'Real-life' experience in asthmatic children treated with omalizumab up to six-years follow-up.

INTRODUCTION AND OBJECTIVES: Omalizumab is present in international guidelines for the control of severe asthma, but data on the long-term effects in children are limited. Our objective was to perform a 'real-life' long-term trial of omalizumab in children with allergic asthma. MATERIALS AND METHODS: An observational single center 'real-life' study was performed. Data for treatment, lung function, side effect, asthma exacerbations and hospitalizations were recorded at six months and annually. RESULTS: Forty-eight patients <18 years of age were enrolled. Median treatment period was 2.9 (0.5-6). Fluticasone dose for the maintenance treatment decreases significantly at six months (452mcg/day to 329.89mcg/day, respectively). This difference was maintained throughout the follow-up. Nobody used oral corticosteroid after six months. The rate of hospital admissions and visits to the emergency department for asthma exacerbations decreased significantly in the third years and fourth years follow-up, respectively. There was an improvement in lung function. Mean values of FEV1 and FEF25-75% before treatment were 79.88 and 62.94, respectively; after six months of treatment a statistically significant change was seen with a mean FEV1 of 92.29 and FEF25-75% of 76.31 (p=0.0001). Lung function values were above normal throughout the six years of treatment. No side effects were reported. CONCLUSIONS: Overall in 'real life' omalizumab in children reduces asthma exacerbations and hospitalizations, improves lung function, and decreases the maintenance therapy. It is shown to be safe for up to six years of treatment in children.

Asymptomatic LTP sensitisation is common in plant-food allergic children from the Northeast of Spain.

BACKGROUND: The sensitisation profile at molecular level in plant-food allergy is complex. Several allergens may be involved, with different potential for severe reactions. lipid transfer proteins (LTP) are considered the most relevant plant-food allergens in adults in Mediterranean countries, but less is known in children. AIM: To describe the clinical pattern and sensitisation profile of children with plant-food allergy and LTP sensitisation from Northeast Spain. METHODS: Children with history of immediate reaction to plant-food(s), positive skin-prick-test to the culprit plant-food(s) and specific-IgE to plant-food LTPs were analysed. RESULTS: 130 children were included. 69.2% (90/130) had reacted to ≥2 taxonomically unrelated plant-foods. Peach, walnut, hazelnut and peanut were most frequently involved. Reactions severity ranged from anaphylaxis (45.4%, 59/130) to oral symptoms only. Sensitisation to a particular plant-food LTP not always caused clinical symptoms with that plant-food; 69% (40/58) and 63% (17/27) of peach- and walnut-tolerant subjects had positive rPru p 3 and nJug r 3 specific IgE, respectively. 65.4% (85/130) of children were also sensitised to storage proteins, which was associated to anaphylaxis and nut allergy. However, 60% of patients without nuts/seeds allergy were sensitised to storage proteins. Specific-IgE levels to LTPs and/or storage proteins were not useful to predict allergy (vs. tolerance) to peach, walnut, peanut or hazelnut. CONCLUSIONS: Sensitisation to LTP and/or storage proteins without clear clinical significance is relatively common. Prospective longitudinal studies are required to evaluate the relevance of these silent sensitisations over time. Caution is required when interpreting the results of molecular-based diagnostic tools in clinical practice.

Tolerance to egg proteins in egg-sensitized infants without previous consumption.

BACKGROUND: Egg-sensitized infants who have never eaten egg may react at first ingestion. We sought to determine the association between skin prick test (SPT) and specific IgE (sIgE) to egg proteins (EP) and oral food challenge (OFC) outcomes to find cut-off points which can diagnose egg allergy. METHODS: One hundred and fifty-four infants up to 18 months, with cow's milk allergy (CMA) and/or atopic dermatitis (AD) without previous egg consumption, were recruited. SPT to EP were performed. If it was positive, sIgE was performed. If positive SPT and/or sIgE (n = 94), OFC was performed between 12 and 18 months. Receiver operating characteristic (ROC) curves were plotted, and the outcome of the OFC was related to SPT and sIgE. The cut-off points with the best diagnostic accuracy were found. RESULTS: Ninety-four patients were sensitized to egg (69%) and 60 nonsensitized (31%). Of the sensitized, 27 tolerated cooked (CE) and raw egg (RE) (28.7%). Sixty-seven were allergic (71.3%): 29 reacted to CE, seven to egg yolk (EY) and 22 to egg white (EW) and 38 reacted to RE. 69.2% tolerated CE. EW SPT and ovalbumin (OVA) sIgE have the best area under the curve (AUC). The higher positive predictive values (PPV) were obtained for EW SPT and EW sIgE. CONCLUSIONS: In egg-sensitized infants with EW SPT ≥8 mm and/or EW sIgE ≥8.36 KU/l, egg diagnostic OFC can be avoided as there is 94% probability of becoming positive. In the other patients, OFC should be performed safely and early to avoid unnecessary diets.

