Oral Lesions and Treatment Recommendations for the HIV-Infected Patient

CME and Dental- Accredited Self-Study Module

Oral Lesions and Treatment Recommendations for the HIV-infected Patient

Release Date: December, 2010 Continuing Education Credit Expiration Date: June 30, 2011 Photocopying contents of this document is allowed. Copyright waived. Albany Medical College is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to CME provide continuing medical education for physicians. ACCREDITATION The Albany Medical College designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Target DENTAL ACCREDITATION

Audience Dentists: The New York State Dental Foundation approved by the NYSDA and the ADA CERP is an approved provider for Physicians, physician assistants, dental continuing education in conjunction with NY/NJ AETC’s Oral Health Regional Resource Center of the New York State pharmacists, nurse practitioners, Health Department/AIDS Institute. nurses, dentists, dental hygienists, dental assistants and other interested Hygienists: The Dental Hygienists’ Association of the State of New York, Inc., an accredited approver by the New York medical providers State Department of Education has approved the NY/NJ AETC’s continuing education learning activities for New York dental hygienists. LEARNING OBJECTIVES OTHER CREDIT REQUIREMENTS After reading this self-study module, Continuing education credits are limited to those listed above. Disciplines with other continuing education requirements for you should be able to: their professional licenses are encouraged to submit evidence of their participation for reciprocity of credits. Please complete the forms at the end of this module to obtain an attendance certificate. 1. Identify clinically relevant oral lesions associated with HIV. 2. Determine when further testing is indicated and which tests should be performed. EDITORIAL PROJECT MANAGERS FACULTY 3. Discuss medications and treatment BOARD Sarah J. Walker, MS DISCLOSURE options available for candidiasis, Associate Director of HIV Correctional Education human papillomavirus (HPV) and Douglas G. Fish, MD xerostomia. COURSE DIRECTORS Division of HIV Medicine Albany Medical College 4. Describe when and how to Douglas G. Fish, MD Albany, New York Speakers’ Bureau consult with and refer patients Medical Director Boehringer Ingelheim to individuals for more AIDS Designated Center Cheryl R. Stolarski, DMD Pharmaceuticals, Inc. specialized care. Associate Professor of Medicine Dental Co-Director Merck & Co., Inc. Albany Medical College Oral Health Regional Resource Center Albany, New York AUTHOR New York/New Jersey AIDS Education Consultant Gwen Cohen Brown DDS, FAAOMP Cynthia H. Miller, MD & Training Center Merck & Co., Inc. Associate Professor Director, Outpatient West Nyack, New York Clinical Services Department of Dental Hygiene AIDS Designated Center Research New York City College of Howard E. Lavigne, BS Assistant Professor of Medicine Gilead Sciences, Inc. Technology, CUNY Program Director Albany Medical College Merck & Co., Inc. Brooklyn, New York Oral Health Regional Resource Center Albany, New York New York/New Jersey AIDS Education Tibotec Therapeutics ACKNOWLEDGEMENTS & Training Center This resource is a collaborative CORRECTIONAL EDITORS Syracuse, New York The following individuals have no initiative among the Division of HIV financial arrangement or affiliation Carl J. Koenigsmann, MD Medicine at Albany Medical College with any corporate organizations that Deputy Commissioner & and the New York State Department Chief Medical Officer offer financial support for continuing of Health AIDS Institute’s Oral Health New York State Department of medical education activities: Regional Resource Center under the Correctional Services Gwen Cohen Brown, DDS, Cynthia New York/New Jersey AIDS Education Albany, New York Miller, MD, Carl Koenigsmann, MD, & Training Center. Sarah Walker, MS, Cheryl Stolarski, Mary J. D’Silva, DDS DMD, Howard Lavigne, BS and This resource is funded in part by Director of Correctional the U.S. Department of Health and Dental Services Jennifer Price. Human Services, Health Resources New York State Department of and Services Administration, HIV/ Correctional Services AIDS Bureau. Albany, New York Caring for the HIV-infected patient: A CME and Dental- Accredited Self-Study Module E an CM d D t e u n t o a b l A To obtain education credit, a minimum of 70% of the questions must be answered correctly on the self assessment test E t d i at the end of this booklet. The estimated time for u c e d completion of this activity is 1 hour. at Cr ion There is no fee for education credit. This learning activity is awarded 1.0 contact hour until June 30, 2011. Directions 1. Time yourself throughout all portions of this activity. 2. Read the enclosed module. 3. Take the self assessment test. 4. Fill out the program evaluation/reader information form including your name and address.

5. Fully complete the HRSA participant information form in black pen. Each bubble must be fully shaded.

6. To assure your receipt of education credit, please CME Credit/Certificate Questions: Contact Jim Ybarra at 518.262.4674 mail your completed self assessment test, program or [email protected] evaluation/reader information form and HRSA participant information form (3 pages total) to: Dental Credit/Certificate Questions: Jim Ybarra Contact Howard Lavigne at Albany Medical College 315.477-8479 or 47 New Scotland Avenue, Mail Code 158 [email protected] Albany, NY 12208

1 A CME and Dental-Accredited Oral Lesions and Treatment Self-Study Module Recommendations for the HIV-infected Patient

also indicate increase in HIV viral resistance, non-adherence with Module Abstract medication or HAART failure. According to the 2008 World Health Organization (WHO) report, close to 33.8 million people worldwide are living with HIV/AIDS. Since the first case of AIDS was reported in 1981, the presence of oral manifestations of HIV infection has HIV-Associated had a significant role in the morbidity and mortality of HIV seropositive patients. (1, 2) Oral lesions occur in 30 - 80% of the affected patient population and their Oral Pathology presence directly affects patients’ quality of life. (3) The presence of oral lesions is strongly associated with a high viral load > 20,000 copies/mL, low CD4 cell count The oral lesions associated with HIV <200 cells/mm3 and treatment failure. disease have traditionally been classified by etiology, degree of immune suppression, Highly active antiretroviral therapy (HAART) has decreased the incidence, frequency, intensity and clinical features. Over the and severity of most, but not all, HIV-associated oral lesions. The focus of this module past thirty years, numerous systems have is the clinical presentation, diagnostic criteria, current treatment modalities and been developed to recognize, diagnose, prognosis of the following HIV-associated oral pathologies: oral candidiasis, human manage, organize, classify and categorize papilloma virus (HPV)-related lesions, salivary gland disease and xerostomia. These the oral manifestations of HIV disease. oral diseases present diagnostic and therapeutic hurdles, are challenging for both the These classification schemas reflect clinician and the patient, and correlate with significant prognostic impact. Inaccurate disparate approaches and differing intent: diagnosis, lack of treatment or inappropriate treatment may result in considerable epidemiologic survey vs. clinical/medical patient morbidity and potential mortality. guidelines, etiology vs. degree of association with HIV infection, clinical presentation (staging) vs. definitive biopsy diagnosis, and inclusion of CD4+ T-lymphocyte/ oral candidiasis and hairy leukoplakia were viral load vs. exclusion of laboratory data. Introduction considered indicators of disease progression Conflicting methodology, interests and HAART was introduced as a first-line to AIDS. (5) Following the introduction pedagogy resulted in inconsistent therapy in 1996. HAART is a combination of new antiretroviral therapies in the late classification systems with often non- drug regimen that targets and interferes 1990s, there was a shift in the incidence comparable data. with viral cell (HIV) replication, thereby and prevalence of most HIV-associated reducing viral load and increasing the oral lesions. Paradoxically, salivary gland In 1989, Pindborg proposed one of the CD4/CD8 ratio. The introduction of disease, xerostomia, and HPV-related first classification systems for oral lesions HAART has dramatically changed the lesions are seen in statistically significant associated with HIV infection. (11) The overall course of HIV infection; patients increasing frequency in patients on system was based on lesion etiology are living longer, healthier lives with HAART. pathogenesis) and intended for use in fewer opportunistic infections and AIDS- epidemiological studies, not clinical defining diseases. (3) HAART has Most researchers consider the proliferation practice. Oral lesions were grouped by decreased the prevalence, rate of of oral HPV-related lesions and salivary type: fungal, viral, bacterial, neoplastic, recurrence, and severity of most, but not gland disease to be a direct result of the neurological and other (unknown). At the all, systemic HIV-associated disease. efficacy of HAART. These pathologies time of publication, 30 oral lesions, many (4) HAART has also significantly reduced increase with the patient’s ability to mount published as individual case reports, were the overall frequency of oral lesions in an inflammatory response. This process, known to be associated with HIV disease. HIV seropositive patients. referred to as the immune reconstitution In the pre-HAART era, approximately syndrome, may lead to increased frequency The European Community (EC) 10% of HIV seropositive patients and severity of select oral lesions. (6, 7, 8, Clearinghouse/WHO publication developed an oral lesion as the initial 9, 10) For individual patients, changes in “Classification and diagnostic criteria clinical sign of immune suppression, and disease presentation or progression may for oral lesions in HIV infection” is

