RESUMO
El tratamiento de la alergia a las proteínas de la leche de vaca se basa en la eliminación completa de las proteínas de leche de vaca de la dieta del niño y de la madre en los que reciben leche materna. Para lograr la remisión de los síntomas y la tolerancia futura, la exclusión debe ser total. En los niños que reciben fórmula, esta deberá tener hidrolizado extenso de proteínas en las formas leves o moderadas, mientras que aquellas a base de aminoácidos se reservan para los casos más graves. El tiempo de tratamiento, la adquisición de tolerancia y el momento para la prueba de provocación oral van a variar según el cuadro clínico, el mecanismo inmunológico implicado y la edad del paciente. El objetivo de este consenso ha sido reflejar el conocimiento actualizado junto con la experiencia de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología.
The treatment of cow's milk protein allergy is based on the complete elimination of cow's milk protein from the diet. To achieve remission of symptoms and future tolerance, exclusion must be total. In formula fed infants the extensively hydrolysed formula is the most appropriate option in mild or moderate forms, while those based on amino acids are reserved for the most severe cases. The treatment time, the acquisition of tolerance and the moment for the oral provocation test will vary according to the clinical picture, the immunological mechanism involved and the age of the patient. The aim of this consensus has been to reflect the updated knowledge together with the experience of neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology
Assuntos
Humanos , Lactente , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapiaRESUMO
Las proteínas de la leche de vaca pueden causar alergia alimentaria. Los distintos mecanismos de acción involucrados y la variabilidad clínica según la etapa de la vida pediátrica en la que se manifieste ocasionan dificultades en su abordaje, con riesgo de sub- o sobrediagnóstico. En este proceso, intervienen profesionales de diversas áreas y es recomendable su interacción. Es por ello que el objetivo de este consenso ha sido reflejar el conocimiento actualizado desde la interdisciplina, generando recomendaciones para su correcto diagnóstico. Hemos trabajado con el método de Delphi para sumarle a la evidencia científica, la experiencia proveniente de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología. Pensamos que este enfoque interdisciplinario de trabajo va a resultar de utilidad práctica y promoverá una atención más integral de estos pacientes.
Cow's milk protein can cause food allergy. The different mechanisms of action involved, the clinical variability depending on the stage of pediatric life in which it manifests, leads to difficulties in its approach, with the risk of under- or over-diagnosis. Professionals from various areas intervene in this process and their interaction is recommended. That is why the objective of this consensus has been to reflect the updated knowledge in an interdisciplinary mode, generating recommendations for its correct diagnosis. We have worked with the Delphi method to add to the scientific evidence, the experience from neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology. We think that this interdisciplinary approach will be of practical use and will promote more comprehensive care for these patients.
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Hipersensibilidade a Leite/diagnóstico , Técnica Delphi , ConsensoRESUMO
Introduction: Aeroallergen exposure has an intra- and extra-domiciliary component and varies according to climatological zones. Mexico is a large country with a great variety of climates. A previous study (2009) evaluated skin prick test results (SPT) in different regions. In this study, we compare previous sensitization patterns from 14y ago with current ones and compare them between different climatological zones. Methods: Mexican allergists were asked to share their last 100 SPT results in patients with respiratory allergy. Clinics were grouped in (semi)humid vs (semi)dry zones. Results were analyzed nationwide and compared to the 2009 results, calculating odds ratio (OR) and 95% confidence intervals (95% CIs), with p <0.05 as cut-off. Similarly, we compared (semi)humid versus dry zones. Results: We collected 2915 SPT results from 28 clinics (19 cities). Dermatophagoides was the most frequently sensitizing allergen. There was a significant increase in SPT positivity from 2009 to 2023 in both in- and outdoor aeroallergens (OR 1.26-2.65, 95% CI from 1.06-1.50 to 1.99-3.52). Comparing dry-humid zones, sensitization to pollen from Oleaceae, Fagaceae (p < 0.0001 all) and most weeds is more frequent in humid zones, as are Dermatophagoides and cockroach (both p < 0.0001). Eucalyptus, mesquite, and all grass pollen sensitizations predominate in dry zones (p < 0.05-0.0001). There are no differences in sensitization to cat or dog between zones. Conclusion: We found a general increase in SPT sensitization over the past fourteen years, suggesting that this is probably not only due to climate change. The different sensitization profile throughout the country was mainly related to humidity. Repeating epidemiologic SPT studies over the years could help tracking changes in allergen sensitization over time.
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INTRODUCTION: Egg allergy usually manifests during the initial 2 years of life, a period in which most vaccinations are administered. This often leads to delays in the application of some vaccines in patients with egg allergies, exposing them to a risk of contracting preventable infections. The aim of the study was to describe the frequency of reactions after applying the yellow fever vaccine (YFV) within a population with egg allergy. METHODS: This was a cohort study with retrospective, multicenter data (2014-2023). Patient records diagnosed with egg allergy were gathered from their initial egg-related reactions until their YFV administration. Information was also collected about hypersensitivity tests conducted for egg and YFV such as the skin prick test (SPT) and intradermal test (IDT). RESULTS: Among the 171 records analyzed, 23.9% of patients had a history of egg anaphylaxis. Out of these, 5 patients had a positive SPT and 21 IDT with the YFV. All patients tolerated the application of YFV without developing hypersensitivity reactions, regardless of the results of the YFV tests, the severity of egg reactions, the number of egg reactions, or the time since the last egg reaction. Out of the total patient cohort, 46.1% (79 individuals) encountered delays in receiving the YFV, and in this subset, 14% faced delays lasting longer than 12 months. CONCLUSION: The risk of allergic reactions with the YFV remains low. YFV tests generate delays in the vaccine application without providing high diagnostic accuracy. YFV should not be deferred even in patients with a history of severe egg reactions.
