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Arch Dis Child 2018 Nov 13. Epub 2018 Nov 13.

Department of Dermatology, Salford Royal NHS Foundation Trust, Manchester, UK.

Front Pediatr 2018 9;6:289. Epub 2018 Oct 9.

Beijing Key Laboratory of Pediatric Respiratory Infectious Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders (EBV T/NK LPD) encompass a heterogeneous group of disorders, including chronic active Epstein-Barr virus infection (CAEBV), Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV T-cell lymphoma of childhood and hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) and so on, predominantly affecting children and young adults with high mortality. Patients with EBV T/NK LPD have overlapping clinical symptoms as well as histologic and immunophenotypic features. In this review, we summarized the clinical features of EBV T/NK LPD in Chinese patients from the published articles. Read More

Zhonghua Er Ke Za Zhi 2018 Oct;56(10):759-764

Department of Infectious Disease, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing 100045, China.

To summarize the clinical characteristics, virological and histopathological features, clinical outcome of Epstein-Barr virus-positive lymphoproliferative disease (EBV(+)LPD) in children. The clinical and follow-up data of 13 children histopathologically diagnosed as EBV(+)LPD in the Department of Infectious Disease of Beijing Children's Hospital between January 2011 and December 2016 were summarized. Of the 13 patients, 5 were males and 8 females. Read More

Adv Anat Pathol 2018 Sep 7. Epub 2018 Sep 7.

Department of Anatomic Pathology, Oakland University William Beaumont School of Medicine and Beaumont Health Systems, Royal Oak, MI.

Cutaneous lymphoproliferative disorders remain a challenging aspect of dermatopathology, in part due to the rarity of the entities and extreme variability in clinical outcomes. Although many of the entities remain unchanged, the approach to some of them has changed in the new 2016 classification scheme of the World Health Organization. Chief among these are Epstein-Barr virus-associated lymphoproliferative disorders such as Epstein-Barr virus-associated mucocutaneous ulcer and hydroa vacciniforme-like lymphoproliferative disorder, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, and breast implant-associated anaplastic large cell lymphoma. Read More

Am J Dermatopathol 2018 Aug 6. Epub 2018 Aug 6.

Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein-Barr virus (EBV)-associated lymphoma that mainly affects children.

Objectives: To examine the similarities and differences in the clinical pathological features, EBV infection status, and gene rearrangements in adults and children patients with HVLPD.

Methods: We compared the clinical manifestations, histopathology, immunophenotypical features, EBV infection status, and T-cell receptor gene rearrangements in the adult and children HVLPD groups. Read More

Clin Rev Allergy Immunol 2018 Jun 27. Epub 2018 Jun 27.

Department of Dermatology, The University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX, 75390-9069, USA.

Photo-contact dermatitis (PCD) describes the adverse cutaneous reaction that occurs in some patients as a result of simultaneous exposure to a contactant and to light. PCD can be subdivided into photo-allergic and photo-irritant dermatitis depending on whether the contactant respectively invokes an allergic or irritant reaction. Photo-irritant reactions are commonly caused by plants, psoralens, and medications taken internally, whereas photo-allergic reactions are commonly caused by sunscreens and topical nonsteroidal anti-inflammatory medications. Read More

Int J Dermatol 2018 Nov 21;57(11):1283-1292. Epub 2018 Jun 21.

National Skin Centre, Singapore, Singapore.

Hydroa vaccinforme-like lymphoproliferative disorder (HVLPD) is a rare T-cell lymphoproliferative disorder driven by the Epstein-Barr Virus (EBV). It was initially designated under the 2008 WHO classification of tumors of hematopoietic and lymphoid tissues as a distinct entity but has been recently reclassified as a lymphoproliferative disorder under the 2016 revision of the 2008 WHO classification of lymphoid malignancies. HVLPD mainly affects Asian, Central, and South American children. Read More

JAAD Case Rep 2018 May 31;4(4):314-317. Epub 2018 Mar 31.

