Association Between the Seed Storage Proteins 2S Albumin and 11S Globulin and Severe Allergic Reaction After Flaxseed Intake.

BACKGROUND: Given the increased popularity of flaxseed in meals, several cases of allergy to these seeds have been reported. Little is known about the allergens implicated in hypersensitivity reactions to flaxseed. The present study aimed to identify the allergens involved in IgE-mediated reactions in 5 patients with a clinical history of severe systemic symptoms after flaxseed consumption. METHODS: Proteins that were potential allergens with IgE-binding capacity were purified from flaxseed extract using chromatography and identified via MALDI-TOF mass spectrometry. Immunoassays were performed using the 5 allergic patients' sera tested individually and as a pool. RESULTS: Immunoblotting of the flaxseed extract revealed a low-molecular-mass protein (around 13 kDa) in 4 of the 5 patients, while a protein of approximately 55 kDa was detected in 2 patients. The proteins were identified by mass spectrometry as flaxseed 2S albumin, which is included in the WHO/IUIS allergen nomenclature as Lin u 1, and 11S globulin. Inhibition assays revealed in vitro IgE-mediated cross-reactivity between Lin u 1 and peanut and cashew nut proteins, while IgE-mediated recognition of 11S globulin by patients' sera was partially inhibited by several plant-derived sources. CONCLUSIONS: Seed storage proteins from flaxseed were involved in the development of severe symptoms in the 5 patients studied and exhibited cross-reactivity with other allergenic sources. Besides the severity of flaxseed allergy in patients sensitized to 2S albumin, this is the first time that 11S globulin has been identified as a potential allergen. Taking these data into account should ensure a more accurate diagnosis.

Predictors of health-related quality of life of European food-allergic patients.

BACKGROUND: Although food allergy has universally been found to impair HRQL, studies have found significant differences in HRQL between countries, even when corrected for differences in perceived disease severity. However, little is known about factors other than disease severity which may contribute to HRQL in food-allergic patients. Therefore, the aim of this study was to identify factors which may predict HRQL of food-allergic patients and also to investigate the specific impact of having experienced anaphylaxis and being prescribed an EAI on HRQL. METHODS: A total of 648 European food-allergic patients (404 adults, 244 children) completed an age-specific questionnaire package including descriptive questions. Multivariable regression analyses were performed to develop models for predicting HRQL of these patients. RESULTS: For adults, the prediction model accounted for 62% of the variance in HRQL and included perceived disease severity, type of symptoms, having a fish or milk allergy, and gender. For children, the prediction model accounted for 28% of the variance in HRQL and included perceived disease severity, having a peanut or soy allergy, and country of origin. For both adults and children, neither experiencing anaphylaxis nor being prescribed an epinephrine auto-injector (EAI) contributed to impairment of HRQL. CONCLUSIONS: In this study, food allergy-related HRQL may be predicted to a greater extent in adults than in children. Allergy to certain foods may cause greater HRQL impairment than others. Country of origin may affect HRQL, at least in children. Experiencing anaphylaxis or being prescribed an EAI has no impact on HRQL in either adults or children.

The EuroPrevall outpatient clinic study on food allergy: background and methodology.

BACKGROUND: The EuroPrevall project aimed to develop effective management strategies in food allergy through a suite of interconnected studies and a multidisciplinary integrated approach. To address some of the gaps in food allergy diagnosis, allergen risk management and socio-economic impact and to complement the EuroPrevall population-based surveys, a cross-sectional study in 12 outpatient clinics across Europe was conducted. We describe the study protocol. METHODS: Patients referred for immediate food adverse reactions underwent a consistent and standardized allergy work-up that comprised collection of medical history; assessment of sensitization to 24 foods, 14 inhalant allergens and 55 allergenic molecules; and confirmation of clinical reactivity and food thresholds by standardized double-blind placebo-controlled food challenges (DBPCFCs) to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple and peach. RESULTS: A standardized methodology for a comprehensive evaluation of food allergy was developed and implemented in 12 outpatient clinics across Europe. A total of 2121 patients (22.6% <14 years) reporting 8257 reactions to foods were studied, and 516 DBPCFCs were performed. CONCLUSIONS: This is the largest multicentre European case series in food allergy, in which subjects underwent a comprehensive, uniform and standardized evaluation including DBPCFC, by a methodology which is made available for further studies in food allergy. The analysis of this population will provide information on the different phenotypes of food allergy across Europe, will allow to validate novel in vitro diagnostic tests, to establish threshold values for major allergenic foods and to analyse the socio-economic impact of food allergy.

The impact of double-blind placebo- controlled food challenge (DBPCFC) on the socioeconomic cost of food allergy in Europe.

