Frequency and Risk Factors of Penicillin and Amoxicillin Allergy in Suspected Patients with Drug Allergy.

BACKGROUND: Unconfirmed beta-lactam allergy is a significant public health problem because of the limitations it imposes in drug selection. In this study, we aimed to evaluate patients referred for beta-lactam allergy to determine the frequency of confirmed beta-lactam allergy and identify some risk factors. METHODS: In a prospective cohort study, all referred patients to Immunology, Asthma and Allergy Research Institute in Tehran University of Medical Sciences (between 2007 - 2009) who suspected to have beta-lactam allergy were entered into this study based on having the inclusion criteria. Follow-up was performed 6 - 8 years after the final diagnosis. Diagnosis of beta-lactam allergy relies on thorough history and specific IgE measurements (ImmunoCAP), skin prick testing (SPT), intradermal testing (IDT), patch testing, and oral drug challenge test. RESULTS: Fifty-one patients with mean age of 24.5 (±18.5) years were enrolled in this study. Based on workups, beta-lactam allergy was confirmed in 16 (31.4%) patients, suspicious in 22 (43.1%) patients and ruled out in 13 (25.5%) patients.  During the follow-up, 3 patients with suspicious drug allergy consumed the culprit drug with no reaction so allergy was finally ruled out in 16 (31.4%) patients. Age, sex, atopy and family history of drug allergies were not significantly different between the patients with confirmed or ruled-out diagnosis of penicillin and amoxicillin allergy. CONCLUSION: At least up to one-third of patients with a history of beta-lactam allergy are proven to be safe using the drug. Also, a clear protocol consists of serum sIgE assay and SPT can be helpful to the physicians in the health care system.

Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients.

OBJECTIVES: Common variable immune deficiency (CVID) is the most frequent form of symptomatic primary immunodeficiency disease, characterized by hypogammaglobulinemia, recurrent infections and increased predisposition to autoimmunity and malignancies. The aim of this study was to reconsider important points of previously performed studies on Iranian CVID patients diagnosed and followed from 1984 to 2013. METHODS: Diagnosis was made using approved criteria including reductions of serum levels of immunoglobulins and exclusion of well-known single gene defects in individuals with an age >4 years and evidence of specific antibody deficiency. RESULTS: Detailed information on demographic data, survival rates, clinical phenotypes, immunologic and genetic data and treatment of 173 patients are provided. The early onset presentation (74.5%) and rate of consanguineous marriage (61.2%) were considerably higher in our cohort. Our study revealed clinically related correlations regarding consanguinity, the population of naïve CD4(+) T cells and switched-memory B cells, cytokine levels and special genetic factors (including HLA and AID genes). CONCLUSION: Despite current efforts, more comprehensive studies are needed, especially for classification and investigation of the genetic background and prognostic factors for patients with CVID in order to better managment and followup of patinets.

Effect of supplementary zinc on body mass index, pulmonary function and hospitalization in children with cystic fibrosis.

Zinc deficiency, which is common in patients with cystic fibrosis (CF), can lead to several complications that may increase the number of hospital admissions in this group of patients. As supplementary zinc can prevent such complications, this study was performed to evaluate the effect of supplementary zinc on body mass index (BMI), forced expiratory volume in one second (FEV1) and number of hospitalizations in CF patients. In this study, 30 children with CF, who were referred to the Digestive Diseases Clinic of the Children's Medical Center in Tehran, were enrolled. Supplementary zinc of 2 mg/kg per day was administered to all patients. Serum level of zinc, alkaline phosphatase, and albumin as well as BMI, FEV1, and number of hospitalizations were compared before and after zinc administration. Height (p<0.001), weight (p<0.001) and BMI (p=0.001) were significantly increased after zinc, while the number of hospitalizations was significantly decreased (p=0.023). In contrast to patients with normal pulmonary function tests who received supplement therapy, BMI was not increased in those with abnormal pulmonary function after supplementary zinc. Supplementary zinc can increase BMI in CF patients, mostly in those with normal pulmonary function. While supplementary zinc may decrease the number of hospitalizations, other factors can also influence the hospitalization number.

Cutaneous granulomas in common variable immunodeficiency: case report and review of literature.

Common variable immunodeficiency (CVID) is a heterogeneous disease characterized by recurrent infections, autoimmunity, malignancies, and granulomatous inflammation. Granulomatous lesion is one of the important manifestations of CVID, which continues to be unknown to many clinicians. While noncaseating granulomatous lesions can be detected in lungs, liver, spleen or conjunctiva of CVID patients, there are only few reported cases with skin granuloma. This report presents a 27-year-old female with multiple persistent cutaneous granulomatous lesions on both hands. The patient had been well until age of 20 years, when she developed these skin lesions and frequent upper respiratory infections and bacterial pneumonia. Also, she experienced recurrent diarrhea (more than 10 episodes). Laboratory evaluation showed decreased serum levels of all immunoglobulin isotypes and low specific antibody responses. The diagnosis of CVID was based on clinical and laboratory findings. Intravenous immunoglobulin therapy at a dosage of 400-500 mg/kg monthly was introduced and improved skin lesions. In conclusion, taking history of recurrent infections and measuring immunoglobulin levels can be suggested in patients with granulomatous lesions instead of other expensive tests.

