Hepatic necrosis associated with drug-induced hypersensitivity syndrome

Abstract

Drug-induced hypersensitivity syndrome (DIHS; also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) is a life-threatening condition first described by Chaiken et al. in 1950. It is characterized by extensive mucocutaneous rash; fever; lymphadenopathy; hepatitis; hematological abnormalities; damage to several organs such as kidney, heart, lungs, and pancreas; and possible reactivation of human herpesvirus-6 (HHV-6) or other herpes virus. Rare and severe cases may present hepatic necrosis, and about 15% of them result in death or liver transplantation. A hallmark of this syndrome is the late onset of symptoms after the drug exposure. The most common culprit drugs are the aromatic anticonvulsants (in almost 30% of the cases) and the antibiotics (which in some series represent 20% of the cases). The authors report a case of a 41-year-old female who presented to the emergency department with erythroderma, acute hepatitis, acute pancreatitis and acute renal failure, and was then treated with corticosteroid after the diagnosis of DIHS/DRESS. A specific culprit drug could not confidently be determined due to the presence of multiple drugs used by the patient. The clinical and laboratory outcome was apparently satisfactory, but unexpectedly, on the sixth day of hospitalization, the patient complained of nonspecific malaise, drowsiness, which progressed in a few hours with signs and symptoms of hepatic failure, refractory shock, and death. The autopsy findings showed submassive hepatic necrosis, and the immediate cause of death was attributed to hepatic failure.

“Heart in DRESS”: Cardiac Manifestations, Treatment and Outcome of Patients with Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome: A Systematic Review

“…The most common co-morbidities were rheumatologic (combined 21.4%) and hypertension (16.7%). Only one patient was immunosuppressed because of therapy for chronic prednisone for rheumatoid arthritis [30]. The presence of co-morbidities and the use of immunosuppression were not associated with patients' outcomes (Table 2).…”

“…The most commonly cited culprit medication was minocycline (19%) followed by allopurinol (12%), dapsone and sulfasalazine (7.1%) and lamotrigine (4.8%, Table 3). There were nine cases that had two or three suspected culprit medications that couldn't be differentiated, and one case had four medications in differential [30].…”

“…Histopathologically, myocarditis in DS manifests mostly as EM or GCM based on case reports in which biopsy was done [10,11,15,17,[19][20][21][22]24,26,[30][31][32][33]35,38,41,[45][46][47][48]. EM is a rare form of myocardial inflammation characterized by an abundant eosinophilic infiltrate.…”

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses

“…Anicteric hepatitis is more prevalent, but, if icteric hepatitis occurs, the prognosis is usually poorer, with progression to hepatic failure [ 80 , 189 ]. Hepatic necrosis may rarely develop, although more than 10% of cases may progress to death or need for liver transplantation [ 83 , 190 , 191 ]. Sulphonamides/sulfones pose the highest risk of inducing liver injury in DRESS, followed by antiepileptic drugs and allopurinol.…”

“…Reactivation of HHV-6 or other herpesviruses could be assessed by serology or viral genome testing by polymerase chain reaction (PCR) in blood or other tissues [ 29 , 56 , 70 , 171 , 190 ]. There is no universal consensus on the methods to assess viral reactivation, and heterogeneity among different laboratories is the rule [ 212 ].…”