Anaphylaxis in children and adolescents: The Portuguese Anaphylaxis Registry.

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.

Anaphylaxis to clavulanic acid: a 7-year survey

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Anaphylaxis caused by lipid transfer proteins: an unpredictable clinical syndrome

INTRODUCTION: Lipid transfer proteins (LTPs) are panallergens found in many plant foods. They are a common cause of food-induced anaphylaxis (FIA) in adults living in the Mediterranean area. LTPs have also been proposed as a main cause of food-dependent exercise-induced anaphylaxis (FDEIA). OBJECTIVES: Describe clinical characteristics and allergen sensitization profiles in patients with FIA related to LTP. MATERIALS AND METHODS: Forty-three patients were included, aged 3-52 years with a clinical history of FIA and proven sensitization to LTP. Patients were tested with a multiple plant food and pollen panel and specific IgE to LTP allergens. LTP sensitization was assessed by in vivo (Pru p 3, LTP extract) and/or by in vitro tests (specific IgE, ImmunoCAP/ISAC(R)). RESULTS: Median age of first anaphylactic episode was 24 years (range 2-51), 44% had asthma, 74% were atopic and 42% had pollinosis (olive, mugwort, plane tree, wall pellitory and cypress). Co-sensitization to profilins was found in 22%. Overall in our center, LTP-induced anaphylaxis represents 17% of all causes of FIA. Foods implicated in anaphylactic reactions were: fresh fruits 51%, tree nuts 42%, vegetables (including peanut) 40% and seeds 14%. Seven patients had FDEIA. CONCLUSIONS: 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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Cow's milk oral immunotherapy in real life: 8-year long-term follow-up study.

BACKGROUND: Oral 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. OBJECTIVE: The authors aimed to assess long-term efficacy and safety of a maintenance phase of OIT in real life. METHODS: Prospective 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). RESULTS: Forty-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. CONCLUSION: This 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.

Anaphylaxis caused by lipid transfer proteins: an unpredictable clinical syndrome.

INTRODUCTION: Lipid transfer proteins (LTPs) are panallergens found in many plant foods. They are a common cause of food-induced anaphylaxis (FIA) in adults living in the Mediterranean area. LTPs have also been proposed as a main cause of food-dependent exercise-induced anaphylaxis (FDEIA). OBJECTIVES: Describe clinical characteristics and allergen sensitization profiles in patients with FIA related to LTP. MATERIALS AND METHODS: Forty-three patients were included, aged 3-52 years with a clinical history of FIA and proven sensitization to LTP. Patients were tested with a multiple plant food and pollen panel and specific IgE to LTP allergens. LTP sensitization was assessed by in vivo (Pru p 3, LTP extract) and/or by in vitro tests (specific IgE, ImmunoCAP/ISAC®). RESULTS: Median age of first anaphylactic episode was 24 years (range 2-51), 44% had asthma, 74% were atopic and 42% had pollinosis (olive, mugwort, plane tree, wall pellitory and cypress). Co-sensitization to profilins was found in 22%. Overall in our center, LTP-induced anaphylaxis represents 17% of all causes of FIA. Foods implicated in anaphylactic reactions were: fresh fruits 51%, tree nuts 42%, vegetables (including peanut) 40% and seeds 14%. Seven patients had FDEIA. CONCLUSIONS: 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.

Perioperative Anaphylaxis Including Kounis Syndrome due to Selective Cefazolin Allergy.

BACKGROUND: Perioperative use of cefazolin has been associated with severe allergic reactions, and patients are usually labelled as allergic to penicillin afterwards. The aim of our study was to describe a group of patients with immediate reactions to cefazolin, with proven selective hypersensitivity reactions. METHODS: Systematic review of all patients followed at our drug centre with cefazolin-related reactions, between January 2012 and December 2016. All patients were investigated according to the European Network for Drug Allergy (ENDA) recommendations through skin testing (major and minor penicillin determinants, penicillin, amoxicillin, cefazolin, cefuroxime and ceftriaxone) and oral challenges tests. RESULTS: We included 7 patients (median age 40 years) with perioperative anaphylactic reactions immediately after cefazolin injection, 4 with hypotension and 1 with Kounis syndrome (KS) type I. The presence of a selective IgE-mediated hypersensitivity through positive skin tests to cefazoline has been proven in all patients. Two patients experienced systemic reactions during skin testing. All patients were successfully challenged with amoxicillin, and they tolerated cefuroxime. CONCLUSIONS: Cefazolin can be responsible for immediate severe allergic reactions in perioperative setting, including KS. Allergological workup is essential for an accurate diagnosis and to explore cross-reactivity between cefazolin and other beta-lactams. Our experience confirmed that patients with IgE-mediated hypersensitivity reactions to cefazolin can tolerate other beta-lactams. This selective pattern of clinical reactivity may be explained by its particular chemical structure, whose R1 side-chain is different from other beta-lactams.

