|Year : 2020 | Volume
| Issue : 1 | Page : 36-42
Viral infections of oral cavity
Arvind Babu Rajendra Santosh1, Keerthi Muddana2
1 Oral and Maxillofacial Pathologist, School of Dentistry, The University of the West Indies, Mona, Kingston, Jamaica, West Indies, Jamaica
2 Oral and Maxillofacial Pathologist, Department of Oral and Maxillofacial Pathology, Kamineni Institute of Dental Sciences, Sreepuram, Narketpally, Nalgonda - 508 254, Telangana, India
|Date of Submission||21-Sep-2019|
|Date of Decision||23-Nov-2019|
|Date of Acceptance||04-Dec-2019|
|Date of Web Publication||28-Jan-2020|
Dr. Arvind Babu Rajendra Santosh
Oral and Maxillofacial Pathologist, School of Dentistry, The University of the West Indies, Mona, Kingston, Jamaica
Source of Support: None, Conflict of Interest: None
Viral infections of the oral cavity usually manifest as either ulceration or blistering presentation of oral tissues. Oral viral infections are encountered in dental practice but received less clinical interest due to the lesser frequency of patients and diagnostic challenges. The clinical presentation, pathogenic mechanism, investigations, and management of oral viral infections are integrated into the article which will enable general dentists to develop critical thinking processes on differential diagnosis and management through a multidisciplinary approach with specialist dentists.
Keywords: Acyclovir, blister, herpes, oral cavity, zoster
|How to cite this article:|
Santosh AB, Muddana K. Viral infections of oral cavity. J Family Med Prim Care 2020;9:36-42
| Introduction|| |
A viral disease of the oral cavity is the infectious type of pathology affecting oral tissues. Viral diseases may either occur due to cellular destruction or consequence of immune reaction following viral proteins. Viral infections typically present with abrupt onset and association of solitary or multiple blister or ulcerations. Concomitant general symptoms such as fever, malaise, and lymphadenopathy are observed in a few viral conditions. Viral infections are also linked to the development and progression of periodontal diseases. A viral disease of oral tissues is often encountered in dental practice, however, limited attention is given in diagnosis and management due to diagnostic challenges. Certain viral infections are associated with tumor formation and, hence, early reporting and referral to oral disease management are essential in dental practice.
| Relevance of Oral Health in Family Medicine and Primary Care Practice|| |
Oral health influences overall health and quality of life. The majority of viral infections tend to have oral manifestations, and general dentists majorly focus on the management of dental and periodontal diseases. Oral manifestations of viral infections may present as (1) preliminary sign of disease, (2) important co-symptom of viral disease, or (3) only sign observed in such viral disease. Although special dentists, for example, oral medicine, oral surgeon, and oral pathologist, may play a significant role in diagnosing and management of oral infections, the specialist dentist usually embraces a multidisciplinary route in such situations. Thus, dental surgeons, specialist dentists, and primary care/family physicians need to be updated with common conditions/emerging oral viral infections in relation to diagnosis and management. Thus, primary care and family physicians have a greater role in managing oral conditions that require multidisciplinary action from dental team. Hence, family physicians are emphasized to incorporate oral health into routine practice through examination of oral cavity and its findings, counseling on dietary and hygiene practice will support in achieving better oral health, and by extension overall health. Primary care and family physicians provide integrated accessible health care services and who are accountable for addressing a large majority of personal health care needs, developing a sustained partnership with patients, and practicing in the context of family and community. The discussion of entire list of oral viral infections is beyond the scope of this article, instead of common and/or important conditions are presented. This article aims to address clinical features, diagnostic concepts, and management of herpes simplex virus (HSV-1), herpes zoster, Epstein-Barr virus, cytomegalovirus, human herpesvirus (HHV) 7 and 8 infections of oral cavity.
