Rahayuningtyas/Setiadhi 37 VIRUS AS A CAUSE OF SALIVARY GLAND DISEASES Etis Duhita Rahayuningtyas*, Riani Setiadhi** Keywords: ABSTRACT Virus, Salivary gland disease, HIV, Background: Enlargement in the extraoral region with the absence of abnormal nonHIV dental and periodontal structures are sometimes seen in dental practice, sometimes followed by xerostomia. Enlargement of the acute nonsuppurative salivary glands has been associated with several types of viruses. The purpose of this paper is to review salivary gland diseases associated with non-HIV and HIV viral infections. Discussion: Non-HIV viruses which were detected in the salivary glands including Paramyxovirus, cytomegalovirus (CMV), Hepatitis C virus (HCV), human papilloma viruses (HPV), Epstein-Barr virus (EBV), human herpes simplex virus (HHSV-8), and coxsackie virus. HIV-associated salivary gland disease typically presents with xerostomia and/or intraglandular lymph nodes, and diffuse infiltrative lymphocytosis syndrome (DILS). The most common viral infection conditions in salivary gland disorders are mumps and HIV. Enlargement and inflammation of the glandular structures will affects the control of salivary secretion by nerves. Parasympathetic nerves block conducted signals to the salivary glands, so the salivary flow is decreased. Conclusion: There is association between viral infection and diseases of the salivary gland. By knowing sequelae viruses on the salivary gland, dentists are expected to understand the clinical condition and therapeutic that should be given to the patients. INTRODUCTION (CMV), hepatitis C virus (HCV), Human Pap- illoma Virus (HPV), Epstein-Barr Virus (EBV), Saliva is a complex combination of fluids, Human Herpes Virus 8 (HHV-8) and HIV. 4,9–15 electrolytes, enzymes, and macromolecules Other virus detected in Saliva are coxsackie vi- that together do several important functions: rus, influenza, parainfluenza virus, echovirus, lubrication to help swallowing; producing am- BK virus, Human T-lymphotropic virus (HTLV), ylase enzymes to help digestion; taste mod- human herpesvirus 6 (HHV-6), human herpes- ulation; protection against caries and patho- virus 7 (HHV-7), Kaposi sarcoma virus (KSHV), gens.1–3 The salivary glands are the paired guinea pig CMV, mouse CMV (MCMV), mouse parotid, submandibular and lingual glands polyomavirus (PyV), encephalomyocarditis along with several hundred minor salivary (EMC).6,9 Sometimes accompanied with xero- glands, distributed through the upper aerodi- stomia as the manifestation of viral infection. gestive system.1,4,5 HIV-associated salivary gland disease typi- Salivary gland disorders are often associ- cally presents with xerostomia and/or swelling ated with viral infections.1,4,6–8 Enlargement of of the major salivary glands. It encompasses the acute nonsuppurative salivary glands has multitude of conditions like lymphoepithelial le- been associated with several types of virus- sions, cysts involving the salivary gland tissue es.4,7 Viruses that cause most gland enlarge- and/or intraglandular lymph nodes, Sjogren’s ment are paramyxovirus, cytomegalovirus syndrome-like conditions, diffuse infiltrative *Oral Medicine Specialist Programme, Faculty of Dentistry, Universitas Padjadjaran, Bandung. **Lecturer Oral Medi- cine Department, Faculty of Dentistry, Universitas Padjadjaran, Bandung Korespondensi: [email protected] ODONTO Dental Journal. Volume 6. Special Issue 1. April 2019 38 VIRUS AS A CAUSE OF SALIVARY GLAND DISEASES lymphocytis syndrome (DILS), and other re- Non-HIV Viral Infection of The Salivary ported lesions of the major salivary glands.16–19 Gland About 5% of HIV patients exhibit HIV-Associat- Paramyxovirus/Mumps ed salivary gland disease (HIV-SGD).8 Mumps is an acute, self-limiting, contagious In this literature study, we dividing viral in- viral infection characterized chiefly by unilateral fections salivary gland disease due to non-HIV or bilateral swelling of the parotid, although all and HIV. The purpose of this paper is to review salivary glands may be involved.8,9 85% of cas- salivary gland diseases associated with non- es occur in children younger than 15 years.1,9 HIV and HIV viral infections. Human are the only natural host. Infection occurs following exposure through the upper LITERATURE REVIEW respiratory tract by droplet, aerosol, direct con- tact, or fomites. The prodromal symptoms are Viruses in Latin means venom or poison. fever, malaise, and headache. Approximately Viruses are ultramicroscopic organisms which 24 hours later, glandular swelling, tenderness, breed in living cells, inert metabolically, capa- and associated earache can occurs. Resolu- ble of infecting other organisms. The size of tion of symptoms generally occur in 10 days.9 viruses ranges from 