Telaprevir Causes a Rare Life Threatening Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome During Chronic Hepatitis C Therapy: Is Obesity a Risk Factor?

Abstract

Purpose: DRESS syndrome is a rare yet severe adverse drug-induced reaction with up to 10% mortality rate. Recent clinical trials' report an association of DRESS with Telaprevir (TVR), a novel NS3/4A Protease Inhibitor of Chronic Hepatitis C (CHC) virus recently approved as part of a triple therapy for CHC genotype 1 patients. Diagnosis of this syndrome is challenging given the variable pattern of cutaneous eruption and the myriad internal organ involvement. However, prompt clinical recognition of DRESS is crucial, as early diagnosis leads to a potentially favorable outcome. We present two patients, both who are middle-aged obese Caucasians, who have CHC Cirrhosis. They both presented at week 8 and 10 of CHC triple therapy with Telaprevir, Peg-Interferon alfa-2a and Ribavirin with a progressive diffuse, painful pruritic maculopapular rash that involved the head, trunk and upper and lower extremities. They had no previous history of a similar skin eruption and were not exposed to other medications that can be suspected of causing such a rash. On exam, they were both febrile, had facial edema and lymphadenopathy. Laboratory investigations revealed eosinophilia >10%, abnormal liver function tests in one patient and elevated serum creatinine in the other. Further work-up excluded infection in both patients. Skin punch biopsy was non-specific in both instances. A clinical diagnosis of “Definite” DRESS syndrome, was supported by the RegiSCAR criteria classification. Thus Telaprevir, Peg-Interferon alfa-2a and Ribavirin were discontinued in both patients. Both patients were hospitalized and received supportive therapy with IV fluids, antihistamines and topical corticosteroids. Oral or IV corticosteroids were not used. There was rapid resolution of the systemic symptoms with gradual improvement of Eosinophilia and the skin eruption. Both patients were discharged 9 and 10 days respectively later, having shown significant improvement. Both were HCV RNA negative at 3 months follow-up. These two cases illustrate the paramount importance of early recognition of DRESS syndrome in CHC patients receiving Telaprevir-based triple therapy. This side effect of TVR therapy requires a high index of suspicion, critical for early diagnosis and prompt management. Immediate discontinuation of TVR is essential and could ensure a good outcome in this potentially life-threatening complication of Telaprevir based therapy. Risk factors for development of DRESS in patients receiving Telaprevir remain to be elucidated. We suggest that obesity might be a risk factor for the development of DRESS in the treatment of Hepatitis C with Telaprevir. Disclosure: Victor Ankoma-Sey-MD: Genentech, Advisory Committee and Speaker's Bureau; Victor Ankoma-Sey-MD: Vertex, Advisory Committee and Speaker's Bureau; Scott Zela-NP: Vertex, Advisory Committee and Speaker's Bureau.