Oral Lesions of HIV in the Era of HAART Roseann Mulligan DDS, MS USC School of Dentistry and the Pacific AIDS Education and Training Center

Impact of Oral Conditions – HIV+ Patients High rate of oral manifestations Oral lesions may be harbinger of change in HIV condition Relative ease of access to identification of lesions by those in clinical practices Potential impact on systemic health care outcomes Potential impact on quality of life Adapted from Sifri R, Diaz V, Gordon L, Glick M, Anapol H. et al. Oral health care issues in HIV disease: developing a core curriculum for primary care physicians. J Am Board Fam Pract 1998; 11(6):434-44

High rate of oral manifestations More than 90% of patients have at least one oral lesion during their disease course. 1 Are almost always accompanied by symptoms Take a variety of appearances that are for the most part characteristic 1 New York State Dept of Health AIDS Institute's Best Practices. Promoting oral health care for people with HIV infection. January 2004.

Oral lesions ~ Harbinger of Δ HIV status Often the first clinical feature of HIV infection is an oral lesion. 1 New lesions in HIV-infected patient - a sign that HIV disease is progressing. Untreated HIV infected with oral candidiasis progress to AIDS within two years. 1 May indicate need for prophylaxis against specific opportunistic infections. 1New York State Dept of Health AIDS Institute's Best Practices. Promoting oral health care for people with HIV infection. January 2004.

Medical history 1. Questionnaires 2. Patient observation 3. Medical Interview 4. Risk Assessment 5. Head/Neck Exam 6. Diagnostic tests

Normal Range Lab Values Lymphocytes Type of Lymphocyte Percentage of Total Lymphocytes Total T, CD3 60- 87% Total T/ mm3 630 - 3170 B cell 1- 25% Suppressor, CD8 10- 40% Suppressor/ mm3 240 – 1200 Helper, CD4 30 - 55% Helper / mm3 600 – 1700 H:S (CD4/CD8) 0.8 - 3.0

CD4 Status and Relationship to Outcomes Description CD4 Count 30-55 Normal value >600 cell/mm³ < 29 Initial Immune Suppression <500 cell/mm³ <29 Manifestations of opportunistic infection including oral lesions <400 cell/mm³ 14 -18 Increase in number of opportunistic infections >201-400 cell/mm³ <14 Severe Immune Suppression (e.g. Apthous Major) <200 cell/mm³ AIDS Dx Continuing decreases Fatal opportunistic infection (e.g. CMV,MAC) <100 cell/mm³

Platelets Number of platelets in a drop (uL) of blood Normal range: 150,000-400,000/uL Unsafe to do invasive dental tx <60,000 Spontaneous bleeding <50,000

Neutrophils Normal range: 3,000-7,000/ mm Neutropenia: <1000/mm3 Severe neutropenia <500/mm3 **May require antibiotic prophylaxis before invasive dental treatment

Oral Manifestations of HIV Infection Oral Disease Fungal Candidiasis - Pseudomembranous, Erythematous, and Angular Cheilitis Invasive Fungal Infections - Histoplasmosis, Cryptococcosis Viral Herpes Simplex Herpes Zoster Cytomegalovirus Hairy Leukoplakia (Epstein Barr Virus) Oral Warts (Human Papilloma Virus) Human Hominus Virus–8 [K.S.] Bacterial Linear Gingival Erythema Necrotizing Ulcerative Periodontitis Tuberculosis* Mycobacterium avium complex* Bacillary angiomatosis* http://www.aids-ed.org/ppt/nw_schubert_oralupdate_03.ppt

Oral Manifestations of HIV Infection Type of Lesion Oral Disease Neoplastic Kaposi’s Sarcoma (KS) [HHV-8] Lymphoma Squamous Cell Carcinoma* Other HIV- Necrotizing Ulceration HIV-Salivary Gland Disease/ Xerostomia Thrombocytopenic Purpura* Abnormal Mucosal Pigmentation http://www.aids-ed.org/ppt/nw_schubert_oralupdate_03.ppt

Oral Candidiasis Candida albicans is the most prevalent Most Common + often predicts HIV progression Candida albicans is the most prevalent 3 types: pseudomembranous ª; erythematous ª; hyperplastic.

