Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome.

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.

Spanish guidelines for diagnosis, management, treatment, and prevention of DRESS syndrome

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. OBJECTIVE: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided

ANTECEDENTES: El síndrome DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) es una reacción cutánea grave inducida por hipersensibilidad a fármacos, compleja y multisistémica. Su diagnóstico y manejo es difícil e implica a diferentes especialistas. Es muy importante una correcta identificación del fármaco responsable para que el paciente disponga de opciones terapéuticas seguras en el futuro. No hay guías ni documentos de consenso españoles previos sobre el síndrome DRESS. OBJETIVO: Realizar una revisión y guía sobre el diagnóstico clínico y alergológico, manejo, tratamiento y prevención del DRESS según la evidencia científica disponible y la experiencia de expertos de diferentes especialidades médicas. MÉTODOS: Esta guía ha sido elaborada por un grupo de alergólogos del Comité de Alergia a Fármacos de la SEAIC, junto a otros especialistas involucrados en el manejo del DRESS e investigadores del Consorcio PIELenRed. Se realizó una búsqueda de publicaciones científicas sobre DRESS y el grupo de expertos evaluó la evidencia científica de la literatura y aportaron grados de recomendación. Cuando no existía evidencia se alcanzó un consenso entre expertos. RESULTADOS: Se publica la guía española sobre DRESS. Incluye aspectos prácticos importantes sobre el diagnóstico clínico, la identificación de fármacos causales a través del algoritmo del Sistema Español de Farmacovigilancia y guía para el diagnóstico alergológico. Se realizan recomendaciones sobre el manejo, tratamiento y prevención del DRESS. Se aportan algoritmos sobre el manejo en la fase aguda y en la de recuperación. Se ha elaborado una guía terapéutica escalonada consensuada por expertos especialistas implicados en el tratamiento del DRESS

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media.

The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported.

Clinical practice guidelines for diagnosis and management of hypersensitivity reactions to contrast media

The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported (AU)

El contenido y las pautas recomendadas en este documento están dirigidas a lograr una práctica clínica más eficiente y eficaz. El panel de expertos que participó en esta guía de consenso desarrolló un protocolo para revisar lo publicado sobre el tema. La prevalencia de las reacciones alérgicas a medios de contraste iodados (MCI) se estima en 1:170.000, lo que representa un 0,05% -0,1% de los pacientes sometidos a estudios radiológicos con MCI (más de 75 millones de administraciones por año en todo el mundo). Las reacciones alérgicas por hipersensibilidad pueden aparecer dentro de la primera hora tras la administración (reacciones inmediatas) o en un rango de tiempo desde una hora hasta varios días después de la administración (reacciones no inmediatas o tardías). Existen factores de riesgo para las reacciones inmediatas tales como: mal control previo del asma bronquial, uso concomitante de inhibidores de la ECA, beta bloqueantes o inhibidores de la bomba de protones, administración rápida del fármaco, antecedente de mastocitosis, coexistencia de enfermedades autoinmunes o de infecciones virales. Los síntomas más comunes de las reacciones inmediatas son eritema y urticaria con o sin angioedema, apareciendo en más de un 70% de los pacientes que sufrieron reacciones. Las reacciones no inmediatas más comunes son las erupciones maculopapulares (30-90%). Para el diagnóstico de reacciones tanto inmediatas como no inmediatas se deben realizar pruebas cutáneas y pruebas in vitro. Para elegir el MCI que posteriormente puede ser administrado se tendrán en cuenta los resultados de las pruebas cutáneas e in vitro realizadas, el MCI que indujo la reacción (si se conoce), la gravedad de la misma, la disponibilidad de otros MCIs alternativos y la información disponible sobre la potencial reactividad cruzada entre los distintos MCIs. Otro tipo de medios de contraste, son los utilizados en la resonancia magnética (RMN), que son derivados de gadolinio. Aunque infrecuentes, se han descrito reacciones mediadas por IgE a estos medios de contraste (AU)

Self-Management of Anaphylaxis Is Not Optimal.