Department of Dermatology, University of Michigan, Ann Arbor, Michigan.

Medicine (Baltimore) 2018 04;97(15):e0319

Department of Pediatrics, West China Second University Hospital.

Rationale: Hydroa vacciniforme (HV)-like T-cell lymphoma is a rare malignancy in childhood associated with Epstein-Barr virus infection.

Patient Concerns: A 6-year old girl presented with complaint of 3-year history of recurrent skin lesions, 3 months of fever accompanied by cough for 8 days.

Diagnoses: Skin biopsy revealed a HV-like lymphoma presentation and positive signals of EBER were detected by in situ hybridization. Read More

Am J Dermatopathol 2018 03;40(3):227-229

Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China.

Front Immunol 2017 22;8:1869. Epub 2017 Dec 22.

Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.

GATA2 is a transcription factor that binds to the promoter of hematopoietic genes. Mutations in one copy of the gene are associated with haploinsufficiency and reduced levels of protein. This results in reduced numbers of several cell types important for immune surveillance including dendritic cells, monocytes, CD4, and NK cells, as well as impaired NK cell function. Read More

J Dermatol 2018 Apr 20;45(4):444-449. Epub 2018 Jan 20.

Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. Read More

Haematologica 2018 Jun 14;103(6):1018-1028. Epub 2017 Dec 14.

Department of Pathology, Kurume University School of Medicine, Niigata University, Japan.

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. Read More

Indian Dermatol Online J 2017 Nov-Dec;8(6):490-491

Department of Dermatology, Pt BD Sharma PGIMS, University of Health Sciences, Rohtak, Haryana, India.

An Bras Dermatol 2017 Sep-Oct;92(5):649-654

Medical Oncology Service, Instituto Nacional de Enfermedades Neoplásicas (INEN) - Surquillo, Peru.

Background: Primary cutaneous T-cell lymphomas constitute a heterogeneous and rare group of diseases with regional particularities in Latin America.

Objective: To determine the clinicopathological features, relative frequency and survival among patients from a Peruvian institution.

Methods: Primary cutaneous T-cell lymphomas were defined based on the absence of extracutaneous disease at diagnosis. Read More

Ann Dermatol 2017 Oct 25;29(5):618-620. Epub 2017 Aug 25.

Department of Dermatology, Seoul National University Hospital, Seoul, Korea.

Unlike typical hydroa vacciniforme (HV), Epstein-Barr virus (EBV)-associated HV-like eruption is more variable in its clinical manifestations. In some patients, progression to lymphoma or leukemia has been reported, which are characterized by the T-cell immunophenotype. Here, we report the first Korean case of EBV-associated vesiculopapular eruption on the face of a patient with natural killer (NK)/T cell lymphoma. Read More

J Am Acad Dermatol 2018 03 28;78(3):637-642. Epub 2017 Sep 28.

Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

KEY TEACHING POINTS. Read More

Photodermatol Photoimmunol Photomed 2017 09 20;33(5):287-290. Epub 2017 Jun 20.

Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Surg Pathol Clin 2017 Jun 18;10(2):429-453. Epub 2017 Mar 18.

Haematological Malignancy Diagnostic Services (HMDS), Level 3, Bexley Wing, St James's University Hospital, Leeds LS9 7TF, UK. Electronic address:

Epstein-Barr virus (EBV)-associated lymphoproliferations involving the skin are a rare but important group of diseases with a broad spectrum of behavior, ranging from self-limiting spontaneously resolving disorders to highly aggressive malignancies. They may be of B, T, or natural killer (NK) cell type and include EBV-positive mucocutaneous ulcer, lymphomatoid granulomatosis, EBV-positive diffuse large B-cell lymphoma, hydroa vacciniforme-like lymphoproliferative disorder, and extranodal NK/T-cell lymphoma of nasal type. Recognition and distinction of these entities is important in view of their differing prognoses and treatments. Read More

Am J Dermatopathol 2018 May;40(5):358-361

Department of Dermatovenereology, West China Hospital, Sichuan University, Sichuan, China.

