Severe Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) induced by telaprevir.   I. Gallais Sérézal1, M. Delage1, V. Grando-Lemaire2, A. Lévy3, L. Laroche1, F. Caux1 Department of Dermatology1 & Anatomopathology3, Avicenne hospital, Bobigny, France, Department of Hepatology2, Jean Verdier hospital, Bondy, France. EADV congress October 2013.

CASE REPORT A 58 year old woman originated from the French Indies was admitted for a skin rash. The rash began four weeks after she started a treatment for chronic C hepatitis, including an inhibitor of the serine protease produced by the C hepatitis virus: telaprevir, ribavirine and pegylated interferon alfa-2a.  She had previously been treated with ribavirin and pegylated interferon alfa-2a with no efficiency and only minor side effects (local injection site reactions with pegylated interferon alfa-2a).

CASE REPORT Diffuse pruritic urticarial lesions located on the trunk, the limbs and the face associated with target lesions, intense facial oedema, fever of 38.5°C and painful peripheral lymphadenopathy. Blood eosinophilia was 2450/mm3, blood gamma-glutamyl transpeptidase level increased to 223 U/L (normal under 30). Skin biopsy showed a dermal infiltrate of lymphocytes and eosinophil cells and necrotic keratinocytes in favor of a drug reaction.  PCR for HHV6 and HCV viral load were negative. A diagnosis of telaprevir induced DRESS was established. Telaprevir only was stopped. The patient was treated with clobetasol propionate and experienced complete resolution of symptoms blood test abnormalities within the next month.

DISCUSSION Telaprevir's skin related side effects are very common. During the phase II/III clinical trials 55% of patients treated by telaprevir had rash, usually eczematous dermatitis or urticaria. 11 cases of DRESS have been suspected and expert dermatologists performed a retrospective assessement, finding two cases probable and 8 possible. The management of the severe telaprevir-related cutaneous side effects proposed in the literature includes discontinuation of all treatment (telaprevir, peginterferon, ribavirin). Due to previous good tolerance of the association ribavirin and pegylated interferon alfa-2a, telaprevir only was stopped in our patient. However outcome was favorable.

CONCLUSION Telaprevir is an inhibitor of the serine protease produced by the C hepatitis virus, used in association with ribavirin and pegylated interferon alfa-2a in the treatment of genotype 1 chronic hepatitis C. We presented a woman with a telaprevir-induced DRESS. Clinicians treating patients with this new drug should be aware of the high incidence and potential severity of the skin side effects. All treatment should be stopped early in case of serious cutaneous side effects.

Drug rash with eosinophilia and systemic symptoms due to telaprevir. Montaudié H et al. Dermatology. 2010;221(4):303-5 Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. McHutchison JG et al. N Engl J Med. 2009 Apr 30;360(18): Dermatological side effects of hepatitis C and its treatment: patient management in the era of direct-acting antivirals. Cacoub P et al. J Hepatol. 2012 Feb;56(2):455-63 Telaprevir 375-mg Film-Coated Tablet for the Treatment of Genotype 1 Chronic Hepatitis C. Antiviral Drugs Advisory Committee April 28, 2011 Briefing Document NDA 201-917