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Table of Contents
Vol. 226, No. 3, 2013
Issue release date: August 2013
Section title: Case Report
Dermatology 2013;226:212-216
(DOI:10.1159/000348709)

Chronic Active Epstein-Barr Virus Infection-Associated Hydroa Vacciniforme-Like Eruption and Behçet's-Like Orogenital Ulcers

Park B.M.a · Ahn J.-S.b · Lee J.B.a · Won Y.H.a · Yun S.J.a
Departments of aDermatology and bHematology-Oncology, Chonnam National University Medical School, Gwangju, South Korea
email Corresponding Author

Abstract

The cutaneous manifestations of chronic active Epstein-Barr virus (EBV) infection can be diverse. Among them, hydroa vacciniforme-like eruption is one of the best-known features. Although rare, mucosal ulcers have been reported to be associated with EBV as a result of primary infection or immune suppression. We describe a 65-year-old female with recurrent necrotic papulovesicles on the face and both arms for 2 years. She also complained of recurrent oral and genital mucosal ulcers developing simultaneously with skin eruptions. They appeared periodically during the spring and summer and were triggered or aggravated by sun exposure. Skin biopsies from the face and genitalia showed identical findings with dense lymphocytic infiltrations. In addition, in situ hybridization revealed EBV-positive lymphoid cells in both specimens. To our knowledge, this is the first case of serologically and pathologically proven chronic active EBV infection presenting hydroa vacciniforme-like eruption and orogenital ulcers at the same time in one patient.

© 2013 S. Karger AG, Basel


  

Key Words


  • Behçet’s disease
  • Chronic active Epstein-Barr virus infection
  • Epstein-Barr virus
  • Hydroa vacciniforme
  • Orogenital ulcer


 Introduction

Chronic active Epstein-Barr virus (EBV) infection is a type of lymphoproliferative disorder caused by reactivation of latent EBV infection. Patients with this disorder present recurrent infectious mononucleosis-like symptoms and serologic evidence of EBV infection with markedly elevated levels of EBV DNA in the peripheral blood or viral RNA and proteins in the tissue [1,2]. Patients often complain of constitutional symptoms such as fever, fatigue and present hepatitis, hepatosplenomegaly and lymphadenopathy. The skin also can be infiltrated by EBV+ lymphocytes and shows variable features, depending on the interaction between virus-infected cells and host immune status [3,4].

Cutaneous manifestations of EBV-associated lymphoproliferative disorders vary from subcutaneous panniculitis-like eruption to exaggerated reactions to mosquito bites to lymphomas. Among them, one of the best-known features is vesiculopapular eruption, termed hydroa vacciniforme (HV)-like eruption [3,4]. The cutaneous manifestations are similar to typical HV with recurrent photodistributed papulovesicles, which ulcerate, crust and heal with vacciniform scars. Although rare, mucocutaneous ulcers can also be a feature of EBV-associated disorders and have been described as a feature of primary infection or immunodeficiency-induced lymphoproliferative disorders [5,6,7,8,9,10,11,12].

Recurrent orogenital ulcers presenting as a feature of chronic active EBV infection have not been reported yet. Herein, we report unusual mucocutaneous manifestations of chronic active EBV infection with HV-like eruption accompanying recurrent orogenital ulcers mimicking Behçet's disease.

 

 Case Report

A 65-year-old female farmer visited our clinic in June 2011 for a recurrent attack of stinging and erythematous papules and vesicles with crusts appearing over her face, neck, hand and upper arms. She also had multiple painful oral and genital ulcers simultaneously. She first noted the recurrent oral and genital ulcers, followed by vesiculopapular eruptions which began in the spring of 2010. The skin lesions relapsed repeatedly throughout the summer. At the beginning of summer, similar orogenital ulcers and vesiculopapular lesions appeared again on her face and upper arms after working outside in the daytime. She also complained of fever, chronic fatigue and wasting. Her past and family histories were non-contributory. Physical examination revealed scattered erythematous maculopapules and yellow-tinted tense vesicles and bullae on her face, upper arms and back, all areas which are exposed to sunlight. Each vesicle ruptured within 1-2 days, became crusted and then gradually healed, leaving scars (fig. 1). She also had recurrent multiple shallow ulcers on her tongue and the mucosal surface of her labia majora (fig. 2). The oral and genital ulcers appeared more frequently, were less related to sun exposure and mirrored the clinical course of vesiculopapular skin lesion.