Ovalbumin-specific IgE/IgG4 ratio might improve the prediction of cooked and uncooked egg tolerance development in egg-allergic children.

BACKGROUND: Accurate predictors of natural tolerance development to cooked and uncooked egg are needed in egg-allergic patients. OBJECTIVE: To compare the diagnostic performance of different immunological tests in relation to egg allergy versus tolerance. METHODS: Children aged 5-18 years diagnosed with IgE-mediated egg allergy were prospectively recruited. All followed an egg-free diet. Prick test and specific IgE (sIgE) to ovalbumin, ovomucoid and egg white, ovalbumin-sIgG4 and ovomucoid-sIgG4 were determined. By boiled and raw egg challenges, children were classified as cooked egg allergic (CEA, n = 50) or tolerant (CET, n = 35), and uncooked egg allergic (UEA, n = 64) or tolerant (UET, n = 21). Statistics. Comparative analysis (CEA vs. CET and UEA vs. UET). Multivariate logistic regression. Partial receiver operating characteristic curve analysis of tests in relation to CEA and UEA. Negative decision points were defined as cut-offs with sensitivity 95%. RESULTS: Ovalbumin-sIgG4 resulted an independent protective factor for uncooked egg allergy. To identify patients with high probability of egg tolerance, ovalbumin-sIgE/sIgG4 tended to perform better than sIgE and prick, specifically in children with ovalbumin-sIgE < 1.9 kU/L (for UEA) and ovomucoid-sIgE < 2.12 kU/L (for CEA). The most accurate cut-offs to recommend challenges were ovalbumin-sIgE/sIgG4 below 2.49 for cooked egg and 1.45 for uncooked egg, which associated 89.5% and 80% probability of tolerance (negative likelihood ratios 0.08 and 0.06), respectively. These cut-offs identified correctly as tolerant an additional 23% and 14% of children with negative challenges to cooked and uncooked egg, respectively, in comparison with sIgE negative decision points. Additionally, prick test tended to perform better than sIgE alone in predicting cooked and uncooked egg tolerance for ovomucoid-sIgE < 0.92 kU/L and ovalbumin-sIgE < 1.37 kU/L, respectively. CONCLUSIONS: Ovalbumin-specific IgG4 is an independent predictor of tolerance development to uncooked egg. Ovalbumin-sIgE/sIgG4 ratio, followed by skin prick test (SPT), seems to perform better than sIgE in identifying egg-allergic children with high probability of tolerance to cooked and uncooked egg over follow-up.

A 10% liquid immunoglobulin preparation for intravenous use (Privigen®) in paediatric patients with primary immunodeficiencies and hypersensitivity to IVIG.

BACKGROUND: The objective of this study was to evaluate safety and efficacy of Privigen®, a 10% intravenous immunoglobulin (IVIG), in a particular group of paediatric patients (highly sensitive to previous IVIG infusion) affected with Primary Immunodeficiencies (PID). MATERIAL AND METHODS: Patients (n=8) from 3 to 17 years old diagnosed of PID who often suffered from adverse events related to the infusion to previous IVIG were switched to Privigen® in an open protocol. Data were prospectively collected regarding Privigen® administration: infusion, safety and efficacy. In parallel, data on safety and tolerance were retrospectively collected from medical charts regarding the previous 10% IVIG product used. RESULTS: 50% of the patients required premedication with previous IVIG. At the end of the study none required premedication with Privigen®. The infusion rate was lower than that recommended by the manufacturer. All patients had suffered through adverse events during previous IVIG infusion being severe in three patients and recurrent in the rest. With Privigen® only three patients suffered from an adverse event (all cases were milder than previous related). Trough levels of IgG remained stable. None suffer from any episode of bacterial infection. CONCLUSION: The present work shows that Privigen® was safe in a group of hypersensitive paediatric patients who did not tolerate the administration of a previous 10% liquid IVIG by using a particular infusion protocol slower than recommended. The number of adverse effects was smaller than published, and all cases were mild. No premedication was needed. Privigen® was also effective in this small group.

