Drug-induced Liver Injury with Serious Multiform Exudative Erythema following the Use of an Over-the-counter Medication Containing Ibuprofen

Abstract

A 36-year-old Japanese woman took over-the-counter (OTC) medication for headaches for 20 days. Subsequently, five days after discontinuing the medication, a skin rash developed over the patient's upper and lower limbs and face, in addition to a fever, brown urine and serious liver dysfunction. Drug lymphocyte stimulation tests implicated ibuprofen, a main component of the OTC drugs, which has the potential to induce this pathology, and a diagnosis of drug-induced liver injury with multiform exudative erythema was made. The patient's symptoms and liver function tests returned to normal following treatment with systemic steroids.

Systematic review: ibuprofen‐induced liver injury

“…Seventeen published case reports and two case series of idiosyncratic ibuprofen‐derived liver injury from 1976 to 2018 were retrieved, carefully analysed and summarised in Tables and S1 . Of the 22 identified cases, 12 involved females (55%) and the mean patient age was 31 years (range 7 months—59 years).…”

“…Seventeen published case reports and two case series of idiosyncratic ibuprofen-derived liver injury from 1976 to 2018 were retrieved, carefully analysed and summarised in Tables 2 and S1. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Of the 22 identified cases, 12 involved females (55%) and the mean patient age was 31 years (range 7 months-59 years). Thirteen patients (59%) had underlying chronic conditions, which were mainly Table S1).…”

“…15 Nevertheless, ibuprofen has been linked to instances of clinically apparent liver injury with injury patterns varying from moderate elevations of aminotransferases to vanishing bile duct syndrome (VBDS) and even acute liver failure (ALF) resulting in death. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] While most reported ibuprofen-induced hepatotoxicity cases to date are idiosyncratic, some cases of liver injury due to ibuprofen overdose have also been described. [35][36][37] The large consumption of ibuprofen worldwide together with the fact that only limited information is available on ibuprofen-induced hepatotoxicity to date, prompted us to look deeper into the phenotypic presentation of this type of DILI.…”

“…Short plasma half‐life and absence of prolonged retention in the organism contribute to a better gastrointestinal safety profile of ibuprofen compared to other NSAIDs . Nevertheless, ibuprofen has been linked to instances of clinically apparent liver injury with injury patterns varying from moderate elevations of aminotransferases to vanishing bile duct syndrome (VBDS) and even acute liver failure (ALF) resulting in death . While most reported ibuprofen‐induced hepatotoxicity cases to date are idiosyncratic, some cases of liver injury due to ibuprofen overdose have also been described …”

Protective role of c‐Jun N‐terminal kinase‐2 (JNK2) in ibuprofen‐induced acute liver injury

“…There is little information on the clinical features of ibuprofen-associated hepatotoxicity and previous patient reports show a variable range of phenotypes in ibuprofen-derived liver toxicity rather than a distinctive signature [12,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. Whereas hepatic compromise has been also described in the setting of ibuprofen overdose [28,29], the majority of earlier published ibuprofen-induced liver injury reports corresponded to hepatic adverse reactions of idiosyncratic nature [12,[22][23][24][25][26][27][30][31][32][33][34][35][36].…”