BACKGROUND: Double-blind placebo controlled food challenge (DBPCFC) is the gold standard diagnostic test in food allergy because it minimizes diagnostic bias. OBJECTIVE: To investigate the potential effect of diagnosis on the socioeconomic costs of food allergy. METHODS: A prospective longitudinal cost analysis study was conducted in Spain and Poland within the EuroPrevall project. Food-allergic patients were enrolled into the study and in all cases diagnosis was confirmed through a standardized DBPCFC. Data were collected through a self-administered survey on all aspects of health and social care resource use, costs of living, and costs of leisure activities. Costs were measured before and 6 months after the DBPCFC and reported in international dollars with 2007 as the benchmark year. RESULTS: Forty-two patients were enrolled. Twenty-one patients had a negative DBPCFC and the suspected food was reintroduced into their diet. Comparing total direct costs before and after the DBPCFC, the reactive group spent a significantly higher amount (median increase of $813.1 over baseline), while the tolerant group's spending decreased by a median of $87.3 (P = .031). The amount of money spent on food 6 months after diagnosis was also significantly higher in the reactive group (P = .040). Finally, a larger, but not statistically significant, decrease in total indirect costs was observed in the tolerant group compared with the reactive group ($538.3 vs $32.3). CONCLUSION: DBPCFC has an impact on indirect and direct costs of living. The main contribution to this increase was money spent on food.

Clinical-haematological changes and predictors of severity in acute food protein-induced enterocolitis syndrome reactions at oral food challenge: a multicentre observational study.

BACKGROUND: Oral food challenge (OFC) is the gold standard for diagnosis of acute Food Protein-Induced Enterocolitis Syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-haematological changes and predictors of severity of FPIES reactions at OFC. METHODS: Observational multicentre prospective study. Children aged 0-18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centres in Spain and Italy. OFC Outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed based on published '2017 FPIES Consensus' criteria. Clinical characteristics were recorded, and full blood count was done at baseline, reaction onset and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: 81 children had positive OFC (mild in 11% (9/81), moderate in 61% (49/81), severe in 28% (23/81)). Increase in neutrophils and reduction in eosinophils, basophils and lymphocytes was observed (P-value<0.05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not gender, age, culprit food, cumulative dose and previous reaction severity) was associated with reduced odds of severe reaction compared to giving multiple doses in a single day. CONCLUSION: Distinct haematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may associate a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Expression levels of parvalbumins determine allergenicity of fish species.

BACKGROUND: Parvalbumins are the most important fish allergens. Polysensitization to various fish species is frequently reported and linked to the cross-reactivity of their parvalbumins. Studies on cross-reactivity and its association to the allergenicity of purified natural parvalbumins from different fish species are still lacking. In addition, some studies indicate that dark muscled fish such as tuna are less allergenic. METHODS: Total protein extracts and purified parvalbumins from cod, whiff, and swordfish, all eaten frequently in Spain, were tested for their IgE-binding properties with 16 fish allergic patients' sera from Madrid. The extent of cross-reactivity of these parvalbumins was investigated by IgE ELISA inhibition assays. Additionally, the cDNA sequences of whiff and swordfish parvalbumins were determined. RESULTS: Extractable amounts of parvalbumins from cod were 20 times and from whiff 30 times higher than from swordfish. Parvalbumins were recognized by 94% of the patients in extracts of cod and whiff, but only by 60% in swordfish extracts. Nevertheless, a high cross-reactivity was determined for all purified parvalbumins by IgE inhibition. The amino acid sequence identities of the three parvalbumins were in a range of 62-74%. CONCLUSIONS: The parvalbumins of cod, whiff and swordfish are highly cross-reactive. The high amino acid sequence identity among cod, whiff and swordfish parvalbumins results in the observed IgE cross-reactivity. The low allergenicity of swordfish is due to the low expression levels of its parvalbumin.

[Tolerance to celecoxib and meloxicam in patients with intolerance to nonsteroidal anti-inflammatory drugs]. / Tolerancia a celecoxib y meloxicam en pacientes con intolerancia a analgésicos no esteroideos.

INTRODUCTION: Hypersensitive reactions to analgesics in the general population are less than 1%. Previous studies have demonstrated that cyclooxigenase 2 (COX-2) inhibitors are an efficient alternative in patients with non-steroidal anti-inflammatory drugs (NSAIDs) intolerance. The aim of our study is to test the tolerance to celecoxib and meloxicam in patients with NSAIDs intolerance, upto dosages higher than those used in previous studies. MATERIAL AND METHODS: The subjects of the study were 38 NSAID-sensitive patients from September 2004 to June 2005. The diagnosis of intolerance to NSAIDs was carried out by means of single-blind placebo-controlled oral challenge with aspirin. We performed single-blind placebo controlled oral challenge tests with celecoxib (accumulated dose of 400 mg) and meloxicam (accumulated dose of 15 mg). RESULTS: There was only one reaction with celecoxib (97.3%) which was generalised urticaria after the dose of 400 mg accumulated, it should be pointed out that this patient tolerated perfectly the dose of 200 mg. For meloxicam, we found 100% tolerance at a dosage of 15 mg, including the patient who showed a reaction to the celecoxib. CONCLUSION: We consider that there are patients with tolerance to low dosages of COX-2 inhibitors who show a reaction on increasing the administered dosage, which means that their tolerance should be taken into account and checked in the long term.

