Direct-Acting Antiviral-Associated Dermatitis During Chronic Hepatitis C Virus Treatment

Abstract

Telaprevir and boceprevir are novel protease inhibitors recently approved for treatment of chronic hepatitis C virus infection, and have gained widespread use. Skin rash has been reported frequently in patients treated with telaprevir, but less commonly with boceprevir. Despite a high incidence in clinical trials, the telaprevir-related eruption has not been fully described in the literature. We describe six patients treated with telaprevir and three treated with boceprevir who developed skin rash related to the antiviral medication. Four patients treated with telaprevir developed laboratory abnormalities and/or systemic symptoms and five required discontinuation of their antiviral medication because of these adverse effects, including two patients who fit criteria for drug reaction with eosinophilia and systemic symptoms (DRESS). Patients with boceprevir-related rash had a milder course and none required discontinuation of the medication. This report confirms that cutaneous adverse effects from telaprevir and boceprevir are common. Patients treated with telaprevir may have a more severe course and more frequently require discontinuation of their antiviral therapy due to extensive rash or laboratory abnormalities. Dermatologists must be aware of these cutaneous adverse effects, as early intervention with topical corticosteroids and antihistamines may minimize the severity of the eruption and allow patients to complete antiviral therapy.

Dermatologic adverse events of protease inhibitor-based combination therapy in patients with chronic hepatitis C

“…Previous data from clinical trials reported DAEs in triple therapy based on TVR more frequent than in BOC (in BOC therapies they were reported with the same frequency as in the dual therapy with PEG-INF and RBV and there was no case of SCARs). 14,[26][27][28] Cases of SCARs occurred only in TVR group during clinical trials and they were also reported in post registration's studies. 12,14,26,[29][30][31][32][33][34][35] The most common skin rashes reported during the study were characterized as mild or moderate (24 patients -85,72%).…”

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

“…These include anti-hepatitis C virus agents (boceprevir and telaprevir) [42,43,44], targeted therapies for oncological diseases (sorafenib [46], vismodegib [47], and vemurafenib [48]), a new anti-coagulant (rivaroxaban) [49], and a new uric acid-lowering agent (fubuxostat) [50]. Although these agents are not notorious for inducing DRESS syndrome, such reports reflect the fact that with increasing introductions of new drugs, the list of culprit drugs for DRESS syndrome will continue to grow.…”

Cutaneous Adverse Events in Chronic Hepatitis C Patients Treated With New Direct-Acting Antivirals

“…A majority of TVR-and BOC-associated cutaneous AEs are mild to moderate in nature, involving localized rash with possible pruritus or diffuse rash (< 50% body surface area, BSA) with possible pruritus, skin peeling, and/or mucous membrane involvement (no ulceration) [6][7][8][9][10][11][12][13][14][15][16][17][18] (see Figure 1). In a minority of patients, severe cutaneous AEs with/without systemic symptoms have been reported.…”

“…In a minority of patients, severe cutaneous AEs with/without systemic symptoms have been reported. 7,8 For TVR, these include generalized rash (>50% BSA); rashes with vesicles, bullae, or ulcerations; or 1 of the following life-threatening conditions: drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), erythema multiforme (EM), and toxic epidermal necrolysis (TEN). 6,7,[9][10][11][12][13][14][15][16][17][18] For BOC, only DRESS is currently described.…”

“…19 While progression in severity is an uncommon phenomenon, it has been reported to occur with TVR-even after discontinued use. 7,8 Recently, the issue of DAA-associated cutaneous AEs has come to new light with the introduction of 2 new DAAs at the end of 2013. These DAAs, simeprevir (SIM) and sofosbuvir (SOF) have been FDA approved for the treatment of CHC genotype 1 and 1, 2, 3, and 4, respectively.…”