| Herpes Simplex Infection|| |
HSV belongs to herpes viridae group and is a significant pathogenic virus that is known to cause mucocutaneous conditions in the oral cavity and genital region. HSV-1 and 2 are the two major types of herpes viruses that can be distinguished by the distinct antibodies. HSV-1 is known to have a significant association with pharyngeal infection, meningoencephalitis, and dermatitis above the waistline; whereas HSV-2 is associated with genital and anal region infections. However, depending on the sexual practices, HSV-1 and 2 can cause primary and/or recurrent infections in the oral and/or genital region. Herpetic infections that develop secondary to salivary contamination over the finger are termed as herpetic whitlow.,
| Primary Herpes Simplex Infection of Oral Cavity: Pathogenesis and Latency|| |
The incidence of primary HSV-1 infections usually occurs at an early age, often results in painful skin or mucosal lesions, but can also be asymptomatic. HSV replicates at the portal of entry, often at oral or genital mucosal tissue, leading to infection of sensory nerve endings. Following to portal into sensory nerve endings, HSV is then transported to regional ganglia and establishes latency.
| Clinical Features|| |
The incidence of primary HSV 1 infection is higher between 2 and 3 years of life, however, HSV-1 may still occur in adolescents and adults and occasionally in individuals older than 60 years., Recurrence is directly related to the severity of primary infection, as reflected by the size, number, and spread of lesions. Primary herpes infections are usually accompanied by prodromal symptoms or systemic symptoms that include fever, headache, malaise, nausea, vomiting, and lymphadenopathy., HSV-1 infection of oral cavity included are vesicles as well as ulcerations that appear on the oral mucosa and generalized acute marginal gingivitis, often follows prodromal symptoms.,
| Management|| |
Primary HSV infections are usually treated with palliative care. Symptomatic and milder patients are managed by supportive care that includes maintenance of fluids, acetaminophen to reduce fever, and use of topical anesthetics such as lidocaine, liquid Benadryl, milk of magnesia, or Carafate to relieve oral burning sensation and/or pain. In patients with prolonged symptoms (more than 24–48 h) with vesicle eruption, anti-HSV medications are employed to accelerate healing by inhibiting DNA replication in HSV-infected oral epithelial cells.
Current drug on antiviral mechanism includes three classes of drugs which target viral DNA replication: acyclic guanosine analogs (licensed drugs: acyclovir, ganciclovir, penciclovir, valacyclovir, valganciclovir, and famciclovir), acyclic nucleotide analogs (licensed drugs: cidofovir, adefovir dipivoxil), and pyrophosphate analogs (licensed drugs: foscarnet). Routinely used drugs from the abovementioned list include acyclovir, valacyclovir, cidofovir, and foscarnet. Acyclovir is a gold standard for prophylactic and treatment of HSV infection  [Table 1]. Acyclovir drug-resistant is rising rapidly with the increasing number of transplant and cancer patients.
|Table 1: Medication management of primary herpes simplex virus (HSV) infection in adults|
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| Recurrent Herpes Simplex Infection|| |
Pathogenesis and latency
Recurrent herpes simplex infection occurs with reactivation of HSV to trigeminal nerve ganglion. Reactivation virus may be a resultant of numerous conditions such as age, exposure to sunlight or cold, trauma, physical or emotional stress, fatigue, pregnancy, immunosuppressive state, fever, respiratory illness, menstruation, systemic illness, or malignancy and lead recurrent herpes simplex infection. The usual incubation period is 3–9 days.
Recurrent herpes lesions are directly related to the severity, size, and a number of lesions in primary infection. Recurrent lesions may occur at primary inoculation site or in the adjacent areas of surface epithelium that is supplied by involved nerve ganglion. Recurrent herpes labialis (RHL) is the most common type of recurrent herpes simplex infection. RHL often appears on the vermillion border or skin of upper and/or lower lip and is commonly referred as cold sore, fever blister, or night fever.
Recurrent HSV infections occur on the lips and keratinized oral mucosal areas such as palate and gingiva. However, a recurrent intraoral herpetic lesion can occur on any oral mucosal site and is usually observed in immunocompromised individuals. Recurrent HSV infections can trigger episodes of erythema multiforme. Antiviral medications are usually administered as prophylactic doses for the patients who have a history of recurrent episodes of erythema multiforme. Recurrent intraoral herpetic lesions are more common in advanced AIDS, transplant patients, and cancer patients receiving chemotherapy or immunosuppressive drugs. Recurrent HSV lesions in immunocompetent patients may appear as large ulcers, which may involve labial, genital, or rectal mucosa if left untreated. These lesions have the potential to disseminate and cause generalized infection. Therefore, it is important for clinicians to rule out HSV as a cause of oral vesicles or ulcerations in patients with immunocompromised conditions.
