D1.53 - Anaphylaxis to Beta-Lactams: The Importance of the Oral Challenge Test in Diagnosis

A 60-year-old patient was assessed at Chivasso Hospital allergy unit for an anaphylactic reaction (diffuse urticaria, palmoplantar itching, desaturation, and severe hypotension) that occurred immediately after taking the first dose of amoxicillin, previously taken and tolerated. The patient has a history of allergic asthma dust mites related, which is currently well-controlled off-therapy.

Laboratory investigations included total IgE measurement (156 kU/L) and specific IgE tests, which were negative for penicilloyl G and V, and cefaclor, but positive for amoxicillin (0.99 kU/L). Skin tests were performed over two days for PPL (Penicilloyl-polylysine) and MDM (minor determinant mixture), and subsequently for amoxicillin/clavulanate, ampicillin, ceftriaxone, and ceftazidime. These tests yielded positive results for amoxicillin/clavulanate (prick test 2 mg/ml) and ampicillin (ID 2 mg/ml). An oral challenge test with cefixime was then performed over two days.

Results of the First Day: about 30 minutes after reaching a cumulative dose of 200 mg, the patient reported mild, unilateral palm itching without associated erythema, which resolved spontaneously within approximately 15 minutes. Results of the Second Day: about 15 minutes after reaching a cumulative dose of 400 mg, the patient developed itching associated with erythema localized to the palm and right forearm. A diffuse rash was observed on the trunk, axillary area, and inguinal folds. Additionally, the patient reported a sensation of chest tightness and nausea.She was treated with 0.5 cc IM adrenaline, 4 mg IM betamethasone, and 10 mg/ml IM chlorphenamine, with a complete resolution of the clinical symptoms within 30 minutes.

The patient presented to our Allergy Unit after an episode of anaphylaxis with amoxicillin. Despite negative skin tests for third generation cephalosporins, the patient developed anaphylactic reactions during an oral challenge with cefixime. Therefore, it was advised to avoid all beta-lactams (incl. penicillins, cephalosporins, and carbapenems), and future testing will be considered to assess the possibility of safely reintroducing carbapenems Although cross-reactivity between beta-lactams is rare (<1%), it is documented in the literature. The cross-reactivity among beta-lactams is typically related to the structural similarity of their side chains, and rarely to sensitization to the beta-lactam ring itself. In this case, the patient reacted to a cephalosporin with a side chain completely different from that of amoxicillin; thus, it cannot be excluded that there was sensitization to common structural components or primary sensitization to both molecules, despite negative skin test results.

This case highlights the importance of the oral drug challenge test in diagnosing beta-lactam allergies, as emphasized in the article by Romano (Allergy 2020), since a negative skin test result has limited value in determining the risk of future reactions.