Dilek Azkur

Successful bone marrow transplantation for DOCK8 deficient hyper IgE syndrome

Dear Editor, We report a girl with AR-DOCK8 deficiency treated successfully with allogeneic bone marrow transplantation (BMT). She was born to consanguineous parents (cousins) originating from and living in eastern Turkey. The first two children of the family were not diagnosed as immunodeficient despite hypereosinophilia and high IgE levels. They had neonatal onset pruritic eczematous dermatitis, food allergies, recurrent and severe pneumonias (LRTI) when they died at five and six yr old, respectively. Sibling 6 (the propositus) who was born after three healthy children, presented with severe neurological disease: beginning nearly 6–8 months ago with mild ataxia and gradual deterioration with restlessness, spasticity, progressive hearing, speech and vision loss, hyperactive deep tendon reflexes, Babinsky and clonus. Radiological diagnosis of progressive multifocal leukoencephalopathy (PML) with serial MRI was supported by high JCV-DNA in serum and cerebrospinal fluid (2200 copies/mL). He also was diagnosed with hyper IgE syndrome (HIES) caused by the dermatitis of neonatal onset, severe food allergies, LRTIs and high peripheral blood eosinophilia and serum IgE. There were no pneumatoceles despite recurrent pulmonary infections and cold abscesses nor joint hypermobility. We treated him with i.v. immunoglobulin (IVIG) 400 mg/kg/day for 15 days with no clinical response. As the response to rh-interferon-gamma (rhIFN-c) stimulation is shown in Tyk-2 deficient patient (1), we gave rhIFN-c to this patient with PML using 50 lg/m, ·3/wk, by sc route. He died at the age of seven yr with sepsis in our intensive care unit. The last child (DOB: 25 October 2006) of this family also presented with neonatal rash. She developed severe eczema with lichenification since the first months of life. She had multiple food, environmental and drug allergies, including lentil anaphylaxis. At the age of 18 months, she underwent further investigations after the diagnosis of her brother s JCV infection. She presented with severe disseminated ichthyosiform eczema, ectropion of the eyelids, recurrent LRTI, oral, cutaneous and ungual candidiasis. Fortunately, her brain CT was normal and the serum and CSF did not reveal JCV infection as her brother. High levels of IgE (>10 000 IU/mL) and hypereosinophilia (>5000/lL) were persistent. Serum immunoglobulin levels (G: 1580, M: 71 and A: 8.7 mg/dL) were normal except for low IgA for age while lymphocyte phenotyping revealed CD4+ T cell lymphopenia (absolute: 250/lL) with CD3+ T cell 28%, CD19+B cell 60%, CD16+56+ NK cell 5% in the peripheral blood. Her serum anti-HBs, antipolio, anti-HSV, anti-CMV, anti-EBV, anti-IgM and anti-IgG antibodies and isohemagglutinins were absent. The girl was also clinically diagnosed as autosomal recessive-HIES and treatment was initiated with IVIG, itraconazole, sulfamethoxazoletrimethoprim and rhIFN-c for prophylaxis and immune modulation. She was not responding to topical steroids, emollients and oral antihistamines. Genomic DNA of the patient, parents and her brother who died with JCV infection were evaluated for the DOCK8 gene as the possible cause for the phenotype at the Department of Immunology and Molecular Pathology of Royal Free Hospital (London, UK). Engelhardt et al. identified a homozygous large deletion up to and including exon 25 of the DOCK8 gene (c.?_3121?del), deleting the first half of the gene (JACI 2009;124:1289, patients with codes of ARH016.6, ARH016.7) (2). It could not be understood where the exact beginning of the deletion was; the first deleted exon they detected was exon 3, but as they did not analyze exon 1 and 2, it was concluded that the deletion began before or at the start of the DOCK8 gene. Because of recurrent sibling deaths, she was considered for hematopoietic stem cell Pediatr Transplantation 2012: 16: 398–399 2012 John Wiley & Sons A/S.

Consistency of GINA criteria and childhood asthma control test on the determination of asthma control

To cite this article: Erkoçoğlu M, Akan A, Civelek E, Kan R, Azkur D, Kocabaş CN. Consistency of GINA criteria and childhood asthma control test on the determination of asthma control. Pediatric Allergy Immunology 2012: 23: 34–39.

Characteristics of anaphylaxis in children referred to a tertiary care center.