10 millimeters or less to Complications including orchitis, acute pan- more than 200 millimicrons. The virus consists creatitis, meningoencephalitis, deafness, and of a DNA or RNA nucleus, surrounded by a mastoiditis.8,9 capsid made of protein or an outer envelope Mumps should be differentiated from other made of glycoproteins and lipids derived from parotid swelling which were caused by influen- the host cell membranes.8,9,11,13,14 za, parainfluenza 1 and 3, coxsackie, HIV, cy- Classification of diseases caused by vi- tomegalovirus, Sjögren’s syndrome, pleomor- ruses is difficult because of the virus size and phic adenoma, etc.8 Diagnosis is confirmed metabolic system that have not been fully un- through viral serology test. The treatment are derstood. International Committee on Nomen- supportive measures, including hydration, rest, clature of Viruses of the International Associa- oral hygiene instruction and pain control or an- tion of Microbiological Societies has classified tipyretic.4,9 According to Centers for Disease them into groups according to the type of nu- Control and Prevention (2014), vaccination is cleic acid, the size, shape, and substructure of 88% effective in preventing mumps and has the particle.8 reduced the incidence by 99%.1 Currently, the Paramyxovirus, cytomegalovirus (CMV), CDC recommends mumps patients should hepatitis C virus (HCV), Human Papilloma Vi- avoid contact with others from the time of di- rus (HPV), Epstein-Barr Virus (EBV), Human agnosis until at least five days after the onset Herpes Virus 8 (HHV-8) and HIV are several of parotitis by staying at home from work or viruses that causing salivary gland enlarge- school and in a separate room if possible.4,23 ment and sometimes xerostomia. 4,9–15 In this Cytomegalovirus (CMV) paper we will review those viruses, divided into CMV (HHV-5) is a member of the Herpes- non-HIV viral infections of the salivary gland viridae family. As the characteristic of other and HIV associated salivary gland disease. members of Herpesviridae, CMV can become latent after initial exposure and infection and ODONTO Dental Journal. Volume 6. Special Issue 1. April 2019 Rahayuningtyas/Setiadhi 39 may become reactivated when favorable con- be in the form of ganciclovir, valganciclovir, ditions are present. The majority of CMV infec- foscarnet, or cidofovir.4,24 tions are asymptomatic, especially in healthy Hepatitis C Virus (HCV) individuals; however, in immunocompromised Hepatitis C virus (HCV) is one of the ma- patients and neonates, the infection can be jor causes of chronic liver disease worldwide, life-threatening. In the young adult, acute CMV as the global estimated prevalence of HCV infection presents with fever, malaise, myalgia; is 2.2% with 40-75% of patients with chronic pharyngitis and lymphadenopathy. Oral and HCV infection exhibit at least one clinical ex- maxillofacial manifestations of CMV in immu- trahepatic manifestation (EHM).15,20 HCV infec- nosuppressed patients typically present as tion has many extrahepatic manifestations, in- persistent oral ulcerations and major salivary cluding sialadenitis and chronic major salivary gland infections, with or without concomitant gland enlargement and complaints of xerosto- alterations in salivary flow.4,24 CMV infection mia and sicca syndrome (Sjogren-like sialade- has been investigated as one of the causative nitis) are common.4,20,27 agents in Sjogren’s syndrome with a molecular The diagnosis of HCV infection is estab- mimicry mechanism of pathogenesis. Viruses lished by the serologic detection of anti-HCV affect exocrine tissue primarily through plas- antibodies by ELISA and HCV DNA by PCR. macytoid dendritic cells (pDCs) and Toll-like-re- Treatment of patients with acute HCV infection ceptors (TLRs).25 Transmission occurs through receives weekly PegIFN-alpha or standard in- blood transfusion, allograft transplants, sexual terferon. Hepatitis-associated sialadenitis and contact, fomites, urine, saliva, and respiratory xerostomia are treated symptomatically.4 secretions.4,24,26 In HIV-positive patients, the Human Papilloma Virus (HPV) degree of CMV-induced sialadenitis and/or xe- Human Papilloma Virus (HPV) has been rostomia was found to be proportional to the vi- demonstrated to be the trigger of neoplastic ral load and inversely proportional to the CD4+ diseases of the head and neck.10,28 Moreover, cell count. the medical literature provides only little evi- Several diagnostic modalities for CMV are dence about the role of HPV in salivary gland available including serology, qualitative and tumors.13,29 HPV-16 and HPV-18 are the most quantitative PCR, as well as histopathology. commonly detected high-risk types.28,30,31 Due The choice of test is based on the status of to the growing rates of