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.

Omalizumab in Chronic Spontaneous Urticaria (CSU): Real-Life Experience in Dose/Interval Adjustments and Treatment Discontinuation.

BACKGROUND: Data on real-life experience with omalizumab dose/interval adjustments are still limited, as well as on omalizumab discontinuation. OBJECTIVE: To evaluate efficacy and safety of omalizumab dose/interval adjustment in a Portuguese cohort of patients with chronic spontaneous urticaria (CSU) and to characterize those who discontinued omalizumab. METHODS: A retrospective study of patients who started omalizumab for CSU at a Portuguese Urticaria Center of Reference and Excellence (UCARE) was conducted between 2009 and 2021. Response criteria were based on a weekly Urticaria Activity Score (UAS7) <7 points (partial: UAS7 7-15 points; nonresponders: UAS7 >15 points) and minimal important difference >10 points. RESULTS: A total of 138 patients were enrolled in the study; 83% of them were women, and the median age was 49 years (interquartile range: 40-58 years). On 300 mg q4 weeks, 96 (70%) patients were responders, 29 (21%) partial responders, and 13 (9%) nonresponders. After dose/interval adjustments (up to 600 mg q2 weeks), 108 (78%) were responders, 27 (20%) partial responders, and 3 (2%) nonresponders. No adverse events were reported. Updosing was more frequent in patients with angioedema, body mass index >30 kg/m2, positive basophil activation test, and autologous serum test. A total of 71 (51%) patients lengthened interval, presenting higher median pre-omalizumab D-dimer (0.2 vs 0 mcg/mL, P = .038) and C-reactive protein (0.3 vs 0.1 mg/dL, P = .030) values than those with a standard dose. In total, 37 patients (27%) stopped omalizumab, but 14 (38%) of them needed retreatment on average 11 months after discontinuation. Patients with angioedema and a longer omalizumab duration had higher chance of relapse. CONCLUSIONS: Omalizumab dose and/or interval adjustment is effective and safe and should be implemented in partial/nonresponders for response improvement and in responders for further discontinuation. A protocol for regimen adjustments is proposed.

An Unusual IgE-Mediated Hypersensitivity: Two Case Reports of Paracetamol Allergy.

Paracetamol is one of the most commonly used analgesic and antipyretic agents worldwide, attributed in part to its excellent safety profile when administered at recommended doses. Paracetamol allergy is not common, and the majority of the reactions are related to the pharmacological action of cyclooxygenase 1 inhibition. Selective and Immunoglobulin E (IgE)-mediated hypersensitivity reactions are rare. In this article, the authors report two cases of paracetamol allergy in which the mechanism of IgE-mediated hypersensitivity was demonstrated by positive skin tests and basophil activation tests. We highlight the relevance of identifying the mechanism underlying the reaction since patients with IgE-mediated paracetamol allergies will be able to tolerate non-steroidal anti-inflammatory drugs.

Sensitization to poultry meat, fish, and coconut in a multiple food allergic young boy / Sensibilização a carne de aves, peixe e coco em um jovem com alergia alimentar múltipla

Poultry meat allergy is rare and may present as primary or secondary, in the context of bird-egg syndrome. Chicken meat is responsible for most of the reactions. Cross-reactive allergens (parvalbumins, enolases, aldolases) between fish and chicken meat have been described. Coconut allergy is also rare. Coc n2 (7S globulin) and Coc n4 (11S globulin) have been implicated. We present a complex multiple food allergy case report where investigation into fish and chicken meat allergies as well as coconut allergy is carried out.

A alergia à carne de aves é rara e pode apresentar-se como primária ou secundária, no contexto da síndrome ovo-ave. A carne de frango é responsável pela maioria das reações. Foram descritos alergênios com reação cruzada (parvalbuminas, enolases, aldolases) entre peixe e carne de frango. A alergia ao coco também é rara. Coc n2 (globulina 7S) e Coc n4 (globulina 11S) foram implicados. Apresentamos um relato de caso complexo de alergia alimentar múltipla, onde é realizada investigação sobre alergia a peixe e carne de frango, bem como alergia ao coco.

