Drug‐induced liver injury with skin reactions: Drugs and host risk factors, clinical phenotypes and prognosis

While dermatologic manifestations of adverse drug reactions are frequent, drug‐induced liver injury is rare. Numerous drugs are implicated in either Drug‐Induced Liver Injury or Drug‐Induced Skin Injury. However, concomitant Drug‐Induced Liver Injury and Drug‐Induced Skin Injury are uncommon, not well characterized and appear to be caused by a limited number of drugs. These are often associated with immuno‐allergic or hypersensitivity features such as fever, skin rash, blisters or peeling of skin, eosinophilia, lymphadenopathy and mucositis. Liver injury can range from asymptomatic elevation of liver biochemical tests to severe hepatitis and acute liver failure needing liver transplantation. Severe cutaneous adverse reaction, particularly drug reaction with eosinophilia and systemic symptoms is commonly associated with internal organ involvement, the liver being the most frequently involved in approximately 90% of the cases. In Stevens‐Johnson Syndrome/Toxic Epidermal Necrolysis, abnormalities in liver biochemistry tests are common but severe liver disease is rare. There is a strong association of Human Leukocyte Antigen genotype with both drug reaction with eosinophilia and systemic symptoms and Stevens‐Johnson Syndrome/Toxic Epidermal Necrolysis. It is likely that the delayed immune‐mediated reaction triggering skin reaction is also responsible for hepatitis. Drug‐specific lymphocytes are found in the organs involved and also in circulating blood, which along with the cytokines and chemokines play a role in pathogenesis. Anti‐epileptic drugs, allopurinol, sulfonamides, antibiotics and nevirapine are the top five causes of concomitant liver and skin injury. This review will focus on drug and host factors causing concomitant Drug‐Induced Skin Injury and Drug‐Induced Liver Injury and discuss the characteristics of liver involvement in patients with severe cutaneous adverse reaction.