D1.37 - Sometimes it is not what it seems

Background:Clavulanic acid is a beta-lactam with mild antibacterial activity and a potent beta-lactamase inhibitor. While most allergic reactions to amoxicillin-clavulanic acid (AX-CA) are attributed to amoxicillin (AX), a minority of cases are caused by clavulanic acid (CA). This possibility should be considered during the diagnostic process.

Case Report:A 51-year-old woman with no known history of allergies presented with generalized urticaria and erythema, after surgery. No dyspnea or cardiovascular involvement was observed. Symptoms resolved after the administration of methylprednisolone and dexchlorpheniramine. Intraoperatively, she received fentanyl, propofol, midazolam, AX-CA, metamizole, and paracetamol. At home, she tolerated paracetamol, metamizole, and AX-CA without any issues.

Materials and Methods:Skin tests (prick and intradermal) were performed following a protocol for perioperative adverse reactions. Tested agents included suxamethonium, cisatracurium, thiopental, propofol, midazolam, morphine, fentanyl, remifentanil, latex, atropine, neostigmine, egg yolk, egg white, ovalbumin, ovomucoid, soy, corn, and povidone-iodine.

Results:All initial skin tests were negative. Medications previously tolerated by the patient were excluded from testing. The initial diagnosis was perioperative urticaria with a negative allergological workup.

Clinical course:Three months later, after a subsequent surgery, the patient developed facial erythema, pruritus, nausea, tachycardia (110 bpm), and hypotension (85/60 mmHg). Symptoms resolved with hydrocortisone and dexchlorpheniramine. During the procedure, she received AX-CA, propofol, and iodinated contrast (Plenigraf®, containing sodium amidotrizoate, meglumine amidotrizoate, and calcium amidotrizoate). At home, she tolerated oral ciprofloxacin without any issues.

Additional prick and intradermal tests with propofol, Plenigraf®, and latex were negative. Specific IgE tests for penicillin G, penicillin V, cefaclor, AX, ampicillin, and latex were also negative. Subsequent skin tests with benzylpenicilloyl-polylisine (PPL), minor determinant mixture (MDM), penicillin G, AX, and CA showed positive results for CA. A controlled oral challenge with therapeutic doses of amoxicillin confirmed good tolerance.

Conclusion:The final diagnosis was immediate hypersensitivity to clavulanic acid. Initially, it was not considered a probable cause as the patient had tolerated it at home and in previous instances. This case highlights how transient desensitization can complicate the identification of the causal agent.