BACKGROUND: Our objective was to ascertain the degree of adherence to recommendations made to patients with anaphylaxis, most of whom were attended in our allergy outpatient clinic. METHODS: A questionnaire was sent to 1512 patients who had experienced anaphylaxis and completed by 887. The chosen definition of anaphylaxis was that of the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network Symposium. We evaluated the prescription, purchase, and use of epinephrine auto-injectors and oral drugs, as well as the avoidance of allergens involved in previous anaphylaxis episodes. RESULTS: Most patients (94.53%) reported that they had received advice on avoidance of responsible allergens after their allergy workup. Epinephrine auto-injectors and oral drugs were prescribed according to the subtype of anaphylaxis. Only 30.74% of patients used the epinephrine auto-injector; 54.26% took oral medication. Most patients (88.3%) avoided the allergen. CONCLUSIONS: Despite general agreement that anaphylaxis occurring in the community should be treated with epinephrine auto-injectors, use of these devices to treat recurrences was low in our patients. Oral medication intake was more common than the epinephrine auto-injector in all subtypes. In order to increase adherence to epinephrine auto-injectors, it is necessary to think beyond the measures recommended during regular visits to allergy outpatient clinics.

Self-management of anaphylaxis is not optimal

Background: Our objective was to ascertain the degree of adherence to recommendations made to patients with anaphylaxis, most of whom were attended in our allergy outpatient clinic. Methods: A questionnaire was sent to 1512 patients who had experienced anaphylaxis and completed by 887. The chosen definition of anaphylaxis was that of the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network Symposium. We evaluated the prescription, purchase, and use of epinephrine auto-injectors and oral drugs, as well as the avoidance of allergens involved in previous anaphylaxis episodes. Results: Most patients (94.53%) reported that they had received advice on avoidance of responsible allergens after their allergy workup. Epinephrine auto-injectors and oral drugs were prescribed according to the subtype of anaphylaxis. Only 30.74% of patients used the epinephrine auto-injector; 54.26% took oral medication. Most patients (88.3%) avoided the allergen. Conclusions: Despite general agreement that anaphylaxis occurring in the community should be treated with epinephrine auto-injectors, use of these devices to treat recurrences was low in our patients. Oral medication intake was more common than the epinephrine auto-injector in all subtypes. In order to increase adherence to epinephrine auto-injectors, it is necessary to think beyond the measures recommended during regular visits to allergy outpatient clinics (AU)

Antecedentes: Guías clínicas y documentos de posicionamiento recomiendan planes de acción urgentes personalizados para los pacientes que han tenido anafilaxia. El cumplimiento de estos planes es generalmente bajo. Objetivo: Nuestro objetivo fue determinar el grado de adherencia a diferentes recomendaciones hechas a los pacientes con anafilaxia, que en la mayoría de los cuales fueron atendidos en la consulta externa de Alergia de nuestro hospital. Métodos: Se envió un cuestionario a 1.512 pacientes que habían sufrido un episodio previo de anafilaxia y este fue completado por 887. La definición elegida de anafilaxia fue la del Instituto Nacional de Alergias y Enfermedades Infecciosas y el Simposio de la Food Allergy and Anaphylaxis Network (NIAID-FAAN). Se evaluó la prescripción, la compra y el uso de auto-inyectores de adrenalina y medicamentos orales, así como la evitación de alérgenos implicados en los episodios de anafilaxia anteriores. Resultados: La mayoría de los pacientes (94,53%) informaron que habían sido aconsejados sobre la evitación de alérgenos responsables después de su evaluación alergológica. Los auto-inyectores de adrenalina y los medicamentos orales se prescribieron de forma diferente según el subtipo de anafilaxia. Sólo el 30.74% de los pacientes utilizaron el auto inyector de adrenalina y el 54,26% tomo la medicación oral. La mayoría de los pacientes (88,3%) evitaron el alérgeno. Conclusiones: A pesar del acuerdo general que los episodios de anafilaxia que ocurren en la comunidad deben ser tratados con autoinyectores de adrenalina, el uso de estos dispositivos para el tratamiento de las recurrencias fue baja en nuestros pacientes. La ingesta oral de medicamentos es más común que el auto inyector de adrenalina en todos los subtipos. Con el fin de aumentar la adherencia a autoinyectores de adrenalina, es necesario investigar más allá de las medidas recomendadas durante las visitas regulares a las consultas de Alergia (AU)