2 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 the most widely accepted and utilized of immunosuppression and decreasing species have also been reported. Since epidemiological classification system for CD4 counts. This is a clinical, not Candida albicans is a normal component oral lesions worldwide. (12, 13) Developed epidemiological, approach to classifying of the oral flora, oral candidiasis is more in the early 1990s, the EC-WHO system HIV-associated oral disease. of a ‘super-infection’ resulting from an classifies oral lesions present in HIV overgrowth of the fungal organisms rather positive patients into three groups The Oral HIV/AIDS Research Alliance than a true infection. Oral candidiasis according to prevalence, relative frequency, (OHARA), as part of the AIDS Clinical presents in both acute and chronic forms intensity and clinical features of the lesion. Trial Group, recently published (2009) and occurs as a result of alterations in Group 1 is composed of lesions that are updated case definitions of oral disease oral flora. strongly associated with HIV infection; endpoints based upon modification of Group 2 lesions are less commonly the 1992 and 1993 EC-WHO criteria. Immune compromised patients lack the associated with HIV infection and Group 3 (19) Oral lesions are presented by etiology systemic and local immunity to prevent lesions are probably associated with HIV. (pathogenesis), clinical descriptors the conversion of yeast from a harmless including color, character, extent and colonizer to opportunistic or invasive Although appropriate for the times, the location, patient-reported symptoms and pathogen. (22) In HIV seropositive parameters set forth in the EC-WHO duration of clinical findings, and whether patients, the incidence of candidal publication are almost twenty years old definitive diagnosis by biopsy is required. carriage may increase and patients with and may not accurately reflect current asymptomatic oral candidiasis may diagnostic criteria, therapeutics and Oral lesions are also included in the demonstrate a rapid conversion to knowledge. Review of recent literature Centers for Disease Control (CDC) and symptomatic infection. (23) Historically, calls for revisiting, updating, standardizing WHO classification systems for HIV/AIDS pre-HAART oral candidiasis was present and calibrating the classification system to systemic disease. Oral candidiasis and oral in up to 90% of HIV seropositive include case-based, medicine-based and hairy leukoplakia are considered HIV- patients. (24) It is one of the most laboratory-based evidence. (14, 15, 16, 17) associated symptomatic diseases in HIV common fungal infections observed in There is a recognized need for a clinically- seropositive patients and have been the initial manifestation of symptomatic based classification system for HIV- included in the clinical classification of HIV infection. associated oral disease that incorporates HIV by CDC in category B. (20) The epidemiology, clinical presentation, WHO developed a staging system for HIV Oral candidiasis may be an indicator of etiology/pathogenesis, stage of disease disease intended for use in epidemiological early HIV infection and may predict progression and therapy. studies of the oral conditions associated advancing immunodeficiency. Without with HIV infection. Oral lesions were appropriate treatment, candidiasis may In 2005 (at the 5th World Workshop organized by clinical presentation and spread to the esophagus resulting in on Oral Health and Diseases in AIDS), symptoms rather than CD4 count and invasive esophageal candidiasis, an AIDS- the *ODHIS Workshop Group, Dental viral load test results. (21) defining disease. (25) Although the Alliance for AIDS/HIV Care, proposed incidence of oral candidiasis has a classification system for HIV-associated significantly declined in patients with oral lesions based upon degree of immune Oral access to antiretroviral therapy, it remains suppression. (18) Group 1 lesions are a problem for patients with limited access associated with severe immune suppression Candidiasis to medication and may be seen in patients CD4<200 cells/mm3, Group 2 lesions Oral candidiasis, colloquially referred with a poor response to HAART. (14) are associated with immune suppression to as ‘thrush’, is a common fungal CD4<500 cells/mm3 and Group 3 lesions infection that may present in both Oral candidiasis is typically observed as are assumed to be associated with immune immunocompetent and immuno- CD4 counts fall below 500/µl. The suppression. The classification system also compromised patients. It is associated with presence of oral candidiasis in HIV includes two groups not previously numerous local and systemic conditions seropositive patients can be a useful clinical identified in the EC-WHO classification including immunosuppression, HIV marker for high viral load and low CD4 system; Group 4 includes therapeutically- infection, chemotherapy, poorly percentage. (26) It has been suggested that induced oral disease and Group 5 includes controlled diabetes, xerostomia, and co-infection with HIV and candida may emerging oral diseases. Although not denture stomatitis. Oral candidiasis may affect both the severity and rate of HIV absolute, as oral lesions can present at result in pain on swallowing, oral disease progression in HIV seropositive different levels of immune suppression, the discomfort, localized swelling, bitter individuals. (27) Some authors have ODHIS classification system recognizes the or sour taste and loss of function. Oral suggested that an HIV viral load greater prognostic significance of oral disease by candidiasis is most often due to the yeast than 10,000 copies/mL is the most correlating specific oral lesions to degree Candida albicans, although non-albicans predictive factor in the development of oral candidiasis. (28) *Oral diseases of HIV-associated immune suppression (ODHIS)

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 3 Clinical Presentation of Oral Candidiasis

1. Acute Pseudomembranous 3. Chronic Denture Stomatitis: 5. Chronic Angular Cheilitis: Presents Candidiasis (Thrush): Presents as Presents in older adults and is typically as perioral erythema and/or cracking, white, curd-like plaques that easily wipe located under dentures as edematous fissuring and superficial ulceration at away leaving a raw, red or bleeding erythematous tissue immediately the corners/commissures of the mouth. surface. May occur throughout the oral subjacent to denture base. May also (Figure 5) cavity and pharynx and is frequently present with papillary hyperplasia of asymptomatic (Figure 1) the palate. (Figure 3)

