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Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B

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World Journal of Gastroenterology 2014年第42期20卷 15931-15936页

作者： Jeong Tae Kim Hye Won Jeong Ki Hwa Choi Tae Young Yoon Nohyun Sung Young Ki Choi Eun Ha Kim Hee Bok Chae Department of Internal Medicine College of Medicine and Medical Research Institute Chungbuk National University Department of Dermatology College of Medicine and Medical Research Institute Chungbuk National University Department of Pathology College of Medicine and Medical Research Institute Chungbuk National University Department of Microbiology College of Medicine and Medical Research Institute Chunguk National University

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 immunemediated 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-yearold 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 selfdiscontinued 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 cutaneo

关键词： Entecavir Delayed type hypersensitivity maculopapu

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