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The ability of organophosphate pesticides to disturb immune function has been demonstrated by in vivo and in vitro studies, but evidence of such effects on humans remains scarce. To assess the association between organophosphate pesticides exposure and cytokine levels in Mexican flower workers, a cross-sectional study was carried out. A questionnaire was provided to 121 male flower workers, and urine and blood samples were collected. Using gas chromatography, urinary concentrations of dialkylphosphate metabolites were determined. The serum cytokine levels, IL-4, IL-5, IL-6, IL-8, and IL-10, were measured using multiplex analysis, and levels of INF-γ and TNF-α by ELISA. We found that a higher dialkylphosphate concentration decreased the pro-inflammatory cytokines INF-γ (ß = -0.63; 95â¯% CI: -1.22, -0.05), TNF-α (ß= -1.18; 95â¯% CI: -2.38, 0.02), and IL-6 (ß= -0.59; 95â¯% CI: -1.29, 0.12), and increased IL-10 (ß=0.56; 95â¯% CI: 0.02, 1.09), the main anti-inflammatory cytokine, suggesting an imbalance of the immune response in flower workers.
Assuntos
Citocinas , Exposição Ocupacional , Praguicidas , Humanos , México , Masculino , Exposição Ocupacional/análise , Adulto , Citocinas/sangue , Praguicidas/urina , Praguicidas/sangue , Praguicidas/toxicidade , Pessoa de Meia-Idade , Estudos Transversais , Flores , Adulto Jovem , Compostos Organofosforados/urina , Organofosfatos/urina , Organofosfatos/sangueRESUMO
OBJECTIVE: To characterize the awareness of, adherence to, and barriers to the 2017 National Institute of Allergy and Infectious Diseases (NIAID) peanut allergy prevention guidelines among the pediatrics health care workforce. STUDY DESIGN: Pediatricians, family physicians, advanced practice providers (APPs), and dermatologists who provide care for infants were solicited for a population-based online survey, administered from June 6, 2022, through July 3, 2022. The survey collected information about NIAID guideline awareness, implementation, and barriers as well as concerns related to the guidelines. RESULTS: A total of 250 pediatricians, 250 family physicians, 504 APPs, and 253 dermatologists met inclusion criteria. Self-reported guideline awareness was significantly higher for pediatricians (76%) compared with dermatologists (58%), family physicians (52%), and APPs (45%) (P < .05). Among participants who were aware of the guidelines, most reported using part or all of the guidelines in their clinical practices. Reported practice patterns for peanut introduction in 6-month-old infants were variable and did not always align with guidelines, particularly for infants with mild-to-moderate atopic dermatitis. CONCLUSIONS: Although pediatricians have the highest self-reported level of NIAID guideline awareness, awareness was suboptimal irrespective of provider type. Education for all pediatric clinicians is urgently needed to promote evidence-based peanut allergy prevention practices.
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BACKGROUND AND OBJECTIVE: Sensitization to Blomia tropicalis is associated with asthma in various tropical and subtropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. RESULTS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. CONCLUSION: Although Blo t 5 and Blo t 21 are considered common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for diagnosis of allergy in the tropics.
Assuntos
Alérgenos , Asma , Imunoglobulina E , Humanos , Asma/imunologia , Asma/diagnóstico , Asma/epidemiologia , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Adulto , Masculino , Feminino , Estudos de Casos e Controles , Criança , Adolescente , Colômbia/epidemiologia , Alérgenos/imunologia , Adulto Jovem , Pessoa de Meia-Idade , Antígenos de Plantas/imunologia , Reações Cruzadas , Clima Tropical , Prevalência , Pré-EscolarRESUMO
The treatment of cow's milk protein allergy is based on the complete elimination of cow's milk protein from the diet. To achieve remission of symptoms and future tolerance, exclusion must be total. In formula fed infants the extensively hydrolysed formula is the most appropriate option in mild or moderate forms, while those based on amino acids are reserved for the most severe cases. The treatment time, the acquisition of tolerance and the moment for the oral provocation test will vary according to the clinical picture, the immunological mechanism involved and the age of the patient. The aim of this consensus has been to reflect the updated knowledge together with the experience of neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology.
El tratamiento de la alergia a las proteínas de la leche de vaca se basa en la eliminación completa de las proteínas de leche de vaca de la dieta del niño y de la madre en los que reciben leche materna. Para lograr la remisión de los síntomas y la tolerancia futura, la exclusión debe ser total. En los niños que reciben fórmula, esta deberá tener hidrolizado extenso de proteínas en las formas leves o moderadas, mientras que aquellas a base de aminoácidos se reservan para los casos más graves. El tiempo de tratamiento, la adquisición de tolerancia y el momento para la prueba de provocación oral van a variar según el cuadro clínico, el mecanismo inmunológico implicado y la edad del paciente. El objetivo de este consenso ha sido reflejar el conocimiento actualizado junto con la experiencia de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología.
Assuntos
Hipersensibilidade a Leite , Hipersensibilidade a Leite/terapia , Hipersensibilidade a Leite/diagnóstico , Humanos , LactenteRESUMO
Cow's milk protein can cause food allergy. The different mechanisms of action involved, the clinical variability depending on the stage of pediatric life in which it manifests, leads to difficulties in its approach, with the risk of under- or over-diagnosis. Professionals from various areas intervene in this process and their interaction is recommended. That is why the objective of this consensus has been to reflect the updated knowledge in an interdisciplinary mode, generating recommendations for its correct diagnosis. We have worked with the Delphi method to add to the scientific evidence, the experience from neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology. We think that this interdisciplinary approach will be of practical use and will promote more comprehensive care for these patients.
Las proteínas de la leche de vaca pueden causar alergia alimentaria. Los distintos mecanismos de acción involucrados y la variabilidad clínica según la etapa de la vida pediátrica en la que se manifieste ocasionan dificultades en su abordaje, con riesgo de sub- o sobrediagnóstico. En este proceso, intervienen profesionales de diversas áreas y es recomendable su interacción. Es por ello que el objetivo de este consenso ha sido reflejar el conocimiento actualizado desde la interdisciplina, generando recomendaciones para su correcto diagnóstico. Hemos trabajado con el método de Delphi para sumarle a la evidencia científica, la experiencia proveniente de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología. Pensamos que este enfoque interdisciplinario de trabajo va a resultar de utilidad práctica y promoverá una atención más integral de estos pacientes.
