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Management of the Oral Infection: Part 2 a Peer-Reviewed Publication Written by Ian Shuman, DDS, MAGD, AFAAID © Stiggdriver | Dreamstime.Com © Stiggdriver

Management of the Oral Infection: Part 2 a Peer-Reviewed Publication Written by Ian Shuman, DDS, MAGD, AFAAID © Stiggdriver | Dreamstime.Com © Stiggdriver

Earn 3 CE credits This course was written for dentists, dental hygienists, and assistants.

Management of the Oral : Part 2 A Peer-Reviewed Publication Written by Ian Shuman, DDS, MAGD, AFAAID © Stiggdriver | Dreamstime.com © Stiggdriver

Abstract Educational Objectives Author Profile This is the second of a two-part course on oral At the conclusion of this educational Ian Shuman DDS, MAGD, AFAAID maintains a full-time general, infection. It includes the clinical and diagnostic activity participants will be able to: reconstructive, and aesthetic dental practice in Pasadena, Maryland. features of that clinicians are most likely to 1. Identify clinical features associated with Since 1995 Dr. Shuman has lectured and published on advanced, encounter: fungal, viral and bacterial. Published clinical different viral, fungal and bacterial minimally invasive techniques. He has taught these procedures to recommendations and current scientific literature are infections thousands of dentists and developed many of the methods. Dr. Shuman reviewed and management strategies are discussed. In 2. Describe the various strategies for has published numerous articles on topics including adhesive resin den- tistry, minimally invasive restorative, cosmetic and implant . addition, scientifically supported alternative therapies treating fungal and viral infection He is a Master of the Academy of General Dentistry, an Associate Fellow are mentioned where applicable. The reader should 3. Implement appropriate of the American Academy of Implant Dentistry, a Fellow of the Pierre refer to current pharmacology and dosing information management of fungal, viral and Fauchard Academy. Dr. Shuman was named one of the Top Clinicians in prior to prescribing any therapy.1 bacterial infections. Continuing Education since 2005, by Dentistry Today.

Author Disclosure Dr. Shuman has no commercial ties with the sponsors or the providers of the unrestricted educational grant for this course. INSTANT EXAM CODE 15154 Go Green, Go Online to take your course

Publication date: Mar. 2017 Supplement to PennWell Publications Expiration date: Feb. 2020

This educational activity was developed by PennWell’s Dental Group with no commercial support. This course was written for dentists, dental hygienists and assistants, from novice to skilled. Educational Methods: This course is a self-instructional journal and web activity. Provider Disclosure: PennWell does not have a leadership position or a commercial interest in any products or services discussed or shared in this educational activity nor with the commercial supporter. No manufacturer or third party has had any input into the development of course content. Requirements for Successful Completion: To obtain 3 CE credits for this educational activity you must pay the required fee, review the material, complete the course evaluation and obtain a score of at least 70%. CE Planner Disclosure: Heather Hodges, CE Coordinator does not have a leadership or commercial interest with products PennWell designates this activity for 3 continuing educational credits. or services discussed in this educational activity. Heather can be reached at [email protected] Educational Disclaimer: Completing a single continuing education course does not provide enough information to result Dental Board of California: Provider 4527, course registration number CA# 03-4527-15154 in the participant being an expert in the field related to the course topic. It is a combination of many educational courses “This course meets the Dental Board of California’s requirements for 3 units of continuing education.” and clinical experience that allows the participant to develop skills and expertise. Image Authenticity Statement: The images in this educational activity have not been altered. The PennWell Corporation is designated as an Approved PACE Program Provider by the Scientific Integrity Statement: Information shared in this CE course is developed from clinical research and represents Academy of General Dentistry. The formal continuing dental education programs of this the most current information available from evidence based dentistry. program provider are accepted by the AGD for Fellowship, Mastership and membership Known Benefits and Limitations of the Data: The information presented in this educational activity is derived from the data and information contained in reference section. The research data is extensive and provides direct benefit to the patient maintenance credit. Approval does not imply acceptance by a state or provincial board of and improvements in oral health. dentistry or AGD endorsement. The current term of approval extends from (11/1/2015) to Registration: The cost of this CE course is $59.00 for 3 CE credits. (10/31/2019) Provider ID# 320452. Cancellation/Refund Policy: Any participant who is not 100% satisfied with this course can request a full refund by contacting PennWell in writing. Educational Objectives Figure 2. At the conclusion of this educational activity participants will be able to: 1. Identify clinical features associated with different viral, fungal and bacterial infections 2. Describe the various strategies for treating acute fungal and viral infection 3. Implement appropriate medication management of fungal, viral and bacterial infections.

Abstract This is the second of a two-part course on oral infection. It in- cludes the clinical and diagnostic features of infections that cli- Figure 3. nicians are most likely to encounter: fungal, viral and bacterial. Published clinical recommendations and current scientific lit- erature are reviewed and management strategies are discussed. In addition, scientifically supported alternative therapies are mentioned where applicable. The reader should refer to current pharmacology and dosing information prior to prescribing any antifungal therapy.1

Oral Fungal Infection Figure 4. Fungi are commonly found in the oral cavity (oral mycoses) and in healthy individuals do not pose a threat of infection. How- ever, in a conducive environment, infection can occur for a mul- titude of reasons. These include but are not limited to aging,2 ,3 organ transplants,4 HIV and AIDS,5 and systemic such as mellitus.6 There over 15 distinct Can- dida species that can cause human with albicans the most common oral fungal organism7 associated with infec- tion.8 (Figure 1) Superficial mucosal infection caused by this organism is classified as acute pseudomembranous , (Figure 2) acute erythematous candidiasis or chronic atrophic (erythematous) candidosis (or chronic hyperplastic candidosis). Infection caused by C. albicans also includes angular (Figure 3) (formed at the commissure of the ), rhomboid Other, species in the genus Candida that can cause oral in- (on the dorsum of the tongue) (Figure 4) and ‘pros- fection includes C. glabrata, C. tropicalis, C. parapsilosis, and thetic’ (commonly found on the ). C. krusei.9,10 Candida Glabrata a common cause of oral thrush is now estimated to be involved in about 15 to 30 percent of yeast Figure 1. infections.11 It is very common in AIDS patients, and involves white, cheese-like lesions on the inside of the cheeks, the and the tongue. C. glabrata infections have a higher mortality rate than most other yeast species. Another species present in otherwise healthy people, Candida dubliniensis, has been re- covered primarily from the oral cavities of human immunode- ficiency (HIV)-infected individuals and AIDS patients.12 The duration of fungal infection is dependent on variables such as immune suppression, and long-term or cor- ticosteroid use, among others.13,14 Symptoms associated with candidiasis can include taste disturbance, dry , oral burning,15 oral ulcers16 and difficulty swallowing.17 The diag- nosis of candidiasis is primarily clinical, based on observable lesions that vary in their presentation:18

