Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta-analysis

Autores da FMUP

• António De Almeida E Sousa Cardoso Fernandes

  Autor

• José Luís Dias Delgado

  Autor

• João De Almeida Lopes Da Fonseca

  Autor

• Luís Filipe Ribeiro De Azevedo

  Autor

• Bernardo Manuel De Sousa Pinto

  Autor

Participantes de fora da FMUP

• Blumenthal, KG
• Chiriac, AM
• Tarrio, I
• Afonso Joao, D

Unidades de investigação

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina da Comunidade, Informação e Decisão em Saúde

• Patologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Background Patients with a penicillin allergy label tend to have worse clinical outcomes and increased healthcare use. Drug provocation tests (DPT) are the gold-standard in the diagnostic workup of penicillin allergy, but safety concerns may hinder their performance. We aimed to assess the frequency of severe reactions following a DPT in patients with reported allergy to penicillins or other beta-lactams. Methods We performed a systematic review, searching MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with a penicillin allergy label who underwent a DPT. We performed a Bayesian meta-analysis to estimate the pooled frequency of severe reactions to penicillin DPTs. Sources of heterogeneity were explored by subgroup and metaregression analyses. Results We included 112 primary studies which included a total of 26,595 participants. The pooled frequency of severe reactions was estimated at 0.06% (95% credible interval [95% CrI] = 0.01%-0.13%; I-2 = 57.9%). Most severe reactions (80/93; 86.0%) consisted of anaphylaxis. Compared to studies where the index reaction was immediate, we observed a lower frequency of severe reactions for studies assessing non-immediate index reactions (OR = 0.05; 95% CrI = 0-0.31). Patients reporting anaphylaxis as their index reaction were found to be at increased risk of developing severe reactions (OR = 13.5; 95% CrI = 7.7-21.5; I-2 = 0.3%). Performance of direct DPTs in low-risk patients or testing with the suspected culprit drug were not associated with clinically relevant increased risk of severe reactions. Conclusions In patients with a penicillin allergy label, severe reactions resulting from DPTs are rare. Therefore, except for patients with potentially life-threatening index reactions or patients with positive skin tests-who were mostly not assessed in this analysis -, the safety of DPTs supports their performance in the diagnostic assessment of penicillin allergy.

© 2021 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Keywords

• adverse drug reactions; anaphylaxis; Bayesian meta-analysis; drug allergy; drug challenge; drug provocation test; penicillin allergy; systematic review