FIG01
Fig. 1.a Multiple erythematous papulovesicular eruptions on the face. b They become crusted within few days after. c Confluent vesicular eruptions and large bullae over the upper back and shoulder. d They heal with scarring.

FIG02
Fig. 2.a Multiple shallow ulcers on the tongue. b Ulcers on the mucosal surface of the labia majora.

The patient experienced severe fatigue and was febrile when the skin lesions appeared. Additionally, the systemic symptoms were more severe when vesicular eruptions developed on the face and trunk than when they accompanied only orogenital ulcers. Multiple enlarged cervical lymph nodes were noted on computed tomography. Skin biopsies taken from the vesicles on her face revealed epidermal necrosis and reticulated epidermal degeneration, intraepidermal vesiculation and dense lymphocytic infiltration surrounding the periappendigeal and perivascular areas in the entire dermis (fig. 3a, b). Biopsy specimens from nearby skin of a genital ulcer showed ulceration and dense lymphocytic infiltration in the dermis, which were similar to the findings of the facial lesion biopsy (online suppl. fig. 1; for all online suppl. material, see www. karger.com/doi/10.1159/000348709). Based on immunohistochemical analysis, most infiltrating cells showed positivity for CD3 and CD45RO and negativity for CD20 and CD56. Direct immunofluorescent examination using antisera to IgG, IgA and C3 showed negative results. Enlarged lymph nodes were also examined. Lymphoid cells had no obvious nuclear pleomorphism or atypia, and T cell receptor gene rearrangement was negative by PCR. EBV in situ hybridization was carried out using an EBV-encoded small nuclear RNA (EBER) probe supplied by Leica on automated stainer (Leica, Wetzlar, Germany) according to the manufacturer's instructions.

FIG03
Fig. 3. Skin biopsy obtained from a vesicular lesion on the face. a, b Intraepidermal vesiculation with dense lymphocytic infiltration is observed in the dermis (HE; a ×100, b ×400). c Cells positive for EBER are present. In situ hybridization, ×200.

EBER transcripts were found in the nuclei of lymphoid cells from all biopsy specimens of the affected area, including lymph nodes. The EBER-positive cells ranged from 10 to 15% of the infiltrating lymphocytes in specimens from the face and genitalia (fig. 3c, online suppl. fig. 1c).

Results of laboratory studies, including the complete blood cell count with differential and lymphocyte subset, platelet count, liver and renal function tests are shown in online supplementary table 1.

Protein electrophoresis showed decreased albumin with elevated alpha1 and gamma globulin pattern, suggesting chronic inflammatory or infection state. HLA B51 genotyping, antinuclear antibody and anti-dsDNA antibody were all negative. Screening tests for urine porphyrin by direct spectrophotometry were negative.

Serum immunoglobulin level against EBV-related proteins was examined using the ELISA method. IgG antibodies to EBV viral capsid antigen, early antigen and nuclear antigen (EBNA) were positive; however IgM antibodies to viral capsid antigen and EBNA were negative.

A quantitative EBV PCR was performed to detect EBV DNA in peripheral blood. At the time the patient suffered from vesicular eruptions and orogenital ulcers, the results showed 708,991 copies/µg of DNA. She was admitted to the ward and treated with famciclovir, a systemic steroid and dapsone. After recovery, EBV DNA titer was decreased to 44,420 copies/µg.

