Systemic and local reactions of bee venom immunotherapy in Iran

Severe allergic reactions during specific immunotherapy may occur in the treatment of hymenoptera sting allergy. The objective of the present study was to examine the characteristics of allergic reactions during specific immunotherapy in patients with allergy towards hymenoptera venom in the Iranian population. A prospective study was performed using the clinical reports of 27 patients with anaphylaxis to bee venom [Apis melifera, Geupes vespula and Geupes Polites]. Ten patients treated with Cluster protocol during 2002 and 2006 After diagnosis of hymenoptera sting allergy according to history and intradermal tests, the patient were treated with Cluster protocol immunotherapy. The protocol lasted 6 weeks with an increase in the concentration of venom from 0.01? g/ml to 100 ? g/ml. None of the patient received premedication. All patients with hymenoptera venom allergy received 120 injections. Anaphylactic reactions were classified according to the Mueller-classification. The frequencies of systemic reactions during Cluster protocol were 8.33% and 5% for yellow jacket and honey bee venom respectively. No patient experienced severe systemic reaction. Cluster protocol for hymenoptera immunotherapy is a reliable method for the treatment of anaphylactic reactions to bee venom. It is safe with low cost and do not need hospitalization

Study of alpha1-antitrypsin phenotypes frequencies in patients with primary antibody deficiency

Primary antibody deficiencies are the most frequent primary immunodeficiency disorders. Bronchiectasis as a feature of these disorders may be developed due to some factors such alpha-1-antitrypsin deficiency. In order to determine the prevalence of two common alpha-1-antitrypsin deficiency alleles [PI*Z and PI*S] in Iranian patients with antibody deficiency, this study was performed. The prevalence of PI*M, PI*S, and PI*Z allele combinations was determined in 40 patients with primary antibody deficiency [with and without bronchiectasis] and compared with 60 healthy control subjects. Phenotyping was performed by isoelectric focusing. The phenotype frequencies among patients were as follow: M in 92.5%, S in 2.5% and Z in 5%. There was not any significant difference in distribution of alleles or phenotypes between patients and control subjects. Moreover, no significant difference was found between patients with and without bronchiectasis. We did not find evidence to support an association between alpha-1-antitrypsin phenotypes and primary antibody deficiencies in a small, controlled study. Larger studies will be required to clarify the relationship between alpha-1-antitrypsin genotype and susceptibility to bronchiectasis in patients with antibody deficiency

Cutaneous manifestations of primary immunodeficiency diseases in children

Primary immunodeficiency diseases [PIDs] are rare but include severe conditions found predominantly in children, Most PIDs have cutaneous manifestations that may be important as early diagnostic features. The purpose of this study was to determine the frequency and nature of cutaneous alterations associated with PIDs. This article is a cross-sectional study at the department of allergy and clinical immunology of children's medical center conducted between December 5, 2001 and April 20, 2002. The subjects included pediatric patients with a diagnosis of PID and dermatological diagnoses were made by a dermatologist. Two hundred and ten patients were studied They consisted of 68 cases of humoral deficiency, 22 cases of cellular and combined deficiencies, 57 cases of phagocytic defects and 63 cases of other PIDs. In 67 cases [31.8%] the cutaneous alterations preceded and were the basis for clinical immunological diagnosis. Overall cutaneous alterations were infections in 99 cases and eczematous dermatitis in 27 cases. Our findings support the results of other studies that most PIDs have cutaneous features which being their typical aspects are highly suggestive for the diagnosis of PIDs

DNA banking of primary immunodeficiency disorders in Iran

Primary immunodeficiency disorders are a heterogeneous group of genetic disorders, with different modes of inheritance, consisting of more than 100 different types. We constructed the DNA banking of primary immunodeficiency disorders for the first time in Iran. The DNA of 31 immunodeficient patients and their families [total of 92 samples] were collected, as the first step for construction of DNA banking. DNA was isolated from whole blood by salting out method. Among our patients, Common variable immunodeficiency was the most common disorder, followed by X-linked agammaglobulinemia, Ataxia-telangiectasia, Chronic granulomatous disease, Severe combined immunodeficiency, Hyper IgM syndromes, and Leukocyte adhesion defects. DNA banking is a useful method for further detection of mutation in immunodeficient patients and prenatal diagnosis for presence or absence of the disorder in the fetus which can be confirmed by molecular genetics testing

High doses intravenous immunoglobulin versus oral cyclosporine in the treatment of severe atopic dermatitis

