Module 8: Oral Manifestations of HIV/AIDS

candidiasis pathophysiology

*Opportunistic fungal infection 

*C. Albicans (67%) or otherwise C. Dubliniensis (oropharyngeal)

candidiasis epidemiology

*Most common intra-oral manifestation of HIV/AIDS

-often presenting sx that leads to diagnosis 

*Predictive of increased immunosuppression and progression to AIDS

candidiasis oral manifestations- pseudomembranous candidiasis

- white removeable plaques 

 - most common form in HIV + with initial progressive immune suppression (CD4 <400 cells/mm3)

candidiasis oral manifestations- erythematous or atrophic candidiasis

- most commonly seen during early stages of HIV (in combination with pseudomembranous form)

candidiasis oral manifestations- hyperplastic candidiasis

 - most often associated with severe immune suppression: long standing HIV disease

  - can NOT be entirely wiped off

+/- sx such as burning, sensitivity to certain foods/beverages, altered taste

candidiasis diagnosis

*Clinical (plaques are removable/non-removeable)

*Smear

*PAS stain show fungal hyphae

candidiasis treatment

*Nystatin oral suspension 

*Clotrimazole (Mycelex) torches 

Fluconazole (Difulcan) tablets (recommended)- contraindicated in liver disease

*Mycolog or Lotrisone cream

histoplasmosis epidemiology

*Most common endemic respiratory fungal infection in US 

-subclinical and self-limiting in healthy pts 

-most common disseminated fungal disease in pts with AIDS

histoplasmosis manifestations

Systemic 

-Flu-like sx

Oral

-Deep fungal ulcers

-Can look like gumma in tertiary syphilis

oral hairy leukoplakia pathophysiology

*EBV-related white mucosal patch that doesn’t rub off (leukoplakia)

oral hairy leukoplakia oral manifestations

*White leukoplakia, non-removable patch (differential dx: EBV, OHL, dysplasia) 

-Lateral tongue

oral hairy leukoplakia diagnosis

*Histology shows balloon cells
*Test balloon cells – EBER (in-situ hybridization for EBV)

oral hairy leukoplakia treatment

*If in non-immunocompromised patients, mandates a thorough PE to r/o immunocompromised status 

*If in immunocompromised patients, indicates severe immune suppression and advanced disease

*None other than referral to MD 

*Surgical excision for aesthetic concerns

HSV oral manifestations

HSV diagnosis

*Cytology/biopsy needs to be done early in disease (1-3 days) – this is when we can visualize herpetic infected cells

*3 Ms: Multinucleation, molding, margination (chromatin at periphery)

HPV pathophysiology

*dsDNA virus that infects epithelial cells of skin and mucosa 

*Oral papillomas, verruca vulgaris, condyloma accuminatum

HPV epidemiology

*Oral warts are becoming more common in HIV+ in era of HAART

-possibly due to immune reconstitution the form of increased numbers of APCs in the oral mucosa may trigger greater recognition of HPV

-present a significant challenge

*Leading cause of oropharyngeal cancer 

*A very small number of oral cavity cancer also occur form HPV

*Of ~20 strains of HPV only 9 are associated with cancer 

-of the 9 that are high risk only HPV16 and HPV18 are strongly associated with oropharyngeal cancer

HPV oral manifestations

*