Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper.

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.

Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. METHODS: The GA2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. RESULTS: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. CONCLUSION: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.

Clinical and immunological determinants of severe/refractory asthma (SRA): association with Staphylococcal superantigen-specific IgE antibodies.

BACKGROUND: Demographic and immunological determinants of severe refractory asthma (SRA) are not well characterized. Because Staphylococcus aureus enterotoxins with superantigenic activity have been associated with upper and lower airway inflammation, we aimed to evaluate the association of sensitization to Staphylococcal enterotoxins with asthma severity and various asthma phenotypes. METHODS: The study included 109 patients with SRA diagnosed according to the American Thoracic Society Workshop 2000, and 101 patients with nonsevere asthma, followed for at least 12 months. Specific IgE to Staphylococcus enterotoxins and total IgE and eosinophil cationic protein concentrations were measured in serum with immunoassays. FINDINGS: A significant risk for severe asthma was associated with female gender [Odds Ratio (OR) = 2.04], history of wheezing in childhood (OR = 2.47), presence of hypersensitivity to aspirin (OR = 1.96) and with body mass index (OR = 3.08). The mean level of enterotoxin-specific IgE was 3-fold higher in patients with severe asthma when compared to patients with nonsevere asthma (P = 0.01). Serum-specific IgE to enterotoxins was significantly associated with low respiratory function parameters (FEV1, FEV1/FVC and MEF 25/75) and increased airway reversibility in response to albuterol. The presence of specific IgE to enterotoxin carried a significant risk for patients to have serum total IgE level above 100 kU/l (OR = 7.84). INTERPRETATION: Specific immunological response to enterotoxins is associated with clinical and immunological parameters of asthma severity, suggesting a role for Staphylococcal enterotoxins in the asthma pathogenesis.

Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis--a GA² LEN study.

BACKGROUND: The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA(2) LEN European survey. METHODS: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. RESULTS: There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I(2) = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. CONCLUSION: Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS.

Lack of association between aspirin-triggered 15-hydroxyeicosatetraenoic acid release and mast cell/eosinophil activation in nasal polyps from aspirin-sensitive patients.

BACKGROUND: The mechanism of aspirin sensitivity in patients with asthma and rhinosinusitis has been attributed to arachidonic acid metabolism abnormalities. OBJECTIVE: We aimed to test whether aspirin-triggered generation of 15-hydroxyeicosatetraenoic acid (15-HETE) in nasal polyp dispersed cells (NPDCs) from aspirin-sensitive patients is associated with activation of inflammatory cells. METHODS: Polyps were obtained from 11 aspirin-sensitive and 19 aspirin-tolerant patients with chronic rhinosinusitis. NPDCs were stimulated by aspirin or calcium ionophore. Levels of 15-HETE, leukotriene (LT) C4, eosinophil cationic protein (ECP), and tryptase were measured in NPDC supernatant. RESULTS: NPDCs from aspirin-sensitive patients contained more eosinophils (14% vs 9%, P < .05) and released 2.4-fold more ECP (P < .01) at baseline. Stimulation with aspirin (200 microM) resulted in a significant increase in 15-HETE generation only in tissue from aspirin-sensitive patients (mean increase, 82%) but did not induce any increase in the release of LTC4, ECP, or tryptase. Preincubation with calcium ionophore resulted in significantly enhanced generation of 15-HETE, ECP, tryptase, and LTC4 in patients from both groups. Incubation of NPDCs with misoprostol inhibited aspirin-induced 15-HETE generation in aspirin-sensitive patients and calcium ionophore-induced 15-HETE, ECP, and tryptase release in both aspirin-sensitive and aspirin-tolerant patients. CONCLUSION: Our study demonstrated that aspirin-induced 15-HETE generation in nasal polyps from aspirin-sensitive patients is not associated with activation of mast cells and eosinophils. Misoprostol has a potent inhibitory effect on the activation of cells derived from the site of nasal mucosal inflammation, regardless of sensitivity to aspirin.