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This systematic review investigated the characterization, epidemiology, risk factors, clinical impact and pharmaco\u2010economics of MDAS and MDIS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Systematic literature search across 11 databases (01 January 2000\u201306 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 &amp; selected populations varied between 2.1%\u20136.4% &amp; 4.9%\u201390% and 1.2% &amp; 0%\u201336% respectively. Reported risk factors included female gender, increasing age, body mass index, anxiety, depression, co\u2010morbidities, concurrent allergies and increased healthcare utilization. Drugs commonly implicated were antibiotics and non\u2010steroidal anti\u2010inflammatory drugs. No studies relating to clinical impact and pharmaco\u2010economics were found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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\u2010designed multi\u2010centre studies applying standardized terminology and diagnostic methodology are needed to gain further insight into these conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clt2.12190","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T06:05:07Z","timestamp":1661234707000},"source":"Crossref","is-referenced-by-count":16,"title":["Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: A systematic review"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0294-1571","authenticated-orcid":false,"given":"Parbir K.","family":"Jagpal","sequence":"first","affiliation":[{"name":"Institute of Clinical Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Alshareef","sequence":"additional","affiliation":[{"name":"University Hospitals Birmingham NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Marriott","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamidipudi Thirumala","family":"Krishna","sequence":"additional","affiliation":[{"name":"University Hospitals Birmingham NHS Foundation Trust  Birmingham UK"},{"name":"Institute of Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Guidance on adverse drug reactions: Medicines and Healthcare products Regulatory Agency:Medicines & Halthcare Products Regulatory Agency.https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/949130\/Guidance_on_adverse_drug_reactions.pdf"},{"key":"e_1_2_8_3_1","unstructured":"Drug Allergies:World Allergy Organization.https:\/\/www.worldallergy.org\/education\u2010and\u2010programs\/education\/allergic\u2010disease\u2010resource\u2010center\/professionals\/drug\u2010allergies"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.12.591"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12350"},{"key":"e_1_2_8_6_1","unstructured":"Drug allergy: diagnosis and management Clinical guideline [CG183]:National Institute for Health and Care Excellence. 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