[Anaphylaxis after carrying out prick tests]. / Anafilaxia tras realización de pruebas cutáneas en prick.

The skin prick test (SPT) is a simple and fast method used routinely in allergology practice. Systemic reactions have been described with this technique on few occasions. We are presenting a case of anaphylaxis with hemodynamic consequences after carrying out skin prick test with a cat dander extract. A 23 years old female who suffered rhinoconjunctivitis and asthma following contact with cats. We performed skin prick test with a battery of the usual inhalants. Twenty minutes after carrying out the prick test the patient showed intense ocular irritation and reddening followed by dysphonia and a feeling of pharyngeal occupation. Although skin prick test is a safe diagnostic approach, it should be performed only in places equipped to treat anaphylaxis and for trained specialists .

Association Between the Seed Storage Proteins 2S Albumin and 11S Globulin and Severe Allergic Reaction After Flaxseed Intake

Background: Given the increased popularity of flaxseed in meals, several cases of allergy to these seeds have been reported. Little is known about the allergens implicated in hypersensitivity reactions to flaxseed. The present study aimed to identify the allergens involved in IgE-mediated reactions in 5 patients with a clinical history of severe systemic symptoms after flaxseed consumption. Methods: Proteins that were potential allergens with IgE-binding capacity were purified from flaxseed extract using chromatography and identified via MALDI-TOF mass spectrometry. Immunoassays were performed using the 5 allergic patients’ sera tested individually and as a pool. Results: Immunoblotting of the flaxseed extract revealed a low-molecular-mass protein (around 13 kDa) in 4 of the 5 patients, while a protein of approximately 55 kDa was detected in 2 patients. The proteins were identified by mass spectrometry as flaxseed 2S albumin, which is included in the WHO/IUIS allergen nomenclature as Lin u 1, and 11S globulin. Inhibition assays revealed in vitro IgE-mediated cross-reactivity between Lin u 1 and peanut and cashew nut proteins, while IgE-mediated recognition of 11S globulin by patients’ sera was partially inhibited by several plant-derived sources. Conclusions: Seed storage proteins from flaxseed were involved in the development of severe symptoms in the 5 patients studied and exhibited cross-reactivity with other allergenic sources. Besides the severity of flaxseed allergy in patients sensitized to 2S albumin, this is the first time that 11S globulin has been identified as a potential allergen. Taking these data into account should ensure a more accurate diagnosis. (AU)

Antecedentes: Dada la creciente popularidad de la linaza en las comidas, se han notificado varios casos de alergia a estas semillas. La información acerca de los alérgenos implicados en las reacciones de hipersensibilidad a estas semillas es escasa. El presente trabajo pretende identificar los alérgenos implicados en las reacciones mediadas por IgE en cinco pacientes con una historia clínica de síntomas sistémicos graves tras el consumo de linaza. Métodos: Las proteínas susceptibles de ser alérgenos con capacidad de unir IgE se purificaron a partir del extracto de linaza mediante técnicas cromatográficas. Su identificación se realizó mediante espectrometría de masas MALDI-TOF. Se realizaron inmunoensayos con los sueros de los cinco pacientes alérgicos, utilizados de forma individual o como mezclas. Resultados: Cuatro de los cinco pacientes reconocieron una proteína de baja masa molecular (alrededor de 13 kDa) en inmunoensayos con extracto de linaza, mientras que dos pacientes reconocieron una proteína de aproximadamente 55 kDa. Se identificaron por espectrometría de masas como albúmina 2S de linaza, incluida en la nomenclatura de alérgenos de la OMS/IUIS como Lin u 1, y globulina 11S, respectivamente. Los ensayos de inhibición in vitro revelaron la existencia de reactividad cruzada de la Lin u 1 con las proteínas del cacahuete y del anacardo, mientras que el reconocimiento por parte de la IgE de la globulina 11S por parte de los sueros de los pacientes fue parcialmente inhibido por varias fuentes vegetales. Conclusiones: Las proteínas de almacenamiento de las semillas de lino estaban implicadas en el desarrollo de síntomas graves en cinco individuos y mostraron una reactividad cruzada con otras fuentes alergénicas. Además de la gravedad de la alergia a la linaza en los pacientes sensibilizados a la albúmina 2S, es la primera vez que se identifica la globulina 11S como un alérgeno potencial.

Fixed exanthema from systemic tobramycin.

Eye drops contain several ophthalmic medications which can produce allergic reactions. We report the case of a patient with contact dermatitis from neomycin and a probable fixed exanthema after parenteral administration of tobramycin who tolerated topical tobramycin and other aminoglycosides.

Usefulness of omalizumab in rapid drug desensitization in patients with severe anaphylaxis induced by carboplatin: open questions

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