Segurança da vacinação contra a COVID-19 em doentes referenciados dos cuidados de saúde primários por alergia ao veneno de himenópteros / COVID-19 vaccination safety in patients with hymenoptera venom allergy referred by primary health care

Introdução: As reações de hipersensibilidade após vacinação contra a COVID-19 têm vindo a ser descritas, embora a anafilaxia seja rara. A hipersensibilidade ao veneno de himenópteros constitui a terceira causa mais frequente de anafilaxia em Portugal, embora não pareça aumentar o risco de anafilaxia à vacinação contra a COVID-19. Objetivos: Avaliar a segurança da vacinação contra a COVID-19 em doentes com história de alergia ao veneno de himenópteros referenciados dos Cuidados de Saúde Primários (CSP). Métodos: Estudo observacional retrospectivo com inclusão dos doentes com alergia ao veneno de himenópteros referenciados pelos CSP ao serviço de Imunoalergologia, para estratificação do risco de reações de hipersensibilidade à vacina contra o SARS-CoV-2, entre janeiro e dezembro de 2021. Resultados: No total, incluíram-se 18 doentes, 72% do sexo feminino, média de idades de 61±18 [21-89] anos. Na caracterização do tipo da reação ao veneno de himenópteros, as reações locais exuberantes corresponderam a 33% de todas as reações referidas. Quanto a sintomas sistêmicos de anafilaxia, foram referidos sintomas mucocutâneos (33%), respiratórios (28%), cardiovasculares (33%) e gastrointestinais (11%). A abelha foi o inseto mais frequentemente implicado (61%). Relativamente aos valores de triptase basal, 3 doentes apresentaram níveis acima do cut-off estabelecido de 11,4 ng/mL, tendo indicação formal para iniciar esquema de vacinação em meio hospitalar. Durante o processo vacinal registrou-se um total de 46 administrações em 18 doentes, todas sem intercorrências. Apenas 5 doentes foram vacinados em meio hospitalar, tendo sido os restantes encaminhados para os CSP. Os doentes com mastocitose confirmada ou suspeita foram submetidos à pré-medicação com anti-histamínico anti-H1 e anti- H2, bem como montelucaste, na véspera e no dia da vacinação. Conclusões: A vacinação contra a COVID-19 é segura em doentes com reação de hipersensibilidade ao veneno de himenópteros. O protocolo utilizado mostrou ser eficaz na segregação de doentes entre CSP e cuidados secundários/terciários.

Introduction: Despite numerous reports of hypersensitivity reactions to COVID-19 vaccination, anaphylaxis is rare. Although hypersensitivity reactions to hymenoptera venom are the third most common cause of anaphylaxis in Portugal, they don't appear to enhance the risk of anaphylactic reaction to COVID-19 vaccination. Objectives: To assess the safety of COVID-19 vaccination in patients with a history of hymenoptera venom allergy. Methods: This retrospective observational study included patients with hymenoptera venom allergy referred by primary health care to the Immunoallergology Outpatient Clinic of a tertiary hospital between January and December 2021 to stratify the risk of hypersensitivity reactions to the SARSCoV- 2 vaccine. Results: A total of 18 patients were included: 72% women; mean age 61 (SD, 18 [range 21-89]) years. One-third of all reported reactions to hymenoptera venom were large and local. Topical systemic symptoms of anaphylaxis were mucocutaneous (33%), respiratory (28%), cardiovascular (33%) and gastrointestinal (11%). The honeybee was the most frequently involved hymenoptera species (61%). The basal tryptase levels of 3 patients were above the established cut-off (11.4 ng/mL) and they were formally indicated for vaccination in a hospital setting. Concerning the vaccination process, 46 doses were administered to the 18 patients and no reactions were recorded. Only 5 patients were vaccinated in a hospital environment; the rest were referred to primary health care centers. Patients with confirmed or suspected mastocytosis were premedicated with anti-H1 and anti-H2 antihistamines, as well as montelukast, the day before and on the day of vaccination. Conclusions: COVID-19 vaccination is safe for patients with hypersensitivity to hymenoptera venom. The risk assessment protocol effectively designated patients to primary or secondary/tertiary health care.

