Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B.
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.
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.
Jeong Tae
JT
Kim
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.
Hye Won
HW
Jeong
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
KH
Choi
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.
Tae Young
TY
Yoon
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.
Nohyun
N
Sung
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.
Young Ki
YK
Choi
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.
Eun Ha
EH
Kim
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.
Hee Bok
HB
Chae
D000998:Antiviral Agents / Q000009:adverse effects*; D001706:Biopsy; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003875:Drug Eruptions / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D057915:Drug Substitution; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013997:Time Factors
D000998:Antiviral Agents; D016207:Cytokines; C413685:entecavir; D006147:Guanine
Adverse drug reaction; Chronic hepatitis B; Delayed type hypersensitivity; Dermatology; Entecavir; Maculopapular drug eruption