INTRODUCTION
Drug rash with eosinophilia and systemic symptoms
(DRESS) is a potentially life threatening adverse drug
reaction1. The “RegiSCAR†group has suggested a series
of diagnostic criteria in which hospitalized patient with a
suspected drug rash must have at least three of following four
systemic features1,2 (fever, lymphadenopathy, internal organ involvement,
and hematological abnormalities). The drugs commonly
known to be associated with DRESS are anticonvulsants,
allopurinol, sulfasalazine, dapsone, minocycline, and abacavir.2
Telaprevir, a NS3/4A protease inhibitor, was FDA approved in
May 2011, is now indicated in combination with pegylated interferon
alfa (peg-IFN) and ribavarin (RBV) for the treatment
of chronic CHC due to HCV genotype 1. Concomitant with improved
drug efficacy is increased adverse effects. Herein, we
report two cases of DRESS secondary to Telaprevir use.
CASE 1
A 60-year-old male with CHC presented with painful, red,
desquamating, pruritic rash involving his trunk, arms, face,
abdomen, and legs bilaterally. The rash started during the 8th
week of his 12-week treatment with Telaprevir, RBV and peg-
IFN. Over the following weeks, the rash became confluent
and started to ooze and desquamate. During the treatment
week 14, severe fatigue, anorexia, fever, and chill ensued necessitating
hospitalization and discontinuation of (RBV and
peg-IFN) therapy. Upon hospitalization, general physical examination
revealed an ill-appearing febrile (T max: 38.5 C)
man. Liver biochemistries were: LDH 332(normal range (NR):
100-200 IU/L), AST 53 (NR: 1-50 IU/L), ALT 21 (NR: 1-50 IU/L),
ALP 113 (NR: 30-110 IU/L), total bilirubin 1.9 (NR: .1-1.2 mg/
dl). BMP and CBC revealed BUN 29 (NR: 10-30 mg/dl), Cr 1.5
(NR: .7- 1.3 mg/dl), Hb 8.7 (NR: 13.9-16.3 g/dl), platelet 150 x
103 (NR: 150-450 X 103/UL), neutrophil 43.7% (NR: 40-78%),
eosinophil 42.0% (NR: 0.0 – 5.0%), and lymphocytes 10% (NR:
15 – 50%). After 4 weeks of triple therapy, he was HCV-PCR
undetectable. Initially, rash was treated with topical steroids and oral hydroxyzine. Due to rash progression, at his 13th
week outpatient visit, he was started on low dose PO prednisone
and given IV diphenhydramine with minimal relief.
Upon hospitalization, he received 2 days of IV methyprednisone
followed by 6 days of PO prednisone taper, and topical
betamethasone and hydrocortisone BID on body and face,
respectively, for 14 days. Based on RegiSCAR criteria, he was
diagnosed with Telaprevir-induced “Definite†DRESS.
CASE 2
A 62-year-old male with PMH of CHC presented with fever,
chills, severe generalized plaque-like pruritic rash involving his
abdomen, back, upper chest, and bilateral upper and lower extremities,
during week 12 of his triple therapy. The rash started
midst the 11th week of triple therapy and subsequently generalized.
The general physical examination revealed a dishevelled
male with chills and generalized rash involving more than 50% of
BSA. Laboratory analysis revealed total bilirubin 1.6 (NR: .1-1.2
mg/dl), AST 56 (NR: 1-50 IU/L), ALP 83 (NR: 30-110 IU/L), and ALT
42 (NR: 1-50 IU/L). CBC revealed Hb 8.0 (NR: 13.9-16.3 g/dl), platelet
72 (NR: 150-450 X 103/UL), neutrophil 61.4% (NR: 40-78%),
and eosinophils 22.1 % (NR: 0.0 – 5.0%), thus being diagnosed as
“probable†cause of DRESS. Patient was HCV- PCR undetectable
at 12 weeks of triple therapy. The antiviral medications were immediately
stopped, and he was managed with IV hydration, and
sent home on oral prednisone 40 mg daily, twice-daily topical
clobetasol ointment and hydroxyzine 25 mg PRN. Follow-up visit
in one week demonstrated significant improvement in rash but
unfortunately patient became HCV VL detectable.
DISCUSSION
Safety data from PROVE 1, 2, 3, REALIZE, and ADVANCE3-7
trials have demonstrated increased incidence and severity
of cutaneous adverse effects with Telaprevir use. PROVE 1
study reported 59 % vs 41 % incidence of any rash in Telaprevir
vs. control (RBV/peg-IFN) group, respectively. Due to