Comparison of pulmonary diseases in common variable immunodeficiency and X-linked agammaglobulinaemia.

UNLABELLED: Patients with CVID are at greater risk of developing lung complications than patients with XLA because of delayed diagnosis and possible immune dysregulation. Early diagnosis and appropriate treatment reduces the incidence of pulmonary infections in both groups of patients. However, CVID patients are prone to progressive lung disease despite optimal immunoglobulin therapy. BACKGROUND AND OBJECTIVE: Pulmonary disease is the most common complication in patients with common variable immunodeficiency (CVID) or X-linked agammaglobulinaemia (XLA). Pulmonary disease may progress despite immunoglobulin replacement therapy. In this study pulmonary complications were compared in patients with CVID or XLA. METHODS: Pulmonary complications were evaluated in 115 patients (76 with CVID and 39 with XLA) by reviewing hospital records of chest infections, pulmonary function tests and high-resolution CT scans. RESULTS: Thirty-two patients with XLA (82%) presented with 59 episodes of pneumonia before diagnosis, whereas 15 patients (38.4%) experienced pneumonia after immunoglobulin replacement therapy (1.67 vs 0.45 episodes per patient per year). Among the CVID patients, 196 episodes of pneumonia were documented in 59 patients (77.6%) before diagnosis, while 36 patients (47.3%) experienced pneumonia after therapy (1.11 vs 0.58 episodes of pneumonia per patient per year). Forty-seven (41%) patients (38 with CVID and 9 with XLA) developed chronic lung disease. The CVID patients developed more complications, including bronchiectasis and lymphoid interstitial pneumonitis, than the XLA patients. CONCLUSIONS: Patients with CVID had a greater likelihood of developing lung disease, possibly due to delayed diagnosis and immune dysregulation, as compared with XLA patients. Early diagnosis of patients with primary antibody deficiencies and adequate i.v. immunoglobulin replacement therapy substantially reduces the number of pulmonary infections. However, CVID patients are prone to progression of lung disease despite optimal immunoglobulin therapy because of the nature of the disease. This important issue should be addressed in further studies.

BAK, BAX, and NBK/BIK proapoptotic gene alterations in Iranian patients with ataxia telangiectasia.

INTRODUCTION: Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder characterized by variable immunodeficiency, progressive neurodegeneration, occulocutaneous telangiectasia, and an increased susceptibility to malignancies. This study was designed to study the role of proapoptotic BAK, BAX, and NBK/BIK genes in a group of patients with AT to elucidate the possible role of these genes in progression of malignancies in this disease. MATERIALS AND METHODS: Fifty Iranian patients with AT were investigated in this study. The entire coding regions of the BAK gene (exons 2-6), NBK/BIK gene (exons 2-5), and BAX gene (exons 1-7) were amplified using polymerase chain reaction (PCR). The PCR products were separated by 2% agarose gel electrophoresis, and all positive samples were verified by direct sequencing of PCR products using the same primers used for PCR amplification, BigDye chemistry, and Avent 3100 Genetic Analyzer following the manufacturer's instructions (Applied Biosystems). RESULTS: Eight of fifty Iranian AT patients (16%) exhibited a C > T transition in exon 2 (c342C > T) of the BAK gene, while none of the healthy controls had such alteration (P = 0.0001). Higher frequency of another nucleotide substitution in the noncoding region of exon 7 in BAX gene (6855G > A) was also identified in 68% of the patient group versus 24% in the controls (P < 0.0001). Sequence alteration in intronic region of the NBK/BIK gene IVS4-12delTC was observed in 52% of AT patients, which was significantly higher than 20% in the control group (P = 0.0023). Another variant IVS1146C > T in the intronic region of the BAX gene was found in 78% of patients, which was significantly higher than 10% in the controls (P < 0.0001). Frequency of alteration in intronic region of exon 3 of the BAX gene (IVS3 + 14A > G) was also significantly higher in the AT patients (P < 0.0001). DISCUSSION: Several alterations in the proapoptotic genes BAK, NBK/BIK, and BAX were found in our study, which could elucidate involvement of the mitochondrial pathway mediated apoptosis in accelerating and developing of cancers and in immunopathogenesis of AT. Such altered apoptosis in AT could play some roles in developing cancers in this group of patients.