D3.16 - Increase of Post–SARS-CoV-2 Rashes Mimicking Penicillin Allergy in Children with Group A beta-hemolytic Streptococcus Infection: an emerging and challenging issue

Group A β-hemolytic Streptococcus (GABHS) infections have surged globally in the post–SARS-CoV-2 era, coinciding with an increase in children referred for suspected delayed hypersensitivity to penicillin administered during acute infection. GABHS-related rashes may resemble non-immediate drug reactions, complicating diagnosis and contributing to inappropriate penicillin allergy diagnosis.

Medical charts from patients followed at Allergy Unit of Meyer Children's Hospital IRCCS, Florence, Italy and Pediatric Department of “Vittore Buzzi” Children’s Hospital, Milan, Italy, who underwent a penicillin drug provocation test (DPTs) between August 2015 and August 2025, were retrospectively reviewed. Only patients with documented, laboratory-confirmed GABHS infection treated with penicillin were included.

Seventy patients treated with penicillin for a concomitant GABHS infections that developed a rash during therapy were included. Median time for rash insurgence was after 7 days of treatment (IQR = 4 days). Maculopapular rash was the most frequent (43/70, 61.4%) followed by urticarial rash in the remaining cases (27/70, 38.6%). No systemic reactions were reported. DPTs were negative in 63/70 (90%), with only mild cutaneous reactions in the remaining cases, all manageable with antihistamines. All patients who experienced a positive DPT had initially reported an urticarial rash as the reason for referral, whereas all those with a history of maculopapular rash as index reaction showed a negative DPT.

GABHS could be associated with a rash that mimics delayed penicillin allergy that is excluded by negative DPTs.