Immunoglobulin G4-Related Disease: What an Allergist Should Know.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder that begins in 1 or more organs as inflammatory tumors that progress toward fibrosis. It is often accompanied by elevated serum IgG4. IgG4-RD was first described in 2003 as a new concept encompassing a number of immunoallergic diseases that had previously been considered unrelated. IgG4-RD mainly affects middleaged and older men. It consists of upregulation and expansion of CD4+ cytotoxic T lymphocytes, oligoclonal plasmablasts, and other inflammatory cells that infiltrate affected tissues and induce inflammation, organ dysfunction, and fibrosis. Symptoms depend on the location, severity, and extent of the disease. Virtually any organ can be affected, including the pancreas, salivary glands, lacrimal glands, thyroid gland, retro-orbital tissue, lymph nodes, retroperitoneum, mediastinum, lung, kidney, aorta, serosal surfaces, and meninges. Patients with widespread disease may present general symptoms. At least 30%-40% of patients are atopic or display atopic traits such as eosinophilia and elevated serum IgE levels. Additional laboratory features include increased serum IgG4 concentrations, increased blood IgG4-plasmablasts, hypergammaglobulinemia, and hypocomplementemia. Diagnosis of IgG4-RD is based on a clinicopathological correlation. Lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells, storiform-type fibrosis, obliterative phlebitis, and tissue eosinophilia are the pathological hallmarks. Therapy for IgG4-RD is based primarily on corticosteroids but may include additional immunomodulatory drugs and monoclonal antibodies such as rituximab. In individuals with allergic features, IgG4-RD should be suspected when a history of unexplained swelling is observed in 1 or more organs, particularly if they respond to corticosteroids and the patients are men in the sixth decade of life and beyond.

Immunoglobulin G4–Related Disease: What an Allergist Should Know

Immunoglobulin G4–related disease (IgG4-RD) is a fibroinflammatory disorder that begins in 1 or more organs as inflammatory tumors that progress toward fibrosis. It is often accompanied by elevated serum IgG4. IgG4-RD was first described in 2003 as a new concept encompassing a number of immunoallergic diseases that had previously been considered unrelated. IgG4-RD mainly affects middleaged and older men. It consists of upregulation and expansion of CD4+ cytotoxic T lymphocytes, oligoclonal plasmablasts, and other inflammatory cells that infiltrate affected tissues and induce inflammation, organ dysfunction, and fibrosis. Symptoms depend on the location, severity, and extent of the disease. Virtually any organ can be affected, including the pancreas, salivary glands, lacrimal glands, thyroid gland, retro-orbital tissue, lymph nodes, retroperitoneum, mediastinum, lung, kidney, aorta, serosal surfaces, and meninges. Patients with widespread disease may present general symptoms. At least 30%-40% of patients are atopic or display atopic traits such as eosinophilia and elevated serum IgE levels. Additional laboratory features include increased serum IgG4 concentrations, increased blood IgG4-plasmablasts, hypergammaglobulinemia, and hypocomplementemia. Diagnosis of IgG4-RD is based on a clinicopathological correlation. Lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells, storiform-type fibrosis, obliterative phlebitis, and tissue eosinophilia are the pathological hallmarks. Therapy for IgG4-RD is based primarily on corticosteroids but may include additional immunomodulatory drugs and monoclonal antibodies such as rituximab. In individuals with allergic features, IgG4-RD should be suspected when a history of unexplained swelling is observed in 1 or more organs, particularly if they respond to corticosteroids and the patients are men in the sixth decade of life and beyond (AU)

False-Positive Results of Serological Tests for Allergy in Alcoholic Patients.

BACKGROUND AND OBJECTIVE: Alcohol consumption is associated with enhanced TH2 immune responses. Objective: To investigate the frequency of false-positive results in serological tests for allergy in alcoholic patients. METHODS: A total of 138 alcoholic patients consecutively admitted to hospital underwent a panel of allergy tests that included serum total IgE, a multiallergen IgE test (UniCAP Phadiatop), and skin prick tests to relevant aeroallergens in the area, which were considered the standard reference for atopy. In selected cases with positive specific IgE (sIgE) to cross-reactive carbohydrate determinants (CCDs) on ImmunoCAP, we determined sIgE to hymenoptera venom components (ADVIA Centaur) and a microarray of 103 allergen components (ISAC). RESULTS: Increased serum total IgE (>170 IU/mL) was observed in 59/110 (54%) of nonatopic (skin prick test-negative) patients. The result of the multiallergen IgE test was positive in 46 nonatopic patients (42%). This finding was closely associated with high serum concentrations of total IgE and sIgE to CCDs. The vast majority of patients with positive CCD-sIgE showed positivity to glycosylated plant and hymenoptera allergen components on ISAC and ADVIA Centaur. Only 1 out of 26 patients with positive sIgE to CCD and hymenoptera venom developed honeybee venom allergy after a median follow-up of 166 months. Correlations between measurements of sIgE to CCD markers on ImmunoCAP, ADVIA Centaur, and ISAC were imperfect. CONCLUSIONS: Serological tests for allergy should be interpreted with caution in alcoholic patients, who frequently have increased levels of total IgE and CCD-sIgE and subsequent positivity of sIgE to glycosylated allergen components, irrespective of the method used.

False-positive results of serological tests for allergy in alcoholic patients

Background: Alcohol consumption is associated with enhanced TH2 immune responses. Objective: To investigate the frequency of false-positive results in serological tests for allergy in alcoholic patients. Methods: A total of 138 alcoholic patients consecutively admitted to hospital underwent a panel of allergy tests that included serum total IgE, a multiallergen IgE test (UniCAP Phadiatop), and skin prick tests to relevant aeroallergens in the area, which were considered the standard reference for atopy. In selected cases with positive specific IgE (sIgE) to cross-reactive carbohydrate determinants (CCDs) on ImmunoCAP, we determined sIgE to hymenoptera venom components (ADVIA Centaur) and a microarray of 103 allergen components (ISAC).Results: Increased serum total IgE (>170 IU/mL) was observed in 59/110 (54%) of nonatopic (skin prick test-negative) patients. The result of the multiallergen IgE test was positive in 46 nonatopic patients (42%). This finding was closely associated with high serum concentrations of total IgE and sIgE to CCDs. The vast majority of patients with positive CCD-sIgE showed positivity to glycosylated plant and hymenoptera allergen components on ISAC and ADVIA Centaur. Only 1 out of 26 patients with positive sIgE to CCD and hymenoptera venom developed honeybee venom allergy after a median follow-up of 166 months. Correlations between measurements of sIgE to CCD markers on ImmunoCAP, ADVIA Centaur, and ISAC were imperfect. Conclusions: Serological tests for allergy should be interpreted with caution in alcoholic patients, who frequently have increased levels of total IgE and CCD-sIgE and subsequent positivity of sIgE to glycosylated allergen components, irrespective of the method used

Antecedentes: El consumo de alcohol se asocia con respuestas inmunes aumentadas de tipo Th2.Objetivo: Investigar la frecuencia de falsos positivos en los tests serológicos de alergia en alcohólicos. Métodos: En un total de 138 pacientes alcohólicos ingresados en el hospital de forma consecutiva se realizó un panel de pruebas de alergia que incluyó la determinación de IgE sérica total, un test de IgE específica multialergeno (UniCAP Phadiatop) y pruebas cutáneas en prick a una batería de aeroalérgenos relevantes en el área, cuya positividad se consideró la referencia para clasificar a los pacientes como atópicos. En casos seleccionados con positividad de IgE específica (sIgE) frente a carbohidratos con reactividad (CCDs) en el ImmunoCAP, se determinó la sIgE a componentes del veneno de hymenópteros (ADVIA Centaur) y a un microarray de 103 componentes alergénicos (ISAC).Resultados: Se observó un aumento de las concentraciones de IgE sérica total (>170 IU/mL) en 59/110 (54%) de los alcohólicos no atópicos (prick test-negativos). Cuarenta y seis alcohólicos no atópicos (42%) presentaban un test de IgE específica multialérgeno positivo. Este hallazgo estuvo estrechamente asociado con la presencia de concentraciones elevadas de IgE total y de sIgE a CCDs. La gran mayoría de los alcohólicos con positividad de sIgE a CCDs mostraron positividad con componentes moleculares glicosilados de plantas e himenópteros en el ISAC y el ADVIA Centaur. Sólo uno de los 26 pacientes con positividad de sIgE a CCDs e himenópteros desarrolló alergia clínica a picadura de abeja tras un seguimiento mediano de 166 meses. La correlación de las determinaciones de sIgE a marcadores de CCD en ImmunoCAP, ADVIA Centaur e ISAC fue imperfecta. Conclusiones: Los tests serológicos de alergia se deben interpretar con precaución en pacientes alcohólicos, que frecuentemente muestran elevación de IgE total, positividad de sIgE a CCDs y, consecuentemente, positividad de sIgE a componentes alergénicos glicosilados, independientemente del método utilizado

Factors Influencing Serum Concentrations of Immunoglobulin D in the Adult Population: An Observational Study in Spain.

Immunoglobulin D (IgD) is the least studied of immunoglobulin classes. This study sought to investigate the potential relationship between demographic, metabolic, lifestyle and immunological factors, and serum IgD concentrations in a general adult population. We measured serum IgD concentrations by means of a commercial turbidimetric assay in 413 individuals (median age, 55 years; 45% males), randomly selected from the adult population of a Spanish municipality. Serum IgD concentrations displayed considerable variation in the population, ranging from undetectable (<6.7 mg/l) to 878 mg/l. Serum IgD concentrations were undetectable in 78 cases (18.9%) and >100 mg/l in 39 cases (9.4%). Median IgD was 21.9 mg/l. Serum IgD concentrations were negatively associated with age and positively associated with smoking, after adjustment for potential confounders. Overweight individuals showed lower concentrations of IgD than did normal-weight individuals. Atopy (positivity of skin tests to aeroallergens) was not significantly associated with IgD concentrations, although non-symptomatic atopics showed higher IgD concentrations. No consistent association was observed between serum IgD concentrations and gender, metabolic syndrome, or alcohol consumption. No significant association was found between baseline IgD concentrations and development of either allergic or immune disease after a median 11.4 years of follow-up. In conclusion, serum IgD concentrations in adults show a wide variation in the population and may be influenced by common factors, particularly age and smoking habit. These factors should be taken into account when defining reference ranges for serum IgD concentrations.

Total and honeybee venom-specific serum IgG4 and IgE in beekeepers

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Validation of the Spanish Version of the Food Allergy Quality of Life Questionnaire–adult form (S-FAQLQ-AF)

Introducción: Se evalúa el impacto de la alergia alimentaria sobre la calidad de vida, mediante cuestionarios específicos integrado en el proyecto EuroPrevall. Validar y adaptar a lengua castellana el cuestionario FAQLQ-AF. Material y métodos: La traducción y adaptación cultural del cuestionario original se realizó siguiendo recomendaciones de la OMS. Los autores del cuestionario original aceptaron la versión en lengua castellana del FAQLQ-AF (S-FAQLQ-AF). Los pacientes fueron incluidos siguiendo los siguientes criterios: (1) Síntomas alérgicos tras ingesta de un alimento y prick test positivos o IgE frente al alimento implicado, (2) Un médico evaluó la capacidad de los pacientes para completar los cuestionarios (S-FAQLQ-AF y el genérico SF-12). Para explorar la fiabilidad de las respuestas entre 10 y 14 días después de rellenar el primer cuestionario, los pacientes rellenaban de nuevo el S-FAQLQ-AF con preguntas en distinto orden. Resultados: Ochenta y dos pacientes (≥18 años) fueron incluidos. La validez de constructo fue evaluada a partir de la correlación entre el S-FAQLQ-AF y el FAIM (Medida Independiente de la Alergia a Alimentos (rho =0.83, p<.0001). El cuestionario S-FAQLQ-AF (Cronbach-alpha =0.95) y sus diferentes dominios mostraron excelente consistencia interna: Evitación de alérgenos (alpha=0.93); impacto emocional (alpha=0.83), riesgo de exposición accidental (alpha=0.85) y salud relacionada con alergia alimentaria (alpha=0.66). No se halló correlación entre el S-FAQLQ-AF y el cuestionario SF-12. Conclusión: La versión Española del cuestionario de adultos FAQLQ-AF es una herramienta válida, fiable, fácil de usar, rápida de completar y sensible al cambio, discriminando pacientes con diferentes fenotipos atópicos, para evaluar el impacto de la alergia alimentaria en la calidad de vida (AU)

Introduction: Specific food allergy quality of life questionnaires have been developed within the context of the EuroPrevall project. We aimed to adapt and validate the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) in the Spanish language. Methods: The original English questionnaire was translated and culturally adapted into Spanish following World Health Organization guidelines. The final Spanish version of the FAQLQ-AF (S-FAQLQ-AF) was approved by the original authors. Consecutive patients (≥18 years old) who fulfilled the following criteria were recruited: 1) diagnosis of food allergy defined as immediate allergic symptoms and a positive prick test or IgE against the culprit food(s) and 2) physician-assessed ability to complete the questionnaires. Patients completed the S-FAQLQ-AF and a Spanish version of the SF-12 questionnaire. Reliability was assessed 10 to 14 days after completion of the first questionnaire. Results: Eighty-two consecutive outpatients were recruited and cross-sectional validity was assessed based on the correlation between the S-FAQLQ-AF and the Food Allergy Independent Measure (FAIM) in this population (rho=0.83, P<.0001). The S-FAQLQ-AF showed excellent internal consistency (Cronbach alpha, 0.95). S-FAQLQ-AF domains also had excellent internal consistency: alpha=0.93 for allergen avoidance-dietary restrictions; alpha=0.83 for emotional impact; alpha=0.85 for risk of accidental exposure, and alpha=0.66 for food allergy related health. Limited correlation was found between the S-FAQLQ-AF and the SF-12. Conclusion: The S-FAQLQ-AF is a valid, short, easy-to-use, and reliable instrument that discriminates between patients with different atopic phenotypes and is suitable for assessing the impact of IgE-mediated food allergy on patient quality of life (AU)

Urticaria recidivante y tiroiditis autoinmunitaria: influencia del tratamiento con tiroxina en la evolución de la urticaria / Recurrent urticaria and autoimmune thyroiditis: The influence of thyroxine treatment on the outcome of the urticaria

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Safety of measles-mumps-rubella vaccine (MMR) in patients allergic to eggs.

INTRODUCTION: Since the measles and mumps components used in MMR vaccine are grown in cultures of fibroblast from chick embryos, for a long time there have been concerns about the presence of egg protein in the vaccine and the recommendations given to egg allergic patients. We include in this paper our clinical experience vaccinating egg allergic patients with a regular triple viral vaccine, as well as an immunological study of each vaccine available in Spain. The aim of this study was to evaluate the clinical safety of a conventional MMR vaccine in a population of egg allergic patients and to determine the presence of egg allergens in a conventional MMR vaccine and if IgE antibodies from egg allergic can recognize egg allergens in this vaccine. MATERIALS AND METHODS: Children 15 months old with a confirmed diagnosed of egg allergy were included. In all patients, a skin prick test with non diluted MMR vaccine (Priorix, GSK) was made. If negative, each patient received a single dose of measles, mumps, rubella (MMR) vaccine. If positive, a fractionated injection of the vaccine was made following SEICAP recommendations (2004). SDS-PAGE immunoblotting was performed with Priorix vaccine. RESULTS: A cumulative total of 26 patients with egg allergy have safely received MMR vaccine in a single-dose (after a negative SPT in all cases) at our department without any reaction. 5 sera of vaccinated patients and 6 control sera of egg allergic patients (positive oral challenge) were used to immunolabel the membranes. No positive bands corresponding to egg proteins were found in any of the patients. CONCLUSION: Negative results found in SPT support the absence of clinical reaction against the components and Immunological studies point that there is no detectable amount of egg protein in this vaccine to produce an IgE mediated reaction. We can conclude that MMR can be safely administrated in children allergic to egg.

