SummaryBackground Characterized native and recombinant Hevea brasiliensis (rHev b) natural rubber latex (NRL) allergens are available to assess patient allergen sensitization profiles.Objective Quantification of individual IgE responses to the spectrum of documented NRL allergens and evaluation of cross-reactive carbohydrate determinants (CCDs) for more definitive diagnosis. Methods Sera of 104 healthcare workers (HCW; 51 German, 21 Portuguese, 32 American), 31 spina bifida patients (SB; 11 German, 20 Portuguese) and 10 Portuguese with multiple surgeries (MS) were analysed for allergen-specific IgE antibody (sIgE) to NRL, single Hev b allergens and CCDs with ImmunoCAP TM technology. Results In all patient groups rHev b 5-sIgE concentrations were the most pronounced. Hev b 2, 5, 6.01 and 13 were identified as the major allergens in HCW and combined with Hev b 1 and Hev b 3 in SB. In MS Hev b 1 displayed an intermediate relevance. Different sIgE antibody levels to native Hevea brasiliensis (nHev b) 2 and rHev b 6.01 allowed discrimination of SB with clinical relevant latex allergy vs. those with latex sensitization. Sensitization profiles of German, Portuguese and American patients were equivalent. rHev b 5, 6.01 and nHev b 13 combined detected 100% of the latex-allergic HCW and 80.1% of the SB. Only 8.3% of the sera showed sIgE response to CCDs. Conclusions Hev b 1, 2, 5, 6.01 and 13 were identified as the major Hev b allergens and they should be present in standardized latex extracts and in vitro allergosorbents. CCDs are only of minor relevance in patients with clinical relevant latex allergy. Component-resolved diagnostic analyses for latex allergy set the stage for an allergen-directed immunotherapy strategy.

Background: Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross-sectional validity, and longitudinal validity. Methods: A prospective observational study was conducted in 11 Portuguese centers. During two visits separated by 6 wk, CARATKids, visual analog scale scales and childhood asthma control test were completed, and participant's asthma and rhinitis were evaluated by his/her physician without knowing the questionnaires' results. Datadriven item reduction was conducted, and internal consistency, responsiveness analysis, and associations with external measures of disease status were assessed. Results: Of the 113 children included, 101 completed both visits. After item reduction, the final version of the questionnaire has 13 items, eight to be answered by the child and five by the caregiver. Its Cronbach's alpha was 0.80, the Guyatt's responsiveness index was À1.51, and a significant (p < 0.001) within-patient change of CARATKids score in clinical unstable patients was observed. Regarding cross-sectional validity, correlation coefficients of CARATKids with the external measures of control were between 0.45 and À0.69 and met the a priori predictions. In the longitudinal validity assessment, the correlation coefficients between the score changes of CARATKids and those of external measures of control ranged from 0.34 to 0.46. Conclusion: CARATKids showed adequate psychometric properties and is ready to be used in clinical practice.

Childhood recurrent wheezing is a very prevalent heterogeneous clinical entity. An 8-year prospective study was performed to correlate the clinical outcome of recurrent wheezing in the first years of life with prognostic risk factors. A cohort of 308 children with recurrent wheezing, aged <7 years, were enrolled in 1993, studied using a questionnaire, skin-prick tests, and serum total IgE. According to the study protocol, in 1996 and 2001, the cohort was assessed. In 2001, 81% of the initial sample was reevaluated (n=249); 61% remained symptomatic. Prevalence of atopy was 48% in 1993, 65% in 1996, and 75% in 2001. By logistic regression analysis, we identified the following as independent risk factors for asthma symptoms in the last year of the follow-up: personal history of rhinitis (odds ratio [OR] = 15.8, 95% confidence interval [CI], 6.1-40.8; p < 0.001), paternal asthma (OR =, 7.2; 95% CI = 1.7-29.7; p = 0.007), personal history of atopic dermatitis (OR = 5.9, 95% CI = 2.2-15.7; p < 0.001), maternal asthma (OR = 5.4, 95% CI = 1.7-17.1; p = 0.004), allergen sensitization (OR = 3.4, 95% CI = 1.2-10.4; p = 0.03), and onset of symptoms in the 2nd year or later in preschool-aged children (OR = 2.1, 95% CI = 1.1-4.8; p = 0.04). Kindergarten attendance before 12 months was identified as a protective factor (OR = 0.4, 95% CI = 0.2-0.9; p = 0.04). Among the 128 nonatopic children in 1993, 52% developed allergen sensitization. We identified as prognostic risk factors for asthma symptoms personal history of allergic disease, parental asthma, atopy, and late onset of symptoms. In a significant number of children clinical symptoms can occur years before allergen sensitization.

