Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.
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...
Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation.Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with preferential localization in skin and bone marrow (BM). The great majority of cases are associated with somatic gainof-function point mutations of KIT, a tyrosine kinase receptor (CD117). The clinical presentation of mastocytosis is heterogeneous ranging from symptoms limited to the skin (with frequent spontaneous regression in pediatric cases) to a more aggressive systemic variant (SM), typical only of adulthood. Mastocytosis patients can experience symptoms due to massive MC activation and release of mediators (e.g., generalized pruritus, urticaria/angioedema, abdominal pain, anaphylaxis), but the presence of mediator symptoms does not correlate with the allele burden of the KIT mutation (1).The current classification of mastocytosis was developed in 2000 (2) and accepted by the World Health Organization (WHO) in 2001 (3) and then updated in 2008 (4) ( Table 1). According to the WHO classification, two major categories are defined: cutaneous mastocytosis (CM), limited to the skin, and systemic mastocytosis (SM), involving extracutaneous organs, mainly BM (Table 1) (4). The diagnosis of SM requires the presence of one major criterion and one minor criterion, or alternatively three minor criteria (Table 2) Systemic variant is suspected in patients with mastocytosis in the skin (MIS) and also in patients without MIS who have systemic symptoms of MC mediator release, including anaphylaxis. Patients without MIS may be a diagnostic challenge. The European Competence Network on Mastocytosis (ECNM) recently ...
Background Anaphylaxis, which is rare, has been reported after COVID‐19 vaccination, but its management is not standardized. Method Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre‐vaccination screening and management of allergic reactions to COVID‐19 vaccines, and literature was analysed. Results No death due to anaphylaxis to COVID‐19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1—anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2—anaphylaxis to oral/topical PEG containing products; 3—recurrent anaphylaxis of unknown cause; 4—suspected or confirmed allergy to any mRNA vaccine; and 5—confirmed allergy to PEG or derivatives. We recommend a prick‐to‐prick skin test with the left‐over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. Conclusions These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID‐19 vaccines and enable more people with history of allergy to be vaccinated.
Subcutaneous infusion ports (SIPs) represent a valid method for long-term chemotherapy. The SIPs have several advantages over other methods of venous access: they are easy to implant under local anaesthesia, have less discomfort for the patients, allow low costs, can be implanted in day hospital, and can be managed ambulatorily. However, SIPs have delayed complications, frequently related to clinical conditions of the neoplastic patients, and immediate complications, often due to the placement technique. From March 1992 to March 1997 we placed, under local anaesthesia and under fluoroscopic control, 102 SIPs in 99 general oncology patients for long-term chemotherapy (88% solid, 12% haematological tumours). The percutaneous venous access devices were in the subclavian vein in 96% of the cases and in the internal jugular vein in 4% of them. Immediate complications were: 1 haemopneumothorax, which required thoracic aspirations and two blood transfusions, 1 loop of the tunneled part of the catheter without alterations in SIP function, and 1 left jugular thrombosis in a patient with subclavian veins already thrombosed. The venous access was in the subclavian vein in the first 2 cases, and it was not necessary to suspend the therapeutic program. In the third instance, implanted in jugular vein, it was necessary to remove the SIP. Delayed complications were: 1 necrosis of the skin over the port, 1 infection of subcutaneous pocket, 2 infections of the system, 1 catheter deconnection, and 3 catheter ruptures with embolization of the catheter tip. The SIPs were removed in all cases but 1 in whom infection was successfully treated by appropriate antibiotic therapy. Embolization of the catheter required removal from the pulmonary artery under fluoroscopic guidance in the cardiac catheterization laboratory. In conclusion, infection and thrombosis are the two major complications of SIP in general oncology patients. In these cases it is not necessary to remove systematically the system, but a cor rect therapy (antibiotic, fibrinolytic agents) can be utilized with good results. The catheter rupture is often due to the wear over the costoclavicular angle. The interventional radiology is the method of choice in the treatment of the catheter embolization by rupture or dislocation. The experience of the surgical and nursing staff is probably the most important factor in decreasing the total rate of complications.
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