2 www.DentalAcademyOfCE.com • Pseudomembranous candidosis presents with white identifying tests does not imply infection. It is the invasion of the plaques on the mucosa and tongue resembling milk mucosa by the fungal organism that is definitive with respect to curds.19 Wiping them exposes an underlying erythematous the diagnosis. Microbiological identification techniques incor- epithelium that may bleeds. porating biopsy and DNA testing may be necessary in question- • Erythematous candidosis is generally found as red areas able clinical diagnosis, resistance to treatment with antifungal on the palate, depapillated areas on the dorsum of the medication, or determination of the responsible organism.24 tongue, and on the buccal mucosa.20 It should be noted that there are several noncandidal oral • Chronic hyperplastic candidosis (candidal ) mycoses and include , blastomycosis, aspergil- usually occur on the buccal mucosa and less commonly on losis, paracoccidioidomycosis, cryptococcosis, and zygomycosis the tongue. They present as raised lesions that may vary from (mucormycosis).25 This group is far less common than oral can- small, palpable, translucent, or whitish, to large, dense, opaque didiasis, producing subclinical infection, especially pulmonary plaque-like lesions that are hard and rough to the touch.21 infections. Immunocompromised persons (including those with • Denture-related stomatitis is a typically asymptomatic, leukemia, leukopenia, solid tumors, transplants, or HIV disease) chronic and of palatal mucosa that contacts are at particular risk from these organisms.26,27 Infection caused the denture intaglio.22 It is rarely seen in mandibular mucosa by these fungal organisms results in solitary erosive oral ulcers. in lower denture wearers. The typical presenting complaint Medical management of these organisms is a must. is most commonly due to an insufficiency of the vertical dimension of occlusion. Management • Angular cheilitis/cheilosis (angular stomatitis) is charac- Management of fungal infection involves the use of topical terized by a crusting and/or fissuring erythema occurring and/or oral antifungal medication. (Table 1) In the patient at the corners of the mouth.23 As mentioned, it is a common with candidiasis or candidosis that does not respond to topi- form of seen in patients with denture-related cal antifungal medication or in which the infection frequently stomatitis. It may also be a sign of diabetes, HIV infection, reoccurs, systemic disease may be the underlying problem. or nutritional issues such as B-12 deficiency. Therefore, the patient with an untreatable oral-fungal infection C. albicans is one of many fungal organisms normally found should be referred for additional medical evaluation to rule out in the mouth and identifying it via Gram stain or through other caused by a systemic disease.28

Table 1: Adult Dosing Antifungal Agents (Lotrimin, Mycelex)* is a broad-spectrum antifungal agent causing Prescription: Clotrimazole troches 10mg (Disp. 70 fungal death by altering cell membrane permeability. It is recommended when infection is troches; dissolve 1 troche in mouth five times a day. widespread as it provides the greatest tissue coverage. It is only used as a topical agent as a Do not chew). 10-mg troche used 5 times/day. (Oravig)* is prescribed for the topical treatment of oropharyngeal Prescription: Recommended prescribing is 50 mg candidiasis. Miconazole mucoadhesive tablets (Loramyc®-; Oravig™-USA) are a recent tablet; 14 tabs; use once daily; hold one tablet in addition to the oral antifungal drugs currently available. place against buccal gingiva/mucosa. (Nizoral)* Oral ketoconazole can be effective for treatment of severe Prescription: Ketoconazole cream 2% (Disp. 15 oral and esophageal candidosis, but patient compliance is often poor because of the drug’s gm. tube; apply small dab to affected areas after taste. The cream form can be used to treat angular stomatitis. 200-400 mg/day PO meals) Fluconazole (Diflucan)* is effective in patients with chronic atrophic oral candidosis, Prescription: A 50 mg dose produces clinical and particularly when administered concurrently with an oral antiseptic such as . mycologic responses in approximately 10 days. It Adhesion of candidal organisms to epithelial cells, widely recognized as an essential step in is active against oral candidosis in HIV disease and the process of candidal colonization and subsequent infection, is inhibited significantly. Since produces remission within approximately 1 week. fluconazole is secreted in in high concentrations, it is tempting to speculate that it may interfere with the synthesis or structure of candidal receptors on buccal epithelial cells. Itraconazole (Sporanox)* is active against all candidal species, is well absorbed, Prescription: 10 milliliters of the solution swish achieves good distribution in the body, and may be more active than ketoconazole. It is elimi- intraorally for approximately 20-30 seconds and nated hepatically and demonstrates adverse effects including hepatotoxicity and hypokale- swallowed, twice daily for one week. If unrespon- mia with hypertension. It is available in 100-mg capsules and 10-mg/mL oral solutions. sive, continue treatment for another week. (Mycostatin)* is used to treat esophageal candidiasis, and may be used to Prescription: oral suspension (100,000 units/m; prevent candidiasis in those who are at high risk. Nystatin may be used by mouth or applied Disp. 240 ml; 2-5 ml qid. Rinse for two minutes to the skin. and swallow), Nystatin ointment (15 gm. tube; apply thin coat to inner surface of denture and to affected area after each meal). * The reader should refer to current pharmacology31 and dosing information32 33 prior to prescribing any antifungal therapy.