Assuntos
Hipersensibilidade a Leite , Criança , Humanos , Lactente , Recém-Nascido , Consenso , Técnica Delphi , Hipersensibilidade a Leite/diagnósticoRESUMO
BACKGROUND: Sublingual immunotherapy (SLIT) using food extracts is safe and effective in desensitizing patients with food allergy, yet not often used in clinical practice. OBJECTIVES: To propose a cost-effective, expedited SLIT protocol using real food. METHODS: Patients with food allergy aged 5 to 50 years (median, 11 years) initiated food SLIT in a single-clinic setting. The daily maintenance dose was 4 to 11 mg protein in 0.1 to 0.5 mL volume, depending on the food. Some foods were available in liquid form at the local grocery (milk, egg white liquid, and cashew/walnut/sunflower/hazelnut milk), whereas others were prepared in the office using flour and 50% glycerin saline (peanut/sesame/wheat). The first cohort of 20 patients began dosing at a 1:1000 dilution, the next 30 patients at 1:100 dilution. An exercise challenge was performed in a subset of patients on maintenance dosing to evaluate the need for a predose or postdose rest period. RESULTS: The 1:1000 and 1:100 cohorts both completed day 1 without adverse reactions beyond itchy mouth. There were no systemic reactions requiring epinephrine throughout the study period and 88% reached their maintenance dose. Skin testing of 6-month-old peanut flour solution was not diminished from fresh solution and similar to food extract. Exercise challenge test results in 12 patients were negative. CONCLUSIONS: Allergen extract food SLIT as used in published trials has limitations of cost and multiple office visits. Inexpensive real food, at the same or slightly higher protein dose, was well tolerated in 4 updose visits, a minimum of a week apart. Unlike food oral immunotherapy, a predose or postdose rest period may not be necessary.
Assuntos
Alérgenos , Hipersensibilidade Alimentar , Imunoterapia Sublingual , Humanos , Imunoterapia Sublingual/métodos , Imunoterapia Sublingual/efeitos adversos , Criança , Adulto , Adolescente , Pré-Escolar , Pessoa de Meia-Idade , Feminino , Masculino , Hipersensibilidade Alimentar/terapia , Alérgenos/administração & dosagem , Alérgenos/imunologia , Adulto Jovem , Alimentos/efeitos adversosRESUMO
Progesterone is an endogenous hormone, produced by the adrenal cortex, the gonads and in women, its source is the corpus luteum. Progesterone is produced in the late phase of the menstrual cycle, when implantation of the zygote does not occur, the corpus luteum involutes and the release of progesterone is suppressed, thus initiating menstruation. Progestogen Hypersensitivity were initially identified as hormone allergy and were related to endogenous reactions to hormones and alteration of ovarian function. Skin manifestations such as dermatitis or urticaria were initially reported and described as progesterone autoimmune dermatitis, although the immune-mediated mechanism was not clear. Currently there is no standardization for in vivo or in vitro tests for Progestogen Hypersensitivity diagnosis. In this review, we will address the different diagnostic methods of this disease.
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INTRODUCTION AND OBJECTIVES: Food allergy has several negative nutritional consequences and may persist beyond the first year of lives. This study aimed to assess the role of a complete oral amino acid-based supplement in the diet of children on cow's milk protein elimination diet because of food allergy. MATERIALS AND METHODS: This study included two groups of children aged 1-5 years paired by age and socioeconomic status: (1) study group, on cow's milk protein elimination diet plus an oral amino acid-based supplement, and (2) control group, on cow's milk protein elimination diet. Sociodemographic, clinical, anthropometric, and dietary data were obtained through online interviews. Two 24-h dietary recalls were collected on nonconsecutive days. Both groups comprised mostly boys. RESULTS: The study group presented lower values of body mass index. The frequency of feeding difficulties was similar between groups. The study group had a higher intake of energy, protein, carbohydrates, calcium, iron, zinc, phosphorus, magnesium, copper, selenium, vitamins D, E, B1, B2, B6, and B12, niacin, and folic acid compared to the control group. A higher proportion of children in the study group had adequate intake according to the recommendations made for energy, carbohydrates, iron, phosphorus, selenium, vitamins A, D, E, B1, B2, and B6, and folic acid. CONCLUSIONS: The use of a complete oral amino acid-based supplement has a positive effect on the diet quality of preschoolers on cow's milk elimination diet because of food allergy, promoting higher intake of energy, calcium, vitamin D, and other essential nutrients.