Recurrent herpetic lesions are usually treated with topical antiviral medications. Topical penciclovir reduces the duration and pain of recurrent lesions by 1–2 days. Patients are recommended to apply topical penciclovir over the affected site for every 2 h for 4 days while awake., Topical acyclovir is also available for topical use and reduces the duration of recurrent herpes lesions by 12 h. Topically acyclovir is also recommended in recurrent herpes infections and is usually effective when the lesions commenced during prodromal symptoms. Vander et al. mentioned that the benefit of applying acyclovir is limited when compared with topical penciclovir. Oral or intravenous administration of acyclovir is usually effective in immunocompetent patients. However, cases of acyclovir-resistant HSV have been reported, and foscarnet has been an effective therapy for acyclovir-resistant patients. Valacyclovir should be used with caution for immunocompetent patients due to the potential risk of hemolytic uremic syndrome. Recommended drug dosage and regimens used to treat recurrent oral HSV infections  are given in [Table 2].
|Table 2: Medication management of recurrent oral HSV infection in adults|
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| Herpes Simplex Virus-1 (Hsv-1) and Bell's Palsy|| |
Bell's palsy occurs with the reactivation of the HSV-1 virus from latency in the geniculate ganglion rather than primary infection. The mechanism through which the virus damages the facial nerve is unclear. Bell's palsy appears to be more common in adult life where HSV-1 is well-established.
| Varicella Zoster Infection|| |
Varicella-zoster virus (VZV) belongs to herpes viridae group, is a significant pathogenic virus that is known to cause mucocutaneous conditions in oropharyngeal mucosa and skin.
| Pathogenesis and Latency|| |
VZV causes both primary and recurrent infections and remains latent in neurons present in sensory ganglia. The incubation period is approximately 2 weeks. VZV is responsible for two major clinical infections: the primary type is chickenpox and the recurrent type is shingles (herpes zoster [HV]).
| Chicken Pox Infection|| |
Chickenpox usually begins with prodromal symptoms such as headache, pharyngitis, rhinitis, and anorexia. The prodromal symptoms are followed by maculopapular rash that are intensely pruritic or vesicular eruptions of the skin and low-grade fever. The eruptions are noted on the trunk and spread to involve the face and extremities. Chickenpox spread from nasopharyngeal secretions or by coming in direct contact with skin lesions of the infected patients. Oral lesions are characterized by small blister-like manifestations that involve various areas of oral mucosa. Oral lesions resemble vesicles of primary HSV, but these lesions are not particularly an important symptomatic, diagnostic, or management problem. Complications of chickenpox include encephalitis, pneumonitis, Reye's syndrome, and Guillain-Barre syndrome.
| Herpes Zoster Infection|| |
Pathogenesis and latency
Following the primary infection of varicella-zoster, virus becomes reactivated from the latency at dorsal root of cranial nerve ganglia. The nerves most commonly affected by HZV infection are C-3, T-5, L-1, and L-2. Serious ophthalmic symptoms are observed, when HZ involves the trigeminal ganglion, the first division (ophthalmic or V1).
Herpes zoster (HZ) is an acute infectious viral condition which is extremely painful and is associated with vesicular eruptions of the skin or mucous membranes in areas supplied by the affected sensory nerves. The cases of paresthesia along the course of the affected nerve have been reported. Ramsay Hunt syndrome is typically characterized by unilateral vesicles of oral mucosa and external ear, unilateral facial paralysis that appear 3–5 days later an inflamed base along the involved nerve. Unilateral vesicles are observed when geniculate ganglion of the facial nerve is involved. Diagnosis of HZ is usually based on typical clinical signs and symptoms, dramatic distribution of unilateral involvement associated with this disease with extreme pain, helping to distinguish it from HSV recurrence., VZV may also cause pain along the course of nerve with no lesions on oral mucosa or external ear; the latter is referred as zoster sine herpete or zoster sine eruption. In immunocompetent patients, HZ may cause large local lesions or disseminated infection. The cases of alveolar bone necrosis with exfoliation of teeth have been reported. Postherpetic neuralgia is a potential consequence of HZ resulting from scarring of the involved nerve during HZ infection. Postherpetic neuralgia is increasingly observed in the adult population aged 50 years and above, sometimes postherpetic neuralgia can last for months to years after the lesions are healed.
| Management|| |
HZ infections are usually treated with acyclovir, valacyclovir, or famciclovir: oral acyclovir 800 mg for five times a day for 7–10 days; valacyclovir 1000 mg for three times a day for 7 days; and famciclovir 500 mg for three times a day for 7 days.
