The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cod.12432

European Society of Contact Dermatitis guideline for diagnostic patch testing – recommendations on best practice

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/all.12350

International Consensus on drug allergy.

The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.

/pdf/the-clinical-utility-of-basophil-activation-testing-in-3zmm2gd9t8.pdf

The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cea.12468

Management of allergy to penicillins and other beta‐lactams

When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical spectrum, and appropriate diagnostic methods particularly in children. Meanwhile, the tools used for DH management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of DH and management differ with age. Most reactions in children are still attributed to betalactams. Some manifestations, such as nonsteroidal anti-inflammatory drug-associated angioedema and serum sickness-like reactions, are more frequent among young patients as compared to adults. Risk factors such as viral infections are particularly frequent in children, making the diagnosis challenging. The practicability and validity of skin test and other diagnostic procedures need further assessment in children. This study presents an up-to-date review on epidemiology, clinical spectrum, diagnostic tools, and current management of DH in children. A new general algorithm for the study of these reactions in children is proposed. Data are presented focusing on reported differences between pediatric and adult patients, also identifying unmet needs to be addressed in further research.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/all.12774

Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group.

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.

http://allergy-society.bg/wp-content/uploads/2014/11/Skin_test_concentrations.pdf

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

IgE-mediated reactions to systemic corticosteroids (CSs) are rare. Hydrocortisone and methylprednisolone succinate ester are the most frequent elicitors. Excipients of depot corticosteroids (like carmellose or macrogol) may also be involved. The involvement of the dipropionate form of betamethasone (present in the depot Diprostène®) has not been studied. To describe the case of a 40-year-old woman, who presented an anaphylactic shock reaction upon intra-articular administration of Diprostène® (Betamethasone sodium phosphate and betamethasone dipropionate), associated with an iodinated radiocontrast media (ICM, Xenetix). An allergy work-up was performed, according to recommendations for severe immediate reactions. Nine months after the reaction [hypotension (7/5 mmHg), erythema and desaturation at 94%, treated with adrenalin, methylprednisolone hemisuccinate, dexchlorpheniramine] the patient underwent skin prick tests (SPT) and intradermal tests (IDT) with ICM, bethamethasone and Diprostène® (commercial molecules). Latex and chlorexidine were also studied. The tests resulted negative for ICM, latex and chlorexidine (including serum specific IgE ImmunoCAP ThermoFisher Scientific®), bethametasone phosphate (IDT 0.4 mg/mL) and carmellose (IDT 0.5 mg/mL). SPT elicited a positive reaction towards Diprostène® in immediate reading, (for 5, 0.5, 0.05 mg/mL) with an erythema (10, 8, 5 mm respectively) and a wheal (of at least 3 mm for each SPT). We performed an oral drug challenge to bethametasone phosphate for a total of 8 mg and it was well tolerated. The basal tryptase was 5.5 microg/mL. Tryptasemia 30 minutes after the reaction was 26.8 microg/mL. We describe an anaphylactic reaction to Diprostène®, proven by positive ST. The hypothesis of allergy to betamethasone dipropionate is under investigation. The hypothesis of allergy to macrogol, the other excipient of (which was not tested separately) is less likely, since the patient received Commirnaty SARS-CoV-2 vaccine 3 months after the reaction. The allergy work-up is ongoing (tests are programmed for betamethasone dipropionate alone). 

Anaphylactic shock induced by a depot corticosteroid: Reflections on a clinical case

Introduction ( contexte de la recherche ) Perioperative anaphylaxis requires thorough explorations. When no active substance is detected as responsible for the anaphylaxis, investigations of potential responsible excipients should be performed. We describe the case of a patient who experienced a perioperative anaphylactic reaction attributed to mannitol. 0. A 15 year-old teenager was admitted to a tertiary care hospital for extraction of her wisdom teeth under general anaesthesia (GA). At the end of the surgery, she suffered from tachycardia, hypotension, bronchospasm and urticaria. She was immediately treated with epinephrine and transferred to the intensive care unit (ICU). One hour after the reaction, her tryptase level was 15.5 μg/L, and it was 14 μg/L two hours after. Her basal level of tryptase was 3.6 μg/L. The patient was discharged from the ICU 24 h later (total recovery) and was further referred to the allergy team for investigations. Drugs used during the GA were Rocuronium, Sufentanyl, Remifentanyl, Dexamethasone, Ketoprofen and Paracetamol. Skin pricks tests (SPT) and intradermal testing (IDT) at the recommended concentrations were performed for all drugs except for paracetamol (given orally in the ICU and well tolerated after the reaction). Skin testing was negative for all drugs, as were oral challenges (OC) for dexamethasone and ketoprofen. Serum specific IgE dosages for quaternary ammonium, latex, chlorhexidine were also negative. In absence of an obvious culprit, SPT and IDT for the intravenous form of paracetamol (containing mannitol) were performed. The SPT exhibited negative result, but the IDT of the pure dilution 10 mg/ml and the 1/10 (1 mg/ml) dilution were positive. It was then decided to perform SPT and IDT for mannitol 10% and 20%, at 1/100 and 1/10 dilutions, which turned out positive (but negative on 2 controls). An OC with an effervescent tablet of paracetamol (2000 mg) containing mannitol was realised and was negative. Oral mannitol was well tolerated. Our clinical case raises awareness about the possible allergy to mannitol when administered through the intravenous route even though the oral route is well tolerated. 

Anaphylactic reaction to mannitol as excipient

Furosemide is a widely used diuretic belonging to the family of loop diuretics, which is potent and rapid acting. It belongs to the chemical family of sulfonamides. Few cases [1], [2] of hypersensitivity reactions to furosemide have been reported. We describe the case and the allergy work-up of a 43-year-old Caucasian woman with a history of an anaphylactic reaction after taking iv furosemide. Skin tests (ST) were performed as recommended, with prick (SPT) and intradermal test (IDT). The concentrations were experimental but verified in controls. The patient had experienced diffuse urticaria, respiratory distress and bradycardia at 40 bpm, 45 minutes after the injection of IV furosemide. Admitted to the emergency room she was treated with IV adrenaline, methylprednisolone hemisuccinate and oxygenotherapy (complete recovery after a few hours). No serum tryptase was collected. Prior to this episode, the patient had never taken furosemide. SPT with furosemide (neat concentration 10 mg/mL) was negative with a normal response to the histamine control and no response to the saline control. The IDT was positive at a concentration of 1:100. Three controls were all negative to the IDT at this concentration. IDT to furosemide at 1:1000 was also positive. Basal tryptase was 5.01 μg/L. We presented a case of anaphylaxis to furosemide, whose mechanism was proven to be IgE-mediated, based on the following arguments: severe clinical history, positive ST with negative controls at the same experimental concentrations. The allergological reasoning is the same, whether the external accountability for a certain drug is high or low. Cross reactivity with other sulfonamides should be further explored [3]. 

Am Chiriac

Papers

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

Anaphylactic shock induced by a depot corticosteroid: Reflections on a clinical case

Anaphylactic reaction to mannitol as excipient

IgE-mediated hypersensitivity to furosemide proven by skin tests

Nonimmediate Maculopapular Erythema Induced by a Gadolinium-Based Contrast Agent