Hydroa vacciniforme-like lymphoma shows a marked predilection for the pediatric population, especially in Latin America and Asia. Here, we present 2 pediatric patients from Tibet of China, which is the first report from this area. Read More

Am J Dermatopathol 2018 Mar;40(3):201-204

Hydroa vacciniforme (HV)-like lymphoma is a rare, usually fatal Epstein-Barr virus-driven lymphoproliferative disease affecting children from Asia, Mexico, and South America. Cutaneous manifestations imitate HV, a benign photodermatosis in which systemic symptoms are not observed, and spontaneous regression occurs later in adolescence or young adulthood. We report a case of HV-like lymphoma in a 12-year-old girl, descendent from an ancient Amazon indigenous tribe that, as far as we know, represents the second Brazilian case ever reported in the medical literature. Read More

Int J Hematol 2017 Apr 16;105(4):406-418. Epub 2017 Feb 16.

Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo, Izumi City, Osaka, 594-1101, Japan.

Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of the EBV-associated T- or NK-cell lymphoproliferative diseases, which also include hypersensitivity to mosquito bites and severe-type hydroavacciniforme. The manifestations of CAEBV are often self-limiting with minimum supportive care or only prednisolone and cyclosporine A with or without etoposide. However, allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure, without which patients with CAEBV die within several years. Read More

Zhonghua Bing Li Xue Za Zhi 2016 Dec;45(12):817-821

Department of Pathology, Beijing Friendship Hospital Capital Medical University, Beijing 100050, China.

In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Read More

Semin Diagn Pathol 2017 Jan 7;34(1):60-75. Epub 2016 Dec 7.

Hematopathology, National Cancer Institute (NCI), Bethesda, MD, USA.

This article will focus on the cutaneous lymphoproliferative disorders associated with EBV, with an emphasis on the upcoming changes in the revised 4th Edition of the WHO classification of tumors of the hematopoietic system, many of which deal with cutaneous disorders derived from NK-cells or T-cells. Extranodal NK/T-cell lymphoma usually presents in the upper aerodigestive tract, but can involve the skin secondarily. EBV-associated T- and NK-cell lymphoproliferative disorders (LPD) in the pediatric age group include the systemic diseases, chronic active EBV infection (CAEBV) and systemic EBV+ T-cell lymphoma of childhood. Read More

Clin Dermatol 2016 Nov - Dec;34(6):724-735. Epub 2016 Jul 12.

University of Connecticut School of Medicine, Department of Dermatology, Farmington, CT.

Photodermatoses are a group of skin disorders caused by abnormal reaction to ultraviolet radiation. Photodermatoses are divided into four groups: (1) immunologically mediated photodermatoses; (2) chemical- and drug-induced photodermatoses; (3) photoaggravated dermatoses; and (4) hereditary photodermatoses. This contribution discusses differences in the approach and diagnosis of pediatric and adult patients with suspected photodermatoses, focusing on immunologically mediated photodermatoses and chemical- and drug-induced photodermatoses. Read More

Acta Derm Venereol 2017 03;97(3):379-380

Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Josef-Schneider-Straße 2, DE-97080 Würzburg, Germany.

QJM 2016 Oct 9;109(10):697-698. Epub 2016 Aug 9.

Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou 310003, Zhejiang, People's Republic of China. email:

J Dermatol Sci 2016 Dec 3;84(3):358-359. Epub 2016 Oct 3.

Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 700-8558, Okayama, Japan. Electronic address:

J Cutan Pathol 2016 Dec 9;43(12):1102-1111. Epub 2016 Sep 9.

Department of Dermatology, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.

Background: Hydroa vacciniforme (HV) is associated with Epstein-Barr virus (EBV) infection and a risk of transformation to lymphoma.