Preschool-age wheezing phenotypes and asthma persistence in adolescents.

BACKGROUND: Predicting long-term outcomes in individuals with childhood wheezing is of major clinical relevance. OBJECTIVE: To identify and characterize childhood wheezing phenotypes related to asthma persistence in adolescence with a multidimensional statistical model, independent of predefined hypotheses. METHODS: This prospective cohort study included 308 children, ages < 7 years, with recurrent wheezing. We systematically evaluated asthma prevalence in children at 3, 8, and 13 years of follow-ups. Risk factors associated with asthma persistence in adolescence were analyzed with multivariable logistic regression. Early childhood wheezing phenotypes were identified with k-means cluster analysis of variables selected with the logistic regression analysis, which were based on questionnaires and skin-prick tests. These phenotypes were compared for predicting asthma prevalence, use of control treatments, and lung function in childhood and adolescence. RESULTS: Asthma prevalence was 58.3% (n = 249) and 53.5% (n = 170) at the 8- and 13-year follow-ups, respectively. Preschool-age diagnoses of atopy (odds ratio 11.8 [95% confidence interval, 4.0-34.6]) and rhinitis (odds ratio 10.4 [95% confidence interval, 3.7-29.1]) were independent risk factors for asthma persistence in adolescence. We identified three early childhood wheezing phenotypes: transient, persistent atopic, and persistent nonatopic. The latter two were characterized by rhinitis during preschool age. These phenotypes could predict the following outcomes: asthma symptom persistence, use of control treatments, and lung function during childhood and adolescence (p < 0.03). CONCLUSION: Asthma persistence through adolescence reflected different wheezing phenotypes based on preschool-age comorbidities, particularly rhinitis, with or without atopy. Our results supported that wheezing phenotypes, identified at early ages from simple measurements, could predict asthma and lung function outcomes.

Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs among Adults: Clinical Features and Risk Factors for Diagnosis Confirmation.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDS) are among the most common causes of drug hypersensitivity (HS) reactions. The diagnosis is based on a careful clinical history, and provocation tests are considered the gold standard for diagnosis. Skin tests have some value to study reactions to pyrazolones. Laboratory investigations are mostly used for research purposes. Different phenotypes have been described. OBJECTIVE AND METHODS: Our aim was to describe the most common clinical manifestations of NSAID HS in a large population of adult patients, the drugs involved, the association with previously described risk factors, and the outcome of diagnostic procedures. The classification of reactions proposed by the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group was adopted. RESULTS: Acetylsalicylic acid was the drug most often involved in reactions (34%), isolated cutaneous symptoms were the most reported (60%), and immediate reactions (58%) were the most common. There was an overall female predominance (64%) and 35% of the patients were atopic. HS to NSAIDs was confirmed in 21% of the patients. The most common phenotypes encountered among HS patients were NSAID-induced urticaria/angioedema and single-NSAID-induced urticaria/angioedema or anaphylaxis. Logistic regression analysis showed that gender and atopy were not significant risk factors for HS confirmation, but diagnosis depended on the number of previous reactions, the type of reaction, and the time interval between drug intake and reaction. CONCLUSION: Only 21% of suspected HS reactions were confirmed after diagnostic workup. Patients describing >1 previous reaction and suffering immediate reactions had a higher probability of a positive investigation.

[Successful desensitization to latex by sublingual immunotherapy in a health worker]. / Desensibilización exitosa al látex con inmunoterapia sublingual en una trabajadora de salud.

Latex allergy is still a public health problem responsible for some occupational diseases tough to be treated without removing the patient from his/her workspace. For patients allergic to latex, sublingual immunotherapy (SLIT) for latex is a tool that can be very useful. We report the case of a nurse with latex allergy who underwent successful desensitization to latex by SLIT, and discuss about possible causes of the success of this therapy.