Oral Candidiasis Pseudomembranous (Thrush) Characterized by the presence of white curds or creamy cotton like appearance Can be easily removed. The underlying mucosa is erythematous and may bleed slightly. Immunosuppresion

Oral Candidiasis Atrophic (Erythematous) In non-immunosuppressed Associated in patients w/ ill-fitting dentures or in those who wear their dentures continuously Generalized red area of atrophic tissue, commonly on the palate Burning sensation, palate, tongue Culture, smear not very effective

Oral Candidiasis In tongue loss of the filiform papilla, a generalized thinning of the epithelium, and excessive inflammation of the connective tissue Median Rhomboid Glossitis

Oral Candidiasis Chronic Hyperplastic usually presents as a white mucosal plaque. Most common location: buccal mucosa along the occlusal line in the commissure, latero-dorsal surface of tongue and the alveolar ridges Frequently term “candidal leukoplakia”

Oral Candidiasis Angular cheilitis

Perspective – Oral Manifestations Volume 13 Issue 5 December 2005/January 2006

Herpes Simplex Recurrent herpes labialis : lips: dry mucosa or skin, fluid-filled vesicle, that rupture, ulcerate, and resolve as crusted brownish lesions. Recurrent intraoral herpes: maxillary gingiva, palate: wet and fragile mucous membranes. Lesions are punctate with red or white bases that slowly disappear.

Epstein-Barr Virus (EBV) Oral Hairy Leukoplakia White, often corrugated in appearance, plaque-like or hair-like projections that are non- wipeable, lateral borders of tongue. It appears in late latency stages HIV or precursor of AIDS. Definitive Dx: Histopathology

Epstein-Barr Virus (EBV) Oral Hairy Leukoplakia Treatment Treat for cosmetic reasons; otherwise no treatment is warranted

Human Papilloma Virus (HPV) HAART   Assoc. w/ ~2.6 -6-fold  incidence of oral warts  aphthous ulcers & salivary gland dz→caries Diz Dios P, Ocampo A, Miralles C. (2000) ; Patton LL, et al. (2000); Patton LL, (2003) .

Human Papilloma Virus (HPV) In the oral cavity the most common are, squamous papilloma HPV 6 & 11; verruca vulgaris HPV 2-4 and condyloma acuminatum HPV 6 & 11 Clinically may appear exophitic, keratinized, sessile papules or nodules “cauliflower-like 2-5mm“

Human Papilloma Virus (HPV) SP: High incidence on the soft palate, faucial pillars, uvula. VV: Lips,hard palate and gingiva→hands and fingers. CA: Presents as a pinkish, sessile papules or plaques w/ pebbled surfaces. Oral lesions occur in nonkeratinized mucosa of lips, floor of the mouth, lateral and ventral surface of tongue, buccal mucosa and soft palate Photo ftom VI Meeks, DDS, U Md Dental School

Human Papilloma Virus (HPV) Treatment indicated (1) Lesion may become traumatized (2) In area that may lead to auto-inoculation (3) For cosmetic reasons

Human Papilloma Virus (HPV) Treatment Cryotherapy; laser or surgical excision. Lesions often recur

Human Papilloma Virus (HPV) Vaccine was approved last June by the FDA Women 9-26 yrs (prefer 11-12 yrs old) 70% cervical cancers HPV 16,18,31,45 Vaccine 6, 11, 16, 18 HPV 16 related to 25% of oral cancer. $300-500 total for 3 dose series

Necrotizing Ulcerative Periodontitis NUP Extensive soft tissue necrosis exposing alveolar bone Severe pain, odor and spontaneous bleeding Compare appearance to aphthous ulcer on right

Necrotizing Ulcerative Periodontitis (NUP)

Povidone Iodine /Chlorexidine

Salivary Gland Involvement http://www.aids-ed.org/ppt/nw_schubert_oralupdate_03.ppt

Salivary Gland Involvement Table: Absence of saliva on palpation of salivary glands the WIHS Mulligan R. et al. Salivary gland disease in human immunodeficiency virus-positive women from the WIHS study. Women's Interagency HIV Study. Oral Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics. 89(6):702-9, 2000 Jun. Medications (side effects) -> xerostomia

Data from the Women’s Interagency HIV Study Greenspan D, Gange S, Phelan J, Navazesh M, Alves M, MacPhail L, Mulligan R, Greenspan J. J Dent Res 83(2):145-150, 2004

Prevalence of Oral Lesions During HIV Medication Usage Greenspan, D et al The Lancet Vol 357 May 5, 2001

In Summary Oropharyngeal Candidiasis (OPC) improves or resolves with response to HAART Oral lesions are fewer as a result of HAART Cavities increase as a result of hyposalivary function due to meds Warts seem to increase

Preventive Oral Health Care Recalls every 3 to 6 months Antimicrobial mouth rinses for patients with periodontal disease, including past history of NUP and LGE Fluoride supplements

Thank You !!