Incidence of Antibiotic-Related Rash in Children with Epstein-Barr Virus Infection and Evaluation of the Frequency of Confirmed Antibiotic Hypersensitivity

Abstract

Background: The incidence of rash after aminopenicillin treatment in children with Epstein-Barr Virus (EBV) infection was reported to be 80–100%. A few recent studies suggested that the incidence may be much lower during EBV infection. There are no clear data on the incidence of true drug hypersensitivity among these patients. The aim of this study is to determine the incidence of rash and antibiotic allergy after antibiotic treatment in children with EBV infection. Methods: Drug hypersensitivity was investigated in antibiotic-treated patients with a positive EBV IgM who developed a rash between 2013 and 2016. Results: During the study period, 221 children were diagnosed with EBV infection, and 120 (54.3%) patients were treated with antibiotics during disease. Rash developed in 41 (41/221, 18.6%) patients, and 20 of them (total 120; 16.6%) were treated with antibiotics (most frequently aminopenicillins: 72.5%), and 21 of them (total 101, 20.8%) were not treated with antibiotics (p = 0.43). For 10 of the 20 antibiotic-treated patients with a rash, parents did not consent to an allergy workup. Three of the 10 patients who were tested for drug allergy were proven to have amoxicillin-clavulanate hypersensitivity (30%). Five of the patients without workup reacted after reuse of the suspected drug for infection treatment. Conclusion: In this study, the incidence of drug hyper­sensitivity was much lower than previously reported. Some of the reactions that occur during infectious mononucleosis are transient, and some are true drug hypersensitivity reactions. Thus, these patients should be evaluated with allergy tests before these drugs are used again after EBV infection.

Skin eruptions in children: Drug hypersensitivity vs viral exanthema

“…The suggestion that EBV is associated with DIE in patients with infectious mononucleosis (IM) has been broadly welcomed in the medical community, but a few studies have failed to generate recurrence of symptoms after drug re‐challenge 13,19 . The mechanism of DIE most commonly proposed with respect to IM is that the viral load and the increasing numbers of activated CD8 + T‐lymphocytes lead to a rise in the levels and activity of interferon‐γ (IF‐γ) and interleukin‐2 (IL‐2).…”

“…Viruses may cause exanthemas either because of the infection (active or latent) or because of the interaction with drugs that are taken simultaneously 12 . Many viruses are implicated in exanthemas, with the most common being the Epstein‐Barr virus (EBV), 13 human herpesvirus 6 (HHV‐6) 14 and cytomegalovirus (CMV) 15 . Since a rash in childhood is a disquieting situation, the exact diagnosis of the specific exanthema subtype is decisive.…”

Recent developments and highlights in drug hypersensitivity

“…45,46 In children with suspicion of DHRs to different drugs, from which NSAIDs and BLs were the most frequent, less than 10%-20% of cases were confirmed as allergic. 12 This mislabelling could be due to the fact that some symptoms (gastrointestinal or headache) are falsely considered as allergic, the virus and antibiotic interaction or the underlying infection itself can lead to cutaneous reactions, 47 the low sensitivity of skin testing (STs) and the natural history with spontaneous resolution over time. 48 This has been shown to be up to 63.15% in NSAID-induced urticaria.…”

Mild to moderate hypersensitivity reactions to beta-lactams in children: a single-centre retrospective review

“…Unlike adults, children usually experience mild non-immediate skin reactions, as maculopapular exanthema and non-immediate urticarial rash 8. Most of these benign skin reactions are not truly allergic but related to the underlying infectious disease or due to the interaction between the antibiotic and the infectious agent 5 9…”