Molecular sensitization profile of patients with lipid transfer protein syndrome and associated clinical characteristics / Perfil de sensibilização molecular de doentes com síndrome de proteínas de transferência lipídica e associação com características clínicas

Introduction: Lipid transfer proteins (LTPs) can cause a diversity of food allergy phenotypes, broadly defined as LTP syndrome. Objective: The aims of this study were to characterize the molecular profile of patients with this syndrome and to evaluate any possible association with clinical phenotypes. Methods: Retrospective study of patients followed up from April 2011 to April 2019. Patients with LTP syndrome and sensitization to Pru p 3, diagnosed by ImmunoCAP ISAC® (Phadia, Thermo Fisher Scientific, Sweden), were selected. Statistical analysis was conducted in IBM SPSS® v20. Results: One hundred patients were assessed, 64% of which were females, with a mean age 27.2±11.8 years (15% pediatric). Mean age at first reaction was 19.9±10 years. According to clinical presentation, two groups were created: local reaction (LR) (n=28) and systemic reaction (SR) (n=72). The following parameters were analyzed in association with the SR group: LTP sensitization profile, co-sensitization to profilins or PR-10 proteins, presence of atopy, and gender. In univariate analysis, a positive association was found between the SR group, female sex (odds ratio [OR] 2.8, p=0.02), and presence of Jug r 3 (OR 2.6, p=0.03). There was a negative association between the SR group, the presence of Par j 2 (OR 0.16, p < 0.01), and co-sensitization to profilins (OR 0.11, p < 0.01). In multivariate analysis, only the presence of Par j 2 kept statistical significance (OR 0.023, p < 0.01). Conclusions: Molecular profile characterization may be useful as a predictor of disease expression in an individual, making a relevant contribution to improved follow-up of these patients. Sensitization to Par j 2 seems to provide protection for the occurrence of SR.

Introdução: As proteínas de transferência lipídicas (LTP) são causa de uma variedade de fenótipos de alergia alimentar globalmente definidos como síndrome LTP. Objetivo: O nosso objetivo é caracterizar o perfil molecular destes doentes e avaliar associação com os fenótipos clínicos. Metodologia: Estudo retrospectivo em que foram selecionados doentes com síndrome de LTP e sensibilização ao alergênio molecular pru p 3 em ImmunoCAP ISAC® (Phadia, Thermo Fisher Scientific, Suécia) realizados de abril de 2011 a abril de 2019. A análise estatística foi realizada através do software IBM SPSS® v20. Resultados: Cem doentes, 64% do sexo feminino, com média de idades à data do exame de 27,2±11,8 anos (idade pediátrica - 15%). A média de idades da primeira reação foi de 19,9±10 anos. Foram constituídos dois grupos com base na apresentação clínica à data da realização do exame: local (LR) n = 28; sistêmica (SR) n = 72. Os seguintes parâmetros foram avaliados em relação ao grupo SR: perfil de sensibilização a LTP, co-sensibilização com profilinas ou PR-10, presença de atopia e gênero. Na análise univariada foi encontrada associação positiva com grupo SR para sexo feminino (Odds ratio (OR) 2,8, p = 0,02) e presença de Jug r 3 (OR 2,60, p = 0,03). Associaram-se negativamente à doença sistêmica a presença de Par j 2 (OR 0,16, p < 0,01) e de profilinas (OR 0,11, p < 0,01). Na análise multivariada apenas manteve significado estatístico a presença de par j 2 (OR 0,023, p < 0,01). Conclusões: A caracterização do perfil molecular pode ser útil como preditos da expressão da doença, sendo uma importante ferramenta no seguimento destes doentes. A presença de Par j 2 parece ser fator protetor de reação grave.

Identification of a thaumatin-like protein as a new allergen in persimmon (Diospyros kaki) with cross-reactivity with banana (Musa acuminata) / Identificação de uma proteína semelhante à taumatina como um novo alérgeno no caqui (Diospyros kaki) com reatividade cruzada com a banana (Musa acuminata)

