Infectious and non-infectious complications among undiagnosed patients with common variable immunodeficiency

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. Patients were divided into two groups including Group 1 [Gl] 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 Gl and duration follow up in G2. The number of infections, non infectious complications, hospitalizations, and mortality rate was compared between the two groups. The patients in Gl 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-up years. Frequency of enteropathies and liver diseases in Gl 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 Gl were the major factors of delayed diagnosis. 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

CD40 ligand expression on stimulated t-helper lymphocytes in patients with common variable immunodeficiency

Common variable immunodeficiency [CVID] is the most common symptomatic primary antibody deficiency, characterized by reduced serum immunoglobulins levels and increased susceptibility to recurrent pyogenic infections. In this study, we evaluated CD40 ligand expression on stimulated versus unstimulated T-helper lymphocytes of nine Common variable immunodeficient patients in comparison with fifteen normal controls. Phorbol myristate acetate [PMA] and Ionomycin were used to stimulate cells in vitro. After six hours stimulation, the cells were subjected to surface staining with three-color staining procedure. Events were analyzed by flow cytometer, using FloMax software. Results were reported as the percentage of lymphocytes expressing CD markers. We did not find any significant statistical difference in CD40 ligand expression between patients and controls [p>0.05], despite having stimulation documented by CD69 expression as activation marker in each run. The results of this study are in agreement with some other studies, indicating that CD40 ligand expression on stimulated T-helper lymphocytes of Common variable immunodeficiency patients is similar to normal controls

Successful management of neufropenia in a patient with CD40 ligand deficiency by immunoglobulin replacement therapy

Hyper-IgM syndromes are characterized by profound reduction of serum IgG, IgA, and IgE levels with normal or increased concentrations of serum IgM. CD40 ligand deficiency is X-linked form of the disease, which results in a lack of immunoglobulin class switching from IgM to IgG in B cells. In addition to the recurrent infections, a number of patients suffer from neutropenia. There are some evidences indicating the effect of G-CSF in combination with intravenous immunoglobulin [IVIG] in improvement of neutrophil counts, which has become the most common procedure to control neutropenia. In this report we present a 6 year-old patient of CD40 ligand deficiency, who suffered from chronic, severe neutropenia. Administration of IVIG was started for him when the diagnosis was made at the age of 1.5 years and he was on the regular IVIG therapy after that time untill now for a period of 4.5 years. IVIG and prophylactic antibiotic therapy, despite cessation of granulocyte colony-stimulating factor, injection after one month, corrected the severe neutropenic state of this patient. It seems that regular administration of sufficient doses of IVIG can be useful in the management of neutropenia in CD40 ligand deficiency, which results in better quality of life with decreasing occurrence of infection

Mortality in primary immunodeficient patients, registered in Iranian primary immunodeficiency registry

Primary immunodeficiencies [PID] are a group of disorders, characterized by an unusual susceptibility to infections. Delay in diagnosis results in increased morbidity and mortality in affected patients. The purpose of this study was to determine the mortality rate of Iranian immunodeficient patients referred to Children Medical Center Hospital affiliated to Tehran University of Medical Sciences over a period of 20 years. In this study, records of 235 [146 males, 89 females] patients with immunodeficiency who were diagnosed and followed in our center, during 22 years period [1979 2001] were reviewed. The diagnosis of immunodeficiency was based on the standard criteria. The cause of death was determined by review of death certificates. Antibody deficiency was the most common diagnosis made in our patients. The overall five-year survival rate was 22.7% in our studied patient group; this was greatest in antibody deficiency. During the 22 year period of study, 32 patients died. As some of the patients could not be located, the true mortality rate ranged between 13.6% and 17.5%. The main leading cause of death were lower respiratory tract involvement in 14 cases [44%]. The most common pathogenic microorganisms causing fatal infections were psudomonas and staphylococcus in 9 cases [28.1%] followed by E. coli in 7 [21.9%], tuberculosis in 13 [40.6%] and salmonella in 1 [3.1%]. Based on our study, delay in diagnosis in patients with PID results in tissue and organ damage and several complications. Mortality and morbidity are increased in undiagnosed patients

Neutropenia in patients with primary antibody deficiency disorders

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases [14 male and 5 female], with a mean age of 10.7 +/- 5.7 years, were associated with neutropenia [9.2%]. The disorders with associated neutropenia were Hyper IgM syndromes [3 of 8], Common variable immunodeficiency [13 of 109], and X-linked agammaglobulinemia [3 of 45]. The median age for the onset of disease and diagnosis age were 15 months [1-134] and 3.8 years [6 months-13 years], respectively. The most common infections during the course of illness were pneumonia [13 cases], diarrhea [12 cases], oral candidiasis [9 cases], otitis media [6 cases], sinusitis [6 cases], cutaneous infections [5 cases], and abscess [5 cases]. Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient

Gastrointestinal manifestations of patients with Chronic Granulomatous Disease

Chronic Granulomatous Disease [CGD] represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients [38 males and 19 females] with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period [1980-2004]. The median age at the time of study was 14.5 years old [1-56 years]. The median onset age of symptoms was 5 months [1 month - 13.75 years], and that of diagnostic age was 5 years [2 months- 54.1 years], with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases [42.1%] had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases [21.1%] had diarrhea, 7 [12.3%] oral candidiasis, 5 [8.8%] hepatitis, 4 [7.0%] hepatic abscess, and 2 cases [3.5%] gastric outlet obstruction. Also, failure to thrive was detected in 6 patients [10.5%]. Four patients died [7%]. CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction

prevalence of asthma among the students [7-18 years old] in Tehran during 2002-2003

Asthma is one of the most common problems of childhood, responsible for a significant proportion of abstinence from school because of chronic illness. This study was carried out among the school-aged children [7-18 years] in Tehran schools during 2002-2003, in order to determine the frequency of asthma. According to the recommendation of WHO [World Health Organization], we designed a questionnaire, containing 8 standard questions, and the students were given necessary information to complete the questionnaires. The pre-high and high schools students completed the questionnaires but the parents of primary school students completed them on their behalf. The prevalence of asthma was 35.4% in Tehran; this prevalence was higher in the boys [37.1%], as compared to the girls [33.5%]. The prevalence of this disease has been estimated about 39.5% in pre-high schools, 35.4% in high schools and 31.6% in primary students. Based on this survey, the most common clinical manifestations of asthma were: prolonged cough lasting more than 10 days [22.4%], and exercise-induced wheezing or dyspnea [16.9%], followed by repeated dyspnea or wheezing [6.4%].The prevalence of asthma is high among the students of Tehran schools and it needs more careful screening programs along with additional information to the patients and parents about the disease