In Vitro Assays in Severe Cutaneous Adverse Drug Reactions: Are They Still Research Tools or Diagnostic Tests Already?

Abstract

Severe cutaneous adverse drug reactions (SCARs) represent life-threatening medical conditions and an appropriate causative diagnosis of these conditions is of the highest importance. Existing in vivo diagnostic methods are risky or are just contraindicated in these patients. Therefore, in vitro tests take on greater significance. In this survey, the studies on in vitro assays in SCARs were identified with a defined searching strategy and strict eligibility criteria. Different methods in the particular clinical manifestations and the groups of drugs were compared in respect to the diagnostic parameters obtained. The lymphocyte transformation test and IFNg-ELISpot (Interferon γ-Enzyme-linked immunospot assay) appeared to have the best evidence currently available. Further diagnostic assays, which are based mostly on distinct mechanisms of SCARs, may outdo previous assays but they still need confirmation in a larger group of patients and in more research centers. Data from pediatric populations and acute generalized exanthematous pustulosis (AGEP) patients are scarce. Some technical issues, limitations, and modifications of routine laboratory methods are also discussed.

The Combined Utility of Ex Vivo IFN-γ Release Enzyme-Linked ImmunoSpot Assay and In Vivo Skin Testing in Patients with Antibiotic-Associated Severe Cutaneous Adverse Reactions

“…Porebski34 recently reviewed the literature of in vitro and ex vivo testing in SCARs, which demonstrated (1) variations in clinical phenotyping methods and measurable in vitro cytokine outputs, (2) grouping of SCARs with other non-SCAR T-cellemediated hypersensitivity phenotypes, and (3) use primarily in nonantibiotic cases. 34 . In comparison, we present one of the largest single cohorts of AA-SCARs with extended patient follow-up, using strict phenotypic scoring algorithms and IFN-g release ELISpot assay.…”

The measurement of drug‐induced interferon γ‐releasing cells and lymphocyte proliferation in severe cutaneous adverse reactions

“…According to our study, the sensitivity of ELISpot was somewhat higher than that of LTT, but statistical significance was not reached. At present, different approaches have been applied to calculate the cut‐off values of drug‐specific IFN‐γ‐releasing cells to identify the culprit drugs . The consensus criteria for culprit drug identification based on the IFN‐γ ELISpot technique need to be established.…”

“…The enzyme‐linked immunospot (ELISpot) assay is a sensitive technique to detect antigen‐specific T cells and has been introduced to identify drug‐specific T cells in SCAR patients . The turnaround time of this technique is shorter than that of LTT and does not involve radioisotope use.…”

“…The enzyme-linked immunospot (ELISpot) assay is a sensitive technique to detect antigen-specific T cells and has been introduced to identify drug-specific T cells in SCAR patients. 12 The turnaround time of this technique is shorter than that of LTT and does not involve radioisotope use. There is evidence that the frequencies of drug-specific IFN-c-releasing cells are significantly correlated with the lymphocyte proliferation response measured by LTT in patients with a history of beta-lactaminduced maculopapular exanthema.…”

Nested case–control study investigating the diagnostic role of tissue eosinophilia in adverse cutaneous drug reactions

“…Laboratory findings are non‐specific in ACDRs, although peripheral eosinophilia has been reported in some cases, mainly manifesting with severe cutaneous reaction, need for systemic treatment and longer recovery time . Several in vivo and in vitro assays have been developed to facilitate the diagnosis and prevention of ACDRs . In vivo assays include dechallenge and rechallenge tests with the suspected drug, patch and skin tests .…”