Allergy to persimmon (Diospyros kaki ) has been only rarely reported. The antigenic composition of the fruit is not entirely known. Thaumatin-like proteins (TLPs) have been described as allergens in pollens and various fruits, such as kiwi and banana, but not in persimmon. We report the case of a 22-year-old man, with persistent moderate-to-severe allergic rhinitis, sensitized to house dust mites. The patient describes an episode of oral mucosa and ear canal pruritus, followed by diffuse urticaria, which rapidly evolved to dysphonia, dyspnea, and dizziness, after eating raw persimmon. A few months later he developed similar cutaneous symptoms accompanied by nausea, vomiting, abdominal colic, and hypotension immediately after the intake of banana. The prick-prick test with raw persimmon and banana were positive, as well as the serum specific IgE to the extract of these fruits. The ImmunoCAP ISAC_112i test demonstrated a positive specific IgE against Act d 2 (kiwi thaumatin), which is homologous to banana TLP (Mus a 4). Serum IgE inhibition test with "sponge" of Diospyros kaki ImmunoCAP (f301) showed partial inhibition (40%) of IgE to Act d 2. This raises the suspicion that a TLP is at least partially responsible for the referred sensitization. This patient is sensitized to Diospyros kaki and Musa acuminata. An anaphylactic reaction to consumed persimmon, presumably as a result from cross-allergy with banana thaumatin was diagnosed in our patient. Thaumatin has not been previously described as an allergen of persimmon with cross-reactivity with banana, and in vitro with Act d 2 (kiwi TLP).

A alergia ao caqui (Diospyros kaki ) tem sido raramente documentada, não sendo a composição antigênica da fruta totalmente conhecida. Proteínas semelhantes à taumatina (TLPs) foram descritas como alergênicos em pólens e várias frutas, como no kiwi e banana, mas não no caqui. Apresenta-se o caso de um doente de 22 anos, com rinite alérgica persistente moderadagrave, sensibilizado a ácaros do pó doméstico. O doente refere episódio de prurido na mucosa oral e canal auditivo, seguido de urticária generalizada, que rapidamente evoluiu para disfonia, dispneia e tontura, após ingestão de caqui. Poucos meses depois, desenvolveu sintomas cutâneos semelhantes, acompanhados de náuseas, vómitos, cólica abdominal e hipotensão imediatamente após ingestão de uma banana. O teste cutâneo por picada com caqui e banana em natureza foram positivos, bem como o doseamento de IgE específica. O teste ImmunoCAP ISAC_112i identificou a presença de IgE específica para Act d 2 (taumatina do kiwi), homóloga da TLP da banana (Mus a 4). O estudo de inibição ImmunoCAP ISAC com "esponja" de Diospyros kaki (f301) produziu uma inibição parcial (40%) da ligação de IgE a Act d 2, permitindo presumir que uma proteína semelhante à taumatina é, pelo menos, parcialmente responsável pela referida sensibilização. Este doente encontra-se sensibilizado a Diospyros kaki e Musa acuminata. Uma anafilaxia ao caqui ingerido, presumivelmente resultante de reatividade cruzada com a taumatina da banana foi diagnosticada. Não estão descritas na literatura TLPs como alergênicos do caqui com reatividade cruzada com a banana e com Act d 2 in vitro (TLP do kiwi).

Characterization of the sensitization profile of bee venom allergic patients ­ Association with the severity of reaction? / Caracterização do perfil de sensibilização molecular de doentes alérgicos à picada de abelha - Associação com a gravidade da reação?

Introduction: Bee venom (BV) allergy, a common cause of anaphylaxis in adults, is often associated with severe reactions. The use of component-resolved diagnostics (CRD) increases diagnostic accuracy. Objectives: To characterize the sensitization profile of BV allergic patients and a possible correlation with the severity of reaction. Materials and methods: We selected patients with a clinical history of BV allergy, positive skin tests, and specific IgE (sIgE) for BV. The allergenic profile was analyzed by both CRD and Western blot using a well-defined and properly characterized BV extract. Results: Forty-four patients were included, 30 (68.2%) were men. Mean age was 48.9 (SD 17.9) years. Eleven (25%) had large local reactions (LLRs) and 33 (75%) had systemic sting reactions (SSRs). One patient with negative sIgE for BV had positive sIgE for Api m 1, Api m 5, and Api m 10. The sensitization frequency for BV, Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was 97.7%, 75%, 47.7%, 20.5%, 40.9%, and 61.4%, respectively. Five patients (11.4%) were sensitized to all BV components. CRD association showed that 5 patients (11.4%) were sensitized only to Api m 1, 8 (18.2%) to Api m 1/Api m 3/Api m 10, and 16 (36.6%) to Api m 1/ Api m 10. Twenty-eight patients (84.8%) with SSRs were sensitized to Api m 1, and concomitant sensitization to Api m 1/Api m 10 was detected in 20 (60.6%). There was a significant difference in Api m 1 between patients with LLRs and SSRs (p = 0.0104). Similar profiles were identified by Western blot analysis, with relevance for the detection of Api m 6 in 28 (64%) and Api m 4 in 16 (36%) patients. Conclusion: The analysis of the sensitization profile using CRD and the association of several of these components can increase diagnostic accuracy in BV allergy. Our data showed that concomitant sensitization to Api m 1 and Api m 10, detected by both CRD and electrophoretic profile, may be associated with SSRs. We emphasize the identification of sensitization to Api m 6 in > 50% of patients, which may be considered a major allergen, and to Api m 4, which may be related to reactions during BV immunotherapy.

