Diseases caused by cytomegalovirus and Epstein-Barr virus are  reported with increasing frequency. Epstein-Barr virus damages usually are due to reactivation of  latent infection.  while cytomegalovirus disease result from  primary  or  reactivated infection  in susceptible hosts. The booth infections can have oral manifestations

Assya Krasteva

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Journal of IMAB - Annual Proceeding (Scientific Papers)

EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS – TWO HERPES VIRUSES WITH ORAL MANIFESTATIONS

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/ J of IMAB. 2013, vol. 19, issue 4/ http://www.journal-imab-bg.org 359http://dx.doi.org/10.5272/jimab.2013194.359EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS- TWO HERPES VIRUSES WITH ORALMANIFESTATIONSAssya Krasteva,Department of Oral and Image Diagnostic, Faculty of Dental Medicine, MedicalUniversity - Sofia, BulgariaJournal of IMAB - Annual Proceeding (Scientific Papers) 2013, vol. 19, issue 4 ISSN: 1312-773X (Online)SUMMARY:Diseases caused by cytomegalovirus and Epstein-Barr virus are  reported with increasing frequency. Epstein-Barr virus damages usually are due to reactivation of  latentinfection. While cytomegalovirus disease result fromprimary  or  reactivated infection  in susceptible hosts.  Thebooth infections can have oral manifestations.Key words:  oral cavity,  cytomegalovirus,  EBVINTRODUCTION:Epstein-Barr virus (EBV) and cytomegalovirus(CMV) are herpesviruses, which  account for the majorityof oral viral infections. Herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus infections nearly alwaysresult from reactivation of latent virus, while cytomegalo-virus infections, besides presenting as reactivated disease,are almost as likely to present as a primary infection insusceptible hosts [1]. Herpesviruses are common in personsinfected with the human immunodeficiency virus (HIV) [2].The diseases or medical treatments that have cytostatic orcytotoxic effects  also increase the risk of viral infections[1].The general characteristic of CMV and EBV ispresented in tabl. 1.Tabl. 1.  The main characteristic of EBV and CMV [1, 3, 4, 5, 6, 7]Cytomegalovirusb-herpesvirus HHV - 5body fluids (breast milk, saliva, urine, respiratorysecretions)sexual contactblood transfusionduring deliveryorgan transplant60-70% of the adult population has been exposedManifestation of CMV are more evident inimmunocompromised population , such  as organtransplant patients and who have AIDSOnce exposed to CMV, this virus establisheslatency within the connective tissue cells, such asthe  endothelium of blood vessels, mononuclearcells, white blood cells, and epithelial cellsPrimary infection may be asymptomatic or causean infectious mononucleosis like diseaseEpstein-Barr virusHHV - 4body fluids (saliva, breast milk, respiratorysecretions)sexual contactblood transfusionor by sharing food, drinks or eating utensils withan infected person80 - 90% of the adult population have beeninfected by the virus (35-40 years)It is frequently seen in individuals infected withthe human immunodeficiency virus (HIV) andless often in other immunosuppressed individualsWhen the virus is dormant, it is hiding in aninactive form in B lymphocytes - “latent” stateEBV can lead to:infection mononucleosisoral hairy leukoplakiaplasmablastic lymphomaBurkitt lymphomaHodgkin lymphomanasopharyngeal carcinomaKikuchi histocytic necrotizing lymphadenitisSignsHerpesviruses typeTransmissionExpositionPredisposed peopleVirus targetsClinical variants360 http://www.journal-imab-bg.org / J of IMAB. 2013, vol. 19, issue 4/CytomegalovirusCytomegalovirus is responsible for a significantpercentage of asymptomatic viral infections worldwide.During childhood, many people acquire primary infectionwith cytomegalovirus and if they later becomeimmunosuppressed, such as occurs with humanimmunodeficiency virus (HIV), CMV is likely to becomereactivated (4).  