[Clinical phenotypes associated with selective IgA deficiency: a review of 330 cases and a proposed follow-up protocol]. / Fenotipos clínicos asociados a la deficiencia selectiva de IgA: revisión de 330 casos y propuesta de un protocolo de seguimiento.

UNLABELLED: Selective IgA deficiency is the most common Primary Immune Deficiency. Only a small proportion of these patients present during childhood, but this proportion increases over the years, and may be associated with an IgG subclass deficiency with increased susceptibility to respiratory and digestive tract infections. During childhood, IgA deficient patients may also refer to symptoms related to allergic and autoimmune diseases or tumours. AIMS: To describe the relationship of selective IgA deficiency with infections, allergic diseases, autoimmune disorders and tumours. To investigate the presence of other immune disorders associated with selective IgA deficiency. To suggest a follow-up protocol for these patients. METHODS: Retrospective study of paediatric patients (<18 years) being followed-up in the Clinical Immunology Department between 1992 and 2007, as well as laboratory records with IgA values below 50mg/L. Clinical records were reviewed (frequency and intensity of diseases associated with selective IgA deficiency) along with immunology tests performed. RESULTS: A total of 330 paediatric patients were identified with a selective IgA deficiency: 39 (11.8%) suffered from recurrent ear infections (2 developed secondary deafness), 58 (17.5%) from recurrent upper respiratory tract infections, and 20 patients (6%) from recurrent pneumonia, 6 of whom developed secondary bronchiectasis and 2 underwent a lobectomy. A relationship with atopic disease was found in 62 (18.78%) of patients. Regarding digestive disorders, chronic diarrhoea was found in 21 (6.5%), coeliac disease in 22 (6.6%), and persistently high plasma transaminases in 3. Autoimmune manifestations were found in 38 (11.5%), juvenile chronic arthritis, type 1 diabetes, vitiligo, cytopenia, and Crohn's disease, amongst others). Tumours were identified in 5 (1.5%). An IgG sub-class deficiency was found in 5 patients (4%), and 6 patients had a confirmed deficiency in antibody production. CONCLUSIONS: In our cohort, 56.6% of patients with IgA deficiency showed other comorbidities which were, in decreasing frequency: recurrent infections (respiratory and ear infections), allergic diseases, autoimmunity and tumours. Some patients will develop a more severe humoral defect (IgG subclass deficiency with or without antibody deficiency).

[Directory of diagnostic tests in primary immunodeficiencies]. / Directorio de pruebas diagnósticas de las inmunodeficiencias primarias.

The clinical and immunological characteristics that suggest diverse forms of primary immunodeficiency are discussed. Data on the hospitals that perform immunological, molecular and genetic tests for the diagnosis of most of the primary immunodeficiencies in Spain are presented.

[Recurrent angioedema and hypereosinophilia]. / Hipereosinofilia y angioedema recurrente.

INTRODUCTION: Among the various causes of eosinophilia are the syndrome first described by Gleich in 1984. This syndrome is characterized by angioedema of the face, neck, extremities and trunk, weight gain, hypereosinophilia (60-70%), fever, and increased serum IgM levels without involvement of the vital organs. CASE REPORT: A 17-year-old non-allergic woman was referred to our hospital for further investigation of recurrent angioedema, initially of the hands and feet and subsequently of the face, with onset 3 years previously. The attacks had become more frequent and severe and had occurred monthly in the previous year. The patient also showed general malaise, without fever. Complementary investigations revealed eosinophils 40.8%, total count 3,300/mm3, and serum IgM levels 343 mg/dl (normal range: 53-300 mg/dl). Possible causes of hypereosinophilia and eosinophilic infiltration of vital organs were ruled out. The patient was treated with oral corticosteroids which produced clinical remission and reduction of eosinophil count (1.7%, total 200/mm3). DISCUSSION: Gleich syndrome is uncommon and has well-defined clinical features and a benign course. We describe a patient who presented the clinical characteristics of this syndrome with good response to steroids and without involvement of vital organs. CONCLUSIONS: Our patient presented clinical features compatible with a diagnosis of Gleich syndrome. Other entities associated with hypereosinophilia were ruled out.