Introdução: A alergia ao veneno de abelha (VA) é uma causa frequente de anafilaxia em adultos e está muitas vezes associada a reações graves. O diagnóstico por componentes moleculares (CRD) contribui para uma melhor caracterização desta alergia. Objetivos: Caracterização do perfil de sensibilização molecular de doentes alérgicos ao veneno de abelha e possível correlação com a gravidade da reação. Material e métodos: Selecionaram-se doentes com história de alergia a VA, testes cutâneos e IgE específica (sIgE) positivos para VA. Avaliou-se o perfil alergênico por CRD e por Western Blot, utilizando extrato de VA bem caracterizado. Resultados: 44 doentes, 30 (68,2%) sexo masculino. Média de idades 48,9 ± 17,9 anos, 11 (25%) com reacções locais exuberantes e 33 (75%) com reações sistêmicas à picada (SSR). Um doente tinha sIgE negativa para VA, mas Api m 1, Api m 5 e Api m 10 positivas. A frequência de sensibilização para VA, Api m 1, Api m 2, Api m 3, Api m 5 e Api m 10 foi 97,7%; 75%; 47,7%; 20,5%; 40,9% e 61,4%, respectivamente. Cinco (11,4%) doentes estavam sensibilizados a todos os componentes. Por associação de CRD, detectaram-se 5 (11,4%) doentes sensibilizados apenas a Api m 1, 8 (18,2%) a Api m 1/Api m 3/Api m 10, e 16 (36,6%) a Api m 1/Api m 10. Vinte e oito (84,8%) doentes com SSR tinham Api m 1 positiva e 20 (60,6%) tinham Api m 1/Api m 10 simultaneamente positivas. Observou-se uma diferença estatisticamente significativa para a Api m 1 entre doentes com reações locais exuberantes e sistêmicas (p = 0,0104). Os perfis detectados por Western Blot foram semelhantes, de referir, à detecção de Api m 6 em 28 (64%) e Api m 4 em 16 (36%) dos doentes. Conclusão: A análise do perfil de sensibilização através de CRD e a sua associação aumentam a precisão do diagnóstico de alergia a VA. Sensibilização simultânea a Api m 1 e Api m 10 identificados tanto por CRD como por perfil eletroforético, pode estar associada à ocorrência de SSR. Destaca-se a sensibilização a Api m 6 em > 50% dos doentes, podendo ser considerado um alergênio major, e a Api m 4, possivelmente associado a reações durante a imunoterapia com VA.

Contribution of molecular diagnosis to bee venom allergic patients with systemic reactions during the build-up phase of bee venom immunotherapy / Contribuição do diagnóstico molecular em doentes alérgicos ao veneno de abelha com reações sistêmicas durante o ultra-rush