Figure 5: Chronic Angular Cheilitis

There are four frequently observed Figure 1: Acute Pseudomembranous Figure 3 : Chronic Denture Stomatitis presentations of oral candidiasis in Candidiasis (Thrush) HIV seropositive patients: 1) acute 4. Chronic Median Rhomboid Glossitis: pseudomembranous candidiasis (thrush), 2. Acute Atrophic Candidiasis: Presents as flat/slightly raised 2) acute atrophic candidiasis, 3) angular Presents as flat/slightly raised erythematous depapillated rhomboid cheilitis, and 4) chronic atrophic candidi- erythematous macules, often seen first shaped lesion on the middle third/ asis in the forms of denture stomatitis, pap- on the soft palate. Often precedes the midline dorsal surface of the tongue. illary hyperplasia of the palate, and median development of pseudomembranous (Figure 4) rhomboid glossitis. The fifth candidiasis. (Figure 2) clinical presentation of oral candidal infection, hyperplastic candidiasis, occurs less often and is a form of chronic candidiasis. Typically a diagnosis of candidiasis can be made on clinical presentation alone or by therapeutic diagnosis whereby the lesions resolve following appropriate drug management.

Figure 2: Acute Atrophic Candidiasis

All photographs were taken by the author, Dr. Gwen Cohen Brown, courtesy of the Department of Dental Hygiene, New York City College of Technology. Figure 4: Chronic Median Rhomboid Glossitis

4 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 Laboratory Treatment See Table 1: Antifungal Agents Topical Creams and Ointments Tests Candidiasis See Table 2: Antifungal Agents Oral candidiasis is treated with either Topical Troches, Pastilles, Tablets, Candidiasis systemic or topical antifungal medicine. Suspensions, Powders Laboratory tests can be used to confirm the The delivery format is relevant, as different See Table 3: Antifungal Agents clinical diagnosis of candidiasis, however, therapeutic modalities are more successful Systemic they are rarely done unless the lesion in treating specific clinical manifestations does not resolve following appropriate of this disease. To determine which vehicle All tables are the creation of the treatment. If lab tests are required, a to use, both the clinical presentation and author, Dr. Gwen Cohen Brown. potassium hydroxide stained cytologic extent of the infection must be taken into Drug information was adapted preparation that demonstrates the fungal account, as different agents may have from the PDR. pseudohyphae penetrating the epithelial preferential activity for each clinical cells can be used for confirmation. appearance. (32) Topical therapies are Confirmation by biopsy and a periodic indicated for limited and easily accessible, Considerations acid Schiff stain (PAS) is also possible, as mild to moderate disease and superficial the stain will turn the spores and candidal infections. Systemic therapy is and Concerns- pseudohyphae bright magenta, making appropriate and effective for patients with them easily visible by light microscope. moderate to severe candidiasis and/or Candidiasis Fungal cultures are not typically used to invasive fungal infections. One consideration in the selection of an confirm the diagnosis of oral candidiasis, as antifungal medication is the likelihood candida albicans is a normal component of Current recommendations from the of a drug-drug interaction, as a large the oral flora. (24) Infectious Diseases Society of America percentage of HIV seropositive patients are (IDSA) 2009 (31) guidelines on the taking concomitant medications. Patients If oral lesions fail to improve following treatment of oropharyngeal candidiasis in should not take antacids within two-hours appropriate therapy, a definitive diagnosis adults state that topical agents are the drugs of systemic oral azole therapy, as this will is indicated utilizing the above laboratory of choice for initial therapy in patients with interfere with the absorption of the azole tests, and the possibility of a resistant a CD4 count greater than 200 cells/mm3. and decrease the antifungal properties. strain of candida should be explored. (29) (33) When using topical agents, the level of Chlorhexidine Gluconate 0.12% oral Prior antifungal drug treatment in either drug concentration and contact time must rinse has been reported to demonstrate prophylactic or suppressive doses of be taken into consideration in order to al- antifungal properties. However, it fluconazole (50-100 mg/day) has low the drug to penetrate the oral biofilm. cannot be used at the same time as contributed to the development of (29) The efficacy of the antifungal medica- topical Nystatin since the combination fluconazole-resistant candida albicans. (30) tions depends upon a multitude of oral and creates a nystatin-chlorhexidine salt Since HAART for the treatment of HIV is systemic conditions. Coexisting factors such precipitate. If both drugs must be used, widely available and utilized in the United as xerostomia, salivary gland hypofunction, they should be administered at least States, routine primary prophylaxis of periodontitis, high HIV viral load and one-hour apart. (35) candidiasis is not indicated. (29) Chronic, low CD4 counts can decrease the efficacy suppressive therapy for patients with of the medication and can affect clinical It is important to remember that human immunodeficiency virus (HIV) outcomes. (34) prolonged use of topical antifungal is not always necessary. If suppressive agents containing fermentable therapy is required, fluconazole is Systemic therapy with fluconazole, carbohydrate substrates may result in recommended. (31) ketoconazole, or itraconazole may be rapid tooth decay. Patients should be considered for the initial treatment of told to rinse their mouth with water moderate to severe disease oropharyngeal after use of any topical antifungal candidiasis. (30) For fluconazole-resistant medication containing sucrose. Patients disease, itraconazole solution or with severe xerostomia or diabetes should posaconazole suspension (Noxafi®), be treated with vaginal Nystatin tablets, voriconazole (Vfend®) or amphotericin as they do not contain sucrose. (36) B oral suspension may be administered.

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 5 and men. (43) Recent literature supports Human the role that high risk HPV subtypes such Clinical as 16 and 18 play in the etiology of oral Papilloma and oropharyngeal squamous cell cancer Presentation of (SCC). Although the association of Virus (HPV) oral cancer with HPV is clear, the Oral HPV Related epidemiology of oral HPV infection HPV/Condyloma Acuminatum: Multiple, remains elusive, and it is still unknown papillary projections on the inner aspect of Lesions how much of the data from cervical HPV the lower labial mucosa. (Figure 6) infection can be extrapolated to oral HPV HPV is one of the most prevalent viral infection. (44) Long-term follow-up is infections worldwide, with several million needed to determine the risk of SCC new cases diagnosed every year. Currently developing from oral dysplastic warts. (45) there are more than 120 identified HPV subtypes, 30 of which have been detected The data on emerging incidence and in the oral cavity. (37) HIV seropositive appropriate treatment modalities for individuals are more likely to carry HPV oral HPV lesions in HIV seropositive in the mouth than immune competent individuals on HAART is still largely individuals and are more likely to be unknown. To this end, a large multicenter infected by more than one HPV genotype. clinical study has been initiated through (38) Oral HPV infection occurs at a higher the National Institute of Allergy and rate among HIV-infected people than Infectious Diseases (NIAID). The purpose among the general population. The most of this study is to evaluate the frequency of common genotypes found in the mouth of oral HPV DNA shedding and oral warts patients with HIV infection are 2, 6, 11, in HIV-infected people prior to HAART Figure 6 : Oral HPV 13, 16, and 32. (39) initiation and at regular time points after HAART initiation. This study, Surveys comparing the incidence of oral ClinicalTrials.gov identifier: Treatment of and cutaneous HPV-related lesions in NCT01029249, is currently HIV seropositive patients (pre- and post- recruiting participants. HPV-Related HAART eras) underscore the complexity of this issue. One report found that oral warts Lesions were six times more common in patients Clinical Treating oral HPV-related lesions in HIV on HAART. (40) Other studies have seropositive patients can be a challenge, linked the presence of oral warts with Presentation as there are no standardized treatment reductions in viral load. (41) Most guidelines, nor is there a consensus on researchers currently believe that this of Oral HPV- the efficacy of available current treatment phenomenon is related to the Immune modalities. There are few published reports Reconstitution-associated Disease (IRAD) Related on the treatment of oral HPV lesions and process. (42) The concept of IRAD seems Lesions most have been case reports. None of the counterintuitive in that more HPV lesions publications has been double-blinded, have been observed in HIV seropositive Oral HPV-related lesions appear papillary placebo-controlled or randomized. (47) patients on HAART, in other words after with either a pedunculated or sessile stalk, The treatment of oral condyloma is restoration of the immune system. and are often found on the palate, buccal difficult because of the number and mucosa, and labial commissures. (46) distribution of the lesions, as well as their The longer survival of HIV seropositive Condyloma may present as a solitary high recurrence rate. patients on HAART has also led to a lesion, or more likely with multiple, florid, high incidence and steady increase in exophytic papillary lesions throughout the Traditional treatments aim at the HPV-related malignancies both in women oral cavity and peri-oral tissues. removal or desiccation of HPV lesions.