www.DentalAcademyOfCE.com 3 In the denture patient, treatment of fungal infection must Oral Viral Infection involve disinfection of the appliances as well. Soaking in an In humans, viral infections can affect the oral cavity as localized antifungal solution followed by the application of antifungal or systemic infections. Infective agents responsible for the powder (e.g. Nystatin topical powder) or an antifungal cream most common primary viral infections of the oral cavity are the to the surfaces of the prostheses contacting the mucosa helps to human herpesvirus (HHV) and human papillomavirus (HPV). prevent reinfection. Antiseptic mouth rinses may also serve as a Other viral infections that can affect the oral cavity either as useful antifungal rinse, but chlorhexidine (Peridex® or Periog- localized or systemic infections include , , ard®) is incompatible with Nystatin so the two should not be , , HIV. This course will focus on the causes and combined as an intervention.29 The soaking of or oral manifestations of these . For treatment guidelines, partial dentures in benzoic acid or an alkaline protease solution the reader should refer to the latest pharmacotherapeutic is also effective in removing C. albicans, but the latter should information. be combined with brushing of the appliance to insure complete eradication.30 Topical antifungal agents include rinses, suspen- Human Herpesvirus (HHV) sions, ointments and creams. Regardless of the formulation, all HHV infections are common in the oral cavity. They may be of these agents should be applied for ten to fourteen days. primary or recurrent infections. Eight types of HHV have been Treatment of angular cheilitis/cheilosis is best managed by linked with oral disease. These types have different disease pat- the application of an antifungal medication such as Nystatin terns in their hosts. that is coupled with an antibiotic because this infection is often Pathophysiology of HHV:42 Herpesviruses are icosahe- mixed (staphylococci and streptococci as well as C. albicans dral DNA viruses, replicating in the host cell nucleus. Infected organisms), particularly in patients with immunosuppres- saliva or droplets in the oral cavity or via oral-genital contact sion.34 Mycolog II™ or Mytrex™ dispensed in a 15 gm. tube with may transmit the viruses. In a localized primary infection, the ointment applied after each meal and at bedtime coupled with virus penetrates the mucosal epithelium and invades the cells the correction of predisposing factors such as licking can of the basal layer, where the viral DNA inserts into the host be an effective treatment strategy. Systemic antifungal drugs DNA. Viral shedding has been detected before, during, and af- are also used to treat cases where the use of topical therapy is ter the appearance of clinical lesions in patients with recurrent either impractical or ineffective. However a medical specialist HHV-1 and HHV-2 infections; therefore, lack of visible lesions should prescribe systemic as drug interactions and does not correlate with lack of potential infectivity. adverse reactions involving organ systems are not uncommon. In HHV-1 and HHV-2 oral infections, viral replication Systemic antifungal drugs are typically used in patients with within the oral epithelium may cause lysis of epithelial cells, significant underlying medical pathology (e.g. AIDS, immuno- with vesicle formation. Shallow ulcers with scabs that heal suppression, diabetes, organ transplants). without scarring follow this. Herpesviruses establish latent Of note is also the antimicrobial resistance demonstrated permanent infections in their hosts, although clinical signs of by C. albicans in biofilms. The antifungal medications with disease may not be detected. HSVs may persist in a quiescent known resistance include fluconazole, , ny- but persistent form known as latent infection, notably in neural statin and chlorhexidine.35 The azoles class of topical drugs ganglia.43 typically used to treat C. albicans has seen the development of • HHV-1 also known as nongenital virus significance resistance, allegedly because of over prescribing type 1 (HSV-1) (Figure 5, 6) is an infection usually during the 1990s and as a result fluconazole, the gold-standard acquired during childhood from ages 6 months to five for antifungal drug treatment, is now reported to be virtually years.44 ineffective against most mycotic infections.36 Hence, antifun- Oral Manifestations begin with an initial presentation of gal medication management should be considered carefully in primary herpetic gingivostomatitis. It is perhaps the most a patient with oral fungal infection. It is worth noting that a common viral infection of the mouth with painful vesicles number of alternative antifungal therapies are being studied on a red, swollen base that occur on the lips, gingiva, oral and many may prove useful for treating superficial oral fungal palate, or tongue. The lesions ulcerate and the can be infections.37 Some of the natural biologically active molecules severe. The onset is abrupt and is accompanied by anterior that have been studied and reported in the literature include cervical lymphadenopathy, chills, and a high (103o- the terpenes (for their antibiofilm activity),38 essential oils39 105oF). The lesions usually heal within 10 to 14 days. and other agents such as saponins, alkaloids, peptides and pro- All subsequent presentations of this virus are known as teins.40 There is also evidence that oral have an effect . These are cold sores that involve the oral on candida infection. For example, in one in vitro animal study, mucosa or lips.45 Approximately 90 percent of recurrent S salivarius K12 was found to inhibit C. albicans invasion of HSV-1 infections cause the orofacial lesions known as mucosal surfaces and adhesion of the to denture acrylic herpes labialis.46 Persistent herpes labialis is indicative of resins.41 an immunocompromised status, including HIV infection.

