Utility and Safety of Skin Tests in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): A Systematic Review.

BACKGROUND: Determination of culprit drug in drug reaction with eosinophilia and systemic symptoms (DRESS) is crucial. Skin tests have been used, although it remains unclear how sensitive these are. OBJECTIVE: To determine the value of skin tests in the assessment of drug causality in DRESS. METHODS: A systematic literature search was conducted for publications from 1996 onward of skin tests (skin prick test = SPT, patch test = PT, intradermal test = IDT) performed in clearly defined DRESS cases. Outcomes of testing, drug culpability assessments, and challenge test data were extracted. RESULTS: A total of 17 articles met inclusion criteria. In 290 patients with DRESS, patch testing was most frequent (PT = 97.2% [n = 282], IDT = 12.4% [n = 36], SPT = 3.1% [n = 9]). Positive results were noted in 58.4% (n = 160 of 282) of PTs, 66.5% of IDTs, and 25% of SPTs. When confidence of drug causality was high (n = 73 of 194), testing did not correlate well with clinical suspicion: PTs, 37.6%; IDTs, 36.5%. Direct comparison of skin testing with provocation testing (n = 12) showed 83.3% correlation. Positive IDT results were reported in 8 negative PT cases. CONCLUSIONS: Skin tests, particularly PTs and IDTs, have been reported as tools for diagnosis of causal drugs in DRESS. Heterogeneity in methodology, results analysis, and reporting of cohorts make meta-analysis to determine sensitivity and specificity of published literature impossible and highlight weaknesses in the field. We propose that international collaboration is essential to harmonize the methodology and reporting measures from hypersensitivity testing studies in larger cohorts.

Potential Biomarker Identification by RNA-Seq Analysis in Antibiotic-Related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Pilot Study.

One of the most severe forms of cutaneous adverse drug reactions is "drug reaction with eosinophilia and systemic symptoms" (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to patient safety reasons. Whilst incidence of DRESS is relatively low, between 1:1000 and 1:10 000 drug exposures, antibiotics are a commoner cause of DRESS and absence of confirmatory diagnostic test can result in unnecessary avoidance of efficacious treatment. We therefore sought to identify potential biomarkers for development of a diagnostic test in antibiotic-associated DRESS. Peripheral blood mononuclear cells from a "discovery" cohort (n = 5) challenged to causative antibiotic or control were analyzed for transcriptomic profile. A panel of genes was then tested in a validation cohort (n = 6) and compared with tolerant controls and other inflammatory conditions which can clinically mimic DRESS. A scoring system to identify presence of drug hypersensitivity was developed based on gene expression alterations of this panel. The DRESS transcriptomic panel identified antibiotic-DRESS cases in a validation cohort but was not altered in other inflammatory conditions. Machine learning or differential expression selection of a biomarker panel consisting of 6 genes (STAC, GPR183, CD40, CISH, CD4, and CCL8) showed high sensitivity and specificity (100% and 85.7%-100%, respectively) for identification of the culprit drug in these cohorts of antibiotic-associated DRESS. Further work is required to determine whether the same panel can be repeated for larger cohorts, different medications, and other T-cell-mediated drug hypersensitivity reactions.

Severe adverse drug reactions.

Severe cutaneous adverse reactions (SCARs) can present in a multitude of ways including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis. While the prognosis and therapy for these conditions may vary, it is crucial that the culprit drug is identified and withheld early as this can influence patient outcome. Mainstay of management is by supportive therapy. In all SCARs, long-term sequelae which may not be apparent initially can be debilitating and cause lasting impact on the quality of life of survivors.