La alergia al látex todavía es un problema de salud pública responsable de algunas enfermedades laborales difíciles de ser tratadas sin la remoción del profesional de su ambiente de trabajo. En caso de alergia al látex, la inmunoterapia sublingual es una herramienta que puede ser muy útil. Comunicamos el caso de una enfermera con alergia al látex que se sometió a la desensibilización exitosa a través de la inmunoterapia sublingual y se discuten las posibles causas del éxito de este tratamiento.

Validation of control of allergic rhinitis and asthma test for children (CARATKids)--a prospective multicenter study.

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. Data-driven 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 -1.51, 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 -0.69 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.

[Eosinophilic esophagitis]. / Esofagite eosinofílica.

Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus characterized by significant and isolated infiltration of the esophageal mucosa by eosinophils, associated with clinical symptoms of esophageal dysfunction, affecting children and adults. It is an increasingly frequent cause of symptoms similar to gastroesophageal reflux disease but refractory to anti-acid therapeutic. It is commonly associated with food allergies or other atopic diseases. Since there are no symptoms, signs, serological biomarkers or endoscopic findings pathognomonic of EE, the diagnosis requires a high degree of suspicion; moreover, due to its chronic relapsing nature the potential to cause major esophageal structural changes, its early recognition and close cooperation between gastroenterologists and immunoallergologists is essential for the timely institution of appropriate therapy. The treatment is based on two main strategies: diet and / or pharmacotherapy, depending on the co-existence of sensitization to food allergens. It is our aim to review this issue, considering recent guidelines, as well as propose a diagnostic and therapeutic algorithm.

Asma grave: epidemiologia / Severe asthma: epidemiology

A asma associa-se a taxas apreciáveis de morbimortalidade, traduzidas por recursos elevados no serviço de urgência e internações hospitalares. Apesar da tendência decrescente observada nas últimas décadas nas taxas de mortalidade associada à asma, verifica-se ainda um número significativo de óbito evitáveis por asma. Os autores apresentam os dados nacionais portugueses relativos aos óbitos por asma (dados fornecidos pelo Instituto Nacional da Estatística de Portugal) e às hospitalizações por asma (dados fornecidos pelo Instituto de Gestão Informática e Financeiro do Ministério da Saúde – Grupos de Diagnósticos Homogêneos: diagnósticos de saída), durante a última década, avaliando também estes dados por sexo, grupo etário e local de residência. Realça-se a importância do diagnóstico e tratamento precoces da asma, prevenindo formas grave, melhorando a qualidade de vida e o controle da doença.

Risk factors for asthma admissions in children.

Bronchial asthma is related to a high morbidity rate, leading to an increasing frequency of emergency room visits and hospital admissions. The aim of this study was to identify severity risk factors for childhood asthma related to hospitalization. The authors studied 124 children admitted to the hospital for asthma, during a 2-year period, correlating the obtained data with a sample of outpatients with asthma matched by age, gender, and socioeconomic status. A standardized questionnaire and skin-prick tests (SPTs) were performed on all children. The significant and independent risk factors identified for hospital admission were prior asthma hospitalization (OR = 7.63; 95% CI = 1.5-39.6; p = 0.01) and last-year admission (OR = 3.18; 95% CI = 1.1-8.9; p = 0.02), environmental tobacco-smoke exposure (OR = 6.63; 95% CI = 2.5-17.8; p = 0.002), allergen sensitization (OR = 3.86; 95% CI = 1.4-10.7; p = 0.009), family history of maternal asthma (OR = 3.58; 95% CI = 1.3-9.6; p = 0.01), and onset of symptoms before 12 months of age (OR = 2.76; 95% CI = 1.0-7.9; p = 0.06). Attendance at day care or kindergarten (OR = 0.38; 95% CI = 0.2-0.9; p = 0.04) and large family size (OR = 0.25; 95% CI = 0.1-0.8; p = 0.01) could be protective factors. Our results stress the importance of early diagnosis and specialized medical care of childhood asthma, mainly in high-risk children, with emphasis on medication planning and the establishment of preventive measures such as environmental tobacco smoke avoidance and limitation of aeroallergen exposure.