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.

What Basophil Testing Tells Us About CSU Patients - Results of the CORSA Study.

Basophil testing is the most effective single approach for diagnosing type-IIb autoimmune chronic spontaneous urticaria (TIIbaiCSU). A positive basophil test has been linked to long disease duration, higher disease activity, a poor response to antihistamines and omalizumab, and a better response to cyclosporine and fenebrutinib. As of now it is unclear what other features are connected to a positive basophil test in chronic spontaneous urticaria (CSU). We aimed to identify features of basophil test-positive CSU patients. We performed a cross-sectional study of 85 CSU patients. Basophil testing was done with the basophil activation test (BAT) and the basophil histamine release assay (BHRA). Data were analysed using SPSS: Student's t-test, Chi-square test, Odds Ratio, Spearman's correlation test. Of 85 CSU patients, 44% and 28% tested positive with the BAT and BHRA, respectively. These patients showed higher disease activity and impact, lower levels of disease control and total serum IgE, as well as higher rates of having a positive autologous serum skin test (ASST), angioedema, nocturnal symptoms, symptoms for >5 days/week, and thyroid autoantibodies. The ASST, by itself, was not a good predictor of basophil test results, but it predicted a positive basophil test in up to 100% of cases when combined with angioedema, thyroid autoantibodies or low IgE. In conclusion, a positive basophil test is linked to known features of TIIbaiCSU and novel characteristics including nocturnal symptoms. Further studies on basophil test-positive and -negative CSU patients can help to better understand CSU endotypes and to develop better management approaches.

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.

Matrix Metalloproteinase-9 Levels are Associated with Brain Lesion and Persistent Venous Occlusion in Patients with Cerebral Venous Thrombosis.

BACKGROUND: Elucidating mechanisms of brain damage in cerebral venous thrombosis (CVT) would be instrumental to develop targeted therapies and improve prognosis prediction. Matrix metalloproteinase-9 (MMP-9), a gelatinase that degrades major components of the basal lamina, has been associated to blood-brain barrier disruption. We aimed to assess, in patients with CVT, the temporal change in serum concentrations of MMP-9 and its association with key imaging and clinical outcomes. METHODS: Pathophysiology of Venous Infarction-PRediction of InfarctiOn and RecanalIzaTion in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Serial collection of peripheral blood samples performed on day 1, 3, and 8, and standardized magnetic resonance imaging on day 1, 8, and 90. MMP-9 was quantified using enzyme-linked immunosorbent assay in 59 patients and 22 healthy controls. Primary outcomes were parenchymal brain lesion, early evolution of brain lesion, early recanalization, and functional outcome on day 90. RESULTS: CVT patients with parenchymal brain lesion had higher baseline concentrations of MMP-9 compared with controls (adjusted p = 0.001). The area under receiver operating characteristic curve value for MMP-9 for predicting brain lesion was 0.71 (95% confidence interval [CI]: 0.57-0.85, p = 0.009). Patients with venous recanalization showed early decline of circulating MMP-9 and significantly lower levels on day 8 (p = 0.021). Higher MMP-9 on day 8 was associated with persistent venous occlusion (odds ratio: 1.20 [per 20 ng/mL], 95% CI: 1.02-1.43, p = 0.030). CONCLUSION: We report a novel relationship among MMP-9, parenchymal brain damage, and early venous recanalization, suggesting that circulating MMP-9 is a dynamic marker of brain tissue damage in patients with CVT.

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.

Chlorhexidine: a hidden life-threatening allergen.

Chlorhexidine is a commonly used antiseptic and disinfectant in the health-care setting. Anaphylaxis to chlorhexidine is a rare but potentially life-threatening complication. Epidemiologic data suggest that the cases of chlorhexidine allergy appears to be increasing. In this article we report a life-threatening anaphylactic shock with cardiorespiratory arrest, during urethral catheterization due to chlorhexidine. The authors also performed a literature review of PubMed library of anaphylactic cases reports due to this antiseptic between 2014 and 2018, demonstrating the increase in the number of cases occurring worldwide and the importance of detailed anamnesis and appropriate diagnostic workup of allergic reactions to disinfectants.