6 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 Although these procedures visually excise effect of over-the-counter and prescription the lesion, they tend to recur due to Salivary Gland medication, smoking, alcohol persistence of the virus in clinically consumption and dehydration. It is not normal surrounding mucosal tissue. (48) Disease, exclusively identified in the HIV Most treatment regimens have targeted positive population. (53) extra-oral warts, and it is still unknown Hyposalivation Xerostomia can be difficult to diagnose if these treatment regimens are and quantify, as dry mouth is often a transferable for the treatment of and subjective finding. Patients may intraoral warts. Topical application Xerostomia present with the feeling of oral dryness of caustic or acid agents including yet demonstrate adequate salivary flow cantharidin, podophyllin resin, tretinoin, Salivary glands are affected in 2–10% clinically. Conversely, they may present topical 5-fluorouracil have been used of HIV seropositive patients. Clinical with visible findings of xerostomia and with mixed results. Intralesional manifestations include hyposalivation objective evidence of hyposalivation, yet bleomycin, interferon-alfa, imiquimod, and dry mouth, or xerostomia. It occurs feel as if their mouth is amply lubricated. etretinate, cimetidine, and zinc either because of a reduction in the (55) Measurement of the salivary flow rate sulfate have all shown varying quantity of saliva produced or as a is indicated and may help to distinguish success as well. (46) qualitative change. (51) Caries and between subjective xerostomia and periodontal disease reduce and alter the objective hyposalivation. The average flow, composition and PH of saliva, while unstimulated whole salivary flow rate is Considerations xerostomia increases the incidence of 0.3 to 0.4 milliliters per minute. An bacterial plaque, gingival bleeding and unstimulated rate of 0.1 mL/minute and Concerns candidal organisms. (52) or less indicates hyposalivation. (56)

HPV Related Salivary gland disease (SGD) in HIV Saliva aids in the chewing, swallowing Lesions seropositive patients is characterized by and digesting of food. Salivary two clinical presentations, major salivary hypofunction may lead to changes in Cryosurgery, electrocautery or gland enlargement and xerostomia. SGD food and fluid selection that potentially electrosurgery, YAG laser and CO2 laser typically presents as bilateral enlargement may result in a compromised nutritional come with their own set of problems. of the Parotid glands, due to either the status. Saliva dilutes and washes away food Although pain and bleeding are reduced development of lymphoepithelial cysts debris, sugars and the acids produced by with use of a laser or cautery, a smoke or a lymphocytic infiltrate within the oral bacteria. Without saliva, the oral cavity plume is produced which may contain parenchyma of the glands. (53, 54) is not ‘buffered’. Reduced salivary flow HPV virions capable of infecting the Xerostomia is the subjective feeling, results in a lower, more acidic intraoral pH patient and the surgeon. (49, 50) Ideally, perception, of oral dryness. True level that in turn increases the likelihood all visible HPV lesions should be removed xerostomia, or dry mouth, occurs when of tooth decay, periodontal disease and oral at the same time. If they are not, the there is a decrease in salivary flow or infections. For edentulous patients, saliva likelihood is great that the open wounds reduced output from the salivary glands. creates the vacuum pressure that is critical will be re-seeded with virus and new Xerostomia is a common finding in for the retention, adhesion and comfort of lesions will develop at the surgical site. adults, associated with different systemic removable dentures. (57) and local factors, and can be a side

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 7 (60) Salivary substitutes available by Clinical Treatment of prescription also may alleviate the discomfort. Increasing fluoride Presentation of Xerostomia percentage in mouth rinses and toothpastes Xerostomia There seems to be little correlation between can help prevent tooth decay in patients the patient’s subjective findings of dry with hyposalivation. mouth and objective testing of salivary flow rate, therefore clinical management can be difficult and primarily based on Summary patient symptoms. The salivary flow rate HAART has significantly changed the will distinguish between the subjective clinical presentation of oral disease in HIV feelings of xerostomia and the objective seropositive patients. Overall, patients are clinical presentation of hyposalivation. living healthier, longer lives with fewer complications from oral disease. However, Figure 7 : Xerostomia If there is a decrease in the salivary flow oral HPV lesions, salivary gland disease, rate, i.e. the glands are not working hyposalivation and xerostomia are on the Patients with xerostomia present with properly but still retain secretory function, rise and are proving to be complex and dry, cracked and peeling lips, a bald or sialogagues may be indicated. If the glands difficult to treat. Oral candidiasis remains depapillated red tongue, erythematous exhibit adequate salivary flow and the a problem especially when coupled with candidiasis, difficulty chewing, swallowing, patient is feeling oral dryness, palliative decreased salivary flow. Oral HPV lesions and speaking as well as mucosal burning, care is indicated. (58, 59) do not yet have definitive treatment soreness, ulceration and halitosis. Often guidelines, and the association of oral patients will complain of dysgeusia, a bad, Lubricating agents in the form of gels, squamous cell carcinoma with certain bitter or metallic taste. Tooth decay is often mouthwashes, sugarless gum and lozenges high-risk HPV subtypes found in oral rampant and found in unusual locations have been used, with varying degrees of warts will change the clinical paradigm like the occlusal (biting) surface of the success, to relieve the symptoms of and treatment methodology in the anterior incisor teeth and the cervical root xerostomia by increasing salivary output. near future. near the gingival margin. (36)

All photographs were taken by the author, Dr. Gwen Cohen Brown, courtesy of the Department of Dental Hygiene, New York City College of Technology.