During clinical remission period, photoprovocation tests were performed using a Waldmann UV 181 AL, BL (Herbert Waldmann, Schwenningen, Germany). Each 1 × 1 cm area on the back was irradiated with UVB (10-60 mJ/cm2, 10 mJ/cm2 intervals) and UVA (5-30 J/cm2, 5 J/cm2 intervals). After 48 h, a papulovesicular eruption developed only in the UVA-exposed area while the UVB exposure site showed only mild erythema. The finding of a skin biopsy taken from the UVA-induced vesicular eruption was consistent with previous skin biopsy specimens and with EBER-positive cells (online suppl. fig. 2). The patient was diagnosed with chronic active EBV infection, advised to avoid direct sun exposure and treated with systemic corticosteroids and famciclovir when the lesions recurred. Her symptoms were controlled by regular follow-up visits; she was also evaluated for the development of lymphomas.

 

 Discussion

HV-like eruption is a representative cutaneous manifestation of EBV-associated lymphoproliferative disorder and is reported mainly in Asia [4,13,14,15,16,17] and Latin America [18,19]. HV-like eruption has similar clinical and pathologic findings to those of HV. However, there are some distinctive features. The skin lesions are much more severe in HV-like eruption and patients present systemic manifestations such as fever, fatigue, lymph node enlargement and hepatosplenomegaly. Additionally, unlike typical HV, the representative photosensitive disease of childhood, HV-like eruption develops in both sun-exposed and non-sun-exposed areas, regardless of age. Of particular concern is the prognosis that HV-like eruption occasionally progresses to hematologic malignancies, whereas typical HV is an almost entirely self-limited disease. Recently, HV and HV-like eruption were considered variants within the same disease spectrum of EBV-associated lymphoproliferative disorders caused by a cytotoxic T cell response against virus-infected cells, and not distinct diseases [13,15,20]. Our patient was diagnosed with chronic active EBV infection with a high peripheral blood viral load. Her cutaneous findings were comparable to those of typical HV-like eruption.

It is of interest that this patient presented with recurrent oral and genital ulcers simultaneously with HV-like eruption; vesicular eruptions and orogenital ulcers followed a similar clinical course. The clinical pattern of orogenital ulcers which were highly associated with HV-like eruption suggests a close link between these lesions. Co-existing oral and buccal ulcers with HV-like eruption have been reported rarely; indeed, there has to our knowledge been no report of a co-existing genital ulcer [16,21]. EBV-associated genital ulcer cases have been reported as a feature of primary EBV infection presenting as transient, relatively large and deep necrotic ulcers. The biopsy findings demonstrated lymphocytic vasculitis. As they occur as a result of viremia and immunologic reaction, viral DNA and protein do not need to be present in the tissue [6,7,8,9,10]. On the other hand, EBV-positive mucocutaneous ulcers also have been described as a distinct clinicopathologic entity secondary to immunosuppression [11,12]. They present as isolated and sharply circumscribed ulcers involving the skin, oropharyngeal mucosa or gastrointestinal tract. Histopathologic findings show a mixture of lymphocytes and immunoblasts, which are Hodgkin-like features [11]. However, the clinical and histological features of our patient's orogenital ulcers differed from EBV-associated mucosal ulcers reported previously. Our immunocompetent patient showed rather small and shallow ulcers with frequent recurrence. In addition, biopsy specimens from genital ulcers showed findings identical to those of vesiculopapular lesions on the face and trunk, including many EBER+ lymphocytes. There was no evidence of immunoblasts or vasculitis. Therefore, the patient's recurrent oral and genital ulcers were understood to be similar to chronic active EBV infection-associated lymphoproliferative lesion, such as HV-like eruptions, which were not reported in prior cases.

HV-like eruption and the relation with UV exposure is well known. A photoprovocation test was performed to confirm the photosensitivity and the diagnosis. HV and HV-like eruptions are known to be induced by repeated irradiation of large doses of UVA, but not UVB [22,23]. However, their exact pathogenesis which induces reactivation of latent EBV infection and lymphoproliferation is yet uncertain. Besides papulovesicular eruptions, some chronic active EBV infection-related cutaneous symptoms do not develop in UV-exposed areas only. Magana et al. [19] and Cho et al. [13] described subcutaneous lesions not directly related with UV light. There have been many studies [13,20] about an increasing tendency of EBER+ cells during disease progression or increasing disease severity. Dojcinov et al. [11] suggested such a mucosal irritation or a trauma might induce lowered resistance over EBV and cause localized proliferation of EBV-infected cell. These suggested that host immunity plays a key role in EBV disease manifestations. In conclusion, besides UV exposure, the decreased host immunity itself could facilitate the development of lymphoproliferative disorder in latent EBV infection.