Atopic dermatitis is one of the most common allergic diseases that almost always respond to conventional therapies with topical emollient, topical corticosteroids, systemic antihistamines and allergic abstinence. However few cases of atopic dermatitis with severe course do not respond to conventional therapies and high dose of intravenous immunoglobulin or cyclosporine are recommended for them. This clinical trial study has been done to compare the last two regimens in patients with severe atopic dermatitis, Scoring Atopic Dermatitis [SCORAD] > 70. We included 14 patients in two groups. In group 1, eight patients were randomly selected and received 4mg/kg cyclosporine daily for 3 months and in group 2, six patients received 2g/kg Intravenous Immunoglobulin [IVIG] as stat infusion. All patients were followed on days 15, 30, 60 and 90 after starting the therapy. About 75% and 62.5% of patients had positive skin tests to egg and to milk respectively. Six patients out of 14 patients did not have skin test, so specific IgE by Radioallergosobent tests [RAST] was used for them. All of these patients had positive RAST to egg and 66.6% against cow's milk. There was a significant difference in the clinical outcomes of these two groups with a marked reduction in SCORAD of day 90[th] in group 1 in comparison to group 2 [Pvalue = 0.005]. No significant adverse drug reaction was seen in these two groups

Chronic mucocutaneous candidiasis; report of three cases with different phenotypes

Chronic Mucocutaneous Candidiasis [CMCC] refers to a group of immunodeficiencies, characterized by persistent or recurrent infections of the skin, nails, and mucus membranes caused by candida. A wide range of immunologic abnormality has been reported in CMCC. Defects in cellular limb of the immune system, mainly the specific response to antigens of candida species, are well documented in CMCC patients. A subgroup of patients is predisposed to development of autoimmune endocrinopathies. These patients need repeated monitoring of endocrine functions. Immunologic studies are needed to identify the extent of immunodeficiency and other abnormalities of immune functions. We report three cases of CMCC. These patients show different phenotypes and highlight the need for complete evaluation and long term follow-up for accompanying disorders

Recurrent infections and bilateral uveitis in a patient with CD8 deficiency

CD8 deficiency is a rare primary immunodeficiency with low or absent peripheral CD8 cells which results from TAP deficiency, Zap 70 deficiency and CD8 alpha gene mutation. We report a 14 year old female who presented with a history of recurrent pneumonia, bronchiectasis, otitis, severe varicella, herpetic lesions of mouth, bilateral uveitis, and cataract formation since the age of 8 years. She had growth failure, a huge spleen and moderate clubbing. In immunologic workup, humoral and phagocytic systems were normal. DTH response to candida, PPD and DT were negative but LTT response to PHA mitogen was normal. HLA typing showed normal class I expression. Flowcytometry of peripheral blood showed CD8: 0 to 2% [absolute count, 0-60 cells/mm3] with increased CD4/CD8 ratio on several occasions. Diagnosis of this patient cannot be HLA class I deficiency [TAP1 or TAP2], because class I expression had been normal. It is possible to be Zap -70 deficiency or CD8 alpha gene mutation. Bilateral uveitis in our patient was a unique presentation which might have resulted because of immune dysregulation in CID

Dificient expression of brouton's tyrosine kinase in monocytes from x linked agmmaglobulinemia as evaluated by a flow cytometric analysis and its clinical application to carrier detection

The B-cell defect in X-linked agammaglobulinemia [XLA] is caused by mutations in the gene for Bruton's tyrosine kinase [BTK]. BTK mutations result in deficient expression of BTK protein in peripheral blood monocytes. Using the anti-BTK monoclonal antibody [48-2H], a flow cytometric analysis of intra cytoplasmic BTK protein expression in monocytes was performed to identify Iranian patients with XLA phenotype. To examine the possible identification of XLA patients and female carriers by this assay, we studied 13 XLA families. The flow cytometric assay showed deficient expression of the BTK protein in 12 [92%] families. One patient exhibited a normal level of BTK expression. The cellular mosaicism of BTK expression in monocytes from obligate carriers was clearly shown in 9 of 12 [75%] families. The results suggested that most XLA patients have deficient expression of the BTK protein; therefore we conclude that deficient expression of BTK protein can be evaluated by a flow cytometric assay

Descriptive study of 226 patients with allergic rhinitis and asthma

The prevalence of allergic diseases such as asthma and allergic rhinitis is high in general population and aeroallergens are the most common allergens that cause air way inflammation. The aim of this study was an evaluation of clinical and laboratory findings in allergic patients and identification of the most common aeroallergen in these patients. A cross–sectional retrospective study was conducted on 226 allergic patients who were referred to allergic clinic of Karaj city, and skin prick test response to aeroallergens were studied. The most common risk factors in these patients were total IgE more than 100 IU/ml and a positive family history of atopy. Skin prick testing results showed that the most common aeroallergens were: herbacee II [62%], sycamore [57%], chenopodium [53%], tree mix [50%], herbacee III [47%], grass [43%], ash [40%], herbacee I [37%], cedar [27%], cockroach [25%], and mite D.P [19%], D.F [18%]. High prevalence of skin reactivity to weeds [chenopodium and herbacee] and sycamore indicates variation in the prevalence of aeroallergen reactivity in different regions with different climates

