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.

Adverse effects of intravenous immunoglobulin therapy in patients with antibody deficiency.

Long-term intravenous immunoglobulin (IVIG) infusion is an effective treatment for children with humoral immunodeficiencies, already be complicated by systemic adverse effects. In order to determine the adverse effects of intravenous immunoglobulin in patients with antibody deficiency, 45 immunodeficient patients receiving intravenous immunoglobulin were studied during a 36 month period at Children's Medical Center. The investigated group included 25 patients with common variable immunodeficiency, 14 patients with X-linked agammaglobulinemia and 6 patients with IgG subclass deficiency. A total of fifty adverse effects occurred through 955 infusions (5.2%). The most frequent immediate adverse effects were mild (40 infusions out of 955) in 22 cases, including: chills, flushing, fever, nausea and headache. Three patients experienced moderate effects (10 infusions out of 955) such as rash, severe headache, joint pain and chest tightness. None of the effects was anaphylactic type. It can be concluded that intravenous immunoglobulin is generally a well-tolerated medical agent for patients with antibody deficiency, but all patients should be monitored by a physician who is familiar with its indications, risks, adverse effects and their appropriate management.