Acyclovir is usually effective in shortening the course of HZ infection for faster healing and reduces pain. Valacyclovir and famciclovir are also reported as effective drug treatment of HZ infection. Acyclovir, valacyclovir, or famciclovir have been reported to reduce the incidence as well as the duration of postherpetic neuralgia cases. Other effective therapy for the treatment of postherpetic neuralgia includes gabapentin, topical capsaicin, tricyclic antidepressants, opioids, and topical lidocaine patches.,
| Epstein-Barr Virus Infection|| |
Epstein-Barr virus (EBV) belongs to the herpes viridae group, is a significant pathogenic virus that is known to infect B cells in the oropharyngeal epithelium.
| Pathogenesis and Latency|| |
The transmission of EBV infection occurs following the contact with oral secretions, saliva on fingers, toys or other objects. EBV replicates in epithelial cells of the oropharynx and viruses are usually shed in the saliva. Cases have been reported with the genital transmission. EBV has an incubation period of 8 weeks. EBV is responsible for infectious mononucleosis. EBV is also reported to be associated with several lymphoproliferative disorders, lymphomas (African Burkitt's lymphoma), and nasopharyngeal carcinoma. Other reported associated conditions are oral hairy leukoplakia, gastric carcinomas, hepatocellular carcinomas, salivary lymphoepithelial carcinomas, oral squamous cell carcinoma, and smooth muscle tumors.,
| Clinical Features|| |
EBV infections of infants and children are asymptomatic, whereas the infections of adolescents and adults result in infectious mononucleosis. The classical triad of EBV includes fever, lymphadenopathy, and pharyngitis. Other symptoms of EBV infection are fever, lymphadenopathy, pharyngitis, hepatosplenomegaly, oral ulcerations, rhinitis, or cough. Hepatomegaly, rhinitis, and cough are less frequently observed in children less than 4 years of age. The complications of EBV include myocarditis, hepatitis, hemolytic anemia, thrombocytopenia, aplastic anemia, splenic rupture, encephalitis, and seizures.
Supportive therapy is adequate in the management of EBV infection. Corticosteroid and antiviral medication are usually employed in immunocompetent patients.
Cytomegalovirus (CMV) belongs to the herpes viridae group, is a frequent cause of asymptomatic infection in humans and may cause significant clinical courses in immunocompetent individuals.
Pathogenesis and latency
Transmission of CMV infection occurs through contaminated blood and body fluid secretions such as saliva, genital secretions, and breast milk. CMV can reside latently in salivary gland cells, endothelium, macrophages, and lymphocytes. Neonates may develop CMV which is also responsible for microcephaly, chorioretinitis, nerve deafness, hepatitis, hepatosplenomegaly, and thrombocytopenia. CMV chorioretinitis is significantly associated with AIDS and tends to progress rapidly. Other complications of primary CMV include myocarditis, pneumonitis, gastrointestinal disease, and aseptic meningitis.
CMV infection often remains asymptomatic in healthy children and adults. Primary CMV infection results from either blood transfusion or sexual contact. Clinical symptoms of CMV include fever, myalgia, cervical lymphadenopathy, and mild hepatitis. The classical features of CMV include hepatosplenomegaly, thrombocytopenia, extramedullary cutaneous erythropoiesis, and petechial hemorrhages. Severe mental and motor retardation are observed in encephalitic conditions. In immunocompetent patients, CMV infection may include unexplained persistent fever and acute sialadenitis. Case reports have been published that there is a relationship between xerostomia and the presence of CMV in saliva of HIV-infected individuals.,
CMV infections resolve spontaneously, medication management is usually required in immunocompetent patients. Antiviral agents such as ganciclovir, foscarnet, and cidofovir have been effective in the management of CMV infection. Newer drugs in the development of CMV infection include maribavir, CMX 001, and AIC246.