Carboplatin-, oxaliplatin-, and cisplatin-specific IgE: cross-reactivity and value in the diagnosis of carboplatin and oxaliplatin allergy.

BACKGROUND: The diagnosis of hypersensitivity reactions (HSR) to platins is based on the characterization of the reaction and the results of skin testing. Platins can be irritants when used in skin testing; therefore, in vitro testing may offer an alternative diagnostic tool. OBJECTIVE: To evaluate sensitivity and specificity of platin specific IgE (sIgE) in patients with HSRs and in controls. METHODS: Twenty-four patients with immediate HSR to platins were included (carboplatin, 12; oxaliplatin, 12): 19 women and 5 men (mean age, 61 years). The control group included 17 patients exposed to platin and with no HSR. Skin testing was performed on 22 patients. Carboplatin sIgE and oxaliplatin sIgE were measured in 24 patients and 17 controls; carboplatin sIgE was measured in 21 patients. RESULTS: Skin test results were positive in 22 patients (carboplatin, 12/12; oxaliplatin, 10/12). Seven of 12 patients sensitive to carboplatin (59%) had positive carboplatin sIgE, 2 also had positive cisplatin sIgE, and all had negative oxaliplatin sIgE; 9 of 12 patients sensitive to oxaliplatin (75%) had positive sIgE to oxaliplatin, 8 of 12 (67%) also had positive carboplatin and cisplatin sIgE, to which they had not been exposed. All 5 carboplatin controls had negative sIgE; 3 oxaliplatin controls (25%) had positive carboplatin sIgE, and 2 had positive oxaliplatin sIgE. CONCLUSION: Carboplatin sIgE is very specific but less sensitive. In contrast, oxaliplatin sIgE had higher sensitivity but lower specificity. Analysis of our data suggests that oxaliplatin exposure was more immunogenic. This could be clinically relevant because patients sensitized to carboplatin may be able to tolerate oxaliplatin, but patients sensitized to oxaliplatin may be at risk when exposed to carboplatin and cisplatin.

Snail allergy without house dust mites sensitisation

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Clinical, anamnestic and serological features of peach allergy in portugal.

BACKGROUND: Peach is a common food allergen source throughout Europe. The aim of this study was to characterize peach allergy in a Portuguese patient population. METHODS: Thirty peach-allergic patients confirmed by double-blind placebo-controlled food challenges and 29 controls were included. All subjects completed a standardized questionnaire regarding symptoms and epidemiologic characteristics, skin prick tests with inhalant allergens and foods as well as specific IgE antibodies to peach, recombinant peach allergens rPru p 1, rPru p 3, rPru p 4 and cross-reactive carbohydrate determinants. RESULTS: Thirty-seven percent of patients reported only oral allergy syndrome, while 37% reported generalized urticaria and/or angioedema, 17% localized contact urticaria and 10% anaphylaxis with peach. Sensitization to other Rosaceae fruits and tree nuts was present in 90 and 77% of the patients, respectively. Respiratory allergy history was associated with less severe symptoms (oral allergy syndrome or contact urticaria; p < 0.01) and positive skin prick test to peach peel or plum with more severe symptoms (urticaria and/or angioedema or anaphylaxis; p < 0.05). Ninety-seven percent were sensitized to Pru p 3, 13% to Pru p 4, 3% to Pru p 1 and 10% to cross-reactive carbohydrate determinants. Pru p 3 specific IgE was associated with Artemisia vulgaris sensitization and tree nut allergy (p < 0.05) but not with clinical severity. CONCLUSIONS: Half the patients reported systemic reactions to peach. Peach allergy appeared predominantly mediated by Pru p 3 but some patients were sensitized to Pru p 4. Applying a 0.10 kU(A)/l cutoff level, the diagnostic value of combining the 3 recombinant allergens was noteworthy, with 100% sensitivity and 90% specificity.