4 www.DentalAcademyOfCE.com Figure 5. harmless and rarely causes illness. Because it is typically asymptomatic, most of those infected have no symptoms. Once infected, the virus remains alive but dormant. Manifestations: Pregnancy and those with a compromised present with concern. Individuals with a compromised immune system can present with symptoms that may include enlarged lymph nodes, sore throat, muscle aches, fever, fatigue, , and . Oral Manifestation primary infection of the salivary glands and other tissues, and it is believed to have a chronic form. In patients with deficient immune systems (common in AIDS) and in Figure 6. transplant patients. • HHV-651 which can produce acute infection in CD4 + T lymphocytes, causes infantum, a febrile illness that affects young children. Oral Manifestation It is believed to chronically persist in tissue in some hosts, and oral shedding is the probable route of disease transmission. Although it has been linked to apical periodontitis in some studies, the evidence so far is mixed, so such an association remains currently Treatment is Acyclovir (Zovirax) for both HHV-1 and unproved. HHV-2. Other antivirals include Valtrex, Famvir, and De- • HHV-752 has been implicated as one cause of roseola navir topical cream. Additional prescribing information can infantum and febrile seizures in children. be found in the Drug Information Handbook for Dentistry, Oral Manifestation has been isolated from the saliva of Wynn R, Meiller T, Crossley H. Lexicomp 21st Edition, healthy adults. Hudson, OH. • HHV-853 evidence links it with body-cavity and Rx: Zovirax 200mg capsules, Disp: 50-60 capsules, Sig: Castleman disease. Take 1 capsule 5x/day for 10 days or 2 capsules 3x/day for Oral Manifestation is associated with Kaposi sarcoma. 10 days. The “potential for oral epithelial cells to serve as replicative • HHV-2 also known as type 2 (HSV-2) sites for HHV-8, as they do for its closest related human causes .47 herpesvirus--EBV, is supported by the localization of Oral Manifestations are occasional with causes of oral disease HHV-8 messenger RNA to oral epithelial cells using in situ expression clinically similar to that of HHV-1 infection. hybridization, the detection of HHV-8 latent antigens in • HHV-3 also known as varicella-zoster virus (VZV) causes salivary glands, and the finding of infectious HHV-8 virions the primary infection and the secondary in saliva.54,55,56 reactivation disease herpes zoster.48 Oral Manifestation In Ramsay Hunt syndrome, VZV Human Papillomavirus (HPV) affects the geniculate giving lesions that follow HPV is a 50-nm virus composed of double-stranded DNA specific branches of the . Symptoms may include with no envelope. The virus penetrates the mucosal epithelium painful on the tongue and along with one-sided and invades the cells of the basal layer, where the viral circular facial weakness and . DNA inserts into the host DNA. Common oral conditions • HHV-4 also known as Epstein-Barr virus (EBV),49 causes include primary herpes gingivostomatitis, recurrent herpes la- the primary infectious mononucleosis, and it is implicated bialis and intraoral recurrent herpes, infectious mononucleosis, in various diseases, such as African Burkitt , oral (herpes zoster), hand-foot-and mouth disease, other immunoproliferative disorders, and nasopharyngeal and erythematous stomatitis. carcinoma. HPV infections have received particular attention in recent Oral Manifestation Most common in young adults, years, as high-risk strains have been linked to some cases of oral with petechiae of hard palate, NUG, lymphadenopathy, .57 pharyngitis and tonsillitis, and fever. oral Pathophysiology of HPV: In addition to the viruses that in patients who are immunosuppressed. cause ulcers, various subtypes of the human papillomavirus • HHV-5 also known as (CMV),50 which are the cause of exophytic or nodules occurring on the may be the most researched of the human herpesvirus, intraoral mucosa. (Figure 7, 8) Lesions may be single or mul- causes a commonly widespread herpes virus that is usually tiple, smooth or corrugated and white or tan in appearance. The

www.DentalAcademyOfCE.com 5 conditions related to this virus include papilloma (squamous on intraoral mucosal surfaces and are a classic sign for diagnos- papilloma), verruca vulgaris, condyloma auminatum and focal purposes of this virus. epithelial hyperplasia (Heck’s disease). Infection with the hu- Treatment includes the MMR . The virus is self- man virus (HIV) indirectly contributes to limiting. the development of a number of oral problems including papil- loma (as well as candidiasis, , necrotiz- Figure 9. ing ulcerative , HIV-related and severe HIV-related aphthous erosions).

Figure 7.

Mumps (Endemic )54 Single stranded RNA virus causes the mumps. It is typically found in parotid, salivary and submandibular glands, with moderate to severe pain. The affected parotid glands may be unilateral or bilateral. Figure 8. Human Immuno Deficiency Virus (HIV) HIV is the etiologic viral agent of Acquired Immunodeficiency Syndrome (AIDS). Oral manifestations are fungal (candidiasis, histoplasmosis, cryptococcosis), viral (herpes simplex, herpes zoster, CMV, EBV with hairy leukoplakia, HHV-8 with Kapo- sis Sarcoma (Figure 10), HPV with oral ), and bacterial (linear gingival erythema, NUP, TB).60

Figure 10. Dentists are most likely to encounter patients with intraoral nodules or papules suggesting verruca vulgaris or condyloma acuminatum and ulcerations suggesting recurrent intraoral or lip HSV infection. The remaining intraoral viral conditions are usually associated with constitutional symptoms such as fever, malaise or fatigue and severe oral and throat pain. As a result, patients will typically seek medical attention before presenting to a dentist. However, when there is significant pain and lim- ited involvement of the , patients often seek dental evaluation and treatment. Oral Bacterial Infection Enteroviruses The oral cavity is home to a wide variety of bacteria, most of This family of viruses is divided into 5 groups: Poliovirus, which are beneficial and non- pathologic.61 Bacterial infec- Coxsackie A & Coxsackie B, Echovirus, and Enterovirus. tion of the oral mucosa is caused by loss of epithelial integrity Herpanginia, hand-foot-and-mouth disease, and acute lym- that allows inoculation of the underlying tissue by aerobic or phonodular pharyngitis characterize them. anaerobic bacteria. Patients who have underlying immune dysfunction (or who are high risk because of sexual activity) Rubeola (Measles) may have a greater chance of developing bacteria-related mu- Rubeola is caused by the Paramyxo RNA virus. Rubeola can cosal disease.62 The most common oral disease, dental caries, is often be diagnosed by the presence of Koplik’s spots.58 (Figure caused by mutans, an intraoral bacterium associ- 9) These are small, red, irregular spots with blue-white centers ated with tooth biofilm.63