8 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 tABLE 1: Antifungal Agents-Topical Creams and Ointments ANTIFUNGAL INDICATION DISPENSE DIRECTIONS CONTRAINDICATION DRUG ADVERSE BRAND AGENT (DISP) (SIG) CAUTION INTERACTIONS REACTIONS NAME Clotrimazole 1% Imidazole 1 tube Apply to None No Irritation Various Cream (OTC) Antifungal, Mild 15 gm clean dry significant Erythema Generic to Moderate 30 gm affected area interactions Burning Manufacturers Cutaneous 4x/day for known or Stinging Candidiaisis, 2-4 weeks found. Acute Angular Cheilitis Miconazole 2% Imidazole 1 tube Apply to None No Irritation Various Cream Antifungal, Mild 15 gm clean dry significant Erythema Generic (OTC) to Moderate 30 gm affected area interactions Burning Manufacturers Cutaneous 2x/day for known or Stinging Candidiaisis, 2-4 weeks found. Acute Angular Cheilitis Ketoconazole 2% Imidazole 1 tube Apply 1x/day Asthma No Irritation Nizoral® Cream; contains Antifungal, Mild 15 gm to affected significant Pruritus Various Sulfites to Moderate 30 gm and adjacent interactions Stinging Generic (RX) Cutaneous 60 gm area. Treat known or Allergic Manufacturers Candidiaisis, for at least 2 found. Reaction Acute Angular weeks Cheilitis Nystatin Cream Polyene 1 tube Apply None No Irritation Mycostatin® or Ointment Antifungal, 15 gm liberally to Patients must sigificant (rare) 100,000 U/1mL Cutaneous or 30 gm corners of remove dentures interactions (gm) Mucocutaneous mouth or to allow known or (RX) Candidiasis, apply to the medication to found. Acute Angular denture base contact mucosa. Cheilitis, before Denture insertion Stomatitis 4x/day for 2-4 weeks Triamcinolone Steroid + 1 tube Apply Varicella No Burning Various Acetonide 0.1%, Polyene, ointment sparingly Avoid prolonged significant Itching Generic Nystatin 100,000 Antifungal 15 gm 2x/day use + large areas. interactions Irritation Manufacturers U/1mL (gm) Mild to Cream Maximum 25 Ointment: known or Mycolog II® Ointment or Moderate 15 gm days high/medium found. Discontinued Cream Cutaneous 30 gm treatment strength in US (RX) Candidiaisis, 60 gm corticosteroid Chronic potency Angular Cream: medium Cheilitis strength corticosteroid potency Betamethasone Steroid + 1 tube Apply Varicella Anthralin Skin Atrophy Lotrisone® as Dipropionate Imidazole, 15 gm sparingly Do not occlude. Topical Hypo- 0.05%, Antifungal 45 gm 2x/day 45 gm per week Combination pigmentation Clotrimazole 1% Mild to maximum; may increase Irritation Cream Moderate Cream: medium symptoms of Burning (RX) Cutaneous strength psoriasis Paresthesia Candidiaisis, corticosteroid Chronic potency Angular Cheilitis Hydrocortisone Steroid + 1 tube Apply to Steroid + Sabril Burning Vytone® 1%, Iodoquinol Antifungal + 30 gm affected area Antibiotic. Low (vigabatrin) Itching 1%; Cream Antibacterial, 3-4 x/day strength Irritation (RX) Short-term, corticosteroid Steroid- potency responsive skin infection with mild bacterial or fungal infection, Chronic Angular Cheilitis

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 9 Notes

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10 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 tABLE 2: A ntifungal Agents-Topical Troches, Pastilles, Tablets, Suspensions, Powders

ANTIFUNGAL INDICATION DISPENSE DIRECTIONS CONTRAINDICATION DRUG ADVERSE BRAND AGENT (DISP) (SIG) CAUTION INTERACTIONS REACTIONS NAME Miconazole Imidazole Buccal 1 tab daily in Apply the tablet Warfarin, Local OravigTM Buccal Tablet Antifungal Tabs the morning directly maxillary Monitor INR, irritation, 50 mg Mild to Moderate 14 count for 14 days. gingiva into the small Combination Nausea (RX) Oropharyngeal Do not crush, depression above may increase Diarrhea Candidiaisis chew or swallow. incisor. Tab will slowly risk of bleeding Taste dissolve during the day. disturbance. Nystatin Lozenge Polyene Pastilles 1 pastille Aniseed licorice No May cause Mycostatin® (Pastilles) Antifungal, 70 count 4-5x/day for flavored. Patients significant mucosal Pastilles 200,000 U/1mL Mild to Moderate 14 day supply 14 days. must remove interactions irritation, (gm) Oropharyngeal Continue for dentures to allow known or Nausea (RX) Candidiaisis at least 2 days medication to found. after all contact mucosa. symptoms Requires adequate have gone. saliva to dissolve. Slowly dissolve Contains Sucrose in mouth; do not + Glucose. Caution: crush, chew or Diabetes Mellitus swallow whole. patients. Cariogenic so adjunctive topical fluoride therapy may be needed. Do not eat for 30 min after use. Nystatin Vaginal Polyene Tablet 1 tablet Patients must No May cause Mycostatin® Tablet 100,000 Antifungal, 70 count 4-5x/day for remove dentures significant mucosal Tablet U/1mL (gm) Mild to Moderate 14 day supply 14 days. to allow medication interactions irritation, (RX) Oropharyngeal Continue for to contact mucosa. known or Nausea Candidiaisis at least 2 days For use with found. after all Caries active symptoms Patients, Diabetes have gone. Mellitus patients Slowly dissolve in mouth; do not crush, chew or swallow whole. Clotrimazole Imidazole Troches Treatment: Requires adequate No Vomiting Various Troches 10 mg Prophylaxis + 70 count 1 troche 5x/day saliva to dissolve. sigificant Nausea Generic (RX) Treatment of 14 day supply for 14 days. Contains Dextrose interactions May cause Manufacturers Mild to Moderate Prophylaxis: Caution: Diabetes known or altered taste Mycelex® Oropharyngeal 1 troche Mellitus patients. found for this Discontinued Candidiaisis 3x/day Cariogenic so drug. in US Slowly dissolve adjunctive topical in mouth; do not fluoride therapy crush, chew or may be needed swallow whole. Do not eat for 30 min after use. Clotrimazole Imidazole Tablet Tablet to be Requires adequate N/A N/A N/A Vaginal Tablet Prophylaxis + cut in half saliva to dissolve. 100 mg Treatment of 2x/day for Patients must remove (RX) Mild to Moderate 14 days. One- dentures to allow Oropharyngeal half slowly medication to Candidiaisis dissolve in contact mucosa. mouth; do not For use with crush, chew or Caries active swallow whole. Patients, Diabetes Mellitus patients Nystatin Oral Polyene 60 mL Swish 1 tsp Shake well before No Vomiting Mycostatin® Suspension Antifungal, with dropper, or 5 mL in mouth, using. Patients must significant Nausea Suspension 100,000 U/1mL Mild to Moderate 473 mL hold 5 minutes remove dentures to interactions Abdominal (gm) Oropharyngeal (1 pint) bottle 4x/day, or 1 tsp allow medication to known or pain (RX) Candidiasis 14 day supply or 5 mL on contact mucosa. found. gauze pad, hold Contains Sucrose in mouth for 5 + Glucose. minutes 4x/day Caution: Diabetes Mellitus patients. Cariogenic so adjunctive topical fluoride therapy may be needed Do not eat for 30 min after use. Nystatin Topical Polyene 15 gm Apply thin film None No Irritation Mycostatin® Powder Antifungal, to the denture Patients must remove significant (rare) 100,000 U/1mL Denture base after meals dentures to allow interactions (gm) Stomatitis before insertion medication to known or (RX) 4x/day for contact mucosa. found. 2-4 weeks

