Case Report
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World J Gastroenterol. Nov 14, 2014; 20(42): 15931-15936
Published online Nov 14, 2014. doi: 10.3748/wjg.v20.i42.15931
Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B
Jeong Tae Kim, Hye Won Jeong, Ki Hwa Choi, Tae Young Yoon, Nohyun Sung, Young Ki Choi, Eun Ha Kim, Hee Bok Chae
Jeong Tae Kim, Hye Won Jeong, Hee Bok Chae, Department of Internal Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-711, South Korea
Ki Hwa Choi, Tae Young Yoon, Department of Dermatology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-711, South Korea
Nohyun Sung, Department of Pathology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-711, South Korea
Young Ki Choi, Eun Ha Kim, Department of Microbiology, College of Medicine and Medical Research Institute, Chunguk National University, Cheongju 361-711, South Korea
Author contributions: Kim JT collected the data and drafted the manuscript; Jeong HW assisted in generating the figures and drafting the manuscript; Chae HB designed the study and revised the manuscript for intellectual content; Choi KH and Yoon TY provided the dermatology images and revised the dermatological content of the manuscript; Sung N provided the microscope images and revised the pathological content of the manuscript; Choi YK and Kim EH performed the immunological experimentation on patient samples.
Supported by Grant from the Chungbuk National University Hospital (2013)
Correspondence to: Hee Bok Chae, MD, Department of Internal Medicine, College of Medicine and Medical Research Institute, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju 361-711, South Korea. hbhcae@chungbuk.ac.kr
Telephone: +82-43-2696363 Fax: +82-43-2733252
Received: February 23, 2014
Revised: May 25, 2014
Accepted: July 24, 2014
Published online: November 14, 2014
Processing time: 267 Days and 15.1 Hours
Abstract

Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.

Keywords: Entecavir; Delayed type hypersensitivity; Maculopapular drug eruption; Dermatology; Adverse drug reaction; Chronic hepatitis B

Core tip: A potent efficacy and good overall safety profile has supported the rapid establishment of entecavir as a frequently prescribed antiviral nucleoside for treatment of chronic hepatitis B (CHB). Among the adverse drug reactions that have been reported in CHB patients, allergic dermatitis is especially rare, with only two cases in the literature to date. This report describes a pathologically and immunologically evidenced case of entecavir (ETV)-induced type IV delayed hypersensitivity reaction, which resolved upon ETV withdrawal.