Guideline sources The following summarized guidelines for the evaluation and management of drug allergy are prepared by our editorial team based on guidelines from the American Academy of Allergy, Asthma & Immunology (AAAAI 2022), the British Society for Allergy and Clinical Immunology (BSACI 2015), and the European Academy of Allergy and Clinical Immunology (EAACI/WAO/iCAALL/AAAAI/ACAAI/ICON 2014). 1 2 3 Guidelines 1. Diagnostic investigations Medical history: elicit a history of drug allergy using specific questioning before issuing a prescription from both a medical and legal viewpoint. B Drug challenge testing: As per AAAAI 2022 guidelines, consider obtaining drug challenge testing with a 1- or 2-step drug challenge when the clinical probability of a drug allergy is low in patients without contraindications for a drug challenge. C Show 2 more As per ICON 2014 guidelines, obtain a drug challenge test as the gold standard to identify the drug eliciting a drug hypersensitivity reaction. B Prefer the oral route whenever possible for drug challenge testing. B Show 2 more Evaluation of penicillin allergy: https://web.pathway.md/diseases/reczar7CgdXY7kEyP 1/4 6/29/23, 10:20 PM Drug allergy Pathway As per AAAAI 2022 guidelines, attempt to de-label patients with reported penicillin allergy, if appropriate. B Show 11 more As per BSACI 2015 guidelines, do not obtain an evaluation in patients with a family history but no personal history of penicillin allergy. D Show 7 more As per ICON 2014 guidelines, consider obtaining retesting 2-4 weeks after the initial evaluation in patients experienced severe immediate reactions to -lactams and displayed negative results at the first evaluation which included a drug challenge test. C Evaluation of sulfonamide allergy: consider obtaining a 1-step drug challenge with TMP- SMX when there is a need to delabel a sulfonamide antibiotic allergy in patients with a history of benign cutaneous reactions (such as morbilliform drug eruption, urticaria) to sulfonamide antibiotics occurred > 5 years ago. C Evaluation of fluoroquinolone allergy: consider obtaining a 1- or 2-step drug challenge without preceding skin testing to confirm tolerance in patients with a history of non- anaphylactic reactions to fluoroquinolones. C Evaluation of macrolide allergy: consider obtaining a 1- or 2-step drug challenge without preceding skin testing to confirm tolerance in patients with a history of non-anaphylactic reactions to macrolides. C Evaluation of aspirin allergy: do not obtain oral aspirin challenge to confirm the diagnosis of aspirin-exacerbated respiratory disease in cases of high diagnostic certainty based on clinical history, recognizing that aspirin desensitization remains a therapeutic option when indicated. D Consider obtaining an oral aspirin challenge to confirm the diagnosis of aspirin-exacerbated respiratory disease in cases of diagnostic uncertainty. D Show 2 more Evaluation of abacavir allergy: obtain HLA-B5701 screening before initiating abacavir to reduce the risk of drug hypersensitivity reactions. A Evaluation of excipient allergy: recognize that excipients are a very rare cause of immediate or delayed reactions associated with drugs. Consider suspecting excipient hypersensitivity in patients with a history of anaphylaxis to 2 structurally unrelated drugs or products sharing a common excipient (such as injectable corticosteroids, polyethylene glycol-based laxatives). B Evaluation of contrast media allergy: consider obtaining skin testing for the diagnosis of immediate drug hypersensitivity reactions to iodinated radiocontrast media. C 2. Medical management Drug desensitization (beta-lactams): consider offering desensitization if there is an absolute requirement for a specific -lactam in the presence of positive skin or challenge tests. C Drug desensitization (aspirin): consider offering desensitization to aspirin as a therapeutic intervention in selected asthmatic patients with aspirin-exacerbated respiratory disease or nasal polyps. C https://web.pathway.md/diseases/reczar7CgdXY7kEyP 2/4 6/29/23, 10:20 PM Drug allergy Pathway Choice of an alternative agent (testing): consider obtaining drug challenge testing in a hospital setting to search for safe alternatives when the alternatives belong to the same drug class. C Choice of an alternative agent (antibiotics): consider administering a penicillin without testing or additional precautions in patients with a history of an unverified non-anaphylactic cephalosporin allergy. C Show 2 more Choice of an alternative agent (analgesics): consider administering a selective COX-2 inhibitor as an alternative analgesic in patients with any NSAID hypersensitivity phenotype when an NSAID is needed. C 3. Preventative measures Avoidance of the drug: Advise lifelong avoidance of the drug and cross-reactive drugs in patients with a history of drug-induced anaphylaxis. B Provide an indicative, regularly updated list of drugs to avoid and the list of possible alternatives in patients with a drug hypersensitivity reaction. B Premedication: offer premedication (slow injection, pretreatment with corticosteroids and H1RAs) for non-allergic drug hypersensitivity reactions, although corticosteroids and H1RAs may not reliably prevent IgE-dependent anaphylaxis. B Clinical findings Symptoms Past medical history Abdominal cramps Anaphylaxis Arthralgia Atopy Chest tightness Stevens-johnson syndrome Cough Ocular exam Diarrhea Dizziness Conjunctival injection Dysphagia Eyelid swelling Fainting Dental exam Fever Generalized pruritus Stomatitis Headache Lightheadedness Integument exam Lip swelling Angioedema Malaise Atypical target lesions Nasal congestion Diaphoresis Nausea Maculopapular rash Seizure Morbilliform rash Shortness of breath https://web.pathway.md/diseases/reczar7CgdXY7kEyP 3/4 6/29/23, 10:20 PM Drug allergy Pathway Skin flushing Nikolsky's sign Vomiting Papulovesicular rash Skin bullae Vital signs Skin desquamation Skin edema Hypotension Urticaria Head and neck exam Diagnostic procedures Periorbital edema drug challenge test Swollen uvula skin patch test Tongue swelling skin prick test Respiratory exam Bronchospasm Laryngeal edema Wheezing Serological findings ll ifi I E References 1. P Demoly, N F Adkinson, K Brockow et al. International Consensus on drug allergy. Allergy. 2014 Apr;69 4 420 37. Open 2. David A Khan, Aleena Banerji, Kimberly G Blumenthal et al. Drug Allergy: A 2022 Practice Parameter Update. J Allergy Clin Immunol. 2022 Sep 16;S0091 6749 22 01186 1. Open 3. R Mirakian, S C Leech, M T Krishna et al. Management of allergy to penicillins and other beta- lactams. Clin Exp Allergy. 2015 Feb;45 2 300 27. Open 4. Knut Brockow, Bernhard Przybilla, Werner Aberer et al. Guideline for the diagnosis of drug hypersensitivity reactions. Allergo J Int. 2015; 24 3 94 105. Open https://web.pathway.md/diseases/reczar7CgdXY7kEyP 4/4