For the medical doctors and dentists isimportant that  between 11 and 24% of children attendingday-care centers have CMV in their saliva [3].Although virtually any cell or organ may be infected[8].  Severe disease caused by CMV have been reported –CMV retinitis, gastritis, colitis, pneumonia, encephalitis andhepatitis [4]. After hematopoietic stem cell transplantationcytomegalovirus is the most common cause of pneumoniawithin the first 120 days [3].  There is a date that CMVwithin endothelial cells may contribute to vascularinflammation, vascular occlusion, and end-organ damage [3].Epstein-Barr virusEBV infection is transmitted from person to personby contact with infectious body fluids (saliva, breast milketc). Oral contact with infectious saliva is the most commonroute of transmission.  The active virus reproduces andenters the person’s saliva, a process known as “shedding”[7]In EBV two peaks of infection are seen: the first invery young preschool children aged 1 - 6and the second inadolescents and young adults aged 14 - 20 [3].In primary infection, EBV infects B cells and cancause mucocutaneous manifestations in infectiousmononucleosis (IM) or acute EBV-associated syndromessuch as Gianotti-Crosti syndrome and hemophagocyticsyndrome [3, 5, 9].There are two different types of chronic activeEpstein-Barr virus (CAEBV) infection: chronic EBV(CEBV) having persistent infectious mononucleosis - likeillness with relatively good prognosis, and severe CAEBV(SCAEBV) infection that has rather severe manifestationsand generally poor prognosis (10). Latent EBV infectionmay result in diseases such as hydroa vacciniforme,hypersensitivity to mosquito bites, and lymphoproliferativedisorders such as plasmablastic lymphoma, oral hairyleukoplakia, and post-transplant lymphoproliferativedisorders, particularly in immunocompromised patients.Latent EBV infection has also been implicated in Burkittlymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma,and Kikuchi histocytic necrotizing lymphadenitis [5, 10].Like all herpesviruses, EBV establishes a life-long,persistent infection of its host  [7] and in the majority ofhumans without causing disease [5]. JA Thomas, etcoworkers published that in the literature are reports of EBVinfection in normal T cells and neoplastic T-cell diseases.Generally EBV is held to infect B cells and epithelial cells[11].In Table 2 are present the clinical findings ofCytomegalovirus infection and infectious mononucleosisconcerning the general health. In Table 3 are present onlythe oral manifestation of Cytomegalovirus infection andinfectious mononucleosisTable 2. Clinical signs of Cytomegalovirus infection and infectious mononucleosis [3, 8, 12]Cytomegalovirus infectionliver and spleen (hepatosplenomegaly)lung (severe viral pneumonia)GI tract (colitis)central nervous system (encephalitis)blood cells (trombocytopenia)and multisystem involvement (fever ofunknown origin)the kidneysadrenalseye (cmv retinitis)pancreas and esophagus involvmentInfectious mononucleosisliver and spleen (splenic enlargement andtenderness and hepatomegaly)significant fatigueheadaches or joint painbilateral edema of the upper eyelids(palpebral edema)nausea and vomiting, or decreasedappetitejaundiceskin rashblood cells (trombocytopenia)fever: adults 38.3–38.9°C; children maynot haveSites most often involvedOther symptomsUncommon sites of infections inimmunocompetent individualsinclude/ J of IMAB. 2013, vol. 19, issue 4/ http://www.journal-imab-bg.org 361EBV• hairy leukoplakiaHairy leukoplakia is the second most common HIV-associated oral mucosal lesion and usually is localisated onthe lateral borders of the tongue.  The typical clinicalappearance is vertical white folds oriented as a palisadealong the borders of the tongue [3].