban physicians, single organ involvement as a site of clinical presenting, and predomination of non infectious presentation in G1 were the major factors of delayed diagnosis.Conclusion: Diagnostic delay is a major concern in CVID patients, which Could result in irreversible complications and mortality, while early diagnosis and proper initial treatment leads to better outcomes and quality of life.

Introduction: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency caused by mutations in the NADPH oxidase system genes responsible for the respiratory burst involved in organism killing. This leads to recurrent life-threatening bacterial and fungal infections. The aim of this study was to determine the skin manifestations of Iranian patients with CGD. Methods: Thirty two patients referring to Children Medical Center (22 males, 10 females), with definite diagnosis of CGD (on the basis of neutrophil oxidative burst assay (NBT slide test and DHR assay) were investigated during 2 years. A questionnaire was completed for them to determine skin manifestations of CGD. Results: Medical files of 52 patients were reviewed (male to female ratio: 2.1). The median age of patients was 7 years (12 months- 22 years). The median age at onset of symptoms was 9 months (1 week to 11 years), and the median diagnostic age was 2 years (1.3 month -16 years). The most common presenting complaint was suppurative lymphadenopathy(65%). Recurrent skin or soft tissue abscess was the most common clinical presentation of disease seen in 29 patients (55%). Skin abscess was the first presenting complaints 10.5% of patients. Carbuncles were noticed in 10 patients (19%). As a whole, Skin involvement was noticed in 39 patients (75%). Discussion: Skin manifestations in CGD as a first presenting symptom is reported to be quite less common than other CGD manifestations. However, in our study skin involvement was the most common presentation of CGD noticed any time during follow up. Delayed diagnosis of CGD could be due to late onset of symptoms or misdiagnoses. So we suggest excluding CGD in any patient with recurrent skin infections; as early diagnosis of CGD together with prophylactic treatment of infection and aggressive therapy, can improve the prognosis.

Background: Cow milk allergy can present as many gasteroenterological manifestations like gasteroesophageal reflux (GER). The aim of this study was to investigate the prevalence of GER in infants with CMA in Imam Khomeini Hospital (2002-2003). Methods: 51 children with CMA were evaluated. Radiographic and endoscopic assessments were performed in GER suspected cases. These cases underwent challenge test and after 2 weeks with cow milk-free diet, they were evaluated again. Findings: 5 cases (10%; 3 females and 2 males) had concomitant GER (age ranged 3-17 months, mean age: 10.6 months). 3 patients took only mother’s milk and 2 cases were fed with both mother’s milk and formula. All mothers took dairy cow products in their daily diet. Skin prick test was positive in only one infant. Interestingly, after 2 weeks of cow milk protein-free diet both allergic and GER manifestations disappeared. Conclusions: Evaluation of children with CMA for concurrent GER seems to be necessary, because treating CMA can control GER as well, suggesting an association between the two conditions. Thus an additional antireflux treatment in these patients can be prevented.

Primary immunodeficiency disorders include a variety of diseases that render patients more susceptible to infections. To determine the percentage of different primary immunodeficiency disorders diagnosed in the Children's Medical Center Hospital affiliated to Tehran University of Medical Sciences in Iran, we retrospectively reviewed the charts of the patients being referred to our hospital for immunologic evaluation of recurrent infections during a 20 year period. Among these patients, antibody deficiencies were the most frequent ones and were found in 52.6% of patients (n = 130). T-cell disorders, phagocytic disorders and complement deficiencies were found to be present in 24.69% (n = 61). 22.2% (n = 55) and 0.4% (n = 1) respectively. On the whole, common variable immunodeficiency was the most frequent disorder (n = 65), followed by ataxia telangiectasia (n = 39), X-linked agammaglobulinemia (n = 33), chronic granulomatous disease (n = 29) and selective IgA deficiency (n = 20). This study reveals that antibody deficiencies are the most common type of disorders as shown in other studies. A comparative study shows some differences between our results and other registries. This article also indicates that immunodeficiency disorders should be considered in patients with recurrent infections.

Background: Although long-term intravenous immunoglobulin infusion is an effective treatment for children with antibody deficiencies, it can be complicated by systemic adverse reactions.Objective: To evaluate the adverse reactions of intravenous immunoglobulin therapy in patients with primary immunodeficiency. Methods: Seventy-one immunodeficient patients receiving intravenous immunoglobulin were evaluated during a 7-year period (1995-2002) at Children's Medical Center in Tehran, Iran. Immunological diagnoses were as follows: common variable immunodeficiency (31 patients), X-linked agammaglobulinemia (25 patients), IgG subclass deficiency (5 patients), hyper-IgM syndrome (2 patients), and ataxia-telangiectasia (8 patients).Results: One hundred fifty-two cases (12.35%) of adverse reactions occurred following 1,231 infusions in 35 patients. The most frequent immediate adverse reactions were mild reactions (131 infusions), including chills, fever, flushing, muscle pains, nausea, headache, and anxiety. Moderate reactions, such as vomiting, chest pain, and wheezing, occurred in 19 infusions. Two patients experienced severe adverse reactions. The highest proportion (23.06%) of reaction to injection was in patients with common variable immunodeficiency.Conclusions: Intravenous immunoglobulin is a well tolerated medical agent for patients with antibody deficiency. However, to prevent occurrence of immediate adverse reactions during infusion in these patients, physicians should perform a detailed history and proper physical examination and check the titer of anti-IgA.

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian primary Immunodeficiencies Registry (IPIDR) was organized in 1999. the diagnosis of immunodeficiency in our patients was based on standard criteria. The patient’s data were extracted, by using a uniform questionnaire from their hospital records. Three hundred and twenty eight patients with PID have been registered in our registry till 2000. Among these patients, the following frequencies were found: predominantly antibody deficiency in 48.48% of patients (n=159), T-cell disorders in 25.91% (n=85), phagocytic disorders in 24.7% (n=81), and complement deficiencies in 0.91% (n=3). Common variable immunodeficiency was the most frequent disorder (n=73), followe by chronic granulomatous disease (n=55), ataxia telangiectasia (n=39), x-linked agammaglobulinemia (n=35), selective IgA deficiency (n=34). This study reveals that antibody deficiencies are the most frequent diagnosed primary immunodeficiency disorder in our patients, which is similar to that observed in other registries. A comparative study shows some differences between our results and other registries

Skin manifestation are common findings in these two primary immunodeficiency syndromes.Patients with hyper IgE syndrome (HIE) present with chroniuc pruritic eczematoid lesions particularly in scalp and flexural areas since infancy, infected pustuls and cold skin abscesses.Scar formations, thick skin and skeletal changes lead to a coarse facies. In chronic granulomatous disease (CGD) skin involvements are granulomatous lesions and recurrent abscesses.In this study we review skin lesions in 5 HIE patients with those of 20 CGD patients during 10 years follow up (1990-2000).

Shwaehman syndrome, next to cystic fibrosis, is the second cause of congenita! exocrine pancreatic insufficiency in children. It appears as steatorrhea, recurrent infections and hematologic abnormalities such as neutropenia, skeletal dysplasia and short stature. In this study, we reviewed 3 patients' histories. All of them showed cellular chemotaxic defect. One of them had been affected by nephrotic syndrome and finally succumbed to septic shock. This patient suffered from skeletal disorders.