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 11 Notes

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12 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 tABLE 3: A ntifungal Agents-Systemic

ANTIFUNGAL INDICATION DISPENSE DIRECTIONS CONTRAINDICATION DRUG ADVERSE BRAND AGENT (DISP) (SIG) CAUTION INTERACTIONS REACTIONS NAME Fluconazole Triazole 15 Tablets 2 tablets Documented Hydrochlorothiazide Photosensitivity Diflucan® Tablets Antifungal loading dose hypersensitivity. Rifampin Nausea 100 mg Oropharyngeal then 1, 100 Monitor liver Warfarin Vomiting and Esophageal mg/day tablet function. Phenytoin Diarrhea Candidiasis with food for Cyclosporine Allergic 7-14 days Zidovudine Reactions Theophylline Tacrolimus Cisapride Erythromycin Fluconazole Triazole 350 mg 10 mL 1x/day Documented Hydrochlorothiazide Photosensitivity Diflucan® Solution Antifungal per bottle hypersensitivity. Rifampin Nausea 10 mg/mL Oropharyngeal 1400 mg Monitor liver Warfarin Vomiting and Esophageal per bottle function. Phenytoin Diarrhea Candidiasis Cyclosporine Allergic Zidovudine Reactions Theophylline Tacrolimus Cisapride Erythromycin Itraconazole Imidazole 15 1 capsule Documented Astemizole Nausea Sporanox® Capsules Antifungal Capsules 100 mg/day hypersensitivity. Bepridil Vomiting 100 mg Oropharyngeal 30 with food. Monitor liver Cisapride Stomach and Esophageal Capsules Tablet with function. Dofetilide Upset Candidiasis food for 15 days Antacids may Levacetylmethadol Increase dose reduce absorption Mizolastine to 200 mg/day of itraconazole. Pimozide for 15 days in Pregnancy + Quinidine AIDS patients congestive Sertindole if impaired heart failure Terfenadine absorption. contraindicated. Ergot alkaloids Triazolam Eletriptan Nisoldipine Itraconazole Imidazole 150 mL Swish 100 mg, Documented Astemizole Headache Sporanox® Solution Antifungal 10 mL 1 measuring hypersensitivity. Bepridil Abdominal pain 10 mg/mL Oropharyngeal measuring cup, in mouth Monitor liver Cisapride Vomiting and Esophageal cup for 20 seconds function. Dofetilide Nausea Candidiasis 1x/day for Antacids may Levacetylmethadol Diarrhea 7 days. Take reduce absorption Mizolastine Dysgeusia without food; of itraconazole. Pimozide refrain from Pregnancy + Quinidine eating for at congestive Sertindole least 1 hour heart failure Terfenadine after use. contraindicated. Ergot alkaloids Triazolam Eletriptan Nisoldipine Ketoconazole Imidazole 15 Tablets 2 tablets Documented Triazolam Nausea Nizora®l Tablets Antifungal Loading dose hypersensitivity. Terfenadine Vomiting Various 200 mg Oropharyngeal then 1 200 Monitor liver Astemizole Diarrhea Generic and Esophageal mg/day tablet function. Cisapride Edema Manufacturers Candidiasis with food or Absorption of Cyclosporine Hypokalemia fruit juice for Ketoconazole is Tacrolimus 7-14 days dependant on Methyl-prednisolone gastric acidity. Rifampin Posaconazole Antifungal 4-ounce 2 tsp daily Shake well Ergot alkaloids Nausea Noxafil® Suspension Oropharyngeal (123 mL) Loading dose before use. Terfenadine Vomiting 100 mg/2.5 mL and Esophageal A measured of 100 mg Astemizole Diarrhea Candidiasis dosing spoon (2.5 mL) Cisapride is provided, twice a day Pimozide marked for on the first day, Halofantrine doses of then 100 mg Quinidine 2.5 mL and (2.5 mL) once Cimetidine 5 mL. a day for Rifabutin 13 days. Phenytoin Efavirenz

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 13 9. Greenspan D, Canchola AJ, MacPhail 19. Shiboski CH, Patton LL, Webster- References LA, Cheikh B, Greenspan JS. Effect Cyriaque J Y, Greenspan D, Traboulsi of highly active antiretroviral therapy RS, Ghannoum M, Jurevic R, Phelan 1. Greenspan JS, Greenspan D. Oral on frequency of oral warts. JA, Reznik D, Greenspan JS. The Complications of HIV Infection. Lancet 2001;357:1411-2. Oral HIV/AIDS Research Alliance: In: Sande MA, Volberding PA, eds. updated case definitions of oral disease Medical Management of AIDS, 6th ed. 10. Patton LL, McKaig R, Strauss endpoints. J Oral Pathol Med (2009) Philadelphia: WB Saunders; 1999: R, Rogers D, Eron JJ. Changing 38: 481-488 157-169. prevalence of oral manifestations of human immuno-deficiency virus in the 20. 1993 Revised Classification System 2. Ceballos-Salobreña A, Gaitán-Cepeda era of protease inhibitor therapy. Oral for HIV Infection and Expanded LA, Ceballos-Garcia L, Lezama-Del Surveillance Case Definition for Valle D. Oral lesions in HIV/AIDS Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Mar;89(3):299-304. AIDS Among Adolescents and Adults. patients undergoing highly active http://www.cdc.gov/mmwr/preview/ antiretroviral treatment including 11. Pindborg J. Classification of oral lesions mmwrhtml/00018871.htm protease inhibitors: A new face of oral associated with HIV infection. Oral AIDS? AIDS Patient Care STDS 2000; Surg Oral Med Oral Pathol Oral Radiol 21. Melnick SL, Nowjack-Raymer R, 14:627-35. Endod. 1989;67:292-). Kleinman DV, Swango PA. A Guide for Epidemiological Studies of Oral 3. Ives NJ, Gazzard BG, Easterbrook PJ. 12. 1991), An update of the classification Manifestations of HIV Infection. The changing pattern of AIDS-defining and diagnostic criteria of oral lesions in Geneva: WHO, 1993 illnesses with the introduction of highly HIV infection. Journal of Oral Pathology active antiretroviral therapy (HAART) & Medicine, 20: 97–100. doi: 10.1111/ 22. Fidel PL Jr. Distinct protective host in a London clinic. J Infect 2001; j.1600-0714.1991.tb00900.x defenses against oral and vaginal 42(2):134-9 candidiasis. Med Mycol 2002;40: 13.(1993), Classification and diagnostic 359-75. 4. Birnbaum W, Hodgson TA, Reichart criteria for oral lesions in HIV PA, Sherson W, Nittayannanta SW, infection. Journal of Oral Pathology & 23. Klein RS, Harris CA, Small CB, Moll Axell TE: Prognostic significance of Medicine, 22: 289–291. doi: 10.1111/ B, Lesser M, Friedland GH. Oral HIV-associated oral lesions and their j.1600-0714.1993.tb01074.x candidiasis in high-risk patients as the relation to therapy. Oral Dis 2002 , initial manifestation of the acquired 8:110-4 14. Hood S, Bonington A, Evans J, immunodeficiency syndrome.N Engl J Denning D. Reduction in oro- Med 1984;311:354-8 5. Itin PH, Lautenschlager S, Fluckiger pharyngeal candidiasis following R, Rufli T. Oral manifestations in introduction of protease inhibitors. 24. Thompson GR, Patel PK, Kirkpatrick HIV-infected patients: diagnosis and AIDS 1998;12:447-8 WR, Westbrook SD, Berg D, management. Journal of the American Erlandsen J, Redding SW, Patterson TF. Academy of Dermatology - November 15. Chapple ILC, Hamburger J. The Oropharyngeal candidiasis in the era of 1993 (Vol. 29, Issue 5, Pages 749-760) significance of oral health inHIV disease antiretroviral therapy Oral Surgery. Oral Sex Transm Infect 2000;76:236-243 Surg Oral Med Oral Pathol Oral Radiol 6. Chattopadhyay A, Caplan DJ, Slade Endod. April 2010 (Vol. 109, Issue 4, GD, Shugars DC, Tien HC, Patton 16. D Greenspan, JS Greenspan. Oral Pages 488-495 LL. Incidence of oral candidiasis and manifestations of HIV infection AIDS oral hairy leukoplakia in HIV-infected Clin Care 1997;9:29-33 25. Coogan MM., Greenspan J, adults in North Carolina. Oral Surg Challacombe SJ. Oral lesions Oral Med Oral Pathol Oral Radiol 17. Weinert M, Grimes RM, Lynch DP. in infection with human Endod 2005;99(1):39-47. Oral Manifestations of HIV Infection immunodeficiency virus. Bull World Ann Intern Med September 15, 1996 Health Organ [serial on the Internet]. 7. Greenspan D, Komaroff E, Redford M, 125:485-496 2005 Sep [cited 2010 Oct 10]; 83(9): Phelan JA, Navazesh M, Alves ME, et 700-706. al. Oral mucosal lesions and HIV viral 18. Glick M, Abel SN, Flaitz CM, load in the Women’s Interagency HIV Migliorati CA, Patton LL, Phelan 26. Campo J, Del Romero J, Castilla J, Study (WIHS). J Acquir Immune Defic JA, Resnick DA. (A-7) Classification García S, Rodríguez C, Bascones A. Syndr 2000;25(1):44-50. of Oral Disease of HIV-Associated Oral candidiasis as a clinical marker Immune Suppression, 5th World related to viral load, CD4 lymphocyte 8. Greenspan D, Gange SJ, Phelan JA, Workshop on Oral Health and Disease count and CD4 lymphocyte percentage Navazesh M, Alves ME, MacPhail LA, in AIDS. ODHIS Workshop Group – in HIV-infected patients Journal of Oral et al. Incidence of oral lesions in USA Pathology & Medicine Volume 31, Issue HIV-1-infected women: reduction 1, January 2002, Pages: 5–10 with HAART. J Dent Res 2004;83(2): 145-50.