Introduction: Bee venom (BV) allergy is one of the most common causes of severe anaphylaxis. Venom immunotherapy (VIT) is considered the most effective treatment, but systemic reactions may occur. This study aimed to characterize the sensitization profile by molecular components of patients with BV anaphylaxis under VIT and to evaluate whether systemic reactions during the build-up phase of VIT protocol are related to different sensitization patterns. Methods: A retrospective study of 30 patients under VIT for 1 year. The group of patients who reacted during the build-up phase (group A) was compared with the group with no reactions (group B). Specific IgE (sIgE) and IgG4 (sIgG4) for BV and recombinants (rApi m1, rApi m2, rApi m3, rApi m5, and rApi m10) were evaluated before and 1 year after VIT. Statistical analysis was performed using GraphPad Prism v5.01. Results: Men accounted for 80% of the sample, and mean age was 47 years (14-74 years). Group A consisted of 10 patients, and group B of 20 patients. Before VIT, sIgE to rApi m1 was detected in 86.7% of patients, rApi m2 in 46.7%, rApi m3 in 16.7%, rApi m5 in 43.3%, and rApi m10 in 70%. Positive results to at least 1 BV allergen were detected in 100%; 73% of patients were sensitized to >1 allergen, and 13.3% to all allergens. The profile of the two groups did not differ significantly before VIT, but group B showed a significant decrease in whole BV extract (p=0.045), rApi m 3 (p=0.017), and rApi m 10 (p=0.021) 1 year after VIT. Regarding sIgG4, there was a significant increase in rApi m1, which was not observed in other allergens, such as rApi m3 and rApi m10. Conclusion: The analysis of a panel of BV recombinants can improve diagnostic sensitivity, when compared to rApi m1 alone. There was no association between systemic reactions during the build-up phase of VIT and molecular sensitization profile. Nevertheless, it is important to study a greater number of patients.

Introdução: A alergia ao veneno de abelha (VA) é uma das causas mais comuns de anafilaxia grave. A imunoterapia com veneno de abelha (VIT) é considerada o tratamento mais eficaz, mas reações sistêmicas podem ocorrer. O objetivo deste estudo foi caracterizar o perfil de sensibilização por componentes moleculares de doentes com anafilaxia a VA e avaliar se reações sistêmicas durante o ultrarush estão relacionadas com diferentes padrões de sensibilização. Métodos: Estudo retrospectivo incluindo 30 doentes submetidos a VIT durante 1 ano. Considerou-se dois grupos: grupo de doentes que reagiu durante o ultra-rush (Grupo A), que foi comparado com o grupo sem reação (Grupo B). Foram avaliadas as IgE (sIgE) e IgG4 (sIgG4) específicas para VA(i1) e componentes moleculares: rApi m1, rApi m2, rApi m3, rApi m5 e rApi m10 antes e 1 ano após VIT. Os testes estatísticos foram realizados com Graph-PadPrism v5.01. Resultados: 80% sexo masculino, média de idade 47 anos (14-74). Grupo A com 10 doentes, Grupo B com 20 doentes. Previamente à VIT, sIgE para rApi m1 foi detectada em 86,7%; rApi m2 em 46,7%; rApi m3 em 16,7%; rApi m5 em 43,3%; e rApi m10 em 70%. Resultados positivos para pelo menos um alergênio de VA foram detectados em 100%. 73% dos doentes eram sensibilizados a mais de um alergênio, e 13,3% a todos os alergênios. Não houve diferenças estatisticamente significativas no perfil dos dois grupos antes da VIT, porém verificouse uma diminuição significativa: p = 0,045; p = 0,017 e p = 0,021 de i1, rApi m3 e rApi m10, respectivamente, no grupo B um ano após VIT. Relativamente à sIgG4, observou-se um aumento significativo de rApi m1, não observado nos restantes alergênios como rApi m3 e rApi m10. Conclusão: A análise de um painel de recombinantes de VA pode melhorar a sensibilidade diagnóstica, quando comparado com rApi m1 isolado. Não se verificou associação entre a ocorrência de reações sistêmicas durante o ultra-rush e o perfil de sensibilização molecular. No entanto, é importante para estudar um maior número de doentes.

[Hypersensitivity to local anesthetics]. / Alergia aos anestésicos locais.

Local anesthetics (LA) are frequently used in medical and surgical and dental procedures. Adverse reactions to LA are rare, and hypersensitivity reactions are very rare. Nevertheless, they are the third more frequent cause of referral to Allergy Clinics due to drug allergy, after betalactamic antibiotics and non-steroidal anti-inflammatory agents. In this paper we review hypersensitivity reactions to LA and propose a diagnostic approach to them.

Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation.

IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21(low)CD38(low)). Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies.