Molecular Allergy Diagnosis in Clinical Practice: Frequently Asked Questions.

Considerable progress has been made in the field of molecular biology in recent years, enabling the study of sensitization to the individual components of an allergenic source, a practice that has been termed molecular allergy diagnosis (MD) or component-resolved diagnosis (CRD). The present review provides the clinician with a practical approach to the use of MD by answering questions frequently asked by physicians on how MD can help improve the diagnosis of allergy in daily clinical practice. The article is divided into 3 sections. First, we provide a brief review of the importance for the clinician of knowing the main allergens in the different allergenic sources, their structure, and their in vitro cross-reactivity before approaching MD (section A). Second, we review the usefulness of MD in clinical practice (section B) and answer frequently asked questions on the subject. Finally, section C addresses the interpretation of MD and its integration with other tools available for the diagnosis of allergy.

Molecular Allergy Diagnosis in Clinical Practice: Frequently Asked Questions

Considerable progress has been made in the field of molecular biology in recent years, enabling the study of sensitization to the individualcomponents of an allergenic source, a practice that has been termed molecular allergy diagnosis (MD) or component-resolved diagnosis (CRD).The present review provides the clinician with a practical approach to the use of MD by answering questions frequently asked by physicianson how MD can help improve the diagnosis of allergy in daily clinical practice.The article is divided into 3 sections. First, we provide a brief review of the importance for the clinician of knowing the main allergens inthe different allergenic sources, their structure, and their in vitro cross-reactivity before approaching MD (section A). Second, we reviewthe usefulness of MD in clinical practice (section B) and answer frequently asked questions on the subject. Finally, section C addresses theinterpretation of MD and its integration with other tools available for the diagnosis of allergy (AU)

En las últimas décadas ha habido un gran avance en el campo de la biología molecular permitiendo el estudio de la sensibilización acomponentes alergénicos individuales de una fuente alergénica. Dicha práctica se ha denominado Diagnóstico Molecular en alergia (DM)o Diagnóstico por Resolución de Componentes (CRD, según las iniciales en inglés).El propósito de la presente revisión es ofrecer al clínico un enfoque práctico para el uso del DM respondiendo preguntas frecuentes entrelos médicos sobre cómo puede ayudarnos a mejorar el diagnóstico de alergia en nuestra práctica clínica diaria.La revisión se divide en tres secciones. En primer lugar, se realiza una breve revisión sobre la importancia que tiene para el clínico conocerlos principales alérgenos de las diferentes fuentes alergénicas, su estructura y su reactividad cruzada in vitro antes de abordar el DM(apartado A). En segundo lugar, está el núcleo de la revisión sobre la utilidad del DM en la práctica clínica (apartado B) respondiendo alas preguntas frecuentes sobre el tema, y, finalmente, se añade un apartado (C) sobre la interpretación e integración del DM con el restode las herramientas disponibles para el diagnóstico de alergia (AU)

Fatal anaphylactic shock induced by intravenous gelatin colloid: a postmortem allergological work-up

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Cypress pollen allergy in a Mediterranean area

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Food allergy in Catalonia: Clinical manifestations and its association with airborne allergens

BACKGROUND: Food allergy affects around 6% of the European population and its prevalence worldwide has been increasing in the last decades, but studies focused on investigating food allergy epidemiology in Europe are lacking. OBJECTIVE: The Cibus project was created to register the main culprit foods and their clinical manifestations in food allergic patients in Catalonia. METHODS: A specific online database was designed. Allergists from eight different Catalan hospitals registered the new diagnoses of food allergy. RESULTS: 618 food allergic patients were included. Egg and milk were the main elicitors in the early ages, while fruits and nuts were the most frequent in patients >14 years old. Fish was more frequent in children, while seafood and Anisakis allergy were more frequent in the >14-year-old group. Overall, peach was the most prevalent food eliciting an allergic reaction (10%). Food allergy diagnosis was reached using compatible clinical history and positive skin prick test to the involved food in 98% of cases. Globally, urticaria was the most frequently reported manifestation in our population (48.2%), followed by oral allergy syndrome (25.6%) and anaphylaxis (24.8%). CONCLUSIONS: The Cibus project gives a full overview of the profile of food allergic patients in Catalonia and reinforces the predominance of plant food allergies in the Mediterranean area

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Immunotherapy in allergic rhinitis and lower airway outcomes.

Allergic rhinitis and asthma constitute two clinical expressions of a single-condition, respiratory allergy. Allergen immunotherapy (AIT) is a form of treatment specifically aimed at modifying the response to sensitizing allergens. The inherent potential benefit of AIT is the simultaneous treatment of all clinical expressions of respiratory allergy. Current data support the effectiveness of subcutaneous and sublingual immunotherapy in rhinitis. Studies also provide proof for a beneficial effect in allergic asthma. Even more, substantial evidence points to the preventive effect on the progression from rhinitis to asthma. Despite the current knowledge on the basic mechanisms underlying the immunological effect of AIT is vast, the specific mechanisms for the preventive effect of primary sensitization or new sensitizations are poorly understood. This review aimed to provide a critical overview of the current knowledge on the effectiveness of AIT and its potential role in secondary prevention of respiratory allergy progression.

Food allergy in Catalonia: Clinical manifestations and its association with airborne allergens.

BACKGROUND: Food allergy affects around 6% of the European population and its prevalence worldwide has been increasing in the last decades, but studies focused on investigating food allergy epidemiology in Europe are lacking. OBJECTIVE: The Cibus project was created to register the main culprit foods and their clinical manifestations in food allergic patients in Catalonia. METHODS: A specific online database was designed. Allergists from eight different Catalan hospitals registered the new diagnoses of food allergy. RESULTS: 618 food allergic patients were included. Egg and milk were the main elicitors in the early ages, while fruits and nuts were the most frequent in patients >14 years old. Fish was more frequent in children, while seafood and Anisakis allergy were more frequent in the >14-year-old group. Overall, peach was the most prevalent food eliciting an allergic reaction (10%). Food allergy diagnosis was reached using compatible clinical history and positive skin prick test to the involved food in 98% of cases. Globally, urticaria was the most frequently reported manifestation in our population (48.2%), followed by oral allergy syndrome (25.6%) and anaphylaxis (24.8%). CONCLUSIONS: The Cibus project gives a full overview of the profile of food allergic patients in Catalonia and reinforces the predominance of plant food allergies in the Mediterranean area.

Component-resolved diagnosis of dog allergy

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Co-factor-enhanced food allergy.

BACKGROUND: Alcohol, exercise or non-steroidal anti-inflamatory drugs (NSAID) are frequently mentioned as amplifiers of food allergic reactions but only individual cases or small series have been previously published. METHODS: Descriptive study including 74 cases of suspected co-factor enhanced food allergy, assessed by skin-prick tests, specific IgE and oral challenges. RESULTS: Anaphylaxis accounted for 85.1% of reactions. In 99% of cases culprit food allergens were plant-derived, mainly vegetables and cereals. NSAID were involved in 58%, exercise in 52.7% and alcohol in 12.2%. Lipid transfer protein was the most frequently involved allergen. CONCLUSIONS: Co-factor enhanced food allergy should be considered when assessing food, alcohol, exercise and NSAID allergic reactions.

Estudio epidemiológico de las enfermedades metabólicas con homocistinuria en España / Epidemiological study of the metabolic diseases with homocystinuria in Spain

Objetivos: Conocer la prevalencia en España de los diferentes errores congénitos del metabolismo que presentan homocistinuria y establecer las medidas oportunas para garantizar su prevención, diagnóstico y tratamiento, en aquellos casos posibles. Material y métodos: En abril 2009 se realizó una encuesta nacional de carácter transversal mediante cuestionario enviado a 35 centros, en los que se atiende a pacientes infantiles y adultos. La finalidad de la encuesta era establecer la prevalencia en ese momento recogiendo el histórico de pacientes que cada centro tuviera documentados. Resultados: A través de los cuestionarios respondidos por 25 médicos de 16 centros, se han identificado 75 pacientes: 41 defectos de transulfuración (uno fallecido), 27 de remetilación (6 fallecidos) y 7 sin diagnóstico etiológico definitivo. La edad de diagnóstico muestra una amplia variación, en 18 casos había más de un hermano afectado. Las manifestaciones clínicas más graves inciden en el grupo de los pacientes afectados de trastornos de la remetilación. Destaca el alto porcentaje de déficit cognitivo, seguido de la patología de cristalino; casi la mitad de los pacientes presentan trastornos neurológicos, es elevada la afectación vascular en los adultos con deficiencia de CBS; las opciones terapéuticas más utilizadas han sido el ácido fólico, la hidroxicobalamina y la betaína. Conclusiones: A la vista de estos resultados, y en especial del escaso número de deficiencias de CBS detectadas, se concluye la necesidad de implantar el cribado neonatal para la homocistinuria clásica y asegurar la puesta en marcha del proceso diagnóstico oportuno en todos los pacientes de riesgo(AU)

Objectives: To determine the prevalence of homocystinuria in Spain and to establish the measures and mechanisms to ensure its prevention, diagnosis and treatment. Material and methods: A national cross-sectional survey was conducted by means of a questionnaire sent to 35 hospitals in which children and adult patients are treated. Results: Using the questionnaires submitted by 25 physicians from 16 centres, 75 patients were identified: 41 transsulphuration defects (one deceased), 27 remethylation (six deaths) and 7 without a syndromic diagnosis. The age at diagnosis varied widely, and 18 cases had more than one sibling affected. The more severe clinical manifestations involved the patients with remethylation defects. There was a high percentage of cognitive impairment, followed by lens diseases. Almost half of the patients had neurological disorders. There was increased vascular involvement in CBS-deficient adults. The therapeutic options most used were, folic acid, hydroxycobalamin and betaine. Conclusions: In view of these results and especially the small number of CBS deficiencies detected, we conclude that there is a need to introduce newborn screening for classical homocystinuria and ensure implementation of an appropriate diagnostic workup in all patients at risk(AU)

[Epidemiological study of the metabolic diseases with homocystinuria in Spain]. / Estudio epidemiológico de las enfermedades metabólicas con homocistinuria en España.

OBJECTIVES: To determine the prevalence of homocystinuria in Spain and to establish the measures and mechanisms to ensure its prevention, diagnosis and treatment. MATERIAL AND METHODS: A national cross-sectional survey was conducted by means of a questionnaire sent to 35 hospitals in which children and adult patients are treated. RESULTS: Using the questionnaires submitted by 25 physicians from 16 centres, 75 patients were identified: 41 transsulphuration defects (one deceased), 27 remethylation (six deaths) and 7 without a syndromic diagnosis. The age at diagnosis varied widely, and 18 cases had more than one sibling affected. The more severe clinical manifestations involved the patients with remethylation defects. There was a high percentage of cognitive impairment, followed by lens diseases. Almost half of the patients had neurological disorders. There was increased vascular involvement in CBS-deficient adults. The therapeutic options most used were, folic acid, hydroxycobalamin and betaine. CONCLUSIONS: In view of these results and especially the small number of CBS deficiencies detected, we conclude that there is a need to introduce newborn screening for classical homocystinuria and ensure implementation of an appropriate diagnostic workup in all patients at risk.

Allergenicity and cross-reactivity of Senecio pollen: identification of novel allergens using the immunoproteomics approach.

BACKGROUND: The genus Senecio is the largest genus of the family Asteraceae (Compositae). The allergenicity of Senecio has not been assessed previously. OBJECTIVE: The aim of this study was to investigate the allergens of Senecio jacobea pollen and to determine their immunological characteristics and clinical relevance. METHODS: Fifty patients with rhinoconjunctivitis and a positive skin prick test (SPT) to Senecio were recruited. The clinical relevance of this pollen was assessed by means of a nasal provocation test (NPT). Allergens were characterized by one-dimensional electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis and immunoblotting. Furthermore, characterization and identification of the allergens were performed by mass spectrometry (MS). In vitro inhibition tests were performed to evaluate cross-reactivity with other pollen. RESULTS: Three predominant allergens, both in the intensity of reaction and the frequency of recognition by human-allergic sera, were 59 (60%), 42 (50%) and 31 kDa (50%). The two-dimensional analysis allowed the identification of several allergens. One spot around 42 kDa was identified as a protein homologous to pectate lyase and three other spots were homologous to malate dehydrogenase by MS. S. jacobea proteins showed cross-reactivity with other proteins of the Asteraceae family and also with Parietaria judaica. This was demonstrated by immunoblotting and ELISA inhibition studies. CONCLUSION: S. jacobea constitute a newly discovered allergenic source. It shows cross-reactivity with other members of the Asteraceae plant family as well as with P. judaica.

Acquired angioedema associated with hereditary angioedema due to C1 inhibitor deficiency.