Assuntos
Aminoácidos , Suplementos Nutricionais , Hipersensibilidade a Leite , Animais , Bovinos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Aminoácidos/administração & dosagem , Estudos Transversais , Dieta de Eliminação , Leite/imunologia , Proteínas do Leite/administração & dosagem , Proteínas do Leite/imunologiaRESUMO
Introdução: As quinolonas, amplamente usadas na prática clínica, correspondem à segunda causa de reações de hipersensibilidade aos antibióticos. Reações às quinolonas (RQ) são um desafio para o alergista, pois ocorrem por mecanismos IgE mediados, mas também por uma via não imunológica, o receptor MRGPRX2. Objetivo: Este trabalho avalia a reatividade cutânea de pessoas sem alergia ao ciprofloxacino em diversas concentrações. Metodologia: Foram realizados prick tests (PT) e testes intradérmicos de leitura imediata (ID) com ciprofloxacino em voluntários atendidos em um ambulatório de serviço terciário. No PT, foram usadas concentrações de 2 mg/mL (solução mãe), 1:10 e 1:50. No ID, 1:10, 1:50, 1:100 e 1:500. Resultados: Foram incluídos 31 indivíduos sem histórico de RQ. A média de idade foi de 40,5 anos, sendo 74,1% do gênero feminino. Doenças atópicas foram encontradas em 48,4% dos participantes, 100% destes com rinite alérgica, 20% com conjuntivite alérgica, 13,3% com asma, e 13,3% com dermatite atópica. Uso prévio de quinolonas foi relatado por 45,2% dos indivíduos. O PT puro e 1:10 foi positivo em 25,8% e 6,5%, respectivamente; na concentração 1:50 não mostrou positividade. O ID 1:10, 1:50 e 1:100 foi positivo em 96,8%, 45,2% e 6,5%, respectivamente, mas foi negativo na diluição 1:500. Nos que já usaram quinolonas, o PT puro e 1:50 foram positivos em 28,6% e 14,3% dos participantes, respectivamente, versus 25% e 0% nos que não usaram. O ID entre os indivíduos que já usaram foi positivo em 100% na diluição 1:10, 57,1% na 1:50, e 14,3% na 1:100. Entre os que não usaram, 93,7% na diluição 1:10, 37,6% na 1:50, e 0% na 1:100. Nos atópicos, o PT foi positivo em 26,7% e 13,3% na concentração mãe e 1:10; e negativo em 1:50. Nos participantes não atópicos, observou-se positividade de 25% no PT com a solução mãe e testes negativos nas demais diluições. O ID com as soluções 1:10, 1:50 e 1:100 foi positivo em 100%, 46,7% e 6,7% dos atópicos, e 93,7%, 43,7%, 6,3% nos não atópicos, respectivamente. Conclusão: O ciprofloxacino apresenta reatividade cutânea através de vias imunológicas e pelo MRGPRX2, sendo recomendada a realização de testes cutâneos em concentrações igual ou menores de 0,02 mg/ mL para investigação de reações de hipersensibilidade imediata, pois essas concentrações apresentam boa especificidade.
Introduction: Quinolones, widely used in clinical practice, are the second leading cause of antibiotic hypersensitivity. Hypersensitivity to quinolone poses a challenge for allergists, as it occurs through immunoglobulin E (IgE)-mediated mechanisms as well as nonimmunologic ones (specifically the MRGPRX2 receptor). Objective: To assess cutaneous hypersensitivity to ciprofloxacin at different concentrations. Methodology: Skin prick test (SPT) and immediate-reading intradermal test (IDT) with ciprofloxacin were performed on volunteers treated at a tertiary outpatient clinic. Concentrations of 2 mg/mL (main solution), 1:10, and 1:50 were used for the SPT, and concentrations of 1:10, 1:50, 1:100, and 1:500 were used for the IDT. Results: Thirty-one individuals with no history of hypersensitivity to quinolone were included, of whom 74.1% were women. Mean patient age was 40.5 years. Atopic diseases were found in 48.4% of participants, of whom 100% had allergic rhinitis, 20% had allergic conjunctivitis, 13.3% had asthma, and 13.3% had atopic dermatitis. Previous quinolone use was reported by 45.2%. SPT performed with the main solution and 1:10 dilution was positive in 25.8% and 6.5% of cases, respectively, whereas SPT with 1:50 dilution was negative in all cases. IDT performed with 1:10, 1:50, and 1:100 dilutions was positive in 96.8%, 45.2%, and 6.5% of cases, respectively, but negative with 1:500. Among the individuals who had used quinolones, SPT with main solution and 1:50 dilution was positive in 28.6% and 14.3% of cases, respectively, compared with 25% and 0% in those who had not used quinolones. Among those who had used quinolones, IDT results were positive in 100% at 1:10, 57.1% at 1:50, and 14.3% at 1:100. Among those who had not used quinolones, IDT results were positive in 93.7% at 1:10, 37.6% at 1:50, and 0% at 1:100. In atopic individuals, SPT was positive in 26.7% with the main solution and 1:10 dilution, and negative with 1:50. Among nonatopic individuals, 25% had a positive SPT with the main solution, and the remaining individuals were negative. IDT results with 1:10, 1:50, and 1:100 dilutions were positive, respectively, in 100%, 46.7%, and 6.7% of atopic individuals and in 93.7%, 43.7%, and 6.3% of nonatopic individuals. Conclusion: Ciprofloxacin triggers cutaneous hypersensitivity via immunologic mechanisms and the MRGPRX2 receptor. It is recommended that skin tests be performed at a dilution of 1:100 or greater to investigate immediate hypersensitivity.
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Humanos , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Introdução: A dermatite de contato alérgica (DCA) corresponde a 20% dos casos de dermatite de contato, sendo recorrente em doenças ocupacionais e causa frequente de procura por profissionais dermatologistas e alergistas. Objetivo: Identificar os principais agentes sensibilizantes na dermatite de contato alérgica em um centro especializado em alergia do oeste de Santa Catarina. Metodologia: Trata-se de um estudo do tipo retrospectivo, descritivo, quantitativo e observacional, no qual se realizou a análise por meio de prontuários médicos de 394 pacientes que realizaram o teste de contato por dermatite de contato alérgica no período de 2018 a julho de 2020 no serviço de referência do oeste de Santa Catarina. Os agentes sensibilizantes avaliados no teste de contato foram conforme as baterias padrão (bateria padrão brasileira, bateria de cosméticos e higiene e bateria regional da América Latina). Foram realizadas análises de frequência para as variáveis qualitativas e avaliação da prevalência dos principais agentes sensibilizantes. Além disso, foram relacionados os principais agentes com as variáveis sexo e idade por meio do teste de Qui-quadrado de Pearson. Resultados: Os agentes sensibilizantes mais prevalentes foram: níquel (33,5%), PPD mix (23,2%), perfume mix (22,4%), fragrância mix (22,0%) e cobalto (18,9%). As substâncias mais prevalentes foram o níquel e o PPD mix, que são agentes sensibilizantes usados amplamente no cotidiano dos pacientes. Conclusão: A identificação dos alérgenos através do patch test possibilita aos pacientes a oportunidade de amenizarem a DCA provocada pelos agentes sensibilizantes encontrados.