Anaphylaxis is a potentially life-threatening condition. There are limited data about the etiology and the clinical characteristics in developing countries. This study aimed to investigate the clinical characteristics of anaphylaxis patients attending our pediatric allergy clinic. We conducted a prospective analysis of patients who were admitted to our allergy clinic for anaphylaxis from 2010 to 2012. Ninety-six patients were evaluated during the study period. The mean age was 7.4 ± 5.2 years. Venom, food, and drugs were the most common causative agents responsible for 31 (32.3%), 30 (31.3%), and 26 (27.1%) of the cases, respectively. Foods implicated most frequently were peanuts and nuts (n = 9; 30.0%), cows milk (n = 7; 23.3%), and egg white (n = 6; 20.0%). The clinical manifestations during anaphylaxis in order of frequency were cutaneous (97.9%), respiratory (86.5%), gastrointestinal (42.7%), neurological (37.5%), and cardiovascular symptoms (30.2%). A biphasic course was noticed in five cases (5.2%). Of the 91 patients, 79 (86.8%) received H1-antihistamines, 73 (80.2%) received corticosteroids, 40 (44.4%) received adrenaline, 38 (41.8%) received fluid replacement therapy, 18 (19.8%) received β2-mimetics, and 8 (8.8%) received H2-antihistamines. According to severity, 7.3% of patients had mild, 59.4% had moderate, and 33.3% had severe anaphylaxis. Food and bee venom allergy were the most common etiologies. Adrenaline, the first-line treatment of anaphylaxis, was administered in only 44.4% of our cases.

The Effect of Obesity on the Level of Fractional Exhaled Nitric Oxide in Children with Asthma

Background: Several studies have demonstrated a relationship between asthma and obesity. However, the results have been conflicting with regard to the relationship between fractional exhaled nitric oxide (FeNO), used as a marker of airway inflammation in asthmatic patients, and obesity. We aimed to evaluate the association of FeNO with obesity and obesity-related metabolic complications in asthmatic and nonasthmatic children. Methods: The study population included children aged between 6 and 17 years and consisted of 4 groups: obese asthmatics (n = 52), normal-weight asthmatics (n = 49), obese nonasthmatics (n = 51) and normal-weight nonasthmatics (n = 42). FeNO measurement and spirometry were performed for all patients. To evaluate the metabolic complications, serum lipids, glucose and insulin levels were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment, HOMA-IR. All participants were evaluated for the presence of metabolic syndrome (MS). Results: The mean age for the 194 subjects participating in the study was 11.6 ± 2.5 years. The FeNO level of asthma patients with MS was not different from those without MS (14.5 ± 8.0 and 16.7 ± 8.7, respectively, p = 0.449). In the nonasthmatic group, subjects with MS had a higher FeNO level than subjects without MS (12.5 ± 5.1 and 17.3 ± 8.3, respectively, p = 0.014). Spearmans rank correlation coefficients revealed a positive correlation between FeNO and body mass index (BMI; p = 0.049, r2: 0.204) in the nonasthmatic group and after multivariate regression analysis, BMI still persisted as an independent risk factor for FeNO. Conclusion: We found a positive correlation between BMI and FeNO level which suggests a link between obesity and increased airway inflammation in nonasthmatic children.

Clinical and etiologic evaluation of the children with chronic urticaria.

BACKGROUND Chronic urticaria (CU) is a skin disorder defined as daily or almost daily exhibition of pruritic and transient wheals that last for >6 weeks. CU is divided into two subtypes: chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). OBJECTIVES To evaluate the clinical features, possible causes, associated findings, and laboratory results of different subtypes of CU in children according to a new classification. METHODS In this study, we evaluated the clinical features, laboratory investigations, and provocation tests of children with different subtypes of CU according to a new classification. RESULTS Two hundred and twenty-two children (59.9% girls) were enrolled in the study. Of the study patients, 59.9% and 40.1% were diagnosed as having CSU and CIndU, respectively. Antithyroid antibody levels were positive in 7.1% of the patients with CSU, 32.8% of the children had positive 14C-urea breath test results, and 6.5% of the patients had positive stool examination results for parasites. Autologous serum skin test results were positive in 53.5% of the patients with CSU. Of the patients with CIndU, 77.5% had symptomatic dermographism, 16.8% had cold urticaria, 2.2% had cholinergic urticaria, 2.2% had solar urticaria, and 1.1% had aquagenic urticaria. CONCLUSION Children with CSU represent the majority of patients with CU, and more than a half of these patients might have autoimmune urticaria. Symptomatic dermographism was the most common type of CIndU.

Characteristics of Children with Non-Hodgkin Lymphoma Associated with Primary Immune Deficiency Diseases: Descriptions of Five Patients

Background: An increased incidence of non-Hodgkin lymphoma (NHL) has been seen in various primary immune deficiency (PID) cases. The present study aimed to evaluate the clinical characteristics and treatment outcomes of five cases with NHL associated with primary immunodeficiency. Methods: We retrospectively evaluated five patients with primary immunodeficiency who developed NHL. Two patients had ataxia-telangiectasia (A-T), one patient had common variable immunodeficiency (CVID), one patient had Blooms Syndrome, and one patient had Wiskott-Aldrich syndrome (WAS). Results: All patients were male (median age, 8 years). Stage distribution was stage III in three patients and stage IV in two patients. Three patients had B-cell lymphoma and two had T-cell lymphoma. Reduced doses of Berlin–Frankfurt–Münster (BFM) and French Society of Pediatric Oncology (SFOP) regimens were used in four patients according to histopathological subtype. The two patients with ataxia and one patient with Blooms Syndrome died of progressive/relapsed disease at months 5, 19, and 6, respectively. The patient with CVID associated with T-cell lymphoma has been in remission for 7 years. A full-dosage regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was successfully used in the patient with WAS and B-cell lymphoma; he was still in remission after 3 years. Conclusion: Primary immunodeficiency diseases are one of the strongest known risk factors for the development of NHL. Management of these patients remains problematic. There is a great need to develop new therapeutic approaches in this group. The use of rituximab in combination with CHOP may provide a promising treatment option for B-cell lymphomas associated with immunodeficiency.