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

Clinical and laboratory findings in Iranian children with cyclic neutropenia

Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia [3 males and 4 females], who experienced neutropenic periods every 3 weeks [5 with severe and 2 with moderate neutropenia], were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years [1980-2003]. The range of patients' ages was from 7 to 13 years [median 11 years]. The median age at the onset of the disease was 12 months [1 month- 2 years] and the median age of diagnosis was 2 [1.5-5] years, with a median diagnosis delay of 1 year [2 months- 5 years]. Neutropenia was associated with leukopenia [3 patients], anemia [3 patients], and thrombocytopenia [1 patient]. Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media [6 cases], oral ulcers [5 cases], abscesses [4 cases], pneumonia [3 cases], diarrhea [3 cases], oral candidiasis [3 cases], cutaneous infections [2 cases], and periodontitis [2 cases]. One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient

ATM gene mutations detection in Iranian Ataxia-Telangiectasia patients

Ataxia-Telangiectasia [AT] is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, radiation sensitivity and cancer predisposition. The ATM gene on human chromosome 11q22.3 has recently been identified as the gene responsible for ataxia-telangiectasia [AT]. The gene mutated in AT, which has been designated as the ATM gene, encodes a large protein kinase with a PI-3 kinase-related domain. More than 100 mutations are broadly distributed throughout the ATM gene. The large size of the ATM gene [66 exons spanning approximate 150kb of genomic DNA] together with the diversity and broad distribution of mutations in AT patients, greatly limits the utility of direct mutation screening as a diagnostic tool. In this study, 20 families with at least one affected child clinically suspected to have ataxia-telagiectasia were examined and their DNA was extracted and amplified with standard methods. Sequencing methods were used to detect the new point mutation. Four exons which were hot spots for point mutations in ATM gene were detected by PCR-SSCP or PCR-RFLP

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

Screening of the Bruton tyrosine kinase [BTK] gene mutations in 13 Iranian patients with presumed x-linked agammaglobulinemia

X-linked agammaglobulinemia [XLA] is an immunodeficiency caused by mutations in the Bruton tyrosine kinase [Btk] gene. In order to identify the mutations in Btk gene in Iranian patients with antibody deficiency, 13 male patients with an XLA phenotype from 11 unrelated families were enrolled as the subjects of investigation for Btk mutation analysis using PCR-SSCP followed by sequencing. Five different mutations were identified in 5 patients from 5 unrelated families. Three mutations had been reported previously including TTTG deletion in intron 15 [4 bps upstream of exon 16 boundary], nonsense point mutation [1896G>A] that resulted in a premature stop codon [W588X] in kinase domain, and nucleotide alteration in invariant splice donor site of exon12 [IVS12+1G>A]. While 2 novel missense mutations [2084A>G, 1783T>C] were identified leading to amino acid changes [I651T, Y551H]. The results of this study further support the notion that molecular genetic testing represents an important tool for definitive and early diagnosis of XLA and may allow accurate carrier detection and prenatal diagnosis

study of malnutrition in Iranian patients with primary antibody deficiency

Nutrition is an important factor that influences immunity, and nutritional deficiencies can impair resistance to infections. Malnutrition is the most common cause of immunodeficiency worldwide. Trace elements such as zinc, selenium, iron, and copper can influence several components of immunity. Primary antibody deficiency disorders are a group of disorders characterized by an unusual susceptibility to infections and malnutrition. Impaired nutritional status has been reported in immunodeficient patients. The aim of this study was to determine anthropometric indices and trace elements status in these patients. Thirty-eight children [28 males, 10 females, aged 2-18 years] with primary antibody deficiency referring to Children's Medical Center of Tehran University of Medical Science were enrolled in this research. Primary immunodeficiency disorders consisting of CVID, XLA, IgA deficiency, IgG subclass deficiency, and hyper IgM were assessed. Anthropometric indices, comprised of height, weight that were measured and body mass index [BMI] was calculated. Height-for-age [HAZ], weight-for-height [WHZ] and weight-for-age [WAZ] were determined according to Z-score to study mild, moderate and severe malnutrition. Serum copper, zinc, selenium and iron levels were measured by an atomic absorption spectrometer. The most common disorders were CVID 52.5% and X-linked agammaglobulinaemia 27.5%. Based on BMI measurements 21.1% of patients had malnutrition. According to HAZ, 13.2%, 13.2% and 36.8% had severe, moderate and mild malnutrition, respectively. According to WAZ, 10.5%, 18.4% and 28.6% had severe, moderate and mild malnutrition, respectively. Regarding to WHZ, 14.3% and 28.6% had moderate and mild malnutrition, respectively. Low selenium levels and high copper levels were observed in 37.5% and 70.3%, respectively. Anthropometric data showed that the frequency of malnutrition in these patients was higher than the CDC standard. Low serum selenium levels and high serum copper levels were observed, suggesting further research is needed on these parameters. Most of the patients had serum zinc and iron levels within the normal range. It is recommeded that clinical immunologists and nutritionists should make a collective effort to provide these patients with standard or specialized diets so as to decrease the risk of infection