Introduction: Allergic contact dermatitis (ACD) corresponds to 20% of contact dermatitis cases, being the most common type of occupational skin disease and a common cause of consultation with a dermatologist or allergist. Objective: To identify the main sensitizing agents involved in ACD at a specialized allergy center in western Santa Catarina, a state in the south of Brazil. Methodology: This retrospective, descriptive, quantitative, and observational study involved the review of medical records of all patients who underwent patch testing for ACD from 2018 to July 2020 in the allergy center. The sensitizing agents evaluated in the patch test followed the standard patch series (including the standard Brazilian patch series, cosmetic series, and regional Latin America series). Frequency analyses were performed for qualitative variables and to assess the prevalence of the main sensitizing agents. In addition, the main agents were correlated with sex and age variables using Pearson's chi-square test. Results: The most prevalent sensitizing agents were nickel sulfate (33.5%), PPD mix (23.2%), perfume mix (22.4%), fragrance mix (22.0%), and cobalt chloride (18, 9%). The most prevalent substances were nickel sulfate and PPD mix, which are widely used in patients' daily lives. Conclusion: The identification of allergens via patch testing provides patients with an opportunity to reduce ACD caused by the sensitizing agents identified.
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Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: To report the Tipuana tipu pollen as a new allergen capable of triggering allergic symptoms. METHODS: The pollen counts were made according to standardized technique with a Burkard seven days following the European Aerobiology Society´s Network Group recommendations.1 The trap was installed on the roof of Clinica SANNA, El Golf, San Isidro, which is 20 m high, 12°5'54"S 77°3'6"W in the west-south of the Lima urban area. The sampling period was performed from September 2020 to October 2021. Collection of Tipuana tipu pollens and Preparation of Tipuana tipu pollen extracts 1:20 w/v was done using a previously described method.2 We carried out systematic skin prick testing with Tipuana tipu pollen extract and other aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis), molds (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, Penicillium notatum), cat and dog danders, Periplaneta americana, grass six mix, weed mix (Inmunotek, Spain) on 80 patients (18 to 50 years old) seen in our allergy center, they suffering from november to january rhinitis and/or conjunctivitis symptoms. The majority living near avenues and large green areas, where Tipuana trees grew. RESULTS: We found a total of 952 grains/m3 of Tipuana tipu pollen between November 2020 to january 2021, with the maximum concentration of 37 grains/m3 on December 10th. We also found other airborne pollen Types: Poaceae, Myrtaceae, Compositae and Betulaceae. 14/80 patients (17,5%) showed positive skin prick test only to Tipuana tipu extract. Most of the patients with positive tests to Tipuana extract presented symptoms of rhinoconjunctivitis during the Tipuana pollination period. Four patients showed positive skin prick test to Tipuana tipu and grass 6 mix extracts, most of the rest of our patients were sensitized to dust mites' extracts (Dermatophagoides pteronyssinus). CONCLUSIONS: The west-south population of Lima urban city is exposed to Tipuana tipu pollen. We do not foud previous publications about Tipuana tipu allergy. Almost 18% of the patients tested in our sample were mono-sensitized to this pollen. The results of this study should be compared with data from the forthcoming years, to identify seasonal and annual fluctuations, extend the traps to other locations in Lima, and of course try to standardize and improve the Tipuana tipu pollen extract.
OBJETIVO: Reportar al polen de Tipuana tipu como un nuevo alérgeno capaz de desencadenar síntomas alérgicos. MÉTODOS: Los conteos de polen se realizaron según la técnica estandarizada con un equipo colector tipo Hirst, Burkard spore trap for seven days, siguiendo las recomendaciones del grupo de la Red Europea de Sociedades de Aerobiología1. El equipo se instaló en la azotea de la Clínica SANNA El Golf, San Isidro, a 20 m de altura desde el nivel del suelo, 12°5'54"S 77°3'6"O en la zona suroeste del área urbana de Lima. El periodo de captación se llevó a cabo entre septiembre de 2020 y octubre de 2021. La recolección de granos de polen de Tipuana tipu, y la preparación del extracto alergénico (peso/volumen) 1:20 p/v, se realizó usando metodología previamente descrita2. Se realizaron estudios de pruebas cutáneas (skin prick test), en 80 pacientes (entre 18 y 50 años), con sintomatología de rinoconjuntivitis; referían, además, mayor intensidad de sus síntomas entre noviembre y enero. La mayoría de pacientes dijeron vivir cerca a avenidas y parques donde había árboles de Tipuana tipu. Fueron evaluados en el servicio de Alergología de la Clínica SANNA, El Golf, San Isidro. Se aplicaron extractos de polen de Tipuana tipu, y otros aeroalérgenos como ácaros del polvo (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis), hongos ambientales (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, Penicillium notatum), epitelios de gato y perro, Periplaneta americana, mezclas de seis gramíneas, mezclas de malezas (Inmunotek, España). RESULTADOS: Encontramos un total de 952 granos/m3 de polen de Tipuana tipu entre noviembre de 2020 y enero de 2021; con la máxima concentración de 37 granos/m3 el 10 de diciembre. También identificamos otras familias polínicas: Poaceae, Myrtaceae, Compositae y Betulaceae. 14/80 pacientes (el 17,5%), resultaron positivos solo al extracto de Tipuana tipu, en el skin prick test. La mayoría de los pacientes con resultado positivo al extracto de Tipuana tipu referían síntomas de rinoconjuntivitis durante el periodo de polinización de los árboles de Tipuana. Cuatro pacientes tuvieron positividad al extracto de Tipuana tipu, y al extracto en mezcla de seis gramíneas; la mayoría del resto de pacientes mostraron sensibilidad a ácaros del polvo doméstico (Dermatophagoides pteronyssinus). CONCLUSIONES: Los habitantes de la zona suroeste de la ciudad urbana de Lima están expuestos al polen de Tipuana tipu. No hemos encontrado publicaciones previas sobre alergia a este tipo de polen. Casi un 18% de pacientes estudiados en nuestra muestra, estuvieron monosensibilizados al extracto del polen de Tipuana tipu. Los resultados de este estudio deberían ampliarse y ser comparados con data en los años siguientes, identificar fluctuaciones estacionales y anuales, extender los captadores a otras locaciones en Lima, y por supuesto, intentar estandarizar y mejorar el extracto del polen de Tipuana Tipu.