Recurrence of Anaphylaxis in a Spanish Series

Background: Anaphylaxis is a potentially fatal condition, and many patients experience recurrence. Objective: We report the incidence of first recurrence of anaphylaxis in our series and examine the risk factors associated with recurrence. Methods: A validated questionnaire was sent to 1512 patients and completed by 887. The chosen definition of anaphylaxis was that of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network Symposium. We evaluated the incidence of first recurrence of anaphylaxis overall and by subtype (eg, drugs and foods) and attempted to determine associated risk factors. Results: The total incidence rate of the first recurrence of anaphylaxis (same subtype) was 3.2 episodes per 100 person-years (95%CI, 2.83-3.63). Incidence was lower in drug anaphylaxis (2.0 episodes per 100 person-years) than in latex and food anaphylaxis (8.6 and 5.6 episodes per 100 person-years, respectively). Cox and ordinal logistic regression models revealed that a first recurrence was less likely with drug anaphylaxis than with food anaphylaxis. The risk of experiencing 1 or more recurrences was higher for foods, exercise, and idiopathic causes than for the other subtypes. Conclusions: The incidence rate for a first recurrence of the same subtype of anaphylaxis was 2 to 6 times lower than that published by other authors. Recurrence of anaphylaxis is more common in subtypes with an increased prevalence of atopy (food, idiopathic, latex) than in other subtypes (drugs, Anisakis). Consequently, particular attention should be paid to prevention and care in this population (AU)

Antecedentes: Aunque la anafilaxia es una enfermedad potencialmente fatal, muchos pacientes sufren recurrencias de la misma. Objetivo: Nuestro objetivo fue conocer la incidencia de la primera recurrencia de la anafilaxia en nuestra serie y examinar los factores de riesgo asociados a la misma. Métodos: Un cuestionario validado fue enviado a 1512 pacientes y completado por 887. La definición de anafilaxia elegida fue la del Simposio NIAID-FAAN (National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network). Se evaluó la incidencia de la primera recurrencia de la anafilaxia en general y por subtipo (por ejemplo, medicamentos y alimentos) y se trató de determinar factores de riesgo asociados a la recurrencia. Resultados: La tasa de incidencia total de la primera recurrencia de la anafilaxia (el mismo subtipo) fue de 3,2 episodios por 100 personas año (95% CI, 2,83 a 3,63). La incidencia fue menor en la anafilaxia por medicamentos (2,0 episodios por 100 personas-año) que en la anafilaxia por látex y alimentos (8,6 y 5,6 episodios por 100 personas-año respectivamente). Los modelos de regresión de Cox y logística ordinal revelaron que la primera recurrencia fue menos probable con anafilaxia por medicamentos que con la anafilaxia alimentaria. El riesgo de sufrir una o más recurrencias fue mayor para los alimentos, el ejercicio, y anafilaxia idiopática que para los otros subtipos. Conclusiones: La tasa de incidencia de una primera recurrencia del mismo subtipo de anafilaxia fue 2-6 veces inferior a la publicada por otros autores. La recurrencia de la anafilaxia es más común en los subtipos con una mayor prevalencia de atopia (alimentos, idiopática, látex) que en los otros subtipos (medicamentos, Anisakis). Por lo tanto, se debería prestar especial atención a la prevención y atención de estas poblaciones (AU)

Incidence of anaphylaxis in the city of Alcorcon (Spain): a population-based study.

