Ribavirin
Ribavirin is used in combination with pegylated-interferon α2a (peg-IFN-α2a) for treating chronic hepatitis C, and both have been associated with several cutaneous DHRs (49). Ribavirin alone causes dermatitis, alopecia, and photoallergic eczematous reactions (50,51), and the risk of DHR increases with combination therapy: rash [response rate (RR,1.74; 95% confidence interval (CI), 1.17-2.6), dermatitis (RR, 1.67; 95% CI, 1.21-2.30), and pruritus (RR, 1.62; 95% CI,1.29-2.02) (52). A meta-analysis revealed that, on combination therapy, mild to moderate cutaneous reactions appear in 13.3% of patients, localized cutaneous reactions in 2.6%, generalized reactions-pruritus, skin xerosis and eczematous changes in 10.3%, alopecia in 4.1%, and exacerbation of lichen planus in less than 1% (43).
The etiological diagnosis is difficult in case of combination therapy. A drug provocation test (DPT) confirmed the diagnosis of ribavirin hypersensitivity in a patient having MPE due to combined use of peg-IFN-α2a and ribavirin (53). In another case, an erythema multiforme type drug eruption occurred with peg-IFN-α2a, ribavirin and/or fluvastatin sodium therapy and a positive lymphocyte transformation test (LTT) confirmed the diagnosis of ribavirin hypersensitivity (54). Successful desensitization protocols were reported (55,56).