Assuntos
Alérgenos , Pólen , Alérgenos/análise , Humanos , Pólen/imunologia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Peru , Adolescente , Adulto Jovem , Testes Cutâneos , Animais , Rinite Alérgica SazonalRESUMO
OBJECTIVE: The objective of the present study was to design a multi-epitope protein from A. lumbricoides and APD allergens and to evaluate its IgE reactivity preliminarily. METHODS: Using computational tools, a molecule containing multiple "T" epitopes of allergens derived from A. lumbricoides and APD was designed "in silico" This multi-epitope protein (MP1) was expressed using an E. coli system and purified by affinity chromatography using Ni-NTA agarose. Anti-MP1 and anti-HDM extract IgE reactivity was evaluated by Dot-Blot and indirect ELISA from sera of HDM-allergic patients and non-allergic individuals from Barranquilla-Colombia. Allergic individuals had a positive skin test to a standardized battery of inhaled allergens (EUROLINE - Ref: DP 3704-1601-1 E) and mite- specific IgE. RESULTS: Multi-epitope (MP1) protein was expressed and purified with high purity. Dot-Blot result showed that all sera from allergic patients showed lower IgE reactivity to MP1 compared to HDM extract. By ELISA, significantly lower concentrations of anti-MP1 IgE (Median: 270.86 ng/ml; IQR: 90.3) were observed in contrast to anti-HDM IgE levels (Median: 988.5 ng/ml; IQR: 1117.6) in sera of patients allergic to HDM. CONCLUSIONS: A protein composed of multiple epitopes of A. lumbricoides and HDM allergens was designed, expressed, and purified. Preliminary Dot-Blot results suggest that this molecule shows hypoallergenic properties with very low IgE reactivity compared to mite extract. Further functional studies are needed to understand better the immune response induced by this molecule.
OBJETIVO: Diseñar una proteína multiepítope a partir de alérgenos de A. lumbricoides y APD; y evaluar preliminarmente su reactividad IgE. MÉTODOS: Mediante herramientas computacionales se diseñó In Silico, una molécula que contiene múltiples epítopos T, de alérgenos derivados de A. lumbricoides y APD. Esta proteína multiepítope (MP1) se expresó utilizando un sistema de E. coli, y se purificó mediante cromatografía de afinidad, empleando agarosa Ni-NTA. La reactividad IgE anti-MP1 y anti-extracto de APD, se evaluó mediante Dot-Blot y ELISA indirecta, a partir de suero de pacientes alérgicos a APD, e individuos no alérgicos procedentes de Barranquilla, Colombia. Los individuos alérgicos contaron con prueba cutánea positiva a una batería estandarizada de alérgenos inhalados (EUROLINE - Ref: DP 3704-1601-1 E) e IgE específica para ácaros. RESULTADOS: La proteína multiepítope MP1 se expresó y purificó con alta pureza. El resultado del Dot-Blot, mostró que todos los sueros de pacientes alérgicos tuvieron una reactividad IgE menor a MP1 en comparación al extracto de APD. Por ELISA, se observaron concentraciones significativamente menores de IgE anti-MP1 (Mediana: 270,86 ng/ml; RIQ: 90,3), en contraste a los niveles de IgE anti-APD (Mediana: 988,5 ng/ml; RIQ: 1117,6), en suero de pacientes alérgicos a APD. CONCLUSIONES: Se diseñó, expresó y purificó una proteína compuesta por múltiples epítopes de alérgenos de A. lumbricoides y APD. Los resultados preliminares de Dot-Blot sugieren que esta molécula muestra propiedad hipoalergénica con una reactividad IgE muy baja, en comparación con el extracto de ácaros. Se necesita continuar con estudios funcionales para comprender mejor la respuesta inmune inducida por esta molécula.
Assuntos
Alérgenos , Epitopos , Imunoglobulina E , Proteínas Recombinantes , Humanos , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Alérgenos/imunologia , Epitopos/imunologia , Proteínas Recombinantes/imunologia , Feminino , Masculino , Animais , Adulto , Clima Tropical , Adulto Jovem , Adolescente , Hipersensibilidade/imunologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Anaphylaxis is a severe systemic allergic reaction that can be life-threatening, timely diagnosis and treatment is required in these patients, one of the most frequent triggers is pharmacological. OBJECTIVE: To report the case of a patient who presented anaphylaxis due to eye drops. CASE REPORT: A 7-year-old male with a history of rhinitis and asthma with good control. It started with itchy eyes, ophthalmic drops were administered, composition: Polyethylene glycol 400, 0.4%, Propylene glycol 3 mg, polyquad 0.001%, presenting at 15 minutes an episode of anaphylaxis initially characterized by pruritus and intense conjunctival erythema, later nausea, vomiting, sweating, weakness, urticaria/facial angioedema and dyspnea were added, this episode was controlled opportunely with Levocetirizine 5 mg sublingual and Betametasona 4 mg intramuscular, progressively improving over the next 2 hours. The patient was evaluated by the Allergist, written recommendations were given to the mother in case this reaction occurred again, the use of the drops was prohibited, and the performance of skin test and a probable conjunctival provocation protocolized with the ophthalmic drops were pending. Accidentally 2 months later the patient was re-exposed with the same eye drops, presenting a similar reaction 15 minutes after the administration of the medication, they went to the emergency room where he received antihistamine and corticosteroid intravenous treatment, after this re-exposure is confirmed to the ophthalmic drops mentioned above as a trigger of anaphylaxis in this patient. CONCLUSIONS: We present a case of conjunctival anaphylaxis after application of eye drops, confirmed by re-exposure to the drug. It is essential to give diagnoses, recommendations with treatments and avoidance of the probable triggering agent of the reaction. The administration of immediate medication when the allergic episode begins in these patients can be vital, even more so when they live far from a health center, as was the case in this patient.