Cho et al. [13] suggested that repeated UV exposure activates circulating EBV-infected lymphocytes; the immunosuppressive action of UV radiation in exposed skin is well known [24]. It can be hypothesized that UV activates EBV-infected lymphocytes and induces lymphoproliferation in directly exposed areas where host immunity is compromised. The oral and genital areas are a natural EBV reservoir and mucosal epithelium is easily shed [6,7]. Therefore, orogenital mucosa could be affected more frequently and preferentially than skin with less relation to sun exposure.

Recurrent oral and genital ulcerations are commonly considered representative manifestations of Behçet's disease. Though the etiology of this condition remains obscure, there is evidence for the involvement of viral infection, including EBV [25,26]. As seen in the present case, the relationship between EBV infection and orogenital ulcers warrants further studies.

We report an elderly female presenting HV-like eruptions and accompanying Behçet's-like orogenital ulcers as a result of chronic active EBV infection. Recurrent orogenital ulcers should be considered as a rare manifestation of EBV infection. Further studies are needed to confirm this association.

 

 Disclosure Statement

The authors declare no conflict of interest.


References

  1. Cohen JI: Epstein-Barr virus infection. N Engl J Med 2000;343:481-492.
  2. Kimura H: Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev Med Virol 2006;16:251-261.
  3. Iwatsuki K, Xu Z, Ohtsuka M, Kaneko F: Cutaneous lymphoproliferative disorders associated with Epstein-Barr virus infection: a clinical overview. J Dermatol Sci 2000;22:181-195.
  4. Iwatsuki K, Ohtsuka M, Harada H, Han G, Kaneko F: Clinicopathologic manifestations of Epstein-Barr virus-associated cutaneous lymphoproliferative disorders. Arch Dermatol 1997;133:1081-1086.
  5. Al-Rawahi GN, Dobson SR, Scheifele DW, Rassekh SR, Murphy JJ: Severe genital ulceration in an acute Epstein-Barr virus infection. Pediatr Infect Dis J 2011;30:176-178.
  6. Barnes CJ, Alio AB, Cunningham BB, Friedlander SF: Epstein-Barr virus-associated genital ulcers: an under-recognized disorder. Pediatr Dermatol 2007;24:130-134.
  7. Cheng SX, Chapman MS, Margesson LJ, Birenbaum D: Genital ulcers caused by Epstein-Barr virus. J Am Acad Dermatol 2004;51:824-826.
  8. Halvorsen JA, Breviq T, Aas T, Skar AG, Slevolden EM, Moi H: Genital ulcers as initial manifestation of Epstein-Barr virus infection: two new cases and a review of the literature. Acta Derm Venereol 2006;86:439-442.
  9. Lampert A, Assier-Bonnet H, Chevallier B, Clerici T, Saiag P: Lipschutz's genital ulceration: a manifestation of Epstein-Barr virus primary infection. Br J Dermatol 1996;135:663-665.
  10. Sardy M, Wollenberg A, Niedermeier A, Flaig MJ: Genital ulcers associated with Epstein-Barr virus infection (ulcus vulvae acutum). Acta Derm Venereol 2011;91:55-59.

