Stevens-Johnson Syndrome in a Chronic Hepatitis C Patient Treated With Zepatier (Elbasvir/Grazoprevir)

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Introduction: Stevens-Johnson syndrome (SJS) is an acute life threatening skin reaction involving mucocutaneous membranes. About 80 to 90% cases are drug induced. The recent introduction of new direct acting antiviral (DAA) agents has commenced a new era of safe and effective treatment of chronic Hepatitis C - previously known to be a difficult-to-treat lifelong infection. While SJS has been reported with the use of first generation DAA agents such as telaprevir, no known cases have been reported till date for patients on Zeptaier (Elbasvir/Grazosprevir combination therapy) for chronic Hepatitis C virus (HCV) infection. We report a case of SJS induced by Elbasvir/Grazosprevir in a patient with Chronic Hepatitis C and HIV.Figure: Mucocutaneous findings.Case Description: A 53-year old male with past history of chronic HCV and HIV presented with a 3-day history of fever, malaise, progressively worsening cutaneous symptoms which included- bilateral periorbital swelling and redness, painful oral ulcers and skin rash. Rash was concentrated on the upper body and was spreading caudally. Rash consisted of erythematous pruritic tender papules and vesicles. Patient had recently started taking Elbasvir/Grazosprevir to treat chronic HCV three weeks ago. He was also on Abacavir/dolutegravir/lamivudine (Triumeq) therapy for HIV with recent non-detectable HIV RNA levels and a CD4 count of 366. His pre-treatment HCV RNA count was 1,780,000 IU/mL (COBAS TaqMan HCV Test version 2.0). He had F3 fibrosis stage via FibroSure testing. Patient's presentation was attributed to early drug induced SJS from Zepatier use. Zepatier was discontinued and patient treated with steroids and antihistamines. He had complete resolution of his symptoms after two weeks. Discussion: Zepatier is a combination drug with Elbasvir, an NS5A inhibitor and Grasoprevir, an NS3/4A protease inhibitor, which was recently approved by the FDA for the treatment of chronic Hepatitis C in patients with genotype 1 and 4. This approval follows several clinical trials establishing the safety and efficacy of Elbasvir/Grasoprevir combination demonstrating a sustained virological response 12 weeks after completing treatment (SVR-12) greater than 92% and a minimal side effect profile. Most common side effects in different trials included headache, nausea and fatigue. In the C-EDGE trial, rash or pruritus was noted in 4% of patients on Elbasvir/Grasoprevir with Ribavirin regimen. However, no rash or pruritus was reported in patients on Elbasvir/ Grasoprevir regimen alone. To the best of our knowledge, serious adverse cutaneous reaction associated with Elbasvir/Grasoprevir therapy has not been previously reported. Possibility of adverse cutaneous drug reaction with Elbasvir/ Grasoprevir use has significant clinical implications. Patients with HIV seem to have a higher incidence of SJS than the general population. Clinicians need to be highly vigilant for cutaneous side effects while treating patients with HIV and HCV with Elbasvir/Grasoprevir combination for chronic HCV treatment. Because of significant mortality associated with SJS - early recognition, offending drug discontinuation and prompt treatment are warranted.