441 International Journal of HEMATOLOGY Case Report 1. Introduction Hypersensitivity to mosquito bites (HMB) is a rare disor- der that is characterized by intense skin reactions at bite sites and general symptoms such as fever and lym- phadenopathy. Most of the reported cases of HMB have been in Japanese patients in the first 2 decades of life [1,2]. These cases have been reported to conceal clonal lympho- proliferation of Epstein-Barr virus (EBV) DNA–positive natural killer (NK) cells [3,4], which infiltrate the skin lesion [5-8]. Recently, HMB has been recognized as one of the manifestations of an EBV-associated NK cell lymphoprolif- erative disease [1,8-10]. We report on an adult with relapsed mantle cell lym- phoma after autologous peripheral blood stem cell trans- plantation who subsequently developed mild clinical mani- Atypical Hypersensitivity to Mosquito Bites without Natural Killer Cell Proliferative Disease in an Adult Patient Takaaki Konuma, a Kaoru Uchimaru, a Rieko Sekine, a Nobuhiro Ohno, a Yasushi Soda, a Akira Tomonari, a Jun Ooi, a Fumitaka Nagamura, a Satoshi Takahashi, a Tohru Iseki, b Naoki Oyaizu, c Arinobu Tojo, a Shigetaka Asano a Departments of a Hematology/Oncology and b Transfusion Medicine, and c Division of Molecular Pathology, Department of Laboratory Medicine,The Institute of Medical Science,The University of Tokyo,Tokyo, Japan Received February 10, 2005; received in revised form August 18, 2005; accepted August 23, 2005 Abstract Hypersensitivity to mosquito bites (HMB) is a rare disorder that occurs in the first 2 decades of life and is considered to be associated with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukemia/lymphoma. EBV- encoded small nuclear RNA (EBER)-positive NK cells infiltrate the skin lesion at the site of the mosquito bite. In this report, we present the case of an adult patient with mantle cell lymphoma complicated by atypical HMB. The anti-EBV antibody titer of the patient indicated reactivation of chronic infection with this virus, and EBV DNA in the peripheral blood mono- nuclear cells was detected after chemotherapy by quantitative polymerase chain reaction analysis. However, an in situ hybridization analysis did not detect EBER-positive cells in the skin lesion at the bite site or in the lymph node. Peripheral NK cell lymphocytosis and EBV-associated lymphoproliferative disease did not develop. These findings suggest that some patients with chronic EBV infection may develop HMB without NK cell proliferative disease. Int J Hematol. 2005;82:441-444. doi: 10.1532/IJH97.05019 ©2005 The Japanese Society of Hematology Key words: Hypersensitivity to mosquito bites; Mantle cell lymphoma; Epstein-Barr virus; Adult; NK cell proliferation Correspondence and reprint requests: Kaoru Uchimaru, MD, PhD, Department of Hematology/Oncology,The Institute of Medical Science,The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku,Tokyo 108-8639, Japan; 81-3-3443-8111; fax: 81-3-5449- 5429 (e-mail: uchimaru@ims.u-tokyo.ac.jp). festations of HMB limited to macular erythema and regional lymphadenopathy, without necrotic skin reactions or high fever. In this case, the anti-EBV antibody titers indicated reactivation of chronic infection with this virus, and EBV DNA in the peripheral blood mononuclear cells (PBMCs) was detected by quantitative polymerase chain reaction (PCR) analysis after chemotherapy. A histologic examina- tion of the skin lesions showed typical allergic dermatitis, and EBV-encoded small nuclear RNA (EBER)-positive cells were not detected in the lesion. These results suggest that HMB in this patient was manifested by an aberrant skin reaction with impaired immunity complicated by chronic EBV infection and was not due to EBV-associated NK cell proliferative disease. 2. Case Report A 55-year-old woman developed cervical lym- phadenopathy and received a diagnosis of mantle cell lym- phoma in 1994. The patient underwent conventional com- bination chemotherapy and achieved complete remission, but she relapsed in 1997. The patient underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and entered a second complete