Human Herpesvirus-6 (HHV-6) infection
HHV-6 infection is a common childhood exanthematous disease. HHV-6 encephalitis usually occurs in severe immunosuppressive states.
Pathogenesis and latency
HHV-6 is significantly associated with CD4 T lymphocytes. CD 45 is an essential component of the membrane receptor for HHV-6. HHV-6 becomes latent in cells of the monocyte-macrophage lineage. CD46 is an HHV-6 receptor that is expressed mostly in macrophages and cells lining blood vessels, and less often in the cells of neuronal origin. Reactivation of latent HHV-6 is significantly associated with drug-induced hypersensitivity, possibly due to a sudden decrease in serum IgG levels. HHV-6 principally targets mature CD4 T lymphocytes and has an ability to dysregulate cellular cytokine production, modulate natural killer cell function, and modify the expression of key cell surface receptors. Two variants of HHV-6 have been identified: HHV-6A and HHV-6B.
The virus is transmitted through the respiratory route, virus particles have been isolated from saliva. Primary infection with HHV-6 is usually asymptomatic. Cases have been reported with unspecified febrile illness and roseola. Oral lesions are not commonly associated with either HHV-6A or HHV-6B infections.,
Ganciclovir and foscarnet have been used in HHV-6 infection, but their efficacy is unknown. There have been no randomized controlled trials of antiviral therapies in immunocompetent and/or immunocompromised individuals.
HHV-7 infection is ubiquitous and is acquired in childhood. The genomic material of HHV-7 and both variants of HHV-6 are closely related. HHV-7 infection in children has been linked with seizures and encephalitis. The transmission of the virus is like HHV-6 infection.
Primary infection with HHV-7 is often asymptomatic. In symptomatic cases, it presents as a single rose-colored, scaling and herald patch. Symptoms in oral tissue are rare and if present, it may have punctuated hemorrhages, ulcers, bullae, or erythematous plaques. Disseminated HHV-7 infection in immunocompromised patients may lead to multiorgan infection that includes encephalitis, pneumonitis, and hepatitis. However, there is only one case report of HHV-7 encephalitis in an immunocompetent patient. Another case presented with meningitis and optic neuritis resulting from reactivation of HHV-7 in a stem cell transplant recipient.,
HHV-8 (HHV-8) or Kaposi's sarcoma-associated virus is the most recently identified HHV type. It is significantly associated with malignant conditions in AIDS patients. HHV-8 infection is strongly associated with malignant diseases, which is Kaposi's sarcoma that involves oropharyngeal and gastrointestinal mucosal membranes., Lesions may be solitary, multifocal, or multicentric red-purple macules, plaques, or nodules of varying size. Posterior hard palate, gingivae, and dorsum of tongue are most common sites of oral tissue involvement in Kaposi's sarcoma. To date, no neurological lesions have been associated with HHV-8 infection. The treatment strategies for oral Kaposi's sarcoma range from monitoring focal, asymptomatic lesions without intervention to initiating systemic chemotherapy for widespread lesions.
| Conclusion|| |
The most common reason for oral ulcerations and blisters is viral infections. A major challenge in the diagnosis of oral viral infections are not due to complex clinical presentations but the long list of viral infections that affect oral tissues and lesser frequency of oral viral infections in their routine dental practice. Early recognition of oral viral infections will reduce the morbidity, comorbidity, and the clinical care cost. Oral lesions possess an advantage for visual access for examination. The symptoms such as blisters, ulcer, color variation, surface/textural changes are easily assessable for differentiating with other conditions. Although it is not always possible to relate the oral findings with medical symptoms for arriving to clinical diagnosis, a careful understanding of oral findings will enhance the scope of Family physicians in clinical relevance for their diagnosis. Hence, formulating diagnostic algorithm of oral lesions with presence of systemic manifestations will serve as a useful tool in clinical situation.
We are grateful to Dr. Orrette Ogle who sedulously supported during proofreading of the manuscript and English language correction.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Baiju RM, Peter E, Varghese NO, Sivaram R. Oral health and quality of life: Current concepts. J Clin Diagn Res 2017;11:ZE21-6.