6 www.DentalAcademyOfCE.com Another common oral condition, periodontal disease, is biotics should be prescribed when there are systemic symptoms associated with initial gingival and subsequent such as fever and malaise or when the patient is known to be bone loss. It is caused by a variety of bacteria (e.g. Porphy- immunocompromised. The antibiotic that has historically been romonas gingivalis and Aggregatibacter actinomycetemcomi- used to treat the condition is (250 mg taken 3 x tans among others).64 The management of dental caries and daily for seven days) but amoxicillin may also be useful (250 mg periodontal disease is a primary function of dental professionals 3 x daily for 7 days). Frequently reoccurring ANUG infection and dental treatment has been extensively covered in multiple in a seemingly healthy person suggests there may be compro- textbooks, monographs and other courses. The rationale for mise of the immune system with medical referral a necessity. treating dental caries and periodontal disease is underscored by Regardless of the cause, mucosal ulcerations may become recent science suggesting that oral bacteria may be associated infected by bacteria. The presence of persistent and increasing with systemic disease. Thus, it is important to educate patients pain, expansion of the surrounding erythema and a deepening to the fact that untreated dental and periodontal disease could of the lesion suggest a superinfection. A useful strategy to treat increase the risk of developing cardiovascular diseases, ath- an with superinfection is to mix 250mg of (re- erosclerosis and diabetic complications, among others.65,66,67,68 moved from a capsule) with 8 oz. of sterile water. The resulting Other mucosal conditions caused by bacteria include the sexu- slurry can be used as a rinse when there are multiple ulcers (one ally transmitted diseases and opportunistic infections. The two tsp. swished throughout the mouth four times a day for seven sexually transmitted diseases most likely to be seen in practice days with expectoration) or delivered directly to a single lesion are gonorrhea and . via cotton swabs (sig: four times a day for seven days). If the Other diseases associated with bacteria are tuberculosis, infected lesion is small it may also be helpful to cover it with a (a rapidly progressive, polymicrobial, opportunistic dissolvable adhesive patch (e.g. CankerMelts GX®, Orahealth infection that occurs during periods of compromised immune Inc.), which slowly releases glycyrrhiza (licorice) extract. The function), and acute necrotizing ulcerative gin- use of CankerMelts® has been shown to reduce lesion size, givitis (ANUG). The identification of gonorrhea, syphilis, tu- duration and the pain associated with inflammation. Other berculosis, actinomycosis and NOMA by dental professionals topical and systemic pain relieving medications may be used as is important as a first step in containing disease, but treatment described above. is best pursued through the patient’s medical provider. Two bacterial conditions where dentists should provide treatment Conclusion are acute necrotizing ulcerative gingivitis (ANUG) (Figure Fungal, viral and bacterial organisms can cause infection of the 11) and superinfection involving major or minor aphthous oral mucosa. In most cases the management of intraoral infec- ulceration. Small oral spirochetes and tious disease simply involves assurance and education regard- in combination with psychological , debilitation, immu- ing risk, palliative home care instructions, recommendations nosuppression, , local trauma, poor and regarding over-the-counter medications and when appropriate, nutrition are thought to contribute to the development of acute prescribed antifungal, antibacterial and antiviral medication. necrotizing ulcerative gingivitis. In this disease the papillae be- The patient with persistent fungal or bacterial lesions may need tween the teeth demonstrate erythema and ultimately become to be further assessed medically to rule out underlying systemic ulcerated and necrotic. The condition is painful and there may pathology. The patient with primary herpetic stomatitis is be a blunting of the papilla and loss of structure. Symptoms can likely to experience reoccurring secondary lip or oral lesions not include fever, malaise and lymphadenopathy. related to immune suppression. These lesions can be managed by topical and in some cases systemic antiviral medication. Figure 11. References 1. Drug Information Handbook for Dentistry, Wynn R, Meiller T, Crossley H. Lexicomp 21st Edition, Hudson, OH. 2. Ouanounou A. Xerostomia in the Geriatric Patient: Causes, Oral Manifestations, and Treatment. Compend Contin Educ Dent. 2016 May;37(5):306-311;quiz312. 3. Anil S, Vellappally S, Hashem M, Preethanath RS, Patil S, Samaranayake LP. Xerostomia in geriatric patients: a burgeoning global concern. J Investig Clin Dent. 2016 Feb;7(1):5-12. 4. Dehghani Nazhvani A, Haddadi P, Badiee P, Malekhoseini SA, Jafarian H. Antifungal Effects of Common on Candida Strains Colonized in the Oral Cavities of Transplant Recipients in South Iran in 2014. Hepat Mon. 2016 Jan 30;16(1):e31245. Recommended ANUG treatment includes warm water 5. Vidya KM, Rao UK, Nittayananta W, Liu H, Owotade FJ. Oral mycoses lavage, rinses with oxygen-releasing formulations or chlorhexi- and other opportunistic infections in HIV: therapy and emerging dine (0.12% - rinse twice daily) and physical . Anti- problems - a workshop report. Oral Dis. 2016 Apr;22 Suppl 1:158-65.