[Otomastoiditis candidiasica and hyper IgE syndrome]. / Otomastoiditis candidiásica y síndrome de hiper Ig E.

PATIENT: A 5-year-old girl presented with chronic otorrhea, cervical adenopathies and cellulitis of the knee. In addition to these lesions, physical examination revealed eczema on the scalp, neck, perineal and umbilical regions and the persistence of deciduous teeth with adult teeth (double dental arch). Complementary investigations showed the following concentrations: IgE 23969 UI/l, IgD 440 U/L, IgG 23000 mg/L, and IgA 4220 mg/L. Intradermal skin testing to Candida was negative and the results of the remaining immunological studies were normal. Computerized axial tomography revealed bilateral otomastoiditis. Candida albicans was isolated from ear secretion cultures. The definitive diagnosis was hyper IgE syndrome. The patient responded favorably to antibiotic and antifungal therapy and is currently undergoing period outpatient monitoring.

Chronic granulomatous disease: six new cases.

We report six new cases of chronic granulomatous disease (CGD) diagnosed at our service. The cases represent 1.1% of all primary immunodeficiencies diagnosed. Four of the children were boys and two were girls. The hereditary mechanism was X-linked in three cases and autosomal recessive in the other three. Clinical manifestations appeared before the age of 2 years in all cases; the illness appeared earlier in males, and was more severe, consisting of bacterial infections such as abscesses in the liver, lungs or skin, suppurating lymphadenitis and mastoiditis. None of the patients had osteomyelitis. The germs isolated were bacteria (Staphylococcus, Salmonella, Serratia, Pseudomonas, Enterococcus) and fungi (Candida, Aspergillus, Trichopyton). Orientative complementary evidence was intense leukocytosis, high levels of acute phase reactants (PCR and VSG), polyclonal hypergammaglobulinemia and high LB ant LT4 levels. Definitive diagnosis was provided by the NBT test and chemiluminescence in all cases.

[Treatment of acute crises of bronchial asthma in children using subcutaneous salbutamol as an alternative to adrenaline: comparative study]. / Tratamiento de las crisis agudas de asma bronquial en niños con salbutamol subcutáneo como alternativa a la adrenalina: estudio comparativo.

A prospective study has been made in order to asses the efficacy of subcutaneous salbutamol as acute treatment for asthmatic crisis, comparing the results with those of adrenaline. The series consisted of 30 cases, divided into two groups according to the administered treatment, with ages ranging between 5 to 18 years. Once the clinical examination and spirometric measurements were made the first group was treated with subcutaneous adrenaline 0.1 cc/kg (max.; 0.5 cc), while the second was treated with subcutaneous salbutamol 20 micrograms/kg (max.: 500 micrograms). A clinical and spirometric examination was performed at 15, 30, 60 and 90 minutes. A similar increase in FEV1 was observed in the two groups at 15 minutes, maintaining this increase for 90 minutes in the group treated with salbutamol and decreasing in the group treated with adrenaline, being the difference statistically significant (p less than 0.001). In view of this results it seems advisable to administer subcutaneous salbutamol as urgent treatment for an acute asthmatic crisis.

[Importance of salivary levels of theophylline in monitoring pediatric asthmatic patients]. / Interés de los niveles salivares de teofilina en la monitorización de pacientes asmáticos pediátricos.

In order to maintain theophylline serum levels between 10 and 20 mcg/ml., obtaining an average dose of 26.36 +/- 6.42 mg/kg/d (range 11.42 mg/kg/d-48 mg/kg/d), authors have determined average dose of oral theophylline intake needed in a group of 212 infants, 1 to 15 years of age. Statistical analysis of 717 salivary and blood theophylline values simultaneously obtained (both at therapeutic and subtherapeutic levels), was carried out reading a lineal correlation coefficient of 0.93. Correlation that has been sufficiently worked out in many other papers. Once necessary dose for obtaining salivary and blood theophylline therapeutic levels is determined, salivary theophylline concentration may be used as a nonaggressive method control of outpatients, assuring their intake continuity between medical controls and as a good seric level index in a given patient.