Angioedema caused by C1 inhibitor deficiency is a rare disorder that may be either hereditary or acquired, the latter being mainly associated with lymphoproliferative disorders. A 51-year-old woman who had suffered from episodes of acute peripheral edema since she was 12 was diagnosed with hereditary angioedema at the age of 40 and remained stable with stanozolol. Due to a worsening of her symptoms she was reassessed and low levels of C1q and an abnormal lymphocyte count were detected. Immunophenotyping of peripheral blood revealed 9% monoclonal lambda B cells with a follicular center phenotype. The histopathology was consistent with a grade II follicular lymphoma stage IV-A.With chemotherapy, the hematologic disease was controlled and C1q levels returned to normal values. This represents a rare case of a patient with hereditary angioedema who developed acquired angioedema due to a lymphoma that was associated with a reduction in the levels of C1q as her symptoms worsened.

Eficacia y seguridad a largo plazo del tratamiento con tacrolimus por vía tópica en niños con dermatitis atópica grave / Efficacy and safet long-term study of tacrolimus ointment in children with severe atopic dermatitis

Introducción: Tacrolimus es un inmunosupresor tipo macrólido. Recientemente se ha introducido como un nuevo tratamiento para la dermatitis atópica (DA). Su acción se basa en la inhibición de la transcripción de citocinas en las células inflamatorias y del sistema inmunitario. Objetivos: Determinar la eficacia y seguridad a largo plazo ( 12 meses) del tratamiento con tacrolimus por vía tópica en pacientes con DA grave. Métodos: Estudio abierto de seguimiento prospectivo de eficacia y seguridad en niños de 2 a 12 años de edad con DA grave. Se prescribió tratamiento durante tres meses con dos aplicaciones diarias de tacrolimus por vía tópica obre las regiones afectas. Durante el .seguirniento se reiniciaron nuevo ciclos cuando presentaron exacerbaciones. La gravedad de la DA e determinó con el índice SCORAD al inicio y mensualmente durante el seguimiento. Se realizaron pruebas de laboratorio al inicio y final de cada tanda de tratamiento. Se pasó un cuestionario de efecto adversos una vez al mes. Resultados: Se incluyeron nueve pacientes en el estudio, 5 varones y 4 mujeres, con una edad media de 6,3 años y una duración media de la DA de 51 meses. Tras el tratamiento se observó una reducción del índice SCORAD estadísticamente significativa (p = 0,011 al mes: p = 0,012 a los dos meses: p = 0,012 a los tres meses de tratamiento y p = O.O 18 al mes de suspenderlo). Un 75% de los pacientes presentaron un aumento leve del prurito y enrojecimiento en las lesiones en las primeras aplicaciones de minutos a horas de duración. o detectamos alteraciones analíticas ni efectos adversos relevantes. Conclusiones: Tacrolimus en su forma de aplicación tópica e un tratamiento eficaz y seguro para los niños afectados de DA grave. El mantenimiento de dicha eficacia a largo plazo parece relacionarse con la gravedad inicial de la DA (AU)

Background: Tacrolimus is a macrolide-immunosupressor. It has recently been introduced as a new treatment of atopic dermatitis (AD). lts action is based on the inhibition of cytokine transcription in inflammatory and immune cell . Objectives: To determine long-term efficacy and safety of tacrolimus ointment treatment in patient with evere AD. Methods: Prospective open long-term study of safety and efficacy of tacrolimus ointment in 2 to 12 year old children with severe AD. Tacrolimus ointment was prescribed for three months twice a day over affected areas. Ewcye les of treatrnent were prescribed during the follow up period when severe AD reappeared. Severity of AD was determined based on SCORAD index, are the beginning and monthly during the follow-up period (12 months). A blood sample was taken at the beginning and after every cycle of treatment. Any adverse effect was registered monthly. Results: Nine patients were included. Five males and four females, with a medium age of 6.3 year and medium duration of AD of 51 months. The SCORAD index was significantly reduced after treatment (p=O.O 11 at first month: p=O.O 12 two month: p=O.O 12 three and p=O.O 18 one month after having finished the treatment). Seventy and five per cent of the patient presented a low increase of pruritus and buming in the first applications that disappeared in minutes-hours. Analytical alterations and clinical adverse events were not detected. Conclusions: Tacrolimus ointment is a safe and effective treatment for children with severe AD. The long-term efficacy seems to be related to the initial severity of AD (AU)