Methods: We retrospectively analyzed six HV cases for EBV association and transformation to HV-like T-cell lymphoma. Clinicopathologic features were reviewed and cases were assessed for EBV-encoded RNA (EBER) by in situ hybridization, double staining with immunohistochemistry and EBER and for T-cell clonality. Read More

Pan Afr Med J 2016 9;23:71. Epub 2016 Mar 9.

Hospital University Hassan II, Department of Dermatology, Faculty of Medicine, Fez, Morocco.

Clin Infect Dis 2016 07 11;63(1):41-7. Epub 2016 May 11.

Laboratorie of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases.

Background: Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer.

Methods: We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Read More

Leuk Lymphoma 2017 01 9;58(1):53-63. Epub 2016 May 9.

a Department of Pathology , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.

Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) include several overlapping EBV-related conditions with variably aggressive courses. For prognostic categorization, we retrospectively analyzed 42 EBV-T/NK-LPD cases. Male (79% [33/42]), young (≤40 years; 83% [35/42]) patients and T-cell lineage (81% [34/42]; CD8/CD4 = 1. Read More

JAAD Case Rep 2015 Mar 6;1(2):63-5. Epub 2015 Feb 6.

Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon.

J Dermatol Sci 2016 Jun 5;82(3):153-9. Epub 2016 Mar 5.

Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address:

Background: Epstein-Barr virus (EBV)-associated T/natural killer (NK)-lymphoproliferative disorders (LPDs) include hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). The pathomechanisms of these diseases are still unclear.

Objective: To understand the inflammatory process, we examined EBV reactivation markers, BZLF1 and BDRF1 mRNA in the tissue and blood from patients with EBV-associated T/NK-LPDs. Read More

Br J Haematol 2016 05 15;173(4):573-81. Epub 2016 Mar 15.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA.

Mature T/Natural killer (NK)-cell neoplasms of children and the young adolescent population exhibit higher prevalence in Central and South American and Asian populations and many are associated with Epstein-Barr virus (EBV). They are represented in large part by extranodal T/NK cell lymphomas- nasal-type or extra nasal-type, chronic lymphoproliferative disorders of T/NK cells or chronic active EBV disease, systemic EBV-positive lymphoproliferative disorders of childhood, hydroa vacciniforme-like lymphoma, hepatosplenic T-cell lymphoma and primary cutaneous gamma/delta T-cell lymphoma among others. Many T/NK cell neoplasms in this age group are derived from cells of the innate immune system, in contrast to adults where they are predominantly from the adaptive immune system. Read More

Ann Lab Med 2016 May;36(3):268-70

Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Am J Dermatopathol 2016 May;38(5):e57-9

Servicio de Patología, Hospital Metropolitano, Quito, Ecuador.

Hydroa vacciniforme-like cutaneous lymphoma is a very rare Epstein-Barr virus positive peripheral T-cell lymphoma affecting Asian and Hispanic children and young adults with a defective cytotoxic immune response to EBV predisposing to the development of the disease. We report on 2 Ecuadorian patients with papulovesicular and ulcerated crusted lesions on the face, upper and lower extremities and abdomen, with aggressive clinical course and, in one case, a fatal outcome. The histological and molecular profiles (immunohistochemistry and in situ hybridization) established a diagnosis of hydroa vacciniforme-like Epstein-Barr virus-encoded small RNAs + cutaneous T-cell lymphoma in both cases. Read More

Clin Case Rep 2016 Feb 6;4(2):120-2. Epub 2015 Dec 6.

Dermatology Service KK Women's & Children's Hospital Singapore Singapore.

Hydroa vacciniforme is a photosensitivity disorder characterized by the childhood onset of necrotic vesiculopapules on exposed areas. We present a case of a 10-year-old boy with a 1-year history of papular lesions over his face. In this report, we discuss the in-depth histology of hydroa vacciniforme, and the management options. Read More

Ann Dermatol 2015 Dec 7;27(6):789-91. Epub 2015 Dec 7.

Department of Dermatology, Ajou University School of Medicine, Suwon, Korea.