• nasopharyngeal carcinomaPreliminary investigations suggest that the presenceof EBV genomes in neck metastases from an occult primarymay be diagnostic and predictive of nasopharyngealcarcinoma [18].IMIn the majority of cases of IM lymphadenopathy ispresent and the cervical lymph nodes are most commonlyinvolved,  but generalized lymphadenopathy may occur [12].Swelling of anterior and posterior cervical lymph nodes plusaxillary, epitrochlear, mediastinal, and mesenteric nodes) orauricular adenopathy, marked adenopathy, or inguinaladenopathy are described [12].Other manifestation of IM can be salivary glandenlargement. Several viruses have been associated with acutenonsuppurative salivary gland enlargement. The virusesresponsible for the majority of virally induced salivary glandenlargement are paramyxovirus, cytomegalovirus HIV, andhepatitis C virus. Echoviruses, Epstein-Barr virus,parainfluenza virus, and choriomeningitis virus infectionshave been linked to occasional reports of nonsuppurativesalivary gland enlargement [3].CMVThe effects of human CMV on cellular functions whichmay be associated with the malignant phenotype include theexpression of oncogenes and transcriptional activation ofgrowth factors and interleukin synthesis [19].In another study M.  Melnick et coworkers discus theassociation of CMV and  variety of malignancies, includingbrain, breast, lung, colon, and prostate. The authors concludedthat CMV is an important component of tumorigenesis (20).In oral cavity CMV may be present as a single largenecrotic painful ulcer and less often as multiple ulcers, presentfor weeks or months at any site may be involved (3). Up toone-third of such ulcers are coinfected with other viruses ofthe herpes family, especially herpes simplex virus andvarizella zoster virus (VZV) [3, 15, 21]. There have beenoccasional reports of mandibular osteomyelitis and toothexfoliation associated with CMV and VZV infection [3].Some authors reported CMV oral lesions in HIVinfected patients and emphasize that CMV mucosal ulcerationmay be the initial manifestation of AIDS [13, 16, 17, 22].The infection of CMV affects also the composition ofthe saliva: IgG, and albumin were higher in patients, but totalprotein were lower [23].CONCLUSION:The clinical manifestations of these viruses are similarand most commonly affected liver, spleen and lymph node.In the oral cavity the viral sins are unspecific and uncommon.The dentist first  can  recognize the oral manifestationsof the underlying disease,  taking in a part that the numberof immunocompromised population will get increase.Oral manifestationsTable 3. Oral manifestations  of CMV, EBV and particularly  IM  [2, 3, 4, 12, 13, 14, 15, 16, 17]EBV• hairy leukoplakia• nasopharyngeal carcinoma• infectious mononucleosisIM• sore throat (pharyngitis )• tonsillitis• petechiae on hard palate• gingivitis (necrotic ulseroza)• lymphadenopathy• salivary gland enlargementCMV• nonspecific oral ulcerations• periodontal disease (resembling)• carcinoma (mucoepidermoid) of  major and minorsalivary glands• polymicrobial infection with HS V or VZV• salivary gland enlargement1. Schubert MM.  Oral manifesta-tions of viral infections in immuno-compromised patients. Curr Opin Dent.1991 Aug;1(4):384-397. [PubMed]2.  Glick M, Cleveland DB, SalkinLM, Alfaro-Miranda M, Fielding AF.Intraoral cytomegalovirus lesion andHIV-associated periodontitis in a patientwith acquired immunodeficiencysyndrome. Oral Surg Oral Med OralPathol.  1991 Dec;72(6):716–720.[PubMed]3. Greenberger M, Glick M, Ship J.Transplantation medicine in: Burket’soral medicine. 2008, 461 -481.4. Dodd CL, Winkler JR, Heinic GSREFERENCES: Daniels TE, Yee K, Greenspan D.Cytomegalovirus infection presenting asacute periodontal infection in a patientinfected with the human immuno-deficiency virus. J Clin Periodontol.1993 Apr;20(4):282-285. [PubMed]5. Mendoza N, Diamantis M, AroraA,  Bartlett B, Gewirtzman A, Tremaine362 http://www.journal-imab-bg.org / J of IMAB. 2013, vol. 19, issue 4/AM, et al. Mucocutaneous manifesta-tions of Epstein-Barr virus infection. AmJ Clin Dermatol. 