14 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 27. Campisi G, Pizzo G, Milici ME, children: recommendations from CDC, 43. Sjoerd H van der Burg, Joel M Palefsky Mancuso S, Margiotta V. Candidal the National Institutes of Health, the Human immunodeficiency virus and carriage in the oral cavity of human HIV Medicine Association. MMWR human papilloma virus-why HPV- immunodeficiency virus–infected Recomm Rep. 2009; 58(RR-11):28-50. induced lesions do not spontaneously subjects Oral Surg Oral Med Oral Pathol resolve and why therapeutic Oral Radiol Endod. March 2002 Vol. 34. Baccaglini L, Atkinson JC, Patton vaccination can be successful. Journal 93, Issue 3, Pages 281-286 LL, Glick M, Ficarra G, Peterson DE. of Translational Medicine 2009 7:108 Management of oral lesions in HIV- doi:10.1186/1479-5876-7-108 28. Mercante DE, Leigh JE, Lilly EA, positive patients Oral Surg Oral Med McNulty K, Fidel PL, Jr. Assessment of Oral Pathol Oral Radiol Endod. March 44. Fakhry C, D’souza G, Sugar E, Weber the association between HIV viral load 2007 (Vol. 103 Supplement, Pages K, Goshu E, Minkoff H, Wright R, and CD4 cell count on the occurrence S50.e1-S50.e23, DOI: 10.1016/j. Seaberg E, Gillison M. Relationship of oropharyngeal candidiasis in HIV- tripleo.2006.11.002) between Prevalent Oral and Cervical infected patients. J Acquir Immune Human Papillomavirus Infections Defic Syndr 2006;42:578-83.)Keith D 35. Barkvoll P, Attramadal A. Effect of in Human Immunodeficiency Virus Hunter, John Gibson, Peter Lockhart, nystatin and chlorhexidine digluconate Positive and Negative Women J. Clin. Alan on Candida albicans. Oral Surg Oral Microbiol. 2006 44: 4479-4485 Med Oral Pathol 1989;67(3):279-81 29. Ship JA, Vissink A, Challacombe 45. Regezi JA, Dekker NP, Ramos DM, SJ. Use of prophylactic antifungals 36. Cohen-Brown G, Ship JA. Diagnosis Li X, Macabeo-Ong M, Jordan in the immunocompromised host. and treatment of salivary gland RC. Proliferation and invasion Oral Surg Oral Med Oral Pathol Oral disorders. Quintessence Int February factors in HIV-associated dysplastic Radiol Endod. March 2007 (Vol. 2004 (Vol. 35, Issue 2, Pages 108-23) and nondysplastic oral warts and in 103Supplement, Pages S6.e1-S6.e14, oral squamous cell carcinoma: an 37. Felefli, S, Flaitz, C M Oral warts in DOI: 10.1016/j.tripleo.2006.11.003) immunohistochemical and RT-PCR HIV-infected individuals Research evaluation. Oral Surg Oral Med Oral initiative, treatment action: RITA 2000 30.Hunter KD, Gibson J, Lockhart P, Pathol Oral Radiol Endod. 2002 Dec Vol 6 issue 3 pgs 19-22 Pithie A, Bagg J. Fluconazole-resistant 94(6) 724-31 Candida species in the oral flora of 38. Fiumara, N. The Management of Warts fluconazole-exposed HIV-positive 46. Moyle, G.J. Outbreaks of Oral Warts of the Oral Cavity Sexually Transmitted patients . Oral Surg Oral Med Oral Coinciding With HAART? Medscape Diseases. 11(4):267-270, October/ Pathol Oral Radiol Endod. May 1998 HIV/AIDS 2002 Vol 8 Issue 2 Pgs 7-8 December 1984. (Vol. 85, Issue 5, Pages 558-564) 47. Baccaglini L, Atkinson JC, Patton 39. Bajpai S, Pazare AR. Oral 31. Pappas PG, Kauffman CA, Andes LL, Glick M, Ficarra G, Peterson DE. manifestations of HIV. Contemp Clin D, Benjamin, DK Jr., Calandra TF, Management of oral lesions in HIV- Dent 2010;1:1-5 Edwards JE Jr., Filler SG, Fisher JF, positive patients Oral Surg Oral Med Oral Kullberg BJ, Ostrosky-Zeichner L, 40. Greenspan D, Canchola AJ, MacPhail Pathol Oral Radiol Endod 2007;103(suppl Reboli AC, Rex JH, Walsh TJ, Sobel LA, Cheikh B, Greenspan JS. Effect 1):S50.e1-S50.e JD. Clinical Practice Guidelines for of highly active antiretroviral therapy 48.Bernard HU. Established and potential the Management of Candidiasis: 2009 on frequency of oral warts. Lancet. strategies against papillomavirus Update by the Infectious Diseases 2001;357:1411-1412. Society of America infections J. Antimicrob. Chemother. 41. Meys R, Gotch FM, Bunker C. Human (2004) 53(2): 137-139 first published 32. Leão JC, Ribeiro CMB, Carvalho papillomavirus in the era of highly online January 7, 2004 doi:10.1093/ AAT, Frezzini C, Porter S. Oral active antiretroviral therapy for human jac/dkh023 complications of HIV disease. Clinics. immunodeficiency virus: an immune 49. Gloster HM Jr, Roenigk RK. Risk 2009;64(5):459-70. reconstitution-associated disease? British of acquiring human papillomavirus Journal of Dermatology. 162(1):6-11, 33. Mofenson LM, Brady MT, Danner from the plume produced by the January 2010. SP, et al. Centers for Disease Control carbon dioxide laser in the treatment and Prevention, National Institutes 42. King MD, Reznik DA, O’Daniels CM, of warts J Am Acad Dermatol. 1995 of Health, HIV Medicine Association Larsen NM, Osterholt D, Blumberg Mar;32(3):436-41. of the Infectious Diseases Society HM. Human papillomavirus- 50. Alpa E, Bijlc D, Bleichrodtd RP, of America, Pediatric Infectious associated oral warts among human Hanssond B, Vossa A. Surgical smoke Diseases Society, American Academy immunodeficiency virus-seropositive and infection control Journal of Hospital of Pediatrics. Fungal infections. In: patients in the era of highly active Infection (2006) 62, 1–5 Guidelines for the prevention and antiretroviral therapy: an emerging treatment of opportunistic infections infection. Clin Infect Dis. 2002;34:641- among HIV-exposed and HIV-infected 648