    External Resources

  11. Dojcinov SD, Venkataraman G, Raffeld M, Pittaluga S, Jaffe ES: EBV positive mucocutaneous ulcer - a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010;34:405-417.
  12. McGinness JL, Spicknall KE, Mutasim DF: Azathioprine-induced EBV-positive mucocutaneous ulcer. J Cutan Pathol 2012;39:377-381.
  13. Cho KH, Lee SH, Kim CW, Jeon YK, Kwon IH, Cho YJ, Lee SK, Suh DH, Chung JH, Yoon TY, Lee SJ: Epstein-Barr virus-associated lymphoproliferative lesions presenting as a hydroa vacciniforme-like eruption: an analysis of six cases. Br J Dermatol 2004;151:372-380.
  14. Xu Z, Lian S: Epstein-Barr virus-associated hydroa vacciniforme-like cutaneous lymphoma in seven Chinese children. Pediatr Dermatol 2010;27:463-469.
  15. Wu YH, Chen HC, Hsiao PF, Tu MI, Lin YC, Wang TY: Hydroa vacciniforme-like Epstein-Barr virus-associated monoclonal T-lymphoproliferative disorder in a child. Int J Dermatol 2007;46:1081-1086.
  16. Cho KH, Kim CW, Heo DS, Lee DS, Choi WW, Rim JH, Han WS: Epstein-Barr virus-associated peripheral T-cell lymphoma in adults with hydroa vacciniforme-like lesions. Clin Exp Dermatol 2001;26:242-247.
  17. Cho KH, Kim CW, Lee DY, Sohn SJ, Kim DW, Chung JH: An Epstein-Barr virus-associated lymphoproliferative lesion of the skin presenting as recurrent necrotic papulovesicles of the face. Br J Dermatol 1996;134:791-796.
  18. Ruiz-Maldonado R, Parrilla FM, Orozco-Covarrubias ML, Ridaura C, Tamayo Sanchez L, Duran McKinster C: Edematous, scarring vasculitic panniculitis: a new multisystemic disease with malignant potential. J Am Acad Dermatol 1995;32:37-44.
  19. Magana M, Sangueza P, Gil-Beristain J, et al: Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): a distinctive type of cutaneous T-cell lymphoma. J Am Acad Dermatol 1998;38:574-579.
  20. Iwatsuki K, Xu Z, Takata M, et al: The association of latent Epstein-Barr virus infection with hydroa vacciniforme. Br J Dermatol 1999;140:715-721.
  21. Nishizawa A, Satoh T, Takayama K, Yokozeki H: Hydroa vacciniforme with mucosal involvement and recalcitrant periodontitis and multiple virus re-activators after sun-exposure. Acta Derm Venereol 2010;90:498-501.
  22. Sunohara A, Mizuno N, Sakai M, Kawabe Y, Sakakibara S: Action spectrum for UV erythema and reproduction of the skin lesions in hydroa vacciniforme. Photodermatology 1988;5:139-145.

    External Resources

  23. Heo EP, Park SH, Kim TH: Artificial reproduction of atypical hydroa vacciniforme caused by latent Epstein-Barr virus infection. Int J Dermatol 2003;42:476-479.
  24. Schwarz T: Photoimmunosuppression. Photodermatol Photoimmunol Photomed 2002;18:141-145.
  25. Sun A, Chang JG, Chu CT, Liu BY, Yuan JH, Chiang CP: Preliminary evidence for an association of Epstein-Barr virus with pre-ulcerative oral lesions in patients with recurrent aphthous ulcers or Behçet's disease. J Oral Pathol Med 1998;27:168-175.
  26. Hooks JJ: Possibility of a viral etiology in recurrent aphthous ulcers and Behçet's syndrome. J Oral Pathol 1978;7:353-364.

  

Author Contacts

Sook Jung Yun, MD, PhD
Department of Dermatology
Chonnam National University Medical School
5 Hak-Dong, Dong-Gu, Gwangju 501-746 (South Korea)
E-Mail sjyun@chonnam.ac.kr

  

Article Information

Received: December 11, 2012
Accepted after revision: February 4, 2013
Published online: June 1, 2013
Number of Print Pages : 5
Number of Figures : 3, Number of Tables : 0, Number of References : 26
Additional supplementary material is available online - Number of Parts : 2

  

Publication Details

Dermatology

Vol. 226, No. 3, Year 2013 (Cover Date: August 2013)

Journal Editor: Saurat J.-H. (Geneva)
ISSN: 1018-8665 (Print), eISSN: 1421-9832 (Online)

