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.

Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria.

BACKGROUND: According to recently published data, low total IgE, elevated IgG-anti-TPO, and a high IgG-anti-TPO/total IgE ratio are good biomarkers for subtype IIb autoimmune chronic spontaneous urticaria (CSU), which is frequently refractory to antihistamines and omalizumab. OBJECTIVES: The aim of the study was to evaluate IgG-anti-TPO/total IgE ratio's utility in omalizumab response prediction. METHODS: Retrospective study of CSU patients treated with omalizumab at a UCARE between January 2009 and February 2022. Patients were grouped according to response in the first 16 weeks of treatment: responders UAS7 < 7 versus partial/non-responders UAS7≥7. Total IgE, IgG-anti-TPO, and IgG-anti-TPO/total IgE ratio were compared. Other inflammatory biomarkers - eosinophils, basophils, C-reactive protein, erythrocyte sedimentation rate, and d-dimer - were analyzed. STATISTICAL ANALYSIS: SPSS® (v25.0), p < 0.05 statistically significant. RESULTS: Total of 175 patients, 140 (80%) women, median age 49 [9-88] years, mean CSU duration pre-omalizumab 5.6 ± 8.2 [0-54] years, omalizumab duration 3.2 ± 2.5 [0-12] years. 116 (66%) had angioedema, 77 (44%) inducible chronic urticaria, 60 (34%) atopy, 24 (14%) autoimmune disease. With omalizumab 300 mg q4 weeks, 69% were responders and 31% partial/non-responders. Although not reaching significant differences, mean total IgE values were lower and mean IgG-anti-TPO values were higher in partial/non-responders versus responders (152 vs. 242 kU/L, p = 0.207, and 38.3 vs. 25.7 U/mL, p = 0.408, respectively). A higher IgG-anti-TPO/total IgE ratio was significantly associated with poorer response to omalizumab (p = 0.040). A cut-off >0.154 increased 10 times the odd of poorer response [95% CI 4.62-22], AUC 0.872, p < 0.001, with 87.7% sensitivity, although the low specificity (22.4%) does not allow the assumption of response with values <0.154. Other laboratory biomarkers did not show significant differences between partial/non-responders versus responders. CONCLUSIONS: A high IgG-anti-TPO/total IgE ratio was a good biomarker of poor response to omalizumab in our CSU cohort, with a cut-off >0.154 increasing 10 times the odd of poorer response.

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.

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.

Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut.

Aneuploidy has been strongly linked to cancer development, and published evidence has suggested that aneuploidy can have an oncogenic or a tumor suppressor role depending on the tissue context. Using the Drosophila midgut as a model, we have recently described that adult intestinal stem cells (ISCs), do not activate programmed cell death upon aneuploidy induction, leading to an increase in ISC proliferation rate, and tissue dysplasia. How aneuploidy impacts ISCs in intestinal tumorigenic models remains to be investigated, and it represents a very important biological question to address since data from multiple in vivo models suggests that the cellular impact of aneuploidy is highly dependent on the cellular and tissue context. Using manipulation of different genetic pathways such as EGFR, JAK-STAT and Notch that cause dysplastic phenotypes in the Drosophila gut, we found that concomitant aneuploidy induction by impairment of the spindle assembly checkpoint (SAC) consistently leads to a more severe progression of intestinal dysplasia or tumorigenesis. This is characterized by an accumulation of progenitor cells, high tissue cell density and higher stem cell proliferation rates, revealing an additive or synergistic effect depending on the misregulated pathway in which aneuploidy was induced. Thus, our data suggests that in the Drosophila gut, both dysplasia and tumorigenic phenotypes can be fueled by inducing genomic instability of resident stem cells.

Rapid desensitization to antineoplastic drugs in an outpatient immunoallergology clinic: Outcomes and risk factors.

BACKGROUND: Hypersensitivity reactions to antineoplastic agents may lead to discontinuation of first-line treatments. Rapid drug desensitization (RDD) allows for a safe reintroduction in patients who are allergic to them. OBJECTIVE: To evaluate the safety and efficacy of the Brigham and Women's Hospital's 12-step RDD in a Portuguese patient population with cancer and to identify markers associated with breakthrough reactions (BTRs) to platins. METHODS: We conducted a retrospective review of desensitizations undertaken at the Immunoallergology Day-Care Unit of the Santa Maria Hospital in Lisbon, Portugal, from July 2008 to July 2019. Adult patients with cancer and with immediate hypersensitivity reactions were included. Skin testing was performed to platins, trastuzumab, and cetuximab. The 12-step protocol was used for most patients, and a shorter protocol was used in 9 patients who were taxane-reactive to resume regular infusions. RESULTS: A total of 1471 RDDs were performed in 272 patients to 136 platins, 124 taxanes, 13 monoclonal antibodies, and 10 other drugs. Skin test results were positive in 127 of patients who were platin-reactive (95.3%) and negative in patients who were cetuximab- and trastuzumab-reactive. There were 141 BTRs during RDD (9.6% of infusions), 79.4% induced by platins with the majority having mild reactions (68.8%). There were 8 patients who were paclitaxel-reactive, and who completed a shorter protocol and resumed regular infusions successfully. Multiple platin infusions (cutoff: ≥10) and total immunoglobulin E greater than or equal to 100 U/mL were identified as independent risk factors for BTRs in patients who were platin-reactive. CONCLUSION: This large single-center study confirmed the safety and efficacy of the 12-step RDD protocol in a diverse cancer population, providing evidence of its universal applications. Total immunoglobulin E is a potentially useful biomarker to identify high-risk patients who are platin-reactive.

Tissue stem cells: the new actors in the aneuploidy field.

The development of multicellular organisms and the maintenance of its tissues relies on mitosis. However, this process represents a major challenge for genomic stability as each time a cell division occurs there are multiple steps where errors can lead to an abnormal chromosomal content in daughter cells - aneuploidy. Aneuploidy was first postulated to act as a tumour promoting agent over one century ago. Since then, we have learned to appreciate the complexity involving the cellular responses to aneuploidy and to value the importance of models where aneuploidy is induced in vivo and in a cell-type specific manner. Recent data suggests that stem cells evolved a distinct response to aneuploidy, being able to survive and proliferate as aneuploid. Since stem cells are the main cells responsible for tissue renewal, it is of the utmost importance to place the spotlight on stem cells within the aneuploidy field. Here, we briefly review some of the biological mechanisms implicated in aneuploidy, the relationship between aneuploidy and tissue pathologies, and summarize the most recent findings in Drosophila on how tissue stem cells respond to aneuploidy. Once we understand how stem cell behavior is impacted by aneuploidy, we might be able to better describe the complicated link between aneuploidy and tumourigenesis.

Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila.

Aneuploidy is associated with different human diseases including cancer. However, different cell types appear to respond differently to aneuploidy, either by promoting tumorigenesis or causing cell death. We set out to study the behavior of adult Drosophila melanogaster intestinal stem cells (ISCs) after induction of chromosome missegregation either by abrogation of the spindle assembly checkpoint or through kinetochore disruption or centrosome amplification. These conditions induce moderate levels of aneuploidy in ISCs, and we find no evidence of apoptosis. Instead, we observe a significant accumulation of ISCs associated with increased stem cell proliferation and an excess of enteroendocrine cells. Moreover, aneuploidy causes up-regulation of the JNK pathway throughout the posterior midgut, and specific inhibition of JNK signaling in ISCs is sufficient to prevent dysplasia. Our findings highlight the importance of understanding the behavior of different stem cell populations to aneuploidy and how these can act as reservoirs for genomic alterations that can lead to tissue pathologies.