Gambhir RS. Primary care in dentistry-An untapped potential. J Family Med Prim Care 2015;4:13-8.
] [Full text]
Cohen LA. Expanding the physician's role in addressing the oral health of adults. Am J Public Health 2013;103:408-12.
Greenberg MS. Herpesvirus infections. Dent Clin North Am 1996;40:359-68.
Sarid R, Klepfish A, Schattner A. Virology, pathogenetic mechanisms, and associated diseases of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8). Mayo Clin Proc 2002;77:941-9.
Mahalingam R, Wellish MC, Dueland AN, Cohrs RJ, Gilden DH. Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia. Ann Neurol 1992;31:444-8.
Jiang YC, Feng H, Lin YC, Guo XR. New strategies against drug resistance to herpes simplex virus. Int J Oral Sci 2016;8:1-6.
Gilden DH, Mahalingam R, Cohrs RJ, Tyler KL. Herpesvirus infections of the nervous system. Nat Clin Pract Neurol 2007;3:82-94.
Fatahzadeh M, Schwartz RA. Human herpes simplex labialis. Clin Exp Dermatol 2007;32:625-30.
Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: Epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol 2007;57:737-63; quiz 764-736.
Balasubramaniam R, Kuperstein AS, Stoopler ET. Update on oral herpes virus infections. Dent Clin North Am 2014;58:265-80.
Stoopler ET, Greenberg MS. Update on herpes virus infections. Dent Clin North Am 2003;47:517-32.
Crimi S, Fiorillo L, Bianchi A, D'Amico C, Amoroso G, Gorassini F, et al
. Herpes virus, oral clinical signs and QoL: Systematic review of recent data. Viruses 2019;11. pii: E463. doi: 10.3390/v11050463.
Greenberg MS, Friedman H, Cohen SG, Oh SH, Laster L, Starr S. A comparative study of herpes simplex infections in renal transplant and leukemic patients. Int J Infect Dis 1987;156:280-7.
Spruance SL, Nett R, Marbury T, Wolff R, Johnson J, Spaulding T. Acyclovir cream for treatment of herpes simplex labialis: Results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials. Antimicrob Agents Chemother 2002;46:2238-43.
Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group. JAMA 1997;277:1374-9.
Vander Straten M, Carrasco D, Lee P, Tyring SK. A review of antiviral therapy for herpes labialis. Arch Dermatol 2001;137:1232-5.
Pittet LF, Curtis N. Does oral antiviral suppressive therapy prevent recurrent herpes labialis in children? Arch Dis Child 2019;104:916-9.
Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell palsy and herpes simplex virus: Identification of viral DNA in endoneurial fluid and muscle. Ann Intern Med 1996;124:27-30.
Kim SH, Jung J, Jung SY, Dong SH, Byun JY, Park MS, et al
. Comparative prognosis in patients with Ramsay-Hunt syndrome and Bell's palsy. Eur Arch Otorhinolaryngol 2019;276:1011-6.
Linnemann CC Jr., Shea L, Partin JC, Schubert WK, Schiff GM. Reye's syndrome: Epidemiologic and viral studies, 1963-1974. Am J Epidemiol 1975;101:517-26.
Cohen JI. Clinical practice: Herpes zoster. N Engl J Med 2013;369:255-63.
Huber MA. Herpes simplex type-1 virus infection. Quintessence Int. (Berlin, Germany: 1985) 2003;34:453-67.
Ji Y, Ma GM, Kang ZL, Zhang Y, Han JZ, Li J, et al
. Ramsay Hunt syndrome with pontine lesion: A case report. Medicine (Baltimore) 2019;98:e14260.
Schmader K. Herpes zoster in older adults. Infect Dis Clin North Am 2001;32:1481-6.
Dwyer DE, Cunningham AL. herpes simplex and varicella-zoster virus infections. Med J Aust 2002;177:267-73.
Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H. Practice parameter: Treatment of postherpetic neuralgia: An evidence-based report of the quality standards subcommittee of the American academy of neurology. Neurology 2004;63:959-65.