For additional information: http://www.karger.com/DRM


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

The cutaneous manifestations of chronic active Epstein-Barr virus (EBV) infection can be diverse. Among them, hydroa vacciniforme-like eruption is one of the best-known features. Although rare, mucosal ulcers have been reported to be associated with EBV as a result of primary infection or immune suppression. We describe a 65-year-old female with recurrent necrotic papulovesicles on the face and both arms for 2 years. She also complained of recurrent oral and genital mucosal ulcers developing simultaneously with skin eruptions. They appeared periodically during the spring and summer and were triggered or aggravated by sun exposure. Skin biopsies from the face and genitalia showed identical findings with dense lymphocytic infiltrations. In addition, in situ hybridization revealed EBV-positive lymphoid cells in both specimens. To our knowledge, this is the first case of serologically and pathologically proven chronic active EBV infection presenting hydroa vacciniforme-like eruption and orogenital ulcers at the same time in one patient.

© 2013 S. Karger AG, Basel


  

Author Contacts

Sook Jung Yun, MD, PhD
Department of Dermatology
Chonnam National University Medical School
5 Hak-Dong, Dong-Gu, Gwangju 501-746 (South Korea)
E-Mail sjyun@chonnam.ac.kr

  

Article Information

Received: December 11, 2012
Accepted after revision: February 4, 2013
Published online: June 1, 2013
Number of Print Pages : 5
Number of Figures : 3, Number of Tables : 0, Number of References : 26
Additional supplementary material is available online - Number of Parts : 2

  

Publication Details

Dermatology

Vol. 226, No. 3, Year 2013 (Cover Date: August 2013)

Journal Editor: Saurat J.-H. (Geneva)
ISSN: 1018-8665 (Print), eISSN: 1421-9832 (Online)

For additional information: http://www.karger.com/DRM


Article / Publication Details

First-Page Preview
Abstract of Case Report

Received: 12/11/2012 8:39:13 AM
Accepted: 2/4/2013
Published online: 6/1/2013
Issue release date: August 2013

Number of Print Pages: 5
Number of Figures: 3
Number of Tables: 0

ISSN: 1018-8665 (Print)
eISSN: 1421-9832 (Online)

For additional information: http://www.karger.com/DRM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Cohen JI: Epstein-Barr virus infection. N Engl J Med 2000;343:481-492.
  2. Kimura H: Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? Rev Med Virol 2006;16:251-261.
  3. Iwatsuki K, Xu Z, Ohtsuka M, Kaneko F: Cutaneous lymphoproliferative disorders associated with Epstein-Barr virus infection: a clinical overview. J Dermatol Sci 2000;22:181-195.
  4. Iwatsuki K, Ohtsuka M, Harada H, Han G, Kaneko F: Clinicopathologic manifestations of Epstein-Barr virus-associated cutaneous lymphoproliferative disorders. Arch Dermatol 1997;133:1081-1086.
  5. Al-Rawahi GN, Dobson SR, Scheifele DW, Rassekh SR, Murphy JJ: Severe genital ulceration in an acute Epstein-Barr virus infection. Pediatr Infect Dis J 2011;30:176-178.
  6. Barnes CJ, Alio AB, Cunningham BB, Friedlander SF: Epstein-Barr virus-associated genital ulcers: an under-recognized disorder. Pediatr Dermatol 2007;24:130-134.
  7. Cheng SX, Chapman MS, Margesson LJ, Birenbaum D: Genital ulcers caused by Epstein-Barr virus. J Am Acad Dermatol 2004;51:824-826.
  8. Halvorsen JA, Breviq T, Aas T, Skar AG, Slevolden EM, Moi H: Genital ulcers as initial manifestation of Epstein-Barr virus infection: two new cases and a review of the literature. Acta Derm Venereol 2006;86:439-442.
  9. Lampert A, Assier-Bonnet H, Chevallier B, Clerici T, Saiag P: Lipschutz's genital ulceration: a manifestation of Epstein-Barr virus primary infection. Br J Dermatol 1996;135:663-665.
  10. Sardy M, Wollenberg A, Niedermeier A, Flaig MJ: Genital ulcers associated with Epstein-Barr virus infection (ulcus vulvae acutum). Acta Derm Venereol 2011;91:55-59.