Bol Med Hosp Infant Mex 2016 Jan - Feb;73(1):10-17. Epub 2016 Feb 1.

Department of Pathology, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea. Electronic address:

Background: Chronic active EBV infection (CAEBV) of T-cell or NK-cell type is an EBV+ polyclonal, oligoclonal or often monoclonal lymphoproliferative disorder (LPD) recognized as representing the spectrum of EBV-associated T-cell and NK-cell LPD with different clinical presentations; one systemic and two cutaneous disorders including hydroa vacciniforme-like T-cell LPD and mosquito bite hypersensitivity. The systemic form of the disease is characterized by fever, persistent hepatitis, hepatosplenomegaly and lymphadenopathy, which shows varying degrees of clinical severity depending on the immune response of the host and the EBV viral load.

Case Reports: We described the clinicopathological findings of two children with CAEBV with a brief review of the literature. Read More

Am J Dermatopathol 2016 Jan;38(1):20-5

*Centre for Dermatology & Dermatopathology and School of Medicine, Universidad Nacional Autónoma de México/Hospital General de México "Eduardo Liceaga," México, DF, Mexico; and †Research Unit Dermatopathology, Department of Dermatology, Medical University of Graz, Graz, Austria.

Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14. Read More

Br J Dermatol 2015 Nov 8;173(5):1266-70. Epub 2015 Sep 8.

Department of Dermatology, CHU Caen, Université de Caen Basse Normandie, 14000, Caen, France.

Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms associated with very high viral load, as assessed by quantitative polymerase chain reaction. We present an unusual case in a French woman who was followed up over 25 years with cutaneous and sinus lymphoproliferation. This white woman presented with a long history of recurrent cutaneous necrotic papules of the skin, which started during childhood and healed spontaneously with depressed scars. Read More

Br J Dermatol 2015 Sep 22;173(3):801-5. Epub 2015 Jul 22.

Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun-exposed areas without systemic symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T-cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Read More

J Eur Acad Dermatol Venereol 2015 Sep 25;29(9):1696-709. Epub 2015 Feb 25.

Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.

Primary cutaneous lymphomas (CL) in children is rare. Only a few studies focused specifically on paediatric CL and therefore little is known whether primary CL in children are similar to or different from their adult counterparts with respect to the clinicopathological presentation, behaviour and prognosis. An extensive literature search using PubMed/MEDLINE from January 1995 through July 2014 was undertaken for articles reporting cases of paediatric CL. Read More

Br J Dermatol 2015 Jan;172(1):5-6

James P. Wilmot Cancer Center, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY, 14642, U.S.A.

Int J Dermatol 2015 Mar 16;54(3):e84-5. Epub 2014 Dec 16.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

J Am Acad Dermatol 2015 Jan;72(1):21-34; quiz 35-6

Cooper Medical School of Rowan University, Camden, New Jersey; Perelman School of Medicine at the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Epstein-Barr virus (EBV) was the first human virus to be associated with oncogenesis. Over the past few decades, cumulative research has revealed that latent EBV infection may be implicated in the pathogenesis of a heterogeneous group of lymphoproliferative disorders and malignancies occurring in both immunocompetent and immunocompromised hosts. Many of these diseases have either primary or secondary cutaneous manifestations. Read More

J Am Acad Dermatol 2015 Jan;72(1):1-19; quiz 19-20

Cooper Medical School of Rowan University, Camden, New Jersey; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Epstein-Barr virus (EBV) is a ubiquitous virus that has been implicated in a wide range of human diseases, many of which have mucocutaneous manifestations. As a member of the herpesviridae family, EBV causes lifelong infection by establishing latency in B lymphocytes. An intact immune response is critical in preventing progression of EBV disease, and the clinical manifestations of infection are dependent on the intricate relationship between virus and host immune system. Read More

J Cutan Pathol 2015 Mar 8;42(3):229-31. Epub 2014 Dec 8.

Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.