Straus SE, Cohen JI, Tosato G, Meier J. NIH conference. Epstein-Barr virus infections: Biology, pathogenesis, and management. Ann Intern Med 1993;118:45-58.
Rahman R, Poomsawat S, Juengsomjit R, Buajeeb W. Overexpression of Epstein-Barr virus-encoded latent membrane protein-1 (LMP-1) in oral squamous cell carcinoma. BMC Oral Health 2019;19:142.
Henke CE, Kurland LT, Elveback LR. Infectious mononucleosis in Rochester, Minnesota, 1950 through 1969. Am J Epidemiol 1973;98:483-90.
Schiodt M, Greenspan D, Daniels TE, Greenspan JS. Clinical and histologic spectrum of oral hairy leukoplakia. Oral Surg Oral Med Oral Pathol 1987;64:716-20.
Maakaroun NR, Moanna A, Jacob JT, Albrecht H. Viral infections associated with haemophagocytic syndrome. Rev Med Virol 2010;20:93-105.
Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med 2010;362:1993-2000.
Rafailidis PI, Mavros MN, Kapaskelis A, Falagas ME. Antiviral treatment for severe EBV infections in apparently immunocompetent patients. J Clin Virol 2010;49:151-7.
Reichart PA. Oral ulcerations in HIV infection. Oral Dis 1997;3(Suppl 1):S180-2.
Samuel Huang ID, Labrousse D. A rare case of cytomegalovirus induced oral ulcer in an immunocompromised patient. J Oral Med Oral Surg 2019;25:22-4.
Greenberg MS, Glick M, Nghiem L, Stewart JC, Hodinka R, Dubin G. Relationship of cytomegalovirus to salivary gland dysfunction in HIV-infected patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:334-9.
Flaitz CM, Nichols CM, Hicks MJ. Herpesviridae-associated persistent mucocutaneous ulcers in acquired immunodeficiency syndrome. A clinicopathologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:433-41.
Emery VC, Hassan-Walker AF. Focus on new drugs in development against human cytomegalovirus. Drugs 2002;62:1853-8.
Lusso P, Gallo RC. Human herpesvirus 6 in AIDS. Immunol Today 1995;16:67-71.
Schirmer EC, Wyatt LS, Yamanishi K, Rodriguez WJ, Frenkel N. Differentiation between two distinct classes of viruses now classified as human herpesvirus 6. Proc Natl Acad Sci USA 1991;88:5922-6.
Zerr DM, Gupta D, Huang ML, Carter R, Corey L. Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:309-17.
Li H, Wang B, Shan L, Du L, Jia F. Spontaneous remission of West syndrome following a human herpesvirus 7 infection in a Chinese infant: A case report. Medicine 2019;98:e16441.
Katsafanas GC, Schirmer EC, Wyatt LS, Frenkel N.In vitro
activation of human herpesviruses 6 and 7 from latency. Proc Natl Acad Sci USA 1996;93:9788-92.
Ward KN, Kalima P, MacLeod KM, Riordan T. Neuroinvasion during delayed primary HHV-7 infection in an immunocompetent adult with encephalitis and flaccid paralysis. J Med Virol 2002;67:538-41.
Yoshikawa T, Yoshida J, Hamaguchi M, Kubota T, Akimoto S, Ihira M, et al
. Human herpesvirus 7-associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation. J Med Virol 2003;70:440-43.
Feller L, Lemmer J. Insights into pathogenic events of HIV-associated Kaposi sarcoma and immune reconstitution syndrome related Kaposi sarcoma. Infect Agent Cancer 2008;3:1.
Iscovich J, Boffetta P, Franceschi S, Azizi E, Sarid R. Classic kaposi sarcoma: Epidemiology and risk factors. Cancer 2000;88:500-517.
Yildirim M, Belli S, Ozsoy S, Taskin U. Primary triple head and neck tumors: Laryngeal squamous cell carcinomas, Kaposi's sarcoma, and non-Hodgkin's lymphoma. Indian J Pathol Microbiol 2019;62:454-6.
] [Full text]
Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, et al
. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266:1865-9.
Jham BC, Montaner S. The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor: Lessons on dysregulated angiogenesis from a viral oncogene. J Cell Biochem 2010;110:1-9.
[Table 1], [Table 2]