Hypersensitivity reactions to aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAIDs) constitute only a subset of all adverse reactions to these drugs, but due to their severity pose a significant burden to patients and are a challenge to the allergist. In susceptible individuals, NSAIDs induce a wide spectrum of hypersensitivity reactions with various timing, organ manifestations, and severity, involving either immunological (allergic) or nonimmunological mechanisms. Proper classification of reactions based on clinical manifestations and suspected mechanism is a prerequisite for the implementation of rational diagnostic procedures and adequate patient management. This document, prepared by a panel of experts from the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity, aims at reviewing the current knowledge in the field and proposes uniform definitions and clinically useful classification of hypersensitivity reactions to NSAIDs. The document proposes also practical algorithms for the diagnosis of specific types of NSAIDs hypersensitivity (which include drug provocations, skin testing and in vitro testing) and provides, when data are available, evidence-based recommendations for the management of hypersensitive patients, including drug avoidance and drug desensitization.Nonsteroidal anti-inflammatory drugs (NSAIDs) induce a whole range of adverse reactions related to their pharmacological properties. In susceptible individuals, NSAIDs may induce hypersensitivity reactions varying in timing (immediate/delayed), organ involvement (skin, airways, or other organs), and severity (from mild dyspnea, rhinorrhea, exanthema, or urticaria, to anaphylaxis and death). Since aspirin (acetylsalicylic acid; ASA), the first synthetic compound with antipyretic, analgesic, and anti-inflammatory activity, was synthesized in 1893, dozens of compounds with similar activity have been developed and commercialized and almost all of them were reported to induce hypersensitivity reactions in susceptible subjects. The large variety of NSAIDs inducing hypersensitivity reactions, the wide spectrum of symptoms observed, and different pathomechanisms involved create a challenge to an allergist especially if an unified and practical Allergy 68 (2013) 1219-1232

Following the first description of hypersensitivity reaction to aspirin (ASA) by Hirschberg in 1902, several types of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) have been described. The NSAIDs-induced hypersensitivity reactions involve different mechanisms and present a wide range of clinical manifestations from anaphylaxis AbstractNonsteroidal 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.

NSAID-exacerbated respiratory disease (N-ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence-based recommendations for the diagnosis and management of N-ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N-ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N-ERD. Recommendations for the most effective management of a patient with N-ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub-phenotypes and emerging sub-endotypes of N-ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N-ERD and unmet needs, which should be addressed in the future.

The outbreak of the SARS‐CoV‐2‐induced coronavirus disease 2019 (COVID‐19) pandemic re‐shaped doctor‐patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS‐CoV‐2 is not known. Severe COVID‐19 patients may experience a “cytokine storm” and associated organ damage characterized by an exaggerated release of pro‐inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti‐inflammatory cytokines and type 2 responses. This expert‐based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID‐19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self‐application. In case of an active SARS‐CoV‐2 infection, biological treatment needs to be stopped until clinical recovery and SARS‐CoV‐2 negativity is established and treatment with biologicals should be re‐initiated. Maintenance of add‐on therapy and a constant assessment of disease control, apart from acute management, are demanded.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on | 389 PAGANI et Al. 1 | INTRODUC TI ON Chemotherapeutic drugs have been used in the treatment of neoplasms since the 1940s. 1,2 Many types of antineoplastic agents were introduced in clinical practice and, despite the great diffusion of biological agents, chemotherapy (CHT) still represents the gold standard for the treatment of the majority of cancers, alone or in combination with the so-called more selective targeted therapies, namely monoclonal antibodies or other biologicals. 3 However, CHT can induce hypersensitivity reactions (HSRs) and remains the third leading cause of fatal drug-induced anaphylaxis in the United States. 4 Deaths related to CHT have also been reported in Europe. 5 This position paper aims to provide consensus on investigating HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections in this paper cover risk factors, pathogenesis, symptoms and signs of reactions, the role of skin tests, in vitro tests, indications and contraindications of drug provocations tests and desensitization of neoplastic patients with allergic reactions to CHT. Table 1 reports the main classes of CHT, their clinical indications, the characteristics of HSRs and their possible pathogenetic mechanisms. 2 | ME THODS This Position Paper was commissioned by the European Academy of Allergy and Clinical Immunology (EAACI). The task force group performed an intensive electronic literature search in MEDLINE, PubMed, databases of scientific societies, and reports of the AEMPS, European Medicines Agency, and the United States Food and Drug Administration by using the primary key words: hypersensitivity to chemotherapeutic drugs, hypersensitivity to antineoplastic agents, platinum compound hype...