2008; 9(5):295-305.[PubMed]6. Wurapa AK, Luque AE, MenegusMA. Oral hairy leukoplakia: amanifestation of primary infection withEpstein-Barr virus? Scand J Infect Dis.1999;31(5):505-506. [PubMed]7. Walling DM.  Oral HairyLeukoplakia: An Epstein-Barr Virus-Associated Disease of Patients withHIV. Res Initiat Treat Action. 2000Dec;6(4):10-5. [PubMed]8. Jones AC, Freedman PD, PhelanJA, Baughman RA,  Kerpel SM.Cytomegalovirus infections of the oralcavity. A report of six cases and reviewof the literature. Oral Surg Oral MedOral Pathol. 1993 Jan;75(1):76-85.[PubMed]9. Jain N, Bhatia V, Lattoo S.Epstein-Barr virus and associated headand neck manifestations. Ann NigerianMed. 2011; 5:38-41. [CrossRef]10. Song HM, Wu XY, Wang W, Xing Y, Li F, Qiu JJ,  et al. Clinicalcharacteristics and follow-up of 12 caseswith severe chronic active Epstein-Barrvirus infection. Zhonghua Er Ke Za Zhi.2009 Sep;47(9):682-6. [PubMed]11. Thomas JA, Cotter F, HanbyAM,  Long LQ, Morgan PR, BrambleB,  et al. Epstein-Barr virus-related oralT-cell lymphoma associated with humanimmunodeficiency virus immuno-suppression. Blood. 1993 Jun 15;81(12):3350-6. [PubMed]12. Ebell MH. Epstein-Barr virusinfectious mononucleosis. Am FamPhysician. 2004 Oct 1;70(7):1279-87.[PubMed]13. Kanas RJ,  Jensen JL,  AbramsAM,  Wuerker RB. Oral mucosalcytomegalovirus as a manifestation ofthe acquired immune deficiencysyndrome. Oral Surg Oral Med OralPathol. 1987 Aug;64(2):183–189.[PubMed]14. Epstein JB, Sherlock CH,Wolber RA. Oral manifestations ofcytomegalovirus infection. Oral SurgOral Med Oral Pathol. 1993Apr;75(4):443–451. [PubMed]15. Birek C, Patterson B, MaximiwWC, Minden MD. EBV and HSVinfections in a patient who hadundergone bone marrow transplantation:Oral manifestations and diagnosis by insitu nucleic acid hybridization. OralSurg Oral Med Oral Pathol.  1989Nov;68(5):612–617. [PubMed]16. Heinic GS, Northfelt DW,Greenspan JS, MacPhail LA, GreenspanD. Concurrent oral cytomegalovirus andherpes simplex virus infection inassociation with HIV infection. A casereport. Oral Surg Oral Med OralPathol. 1993 Apr;75(4):488-94.[PubMed]17. Heinic GS, Greenspan D,Greenspan JS. Oral CMV lesions andthe HIV infected. Early recognition canhelp prevent morbidity. J Am DentAssoc. 1993 Feb;124(2):99-105.[PubMed]18. Macdonald MR, Freeman JL,Hui MF,  Cheung RK, Warde P, McIvorNP, et al. Role of Epstein-Barr virus infine-needle aspirates of metastatic necknodes in the diagnosis of naso-pharyngeal carcinoma. Head Neck. 1995Nov-Dec;17(6):487-93. [PubMed]19. Cinatl J Jr, Cinatl J, Vogel JU,Rabenau H, Kornhuber B, Doerr HW.Modulatory effects of humancytomegalovirus infection on malignantproperties of cancer cells. Intervirology.1996;39(4):259-69. [PubMed]20. Melnick M, Deluca KA,Sedghizadeh PP, Jaskoll T.Cytomegalovirus-induced salivary glandpathology: AREG, FGF8, TNF-á, andIL-6 signal dysregulation and neoplasia.Exp Mol Pathol. 2013 Apr;94(2):386-97. [PubMed] [CrossRef]21.  Regezia JA, Eversoleb LR,Barkerc BF, Rick GM, Silverman S Jr.Herpes simplex and cytomegaloviruscoinfected oral ulcers in HIV-positivepatients. Oral Surg Oral Med OralPathol Oral Radiol Endod. 1996Jan;81(1):55-62. [PubMed]22. Firth NA, Rich AM, Reade PC.Oral mucosal ulceration due tocytomegalovirus associated with humanimmunodeficiency virus infection. Casereport and brief review. Aust Dent J.1994 Oct;39(5):273-5. [PubMed]23. Marder M, Barr CE, Mandel ID.Cytomegalovirus presence and salivarycomposition in acquired immuno-deficiency syndrome. Oral Surg OralMed Oral Pathol. 1985 Oct;60(4):372-376. [PubMed]Corresponding author:Assya Krasteva-Panova,Department of Oral Imaging and Oral Diagnostic, Faculty of Dental Medicine,1, Georgi Sofiyski blvd., 1431 Sofia, Bulgaria,Tel.+359 887 87 54 66;E-mail: asyakrasteva@abv.bg,

EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS – TWO HERPES VIRUSES WITH ORAL MANIFESTATIONS.

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