www.DentalAcademyOfCE.com 7 6. Olczak-Kowalczyk D, Pyrżak B, Dąbkowska M, Pańczyk-Tomaszewska North Am. 2013 Oct. 57 (4):561-81. M, Miszkurka G, Rogozińska I, Swoboda-Kopeć E, Gozdowski D, 27. Iatta R, Napoli C, Borghi E, Montagna MT. Rare mycoses of the oral Kalińska A, Piróg A, Mizerska-Wasiak M, Roszkowska-Blaim M. cavity: a literature epidemiologic review. Oral Surg Oral Med Oral Candida spp. and gingivitis in children with nephrotic syndrome or type Pathol Oral Radiol Endod. 2009 Nov. 108 (5):647-55. 1 diabetes. BMC Oral Health. 2015 May 8;15:57. 28. Farah CS, Lynch N, McCullough MJ.Oral fungal infections: an update 7. http://emedicine.medscape.com/article/1077685-overview accessed for the general practitioner. Aust Dent J. 2010 Jun;55 Suppl 1:48-54. May 30, 2016 29. Epstein J, Silverman S. Oral Fungal Infections. Chapter 18, 170-179; 8. Muzyka BC, Epifanio RN. Update on oral fungal infections. Dent Clin in: Essentials of Oral Medicine. Eds Sol Silverman, L. Roy Eversole, North Am. 2013 Oct;57(4):561-81 Edmond L Truelove. 2001,BC Decker Inc. Hamilton, London. 9. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky- 30. http://emedicine.medscape.com/article/1075227-treatment; title: Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis mucosal candidiasis, treatment and management; author Crispian TE, Sobel JD. Clinical Practice Guideline for the Management of Scully; accessed June 03, 2016. Candidiasis: 2016 Update by the Infectious Diseases Society of 31. Lewis RE. Current Concepts in Antifungal Pharmacology Mayo Clin America. Proc. 2011 Aug; 86(8): 805–817. 10. Rex JH, Walsh TJ, Sobel JD, Filler SG, Pappas PG, Dismukes WE, 32. http://emedicine.medscape.com/article/1075227-medication#2 Edwards JE. Practice guidelines for the treatment of candidiasis. 33. http://www.accessdata.fda.gov/drugsatfda_docs/ Infectious Diseases Society of America. Clin Infect Dis. 2000 label/2013/022404s003lbl.pdf Apr;30(4):662-78. 34. Krishnan PA, Kannan R. Comparative study on the microbiological 11. Hertel M, Hartwig S, Schütte E, Gillissen B, Preissner R, Schmidt- features of angular cheilitis in HIV seropositive and HIV seronegative Westhausen AM, Paris S, Kastner I, Preissner S. Identification of patients from South India. J Oral Maxillofac Pathol. 2013;17(3):346-350. signature volatiles to discriminate , glabrata, krusei and 35. Anibal PC, et al. Conventional and alternative antifungal therapies to tropicalis using gas chromatography and mass spectrometry. Mycoses. oral candidiasis; Braz J Microbiol. 2010 Oct-Dec;41(4): 824–831. 2016 Feb;59(2):117-26. 36. Vandeputte P, Ferrari S, Coste A. Antifungal Resistance and New 12. Coleman, D., D. Sullivan, K. Haynes, M. Henman, D. Shanley, D. Strategies to Control Fungal Infections Int J Microbiol. 2012. Bennett, G. Moran, C. McCreary, L. O’Neill, and B. Harrington. 1997. 37. Spampinato D, Leonardi D. Candida Infections, Causes, Targets and Molecular and phenotypic analysis of Candida dubliniensis: a recently Resistance Mechanisms: Traditional and Alternative Antifungal Agents. identified species linked with oral candidosis in HIV-infected and AIDS Biomed Res Int. 2013. patients. Oral Dis.3(Suppl. 1):S96–S101. 38. Dalleau S, Cateau E, Bergès T, Berjeaud J-M, Imbert C. In vitro 13. Fardet L, Petersen I, Nazareth I. Common Infections in Patients activity of terpenes against Candida biofilms. International Journal of Prescribed Systemic in Primary Care: A Population- Antimicrobial Agents. 2008;31(6):572–576. Based Cohort Study. PLoS Med. 2016 May 24;13(5):e1002024. 39. Mondello F, de Bernardis F, Girolamo A, Cassone A, Salvatore G. 14. Neves N, Santos L, Reis C, Sarmento A. Candida albicans In vivo activity of terpinen-4-ol, the main bioactive component of in an drug user patient: a case report. BMC Res Melaleuca alternifolia Cheel (tea tree) oil against azole-susceptible Notes. 2014 Nov 25;7:837. and -resistant human pathogenic Candida species. BMC Infectious 15. Alt-Epping, et al. Symptoms of the oral cavity and theirassociation with Diseases. 2006;6, article 158. local microbiological and clinical findings—a prospective survey in 40. Abad MJ, Ansuategui M, Bermejo P. Active antifungal substances from palliative care Support Care . Mar 2012; 20(3): 531–537. natural sources. Arkivoc. 2007;2007(7):116–145. 16. Lu SY. Perception of deficiency from oral mucosa alterations that 41. Ishijima SA, Effect of Streptococcus salivarius K12 on the In Vitro show a high prevalence of Candida infection. J Formos Med Assoc. Growth of Candida albicans and Its Protective Effect in an Oral 2016 Apr 28. pii: S0929-6646(16)30040-7. Candidiasis Model. Appl Environ Microbiol. Apr 2012; 78(7): 2190– 17. Simi SM. White Lesions in the Oral Cavity: A Clinicopathological 2199. Study from a Tertiary Care Centre in Kerala, India. Indian 42. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. J Dermatol. 2013 Jul-Aug; 58(4): 269–274. Chapter 32Pathogenesis and disease. Richard Whitley, David W. 18. http://emedicine.medscape.com/article/1075227-clinical Accessed Kimberlin, and Charles G. Prober. Cambridge: Cambridge University June 08, 2016 Press; 2007. 19. Stoopler ET, Sollecito TP. Oral mucosal diseases: evaluation and 43. Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th management. Med Clin North Am. 2014 Nov. 98 (6):1323-52. ed.). McGraw Hill. pp. 555–62. 20. Scully C, el-Kabir M, Samaranayake LP. Candida and oral candidosis: 44. Usatine RP, Tinitigan R. Nongenital Herpes Simplex Virus Am Fam a review. Crit Rev Oral Biol Med. 1994. 5(2):125-57. Marsot- Physician. 2010 Nov 1;82(9):1075-1082. Dupuch K, Quillard J, Meyohas MC. Head and neck lesions in the 45. Cernik C, Gallina K, Brodell RT. The treatment of herpes immunocompromised host. Eur Radiol. 2004 Mar. 14 Suppl 3:E155-67. simplex infections: an evidence-based review. Arch Intern Med. 21. Campois TG, Zucoloto AZ, de Almeida Araujo EJ, Svidizinski TI, 2008;168(11):1137–1144. Almeida RS, da Silva Quirino GF, Harano RM, Conchon-Costa I, 46. Gilbert S, Corey L, Cunningham A, et al. An update on short-course Felipe I. Immunological and histopathological characterization of intermittent and prevention therapies for herpes labialis. Herpes. cutaneous candidiasis. J Med Microbiol. 2015 Aug;64(8):810-7. 2007;14(suppl 1):13A–18A. 22. Denture-related stomatitis; a common form of oral candidiasis. From 47. Corey L., Adams H. G., Brown Z. A., Holmes K. K. Genital Scully C, Flint SF, Bagan JV, Porter SR, Moos K. Atlas of Oral and herpes simplex virus infections: clinical manifestations, course and Maxillofacial Diseases. 2010. Informa, London. complications. Ann. Intern. Med. 1983;98:958–972. 23. Park KK, Brodell RT, Helms SE. Angular cheilitis, part 2: nutritional, 48. Kennedy PG, Rovnak J, Badani H, Cohrs RJ. A comparison of herpes systemic, and drug-related causes and treatment. Cutis. 2011 simplex virus type 1 and varicella-zoster and reactivation. J Jul;88(1):27-32. Gen Virol. 2015 Jul;96(Pt 7):1581-602. 24. Green CB, Marretta SM, Cheng G, Faddoul FF, Ehrhart EJ, Hoyer 49. Makielski KR, Lee D, Lorenz LD, Nawandar DM, Chiu YF, Kenney LL. RT-PCR analysis of Candida albicans ALS gene expression in a SC, Lambert PF. Human papillomavirus promotes Epstein-Barr virus hyposalivatory rat model of oral candidiasis and in HIV-positive human maintenance and lytic reactivation in immortalized oral keratinocytes. patients. Med Mycology. 2006;44:103–11. Virology. 2016 May 11;495:52-62. 25. Scully C, de Almeida OP, Sposto MR. The deep mycoses in HIV 50. Mainville GN, Marsh WL, Allen CM. Oral ulceration associated with infection. Oral Dis. 1997 May. 3 Suppl 1:S200-7. concurrent herpes simplex virus, cytomegalovirus, and Epstein-Barr 26. Muzyka BC, Epifanio RN. Update on oral fungal infections. Dent Clin virus infection in an immunocompromised patient. Oral Surg Oral Med