BackgroundOral immunotherapy (OIT) has been recognized as a promising treatment for severe and long-lasting cow's milk (CM) allergy. Once maintenance has been achieved, patients should maintain daily intake of CM to ensure desensitization. Clinical experience concerning long-term follow-up is scarce.ObjectiveThe authors aimed to assess long-term efficacy and safety of a maintenance phase of OIT in real life.MethodsProspective study of all children and adolescents, who underwent CM-OIT and were subsequently followed at our allergy center on maintenance dose (200 mL daily) for at least 36 months after reaching the maintenance phase (from 2009 to 2016).ResultsForty-two patients were enrolled: 60% male, 36% with history of anaphylaxis and 57% with asthma. The median time of follow-up was 69 months (range, 39–105 months) and the median age at the last clinical evaluation was 13 years (range, 6–23 years). Regarding adherence to the protocol: 92% are on free diet (at least 200 mL of CM daily; 7-g protein); 14% had transient interruptions and 7% definitely withdrawn with loss of tolerance. During maintenance, 45% developed mild to severe allergic reactions, and 7% had more than 3 episodes. A positive correlation between the occurrence of allergic reactions and history of anaphylaxis (p < 0.001) was found. The coexistence of asthma was risk factor for the occurrence of allergic reactions during maintenance.ConclusionThis real-life study supports long-term efficacy and safety of CM-OIT. Despite daily intake, 41% had symptoms at some moment during the complete follow-up period; a total of 33 symptomatic days in patients with mean follow-up time of 67.5 months. Clinical tolerance depends on daily intake. The protective effect reached can be lost after CM withdrawal. History of anaphylaxis was a risk factor for the occurrence of allergic reactions during the maintenance phase.

Background:Anaphylaxis is increasing at pediatric age; however, its characterization is hampered by underdiagnosis and underreporting. The aim of this study was to identify the causes of anaphylaxis in children and adolescents in Portugal, thus contributing to a better knowledge of its etiology, clinical manifestations, and management.Methods: During a 10-year period, a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 533 patients under 18 years of age with anaphylaxis were included.Results: Mean age was 8.5 ± 4.9 years, 61% were male; 45% had asthma. Mean age at the first anaphylaxis episode was 5.3 ± 4.7 years (ranging from 1 month to 17 years of age), 63% at pre-school age. Most reactions occurred at home (57%). Food-induced anaphylaxis was the leading cause (77%). The main culprit foods were cow's milk (32%), tree nuts (16%), shellfish (13%), egg (12%), fresh fruits (11%), fish (8%), and peanut (8%). Other causes included drugs (11%), insect sting (5%), cold-induced anaphylaxis (4%), exercise-induced anaphylaxis (2%), latex (1%), and idiopathic anaphylaxis (1%). Most patients (83%) were admitted to the emergency department; only 46% received adrenaline treatment. Recurrence of anaphylaxis occurred in 41% of the patients (3 or more episodes in 21%). An adrenaline autoinjector was used in 9% of the patients. Conclusions:In the Portuguese pediatric population, food is the leading cause of anaphylaxis. Undertreatment with adrenaline and high recurrence of anaphylaxis highlight the need to improve both the diagnosis and the therapeutic management of this life-threatening entity.

LTPs are important allergens of FIA in Portugal. Clinical reactivity to several taxonomically unrelated plant foods may raise suspicion toward LTP sensitization. The association of LTP-induced anaphylaxis with pollinosis is relevant in our country. The unpredictable clinical expression depends on the effect of cofactors such as exercise. The management of avoidance plans can be challenging due to LTP being a widely cross-reacting allergen in plant foods.

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Drug-induced anaphylaxis (DIA) is the most common cause of fatal anaphylaxis. We aimed to characterize patients with DIA and their allergological workup. Systematic review of patients with history of DIA referred to our center over 7 years. Included 125 patients (10% pediatric age), being 36 years the median age of first episode (from 1 to 74 years). The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (43%), antibiotics (42%) and anesthetic agents (6%). In 24% the reactions occurred in hospital setting and 14% perioperative. The etiology was confirmed in 75% through allergological workup. NSAIDs and antibiotics were responsible for most of DIA. The heterogeneity of mechanisms, the severity of the reactions and the lack of standardized in vivo and/or in vitro tests for some drugs do not allow to confirm the diagnosis in all cases. Patients with DIA should be evaluated in specialized centers to perform accurate diagnosis, to prevent recurrence and to find safe alternatives.