In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis.

Drug-induced anaphylaxis survey in Portuguese Allergy Departments.

BACKGROUND AND OBJECTIVE: Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal. METHODS: During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects. RESULTS: The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1.The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved. CONCLUSIONS: NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis.

Drug-induced anaphylaxis survey in Portuguese Allergy Departments

Background and Objective: Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal. Methods: During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects. Results: The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1. The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved. Conclusions: NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis (AU)

Antecedentes: La anafilaxia inducida por medicamentos es una reacción adversa impredecible y potencialmente fatal. El objetivo de este estudio fue identificar las causas de la misma en Portugal. Método: Durante un periodo de 4 años fue desarrollado un sistema de notificación nacional de anafilaxia enfocado al informe voluntario de los alergólogos. Se recopilaron 313 casos de pacientes con anafilaxia por medicamentos. El análisis estadístico incluyó test de distribución y regresión logística múltiple para analizar la significación y los coeficientes de regresión y efectos marginales. Resultados: La edad media de los pacientes fue de 43.8 ± 17.4 años, 8.3% menores de 18 años. La relación mujer/varón fue de 2:1. El grupo más frecuentemente implicado fue el de los analgésicos antiinflamatorios no esteroideos (AINEs), seguido de los antibióticos y anestésicos en 47.9%, 35.5% y 6.1% de los casos respectivamente. Se observó un predominio de los síntomas mucocutáneos (92.2%), seguidos de los respiratorios (80.4%) y cardiovasculares (49.0%). Los pacientes con anafilaxia por AINEs mostraban más síntomas respiratorios y mucocutáneos. No se encontró asociación entre edad, género y atopia con los diferentes grupos de medicamentos. La recurrencia de anafilaxia se observó en el 25.6% de los casos, con un riesgo incrementado cuando los AINEs eran los responsables. Conclusiones: En este estudio, los AINEs fueron los medicamentos más frecuentemente implicados en las reacciones de anafilaxia y mostraron más frecuencia de reincidencia de las reacciones. Es importante evaluar bien los tratamientos y prevenir la reincidencia de anafilaxia por medicamentos (AU)

Determining the negative predictive value of provocation tests with beta-lactams.

BACKGROUND: The beta-lactam allergic work-up is mostly standardized. However, the negative predictive value of drug provocation tests is not yet well established. METHOD: A historical-prospective multicentre cohort study was conducted in four centres (one in France, one in Portugal, two in Italy) to assess the negative predictive value of provocation tests with beta-lactams in patients initially tested for a suspicion of drug allergy/hypersensitivity. Patients were contacted at least 6 months after the work-up, between 2003 and 2007. A new allergic work-up was proposed to reacting patients. RESULTS: Among the 457 patients included, 365 (79.9%) were followed up (159 [79.1%] from France, 153 [82.7%] from Italy and 53 [74.6%] from Portugal). Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). CONCLUSION: Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups.

Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study.

BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. METHODS: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. RESULTS: Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.