Conclusion
Although current knowledge has highlighted the contributing role of different HLA alleles or other genotypic markers in the pathogenesis of DISI and DILI, their role in concurrent DILI and DISI is lacking. Although conditions such as DRESS and to a lesser extent SJS/TEN are associated with liver injury of varying severity, there is lack of information why certain individuals develop the subtype with concurrent liver and skin injury. HLA alleles are necessary for occurrence of many of the skin reactions, but they are not sufficient, suggesting involvement of non-genetic factors in adverse drug reaction. The high negative predictive value of these tests combined with high prevalence of the specific genotypes in the population have resulted in some societies and countries recommending genetic testing before the use of drugs with the potential for adverse drug reaction; this is in order to prevent cutaneous SCAR and associated organ involvement. However, more research is needed in order to understand the various facets including pathogenesis, severity and outcome of concurrent skin and liver injury phenotype.
Abbreviations
AC, Amoxicillin-clavulanate; ADR, adverse drug reaction; AED, anti-epileptic drug; AGEP, acute generalized exanthematous pustulosis; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSA, body surface area; CBZ, carbamazepine; CD, cluster of differentiation; DILI, drug-induced liver injury; DILIN, drug-induced liver injury network; DISI, drug-induced skin injury; DRESS, drug reaction with eosinophilia and systemic symptoms; EM, erythema multiforme; HIV, human immune deficiency virus; HLA, human leucocyte antigen; HSR, hypersensitivity reaction; PCP, Pneumocystis carinii pneumonia; RegiSCAR, Registry of Severe Cutaneous Adverse Reactions; SCAR, severe cutaneous adverse reaction; SJS/TEN, Stevens-Johnson syndrome/toxic epidermal necrolysis; TNF, tumour necrosis factor; ULN, upper limit of normal.
Liver International. 2019;39(5):802-811. © 2019 Blackwell Publishing
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