Safety of measles-mumps-rubella vaccine (MMR) in patients allergic to eggs / Seguridad de la vacuna anti-sarampion-parotiditis-rubeola en pacientes alergicos al huevo

Introduction: Since the measles and mumps components used in MMR vaccine are grown in cultures of fibroblast from chick embryos, for a long time there have been concerns about the presence of egg protein in the vaccine and the recommendations given to egg allergic patients. We include in this paper our clinical experience vaccinating egg allergic patients with a regular triple viral vaccine, as well as an immunological study of each vaccine available in Spain. The aim of this study was to evaluate the clinical safety of a conventional MMR vaccine in a population of egg allergic patients and to determine the presence of egg allergens in a conventional MMR vaccine and if IgE antibodies from egg allergic can recognize egg allergens in this vaccine Materials and methods: Children 15 months old with a confirmed diagnosed of egg allergy were included. In all patients, a skin prick test with non diluted MMR vaccine (Priorix, GSK) was made. If negative, each patient received a single dose of measles, mumps, rubella (MMR) vaccine. If positive, a fractionated injection of the vaccine was made following SEICAP recommendations (2004). SDS-PAGE immunoblotting was performed with Priorix vaccine. Results: A cumulative total of 26 patients with egg allergy have safely received MMR vaccine in a single-dose (after a negative SPT in all cases) at our department without any reaction. 5 sera of vaccinated patients and 6 control sera of egg allergic patients (positive oral challenge) were used to immunolabel the membranes. No positive bands corresponding to egg proteins were found in any of the patients. Conclusion: Negative results found in SPT support the absence of clinical reaction against the components and Immunological studies point that there is no detectable amount of egg protein in this vaccine to produce an IgE mediated reaction. We can conclude that MMR can be safely administrated in children allergic to egg

INTRODUCCIÓN. La vacuna triple vírica (sarampión, parotiditis y rubéola), incluida en el calendario vacunal español, se cultiva en embrión de pollo y esto ha creado controversia durante años acerca del posible presencia de proteínas de huevo y por lo tanto el riesgo de vacunar a niños alérgicos a este alimento. Incluimos en este artículo nuestra experiencia vacunando a niños alérgicos al huevo con la vacuna triple vírica convencional y un estudio inmunológico con las vacunas comercializadas en España. OBJETIVO. Evaluar la seguridad clínica de la vacuna triple vírica comercializada en España en pacientes alérgicos a proteínas de huevo. Evaluar el reconocimiento inmunológico de posibles alergenos de huevo presentes en esta vacuna por pacientes alérgicos a huevo. MATERIAL Y MÉTODOS. Se incluyeron en el estudio niños de 15 meses con diagnóstico confirmado de alergia a proteínas de huevo. En todos los casos se realizó prueba cutánea con la vacuna sin diluir (Priorix, GSK). En caso de que la prueba cutánea fuese negativa se administró la vacuna en dosis única. En caso de positividad de la prueba cutánea, la vacuna se administró de forma fraccionada. Se realizó SDS-PAGE inmunoblot con la vacuna. RESULTADOS. 26 pacientes alérgicos al huevo fueron vacunados con la vacuna triple vírica convencional sin presentar ninguna reacción. Se utilizaron sueros de 5 niños alérgicos vacunados y 6 de niños alérgicos no vacunados en el estudio inmunológico. Ninguno de ellos reconoció ninguna banda correspondiente a proteínas de huevo. CONCLUSIÓN. Los resultados negativos demuestran la ausencia de reactividad clínica frente a los componentes de la vacuna y el estudio inmunológico indica que no hay cantidades detectables de proteínas de huevo en esta vacuna para inducir una respuesta alérgica IgE mediada. Concluimos que la vacuna triple vírica se puede administrar de forma segura en niños alérgicos al huevo

Proyecto de intercambio generacional: aprendamos juntos / A generation exchange project: aprendamos juntos

Introducción: Con el objetivo de promover la interrelación entre jóvenes y mayores institucionalizados se inició, en la isla de Lanzarote, el proyecto Aprendamos Juntos. Resultados: El nivel de satisfacción de los participantes fue elevado. Se apreció en los niños un cambio de actitud respecto a la figura del mayor. Se constató en los ancianos un aumento de la motivación y de la actividad habitual. Se incrementó la satisfacción laboral de los profesionales. Conclusiones: Las acciones emprendidas no actúan como mera actividad lúdica, sino que tienen una función terapéutica. Son significativos los cambios de actitud que se producen en los niños con respecto al mayor. El abordaje interdisciplinar permite a los profesionales alcanzar más fácilmente los objetivos terapéuticos. Destacamos los beneficios obtenidos a pesar del reducido coste del proyecto