ANTECEDENTES: La anafilaxia es una reacción alérgica sistémica severa que puede llegar a comprometer la vida. Se requiere de un diagnóstico y tratamiento oportuno en estos pacientes, uno de los desencadenantes más frecuente es el farmacológico. OBJETIVO: Reportar el caso de un paciente que presentó anafilaxia a gotas oftálmicas. REPORTE DE CASO: Varón de siete años de edad con antecedentes de rinitis y asma con buen control. Inició con picor ocular, se le administraron gotas oftálmicas, composición: Polietilenglicol 400, 0,4%, Propilenglicol 3 mg, polyquad 0,001%, y a los 15 minutos presentó un episodio de anafilaxia caracterizado, inicialmente, por prurito y eritema conjuntival intenso; posteriormente, presentó náuseas, vómito, sudoración, debilidad, urticaria/angioedema facial y disnea. Este episodio fue controlado en el momento, con tratamiento de Levoceterizina 5 mg s.l. y Betametasona 4 mg i.m., con mejoría progresiva en las siguientes dos horas. El paciente fue evaluado por la especialidad de alergología. A su madre se dieron recomendaciones por escrito, por si se presentaba nuevamente la reacción. Se prohibió la utilización de las gotas, y quedó pendiente la realización de las pruebas cutáneas y una probable provocación conjuntival protocolizada con las gotas oftálmicas. Accidentalmente, dos meses después se reexpuso al paciente con las mismas gotas oftálmicas, y a los 15 minutos de la administración del medicamento, presentó una reacción similar, por lo que acudieron a emergencias donde recibió tratamiento antihistamínico y corticoides vía i.m.; tras esta reexposición, se confirma a las gotas oftálmicas mencionadas anteriomente, como desencadenantes de anafilaxia en el paciente. CONCLUSIONES: Presentamos un caso sobre anafilaxia por vía conjuntival tras aplicación de gotas oftálmicas, confirmado por la reexposición al fármaco. Es esencial dar diagnósticos, recomendaciones con tratamientos y evitar el probable agente desencadenante de la reacción. La administración de medicación inmediata cuando inicia el episodio alérgico en estos pacientes, puede ser vital, más aún cuando viven lejos de un centro de salud, como era el caso referenciado.
Assuntos
Anafilaxia , Soluções Oftálmicas , Humanos , Masculino , Soluções Oftálmicas/efeitos adversos , Anafilaxia/induzido quimicamente , CriançaRESUMO
OBJECTIVE: To identify through In Silico analysis the possible molecular mimicry between Der p 23 and antigens from allergenic sources. METHODS: Identity was sought between Der p 23 and proteins from the mite families Pyroglyphidae, Acaridae, Chortoglyphidae and Echimyopodidae, through PSI-BLAST and They used PRALINE and EMBOSS for the alignments. Antigens with resolved experimental structure were obtained from Protein Data Bank and those not reported were generated using Swiss Model server and ALPHAFOLD 2. Epitope prediction was carried out with the Ellipro server and Pymol 2.3 was used to visualize the 3D models. RESULTS: The analysis between Pyroglyphidae allergens and Der p 23 showed identity with the endochitinase-like protein of D. pteronyssinus, and the type 2 chitin binding domain of D. farinae, with identities between 85 and 100%, with coverage of 100%, and 75% respectively. The allergens Der f 23 and Der p 23 of D. farinae and D. pteronyssinus had 100% coverage with identities of 85.42% and 79.59%, respectively. Among the allergens of Tyrophagus putrescentiae, binding to chitin, oviduct-specific glycoprotein and Cda4p were included, which had identity values corresponding to 40%, 42.22% and 34.78%, with coverage values that did not exceed the 55%. No results were found for Chortoglyphidae and Echimyopodidae. CONCLUSION: There is molecular mimicry and structural homology between Der P 23 and allergens from allergic sources of the Pyroglyphidae and Acaridae families. Potential epitopes were identified in Der p 23, which could present cross-reactivity with the proteins of the allergenic sources studied, which must be demonstrated in In vitro and In vivo studies. In vitro and in vivo work is needed to demonstrate the results obtained in the In Silico analysis.
OBJETIVO: Identificar, a través de análisis In Silico, el posible mimetismo molecular entre Der p 23 y antígenos de fuentes alergénicas. MÉTODOS: Se buscó identidad entre Der p 23 y proteínas de las familias de ácaros Pyroglyphidae, Acaridae, Chortoglyphidae y Echimyopodidae, a través de PSI-BLAST, y se utilizaron PRALINE y EMBOSS para los alineamientos. Los antígenos con estructura experimental resuelta se obtuvieron de Protein Data Bank, y aquellos no informados, se generaron mediante Swiss Model Server y ALPHAFOLD 2. La predicción de epítopes se realizó con el servidor Ellipro y para la visualización de los modelos en 3D, se utilizó Pymol 2.3. RESULTADOS: El análisis entre alérgenos de Pyroglyphidae y Der p 23, mostró identidad con la proteína parecida a endoquitinasa de D. pteronyssinus, y el dominio de unión a quitina tipo 2 de D. farinae, con identidades entre 85 y 100%, con coberturas de 100% y 75%, respectivamente. Los alérgenos Der f 23 y Der p 23 de D. farinae y D. pteronyssinu,s tuvieron una cobertura del 100% con identidades del 85,42% y 79,59%, respectivamente. Entre los alérgenos de Tyrophagus putrescentiae, se incluyeron la unión a quitina, glicoproteína específica del oviducto y Cda4p, las cuales tuvieron valores de identidad correspondientes al 40%, 42,22% y 34,78%, con valores de cobertura que no superan el 55%. No se encontraron resultados para Chortoglyphidae y Echimyopodidae. CONCLUSIÓN: Existe mimetismo molecular y homología estructural entre Der P 23 y alérgenos de fuentes alérgicas de las familias Pyroglyphidae y Acaridae. Se identificaron potenciales epítopes en Der p 23, los cuales podrían presentar reactividad cruzada con las proteínas de las fuentes alergénicas estudiadas, lo cual debe ser demostrado en estudios In Vitro e In Vivo. Se necesitan trabajos In Vitro e In Vivo que demuestren los resultados obtenidos en el análisis In Silico.