BACKGROUND: Relatively few studies have examined the incidence of anaphylaxis in the general population. OBJECTIVE: To report the incidence of anaphylaxis among the general population of the city of Alcorcon, Spain, using various public health care databases. METHODS: Episodes of anaphylaxis were recovered using validated alphanumeric strings in different fields of electronic clinical records used in the different public health settings in the city of Alcorcon (primary care, Emergency Department, hospitalized patients and Allergy Outpatient Clinic). Patients with anaphylaxis were tracked across the different clinical settings in Alcorcon. RESULTS: The incidence of anaphylaxis in Alcorcon was 103.37 episodes per 100 000 person-years (total standardized incidence rate of 112.2). There was a peak of 313.58 episodes in the 0-4 years age group and a different distribution of incidence rates (although non-significant) among different age groups between male patients and female patients. In most age groups, incidence tended to be higher for female patients aged over 10 years. Patients were attended at two or more levels in 76.78% of episodes, and a new evaluation was often made at a primary care centre (71.43%), Allergy Outpatient Clinic (75.6%), or both after the episode (58.93%). CONCLUSION AND CLINICAL RELEVANCE: This study revealed a higher rate of anaphylaxis than that in previous studies, although this incidence rate is probably lower than the real incidence rate. Studies exploring potential methodological, genetic and environmental factors accounting for these higher rates of anaphylaxis are required.

Incidence of anaphylaxis and subtypes of anaphylaxis in a general hospital emergency department.

BACKGROUND: The absence of large-scale international studies means that data on anaphylaxis in emergency departments in different geographic areas are still necessary. OBJECTIVE: To determine the incidence of anaphylaxis and subtypes of anaphylaxis and their distribution by age group in the emergency department of Hospital Universitario Fundación Alcorcon, Alcorcon (Madrid), Spain. METHODS: Our study was performed between 2004 and 2005. We used the definition of anaphylaxis established by the NIAID-FAAN Symposium. Patient information was collected from the electronic clinical records of the emergency department using alphanumeric strings to identify acute allergic illnesses. This strategy recovered 91.7% of all anaphylaxis episodes in a pilot study. RESULTS: We observed a crude cumulative incidence of 0.9 episodes of anaphylaxis per 1000 emergency episodes (95% confidence interval [CI], 0.8-1.1), and 0.8 episodes per 1000 people (95% CI, 0.7-0.9). Standardized cumulative incidence of anaphylaxis according to the Standardized European Population was 1.1 (95% CI, 0.9-1.2). On analyzing the 213 cases of anaphylaxis, we discovered that the main cause was food (28.6%), followed by drugs (28.2%), unknown causes (27.2%), Anisakis (10.8%), Hymenoptera venom (3.3%), exercise (2.4%), and latex (0.9%). Food-induced anaphylaxis was less frequent in all groups older than the 0-4 age group in both reference populations (people who attend the emergency department and the general population). CONCLUSIONS: The cumulative incidence of anaphylaxis in our emergency department is low. Anaphylaxis by foods is more frequent in the 0-4 year group than in the other age groups. Drugs and food are the most frequent causes of anaphylaxis in our emergency department.

Thrombocytopenia and anaphylaxis secondary to heparin in a hemodialysis patient.

AIMS: We describe a rare case of anaphylaxis and thrombocytopenia whose cause was heparin used during hemodialysis sessions. CASE REPORT: A 77-year-old woman suffered five consecutive episodes of vomiting, tachypnea, wheezing or rales, immediately after initiating hemodialysis. In the first of these episodes, arterial pressure was undetectable. In all of the episodes there was evidence of the presence of hypoxia (always below 60 mmHg) and thrombocytopenia (always below l00,000/microl,, with partial platelets recovery among episodes. The episodes started immediately after hemodialysis sessions and heparin infusion; either sodium heparin or enoxaparin was used. Utilization of different filters was not able to stop the episodes. These were stopped when a switch from heparin to hirudin was tested. Tryptase levels, as a marker of mast cells activation and anaphylaxis, were not increased in two of the episodes which were assessed. IgG antibodies against heparin-PF4 complex was detected at high levels. DISCUSSION: A diagnosis of concomitant anaphylaxis and thrombocytopenia caused by sodium heparin and a low-molecular weight heparin (enoxaparin) were assumed.