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 15 51. Kaplan I, Zuk-Paz L, Wolff A. 55. Guggenheimer J, Moore PD. ADA 59. V. Visvanathan, P. Nix Managing Association between salivary flow rates, Continuing Education Xerostomia the Patient Presenting with oral symptoms, and oral mucosal status Etiology, recognition and treatment Xerostomia: A Review Int J Clin Pract. Surg Oral Med Oral Pathol Oral Radiol J Am Dent Assoc, Vol 134, No 1, 2010;64(3):404-407. © 2010 Endod 2008;106:235-41 61-69. © 2003 60. Shetty K. Implications and management 52. César J. Filho C, Giovani EM. 56. Wiener RC, Wu B, Crout R, Wiener of xerostomia in the HIV-infected Xerostomy, Dental Caries and M, Plassman B, Kao E, McNeil patient HIV Clinician Special Dental Periodontal Disease in HIV+ Patients D. Hyposalivation and xerostomia Issue March 2005 pgs 1-4 The Brazilian Journal of Infectious in dentate older adults JADA Diseases 2009;13(1):13-17. 2010:141(3):279-284.

53. Schiødt M. HIV-associated salivary 57.Turner M, Jahangiri L, Ship JA. gland disease: A review Oral Surg Oral Continuing Education Hyposalivation, Med Oral Pathol Oral Radiol Endod. xerostomia and the complete denture A Volume 73, Issue 2, February 1992, systematic review J Am Dent Assoc, Vol Pages 164-167 139, No 2, 146-150. © 2008

54. Mulligan R, Navazesh M, Komaroff 58. Von BultzingsloÅNwen I, Sollecito TP, E, Greenspan D, Redford M, Alves Fox PC, Daniels T, Jonsson R, DMD, M, Phelan JA. Salivary gland disease Lockhart B, Wray D, Brennan MT, in human immunodeficiency virus- Carrozzo M, Gandera BI, Fujibayashi positive women from the WIHS study. T, Navazesh M, Rhodus NL, Schiødt Oral Surg Oral Med Oral Pathol Oral M. Salivary dysfunction associated with Radiol Endod. June 2000 (Vol. 89, Issue systemic diseases: systematic review and 6, Pages 702-709) clinical management Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(suppl 1):S57.e1- S57.e15

16 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7 self-assessment test

Oral Lesions and Treatment Directions: Referring to the module text, please select Recommendations for the the BEST answer by circling your response directly on this HIV-infected Patient test. To obtain education credit, a minimum of 70% of the questions must be answered correctly. This learning activity is awarded 1.0 contact hour until June 30, 2011.

1. Since HAART therapy was introduced, the overall 7. There are no standardized treatment guidelines for the incidence of oral lesions has increased. treatment of HPV. A. True A. True B. False B. False

2. Oral lesions associated with HIV disease have 8. Treatment for HPV lesions includes all of the below traditionally been classified by the following: except: A. Etiology A. Desiccation of the lesion(s) B. Degree of immune suppression B. Caustic or acid agents C. Intensity C. Intralesional bleomycin D. Clinical features D. Antifungal therapy E. All of the above E. Cryosurgery

3. Candida albicans is a normal component of the 9. Xerostomia can be a side effect of: oral flora. A. Over-the-counter medications A. True B. Smoking B. False C. Prescription medications D. Alcohol consumption 4. Oral candidiasis may be: E. Dehydration A. An indicator of HIV infection F. All of the above B. Found when CD4 is high C. Found when viral load is low 10. Reduced salivary flow can lead to adecrease in tooth D. Diagnosed only with certain laboratory tests decay. A. True 5. Patients should not take antacids within 2 hours of B. False systemic oral azole therapy. A. True B. False

6. Candidiasis can be treated with: A. Topical therapy B. Systemic therapy C. Antibiotics D. All of the above E. A and B (over)

Oral Lesions and Treatment Recommendations for the HIV-infected Patient edition 7 17 Program Evaluation & Reader Information Form Continuing Education Credit Expiration Date: June 30, 2011

To assure your receipt of education credit, please mail your Oral Lesions and Treatment completed self assessment test, program evaluation/reader Recommendations for the information form and HRSA participant information form. HIV-infected Patient (3 pages) to: Jim Ybarra Albany Medical College 47 New Scotland Avenue, Mail Code 158 Albany, NY 12208 EVALUATION

1. Please select the type of education credit you are seeking: 7. Did you notice any commercial bias in this resource? CME* (proceed to question 3) Yes No Dental Credit (go to question 2) I completed the above activity and am claiming (hour) *By selecting CME, you will receive a CME certificate. Disciplines with other continuing education requirements (e.g. nurses etc.) are encouraged to of credit (number of hours you actually participated). If you submit this CME certificate as evidence of participation for reciprocity of completed the entire activity, please write 1.0 hour in the space credits. provided.

2. If you are a member of the American Dental Association Signature: (ADA), please cite your ADA number here for education credit tracking: reader information form If you do not have an ADA number, please check here** Please print legibly as all information is needed for **You are still eligible for dental credit, but will need to submit your dental education credit processing attendance certificate to your credentialing board for credit.

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Comments: Organization Address:

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Please proceed to the next page and complete the HRSA participant information form. 4. Did this resource meet its stated learning objectives? Yes No

5. Do you think that this resource will help you in your work? CME Credit/Certificate Questions: Yes No Why/why not: Contact Jim Ybarra at 518.262.4674 or [email protected]

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18 Oral Lesions and Treatment Recommendations for the HIV-infected Patient e d i t i o n 7