Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: a systematic review

Parbir Jagpal*, John Marriott, Mamidipudi Thirumala Krishna (Contributor), Saad Alshareef (Contributor)

*Corresponding author for this work

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Background: Multiple drug allergy and multiple drug intolerance syndrome (MDAS/MDIS) labels are an impediment to clinical care and knowledge regarding these conditions is limited. This systematic review investigated the characterization, epidemiology, risk factors, clinical impact and pharmaco-economics of MDAS and MDIS.

Methods: Systematic literature search across 11 databases (01 January 2000–06 November 2020) for MDIS, MDAS and related terminology. Studies were reviewed for quality of evidence and risk of bias by employing Critical Appraisal Skills Programme cohort study checklist. A narrative synthesis approach facilitated by systematic textual descriptions, tabulation and thematic analysis was adopted.

Results: There was heterogeneity in terminology and methodology. Few studies applied standard drug allergy diagnostic methods. There is some evidence to suggest that multiple drug hypersensitivity syndrome (MDHS; i.e., confirmed allergies in MDAS) is a distinct clinical entity. Prevalence of MDIS and MDAS labels in unselected & selected populations varied between 2.1%–6.4% & 4.9%–90% and 1.2% & 0%–36% respectively. Reported risk factors included female gender, increasing age, body mass index, anxiety, depression, co-morbidities, concurrent allergies and increased healthcare utilization. Drugs commonly implicated were antibiotics and non-steroidal anti-inflammatory drugs. No studies relating to clinical impact and pharmaco-economics were found.

Conclusion: There is considerable burden of MDAS and MDIS labels. Data needs cautious interpretation as majority of studies described involved unverified labels. Despite this limitation and heterogeneity of studies, there is some evidence to suggest that MDHS is a distinct clinical entity. Well-designed multi-centre studies applying standardized terminology and diagnostic methodology are needed to gain further insight into these conditions.
Original languageEnglish
Article numbere12190
Number of pages18
JournalClinical and Translational Immunology
Issue number8
Early online date22 Aug 2022
Publication statusPublished - 22 Aug 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.


  • multiple drug allergy syndrome
  • multiple drug intolerance syndrome
  • multiple drug allergy
  • multiple drug intolerance
  • multiple drug hypersensitivity


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