Introduction: T In order to promote the interaction between children and elderly, the project Aprendamos Juntos (Let's Learn Together) was carried out in Lanzarote (Canary Islands) Methodology: Students from a local school and the residents of a nursing home, with moderate physical impairment, participated in the project. Two sessions took place in the school and two in the nursing home. Results: There was a high level of satisfaction. It was noticed that the children had a change of attitude with regard to their respect of the elderly. We verified that there was an increase in the motivation and in the daily activity of the latter. The professionals also experienced increased work satisfaction. Conclusions: The activities that have been undertaken work not only as playful activity, but also have a therapeutic function. The changes in the attitude of the children with respect to the elderly are very significant. The interdisciplinary vision allowed the professionals involved to achieve their therapeutic objectives with ease. We point out the numerous benefits which have been attained in spite of the very low cost of the project

Osteosarcoma en niños y adolescentes: reporte definitivo del brazo pediátrico del grupo cooperativo venezolano para el estudio de los tumores óseos (GCVETO): octubre 1995-diciembre 1999 / Osteosarcoma in children and adolescen: report definitive of the arm pediatric of the group cooperative venexuelan for study od the tumors osseous (GCVETO): octuber 1995-december 1999

En 1995 se integró el GCVETO, y en octubre 1995 se inicia el Protocolo 003/95 para el estudio y tratamiento del Osteosarcoma (OS). Durante el período comprendido entre el 01.10.1995 y el 31.12.1999, 39 pacientes menores de 20 años ingresaron al brazo pediátrico del protocolo 003/95. El esquema de quimioterapia incluyó: Ifosfamida (IFOS)/Mesna 1800 mgr/m²/día/5 días, Doxorubicina (DOXO) 25 mgr/m²/día/3 días asociado a ICRF-187 (Desraxozane)250 mgr/m²/día/3 días, Cisdiaminodicloroplatino (CDDP) 40 mgr/m²/día/3 días. 64,10 por ciento eran varones, con una relación sexo V:H 1,78:1. 53,84 por ciento tenían edades comprendidas entre 10 y 15 años, edad mínima 6 a. y máxima 20 a., con un promedio de 12,53 a. Dolor, aumento de volumen e incapacidad funcional fueron los datos clínicos más frecuentes. 100 por ciento de los casos presentaban compromiso de partes blandas, y en 30,78 por ciento el volumen tumoral fue > 20 cm. El sitio de localización más frecuente: Femúr 48,7 por ciento, seguido por Tibia 23,07 por ciento y Húmero 20,51 por ciento. 14 pacientes presentaron enfermedad metastásica al ingreso. Las alteraciones de laboratorio más relevantes: Velocidad Sedimentación Globular (VSG), niveles séricos de Fosfatasa Alcalina (FA) y Deshidrogenasa Láctica (LDH). Los estudios imagenológicos del hueso comprometido fueron positivos en todos los casos, orientando el diagnóstico clínico en el 100 por ciento de los mismos. En todos los casos se estableció el diagnóstico a través del estudio histológico. 34 pacientes (87,18 por ciento) se consideraron evaluables para la terapia. Cirugía definitiva se realiza en el 61,76 de los casos: Injerto Oseo 11 pacientes, Desarticulación 8 pacientes, Resección tumoral 1 paciente, Amputación 1 paciente, Endoprótesis 1 paciente. 226 cursos de quimioterapia fueron administrados, promedio de 5,79 ciclos. 17 pacientes (50 por ciento) han finalizado la terapia. La respuesta histológica se evaluó según porcentaje de necrosis sólo en 16 pacientes (72,72 por ciento): Grado I 2/16, Grado II 3/16, Grado III 7/16, Grado IV 3/16, N.R. 6/22. R.C., fue obtenida en 19 pacientes (55,88 por ciento): 16/22 pacientes sin enfermedad metastásica y 3/12 con enfermedad metastásica. R.P. 13 pacientes, Progresión 2 pacientes, 8 pacientes fallaron a la terapia: Los sitios de recaída más frecuentes: Pulmón y Hueso (50 por ciento)