8 www.DentalAcademyOfCE.com Oral Pathol Oral Radiol. 2015 Jun;119(6):e306-14. Linked to Multiple Species by 16S rRNA Community Analysis. PLoS 51. Pereira CM, de Almeida OP, Corrêa ME, Costa FF, de Souza CA, One. 2012; 7(10) Barjas-Castro ML. Detection of in patients with 64. Cortelli JR, Aquino DR, Cortelli SC, Fernandes CB, de Carvalho- oral chronic graft-vs-host disease following allogeneic progenitor cell Filho J, Franco GC, et al. Etiological analysis of initial colonization of transplantation. Oral Dis. 2007 May;13(3):329-34. periodontal in oral cavity. J Clin Microbiol. 2008;46:1332–29. 52. Bezerra TM, et al. Herpesvirus in the oral cavity of children with 65. Burazor I, Vojdani A. Chronic exposure to oral pathogens and leukemia and its impact on the oral bacterial community profile. J Clin autoimmune reactivity in acute coronary atherothrombosis. Pathol. 2015 Mar;68(3):222-8. Autoimmune Dis. 2014 53. Bender Ignacio RA, et al. Patterns of human herpesvirus-8 oral 66. Velsko IM, et al. Active Invasion of Oral and Aortic Tissues by shedding among diverse cohorts of human herpesvirus-8 seropositive in Mice Causally Links Periodontitis and persons. Infect Agent Cancer. 2016 Feb 10;11:7. Atherosclerosis. PLoS One. 2014 May 16;9(5) 54. Pauk J, Huang ML, Brodie SJ, Wald A, Koelle DM, Schacker T, Celum 67. Han YW, et al. Periodontal Disease, Atherosclerosis, Adverse C, Selke S, Corey L. Mucosal Shedding of Human Herpesvirus 8 in Pregnancy Outcomesand Head-and-Neck Cancer. Adv Dent Res. 2014 Men. N Engl J Med 2000; 343:1369-1377. May;26(1):47-55. 55. Webster-Cyriaque J, Edwards RH, Quinlivan EB, Patton L, Wohl D, 68. Hyvärinen K, et al. A common periodontal has an adverse Raab-Traub N. Epstein-Barr virus and human herpesvirus 8 prevalence association with both acute and stable coronary artery disease. in human immunodeficiency virus-associated oral mucosal lesions. J Atherosclerosis. 2012 Aug;223(2):478-84 Infect Dis 1997; 175:1324-32. 56. Vieira J, Huang ML, Koelle DM, Corey L. Transmissible Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in saliva of men Author Profile with a history of Kaposi's sarcoma. J Virol 1997; 71:7083-7. Ian Shuman DDS, MAGD, AFAAID maintains a full- 57. Dvoryaninova OY, Chainzonov EL, Litvyakov NV. The clinical aspects time general, reconstructive, and aesthetic dental practice in of HPV-positive cancer of the oral cavity and oropharynx. Vestn Pasadena, Maryland. Since 1995 Dr. Shuman has lectured and Otorinolaringol. 2016;81(1):72-7. 58. Markel H. Koplik's Spots: The Harbinger of a Measles Epidemic. published on advanced, minimally invasive techniques. He has Milbank Q. 2015 Jun;93(2):223-9. taught these procedures to thousands of dentists and developed 59. Mammas IN, et al. Current views and advances on Paediatric Virology: many of the methods. Dr. Shuman has published numerous ar- An update for pediatric trainees. Exp Ther Med. 2016 Jan;11(1):6-14. ticles on topics including adhesive resin dentistry, minimally in- Epub 2015 Nov 24. 60. Tappuni AR, Shiboski C. Overview and research agenda arising from vasive restorative, cosmetic and implant dentistry. He is a Master the 7th World Workshop on Oral Health and Disease in AIDS. Oral of the Academy of General Dentistry, an Associate Fellow of the Dis. 2016 Apr;22 Suppl 1:211-4. American Academy of Implant Dentistry, a Fellow of the Pierre 61. Dewhirst FE, et al. The human oral microbiome. J Bacteriol. Oct 2010; Fauchard Academy. Dr. Shuman was named one of the Top Cli- 192(19): 5002–5017. 62. Edward E. Herschaft, Charles A Waldron. Bacterial Infections, Fungal nicians in Continuing Education since 2005, by Dentistry Today. and Protozoal Diseases, Viral Infections. In: Brad W Neville, Douglas D Damm, Carl M Allen, Jerry E Bouquot. Oral and Maxillofacial Author Disclosure Pathology. 1st Edition. Philadelphia: W.B. Saunders Company; 1995:Chapters 5,6,7. Dr. Shuman has no commercial ties with the sponsors or the 63. Erin L. Gross, et al. Beyond Streptococcus mutans: Dental Caries Onset providers of the unrestricted educational grant for this course.

