Lene H. Garvey

Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group position paper

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.

Standardized testing with chlorhexidine in perioperative allergy--a large single-centre evaluation

Perioperative allergic reactions to chlorhexidine are often severe and easily overlooked. Although rare, the prevalence remains unknown. Correct diagnosis is crucial, but no validated provocation model exists, and other diagnostic tests have never been evaluated. The aims were to estimate (i) the prevalence of chlorhexidine allergy in perioperative allergy and (ii) the specificity and sensitivity for diagnostic tests for chlorhexidine allergy.

No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut

BACKGROUND Propofol is thought to be a potential cause of allergic reactions in patients allergic to egg, soy or peanut, since current formulations contain an emulsion that includes egg lecithin and soybean oil. However, other than six case reports lacking in confirmatory evidence of an allergic reaction, there is no evidence linking the two types of allergies. The aim of this study was to examine the frequency of propofol allergy and to investigate if patients with specific immunoglobulin E (IgE) to egg, soy or peanut tolerated propofol. METHODS Study A examined the frequency of propofol allergy in 273 patients systematically investigated for suspected perioperative allergic reactions. Of these, 153 had been exposed to propofol and underwent skin tests and intravenous provocation. Study B retrospectively investigated propofol exposure and tolerance in 520 adult patients with a positive specific IgE to egg, soy or peanut. RESULTS Four of the 153 propofol-exposed patients (2.6%) investigated in study A were diagnosed with propofol allergy. Of these, three tested positive only on intravenous provocation. None of the four had allergic symptoms when eating egg, soy or peanut and none had detectable levels of specific IgE to egg or soy in their serum. In study B we found no signs of allergic reactions towards propofol in 171 retrieved anaesthetic charts from 99 patients with specific IgE to egg, soy or peanut. CONCLUSION No connection between allergy to propofol and allergy to egg, soy or peanut was found. The present practice of choosing alternatives to propofol in patients with this kind of food allergy is not evidence based and should be reconsidered.

Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper

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.

Effect of General Anesthesia and Orthopedic Surgery on Serum Tryptase

Background:Mast cell tryptase is used clinically in the evaluation of anaphylaxis during anesthesia, because symptoms and signs of anaphylaxis are often masked by the effect of anesthesia. No larger studies have examined whether surgery and anesthesia affect serum tryptase. The aim of this study was to investigate the effect of anesthesia and surgery on serum tryptase in the absence of anaphylaxis. Methods:The study included 120 patients (median age, 54 yr; range, 19–94 yr) undergoing elective orthopedic surgery in general anesthesia. Exclusion criteria were allergic reactions during this or previous anesthesia, hematologic disease, or high-dose corticosteroid treatment. Blood samples for tryptase analysis (ImmunoCAP®; Phadia, Uppsala, Sweden) were drawn shortly before anesthesia and after anesthesia and surgery. Results:Median duration of anesthesia was 105 min (range, 44–263 min). Median interval between blood samples was 139 min (range, 39–370 min). Mean tryptase before surgery was 5.01 &mgr;g/l, with a mean decrease of 0.55 &mgr;g/l (P < 0.0001; 95% CI, 0.3–0.8) postoperatively. All patients received intravenous fluid (median value 750 ml; range, 200–2000 ml) perioperatively. There was no significant effect of gender, age, American Society of Anesthesiologists physical status classification, or self-reported allergy on serum tryptase. Conclusions:Serum tryptase shows small intraindividual variation in the absence of anaphylaxis. A small decrease was observed postoperatively, likely due to dilution by intravenous fluid. On suspected anaphylaxis during anesthesia, tryptase values, even within the normal reference interval, should, when possible, be compared with the patients own basal level taken more than 24 h after the reaction.

Immediate-type hypersensitivity to polyethylene glycols: a review

Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life‐threatening immediate‐type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness of PEGs allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate‐type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross‐sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEGs as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re‐exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management.

Chlorhexidine allergy: sources of exposure in the health-care setting

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Dynamics of plasma levels of specific IgE in chlorhexidine allergic patients with and without accidental re-exposure.

Chlorhexidine is an effective disinfectant, which may cause severe allergic reactions. Plasma level of specific IgE to chlorhexidine (ImmunoCAP®) has high estimated sensitivity and specificity when measured within 6 months of allergic reaction, but knowledge of the dynamics over longer time periods is lacking and it is unknown whether levels fall below <0.35 kUA/L in patients with previously elevated levels. It is also unclear whether re‐exposure influences levels of specific IgE.

Clinical and diagnostic features of perioperative hypersensitivity to cefuroxime

The Danish Anaesthesia Allergy Centre (DAAC) investigated 89 adult patients with suspected perioperative cefuroxime‐associated hypersensitivity reactions between 2004 and 2013. The goals were to determine whether the time to index reaction after cefuroxime exposure could be used to implicate cefuroxime as the cause of the reactions and explore different test modalities in diagnosing cefuroxime hypersensitivity.

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.