Methods for identifying culprit drugs in cutaneous drug eruptions: A scoping review

Abstract

Background: Cutaneous drug eruptions are a significant source of morbidity, mortality, and cost to the healthcare system. Identifying the culprit drug is essential; however, despite numerous methods being published, there are no consensus guidelines. Objectives: Conduct a scoping review to identify all published methods of culprit drug identification for cutaneous drug eruptions, compare the methods, and generate hypotheses for future causality assessment studies. Eligibility criteria: Peer-reviewed publications involving culprit drug identification methods. Sources of evidence: Medline, Embase, and Cochrane Central Register of Controlled Trials. Charting methods: Registered PRISMA-ScR format protocol on Open Science Forum. Results: In total, 135 publications were included comprising 656,635 adverse drug events, most of which were cutaneous. There were 54 methods of culprit drug identification published, categorized as algorithms, probabilistic approaches, and expert judgment. Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. Studies suggest that greater accuracy may be achieved by specifically assessing cutaneous drug eruptions and using combinations of causality assessment categories. Conclusions: Culprit drug identification for adverse drug reactions remains a challenge. Many methods have been published, but there are no consensus guidelines. Using causality assessment methods specifically for cutaneous drug eruptions and combining aspects of the different causality assessment categories may improve efficacy. Further studies are needed to validate this hypothesis.

Polypharmacy as a Risk Factor for Exanthematous Drug Eruption

“…DRESS can be excluded because there is no fever and complaints are generally felt 14-42 days after drug exposure accompanied by lymphadenopathy and eosinophilia. Viral exanthema is generally preceded by prodromal symptoms such as fever, cough, and sore throat, but in this case, there was no history [2,4,8].…”

“…Cutaneous adverse drug reactions have several risk factors and one of them is polypharmacy [4,7,21]. Based on research by Jatana G et al, exanthematous drug eruption can be caused by one drug (78.9%) or several drugs (21.1%) [22].…”

“…The causality assessment method cannot provide information regarding the suspected drug trigger in patients with polypharmacy, especially on concurrent drug administration. In the use of polypharmacy therapy, discontinuation of the suspected drug concurrently can cause the patient's comorbidities to be left untreated [4].…”

“…Several reactions occur on the skin, both mild to severe, such as exanthemata's drug eruptions, urticaria, Steven-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN) [1][2][3]. Several risk factors that influence the severity and frequency of CADR are polypharmacy, old age, female, liver and kidney disease, malignancy, diabetes, Human Immunodeficiency Virus(HIV), and certain subtypes of Human Leukocyte Antigen(HLA) [4]. CADR diagnosis has only been clinical, and most CADRs resolve on their own with discontinuation of the precipitating drug [2].…”

“…There is the various definition used for polypharmacy, but the most often one is the use of five or more drugs [6]. Polypharmacy can cause interactions between drugs and make it difficult to identify drugs that cause CADR [4,7]. This makes information related to drugs that most often cause CADR can help in providing clinical decisions regarding drug discontinuation, especially in polypharmacy therapy.…”