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Questions

1. Oral fungal infections can occur for 3. Which of the following is estimated 5. The duration of fungal infection is which of the reasons: to be involved in about 15 to 30% of dependent on which of the following a. aging yeast infections: variables: b. xerostomia a. histoplasmosis a. immune suppression b. blastomycosis b. long-term antibiotic use c. diabetes c. a short course of c. aspergillosis d. all of the above d. a and b d. C. Glabrata 2. The most common oral fungal 6. Symptoms associated with candidia- 4. Solitary erosive oral ulcers are sis can include all but which of the organism is: caused by which of the following: a. C. glabrata following: a. C. dubliniensis a. taste disturbance b. C. tropicalis b. C. tropicalis b. oral burning c. C. albicans c. C. parapsilosis c. d. C. parapsilosis d. none of the above d. dry mouth

www.DentalAcademyOfCE.com 9 Questions (continued)

7. Pseudomembranous candidosis 15. An in vitro animal study showed 23. Human papillomavirus is the cause presents with white plaques on the inhibition of C. albicans invasion of exophytic papules or nodules oc- mucosa and tongue resembling: of mucosal surfaces and adhesion curring on the intraoral mucosa. The a. smooth butter to denture acrylic resins by which b. milk curds appearance of these lesions may be: microorganism: a. single or multiple c. swiss cheese a. HHV-1 d. b and c b. Epstein-Barr virus b. smooth or corrugated 8. Red areas on the palate, and c. S salivarius K12 c. white or tan depapillated areas on the dorsum of d. none of the above d. all of the above the tongue are indicative of: 16. Viral infections that can affect the 24. The conditions related to the a. Erythematous candidosis oral cavity either as localized or human papillomavirus include: b. Pseudomembranous candidosis systemic infections include all but c. Chronic hyperplastic candidosis a. papilloma (squamous papilloma) d. Angular cheilitis/cheilosis which of the following: b. verruca vomitaris a. coxsackievirus c. condyloma excomunicata 9. Denture-related stomatitis is often b. sporanox d. Shrek’s disease associated with: c. mumps a. white plaques on the mucosa and tongue d. rubella 25. The family of Enteroviruses in- b. depapillated areas on the dorsum of the tongue c. angular cheilitis 17. Nongenital herpes simplex virus cludes all but which of the following: d. chronic hyperplastic candidosis type 1 (HSV-1) is an infection usu- a. Echovirus ally acquired: b. Poliovirus 10. Angular cheilitis/cheilosis may be a. during childhood c. Coxsackie A & Coxsackie B a sign of: b. from ages 6 months to five years d. Marburg virus a. diabetes c. before 6 months of age b. vitamin B-12 deficiency d. a and b 26. Endemic Parotitis may present c. HIV infection d. all of the above 18. Which of the following is true of with which of the following: primary herpetic gingivostomatitis: a. hemorrhagic fever 11. Which of the following noncan- a. it presents with painful vesicles b. pulmonary edema didal oral mycoses may cause oral b. It is perhaps the most common viral infection of c. vasovagal syncope infection: the mouth d. unilateral or bilateral swollen parotid glands a. Arapaima gigas c. The lesions ulcerate and the pain can be severe b. Aspergillosis d. all of the above 27. Which of the following is an oral c. Actinopterygii manifestation of HIV: d. Atractosteus spatula 19. All subsequent presentations of HSV-1 is known as: a. Pica 12. In questionable clinical diagnosis, a. herpes zoster b. hydrophobia which of the following microbiologi- b. genital herpes c. cryptococcosis cal identification techniques may be c. CMV d. salmonellosis required: d. herpes labialis 28. The oral cavity is home to a wide a. biopsy 20. HHV-4 is also known as: b. Gram stain a. Epstein-Barr virus variety of bacteria, most of which c. DNA testing b. Burkitts lymphoma are: d. a and c c. varicella-zoster virus a. beneficial and pathologic d. Ramsay Hunt syndrome 13. Which of the following broad- b. non-beneficial and pathologic spectrum antifungal agents causes 21. Varicella-zoster virus (VZV) affects c. beneficial and non-pathologic fungal death by altering cell the geniculate ganglion giving d. non-beneficial and non-pathologic membrane permeability: lesions that follow specific branches 29. The most common oral disease is: a. Glyceryl trinitrate of the: b. Betnovate a. a. gingivitis c. Scheriproct b. facial nerve b. dental caries d. Mycelex c. accessory nerve c. periodontitis 14. Which agent is particularly effec- d. hypoglossal nerve d. a and c tive in patients with chronic atrophic 22. HPV infections have received 30. The two sexually transmitted oral candidosis when administered particular attention in recent years, diseases most likely to be seen in the as high-risk strains have been linked concurrently with an oral antiseptic dental practice are: to some cases of oral: such as chlorhexidine: a. chancroid and trichomoniasis a. Balanitis a. malignant b. Tri-Previfem b. squamous cell carcinoma b. and herpes c. Fluconazole c. glioblastoma c. human papillomavirus and genital warts d. keratolytics d. neuroblastoma d. gonorrhea and syphilis

10 www.DentalAcademyOfCE.com INSTANT EXAM CODE 15154 ANSWER SHEET Management of the Oral Infection: Part 2

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