The evaluation of drug provocation tests in pediatric allergy clinic: a single center experience.

Drug provocation tests (DPTs) are gold standard to diagnose drug allergy. Our goal was to evaluate the results and safety of diagnostic methods including DPTs during childhood. Between January 2010 and February 2013 DPTs were performed and evaluated, prospectively, in children who attended our pediatric allergy clinic with a suspected drug hypersensitivity reaction. One hundred ninety-eight suspected drug reactions in 175 patients (88 boys and 87 girls) were evaluated. The median age of the subjects at the time of the suspected drug-induced hypersensitivity reaction and at the time of the study was 56 (interquartile range [IQR] = 24-120 months) months and 76 (IQR = 35-149 months) months, respectively. Suspected drugs were beta-lactam antibiotics in 108 cases (54.5%), non-beta-lactam antibiotics in 22 cases (11.1%), and nonsteroid anti-inflammatory drugs in 52 cases (26.3%). The history was compatible with immediate-type reactions in 69 cases (34.8%). Skin-prick tests were not positive in any of the cases. Intradermal tests were positive in three cases (4%). DPTs were positive in 13 (6.8%) of 191 provocation cases, which were performed with culprit drugs. Our results suggest that a positive clinical history is not enough to make a diagnosis of drug allergy, which highlights the significance of undertaking further diagnostic evaluation especially for DPTs.

Anaphylaxis/angioedema caused by honey ingestion

Honey allergy is a very rare, but serious health condition. In this study, we presented six patients who described systemic allergic reactions after ingestion of honey. Three of the six patients had suffered from anaphylaxis. Honey-specific IgE was measured and skin-prick tests for honey were performed to diagnose honey allergy. The results of honey-specific IgE of all patients were positive. Four patients had high serum-specific IgE for honey bee venom and two of five patients had also experienced anaphylaxis due to bee stings. Skin-prick tests with honey and pollens were positive in five patients. Honey is one of the foods that can cause severe systemic reactions. Specific IgE and skin-prick tests are helpful for the diagnosis of honey allergy.

IgE-Mediated Hypersensitivity and Desensitisation with Recombinant Enzymes in Pompe Disease and Type I and Type VI Mucopolysaccharidosis

Enzyme replacement therapy (ERT) is important for the treatment of lysosomal storage disorders. Hypersensitivity reactions with ERT have been reported, and in these cases, desensitisation with the enzyme is necessary. Here we report the cases of 3 patients with lysosomal storage disorders, including Pompe disease and mucopolysaccharidosis type I and VI, who had IgE-mediated hypersensitivity reactions and positive skin tests. Successful desensitisation protocols with the culprit enzyme solution were used for these patients. All 3 patients were able to safely receive ERT with the desensitisation protocol.

TRACK as a complementary tool to GINA and NAEPP guidelines for assessing asthma control in pre-school children

Abstract Background: In this study, our goal is to evaluate the consistency between TRACK and the asthma control levels assessed according to the GINA and NAEPP guidelines in children younger than 5 years of age. Methods: Patients under 5 years old, who were followed up for recurrent wheezing for at least 1 year have been included. Parents were given the TRACK questionnaire and the control level of asthma according to GINA and NAEPP guidelines were determined by a pediatric allergist blinded to TRACK scores. Patients were classified into two groups regarding the compatibility of the control level between TRACK and both GINA and NAEPP guidelines. Results: A total of 365 questionnaires were evaluated. The TRACK cut-off point of 80 provided the most consistent balance between sensitivity and specificity for the compatibility with both GINA and NAEPP (for GINA 0.763 and 0.663, kappa = 0.487, p < 0.001 and for NAEPP 0.761 and 0.769, kappa = 0.524, p < 0.001, respectively). When 80 was taken as the cut-off value for TRACK, the compatibility rate of asthma control levels between TRACK and GINA and TRACK and NAEPP was 71.0 and 76.4%, respectively. About 70.1% of the patients who had TRACK scores over 80 and had mild asthma were grouped as controlled according to GINA and 50.0% of patients who had TRACK scores over 80 and had moderate to severe asthma was grouped as uncontrolled according to GINA (p = 0.019). Conclusion: TRACK is compatible with NAEPP and GINA in majority of asthmatic children under 5 years of age. Nevertheless, there is a discrepancy between guidelines and TRACK scores; therefore, it should be used in conjunction with a detailed clinical examination in order to make a better decision for assessing the control levels and management plan.