Assuntos
Alérgenos , Antígenos de Dermatophagoides , Mimetismo Molecular , Animais , Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Simulação por Computador , Mimetismo Molecular/imunologiaRESUMO
OBJECTIVE: Review the historical records of house dust mites in the countries of the Pacific and continental Caribbean of Latin America. METHODS: A systematic review was carried out, adapting the PRISMA method, in digital repositories using a combination of the terms in Spanish: "ácaros domésticos" "alergia" and in English: "dust mites" "allergy" with the names of the countries "Costa Rica". "Panamá" "Venezuela" "Colombia" "Ecuador" "Peru" between 1970-2022. The inclusion criteria were presence of the mite species, city or municipality, country, height above sea level and year. A database was built in Microsoft Excel Office 365®. Maps were created using QGIS 3.30 geographic information systems and descriptive statistics were used to analyze the findings. RESULTS: From the search and identification, 3959 references were obtained, of which 133 were considered potentially eligible, of these 45 met inclusion criteria, and only 32 presented records of domestic mite species. Historically there were 424 records and 27 species (18 genera and 9 families). The countries with the most studies and records were Colombia (14 and 242), Panama (8 and 64) and Peru (5 and 74). 66% (281/424) of the records were of the species Dermatophagoides pteronyssinus (81), followed by Blomia tropicalis (58), D. farinae (40), Chortoglyphus arcuatus (39), Cheyletus sp. (33) and Euroglyphus maynei (30). The species with the greatest altitudinal range were D. pteronyssinus, (2-4800 m.a.s.l) and E. maynei (2- 3399 m.a.s.l). CONCLUSIONS: A synthesis was presented on the historical geographical and altitudinal distribution of house dust mites in countries of the Pacific and continental Caribbean of Latin America, which in turn allowed us to determine the species with the greatest records, highlighting those of importance in allergology. These findings are an input for acarological surveillance in public health.
OBJETIVO: Revisar los registros históricos de ácaros del polvo doméstico en los países del Pacífico y Caribe continental de Latinoamérica. MÉTODOS: Se realizó una revisión sistemática adaptando el método PRISMA, en repositorios digitales empleando una combinación de los términos en español: "ácaros domésticos" "alergia" y en inglés: "dust mites" "allergy" con los nombres de los países "Costa Rica", "Panamá", "Venezuela", "Colombia", "Ecuador" y "Perú", entre 1970 y 2022. Los criterios de inclusión fueron: presencia de la especie de ácaro, ciudad o municipio, país, altura sobre el nivel del mar y año. Se construyó una base de datos en Microsoft Excel Office 365®. Se elaboraron mapas mediante sistemas de información geográfica QGIS 3.30, y se utilizó estadística descriptiva para el análisis de los hallazgos. RESULTADOS: De la búsqueda e identificación se obtuvieron 3.959 referencias, de las cuales 133 fueron consideradas potencialmente elegibles; de estas, 45 cumplieron con criterios de inclusión, y solo 32 presentaron registros de especies de ácaros domésticos. Históricamente se tuvieron 424 registros y 27 especies (18 géneros y 9 familias). Los países con mayores estudios y registros fueron Colombia (14 y 242), Panamá (8 y 64) y Perú (5 y 74). El 66% (281/424) de los registros, fueron de las especies Dermatophagoides pteronyssinus (81), seguida de Blomia tropicalis (58), D. farinae (40), Chortoglyphus arcuatus (39), Cheyletus sp. (33) y Euroglyphus maynei (30). Las especies con mayor rango altitudinal fueron D. pteronyssinus, (2-4800 msnm) y E. maynei (2 3399 msnm). El ácaro D. siboney, considerado endémico de Cuba, se reporta en Colombia y Panamá. CONCLUSIONES: Se presentó una síntesis sobre la distribución histórica a nivel geográfico y altitudinal de ácaros del polvo doméstico en países del Pacífico y Caribe continental de Latinoamérica, a su vez permitió determinar las especies con mayores registros, destacando aquellas de importancia en alergología. Estos hallazgos son un insumo para la vigilancia acarológica en salud pública.
Assuntos
Pyroglyphidae , Animais , História do Século XX , História do Século XXI , América Latina , Oceano Pacífico , Região do CaribeRESUMO
Background: Outdoor aeroallergens, such as pollens and molds, are known triggers of asthma exacerbation; however, few studies have examined children's aeroallergen response based on sensitization. Objective: Our aim was to compare the relative impact of aeroallergen levels on asthma exacerbation between pediatric patients with asthma who tested positive or negative for sensitization to particular allergens. Methods: A case-crossover design study was conducted to examine associations between outdoor aeroallergen levels and asthma exacerbation events among children living in Philadelphia, Pennsylvania, who were treated within a large pediatric care network. Sensitization to common allergens was characterized in a subset of patients with asthma exacerbation who had undergone skin prick testing (5.5%). Odds ratios (ORs) and 95% CIs were estimated in all patients with asthma exacerbation and in those sensitized or not sensitized to aeroallergens. Results: Children who were sensitized to a particular allergen had higher odds of asthma exacerbation with exposure to the allergen (ie, early-season tree pollen, oak tree pollen, early-season weed pollen, and late-season molds) than did all patients with asthma or nonsensitized patients. For example, the association between early-season tree pollen and asthma exacerbation among sensitized children (>90th percentile vs ≤25th, OR = 2.28 [95% CI = 1.23-4.22]) was considerably stronger than that estimated among all patients (OR = 1.34 [95% CI = 1.19-1.50]), and it was also substantially different from the lack of association seen among nonsensitized children (OR = 0.89 [95% CI = 0.51-1.55] [P value for heterogeneity = .03]). Conclusion: More prevalent allergy testing may be useful for prevention of asthma exacerbation by informing interventions targeted to sensitized children and tailored for particular aeroallergens.