    External Resources

  11. Dojcinov SD, Venkataraman G, Raffeld M, Pittaluga S, Jaffe ES: EBV positive mucocutaneous ulcer - a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010;34:405-417.
  12. McGinness JL, Spicknall KE, Mutasim DF: Azathioprine-induced EBV-positive mucocutaneous ulcer. J Cutan Pathol 2012;39:377-381.
  13. Cho KH, Lee SH, Kim CW, Jeon YK, Kwon IH, Cho YJ, Lee SK, Suh DH, Chung JH, Yoon TY, Lee SJ: Epstein-Barr virus-associated lymphoproliferative lesions presenting as a hydroa vacciniforme-like eruption: an analysis of six cases. Br J Dermatol 2004;151:372-380.
  14. Xu Z, Lian S: Epstein-Barr virus-associated hydroa vacciniforme-like cutaneous lymphoma in seven Chinese children. Pediatr Dermatol 2010;27:463-469.
  15. Wu YH, Chen HC, Hsiao PF, Tu MI, Lin YC, Wang TY: Hydroa vacciniforme-like Epstein-Barr virus-associated monoclonal T-lymphoproliferative disorder in a child. Int J Dermatol 2007;46:1081-1086.
  16. Cho KH, Kim CW, Heo DS, Lee DS, Choi WW, Rim JH, Han WS: Epstein-Barr virus-associated peripheral T-cell lymphoma in adults with hydroa vacciniforme-like lesions. Clin Exp Dermatol 2001;26:242-247.
  17. Cho KH, Kim CW, Lee DY, Sohn SJ, Kim DW, Chung JH: An Epstein-Barr virus-associated lymphoproliferative lesion of the skin presenting as recurrent necrotic papulovesicles of the face. Br J Dermatol 1996;134:791-796.
  18. Ruiz-Maldonado R, Parrilla FM, Orozco-Covarrubias ML, Ridaura C, Tamayo Sanchez L, Duran McKinster C: Edematous, scarring vasculitic panniculitis: a new multisystemic disease with malignant potential. J Am Acad Dermatol 1995;32:37-44.
  19. Magana M, Sangueza P, Gil-Beristain J, et al: Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): a distinctive type of cutaneous T-cell lymphoma. J Am Acad Dermatol 1998;38:574-579.
  20. Iwatsuki K, Xu Z, Takata M, et al: The association of latent Epstein-Barr virus infection with hydroa vacciniforme. Br J Dermatol 1999;140:715-721.
  21. Nishizawa A, Satoh T, Takayama K, Yokozeki H: Hydroa vacciniforme with mucosal involvement and recalcitrant periodontitis and multiple virus re-activators after sun-exposure. Acta Derm Venereol 2010;90:498-501.
  22. Sunohara A, Mizuno N, Sakai M, Kawabe Y, Sakakibara S: Action spectrum for UV erythema and reproduction of the skin lesions in hydroa vacciniforme. Photodermatology 1988;5:139-145.

    External Resources

  23. Heo EP, Park SH, Kim TH: Artificial reproduction of atypical hydroa vacciniforme caused by latent Epstein-Barr virus infection. Int J Dermatol 2003;42:476-479.
  24. Schwarz T: Photoimmunosuppression. Photodermatol Photoimmunol Photomed 2002;18:141-145.
  25. Sun A, Chang JG, Chu CT, Liu BY, Yuan JH, Chiang CP: Preliminary evidence for an association of Epstein-Barr virus with pre-ulcerative oral lesions in patients with recurrent aphthous ulcers or Behçet's disease. J Oral Pathol Med 1998;27:168-175.
  26. Hooks JJ: Possibility of a viral etiology in recurrent aphthous ulcers and Behçet's syndrome. J Oral Pathol 1978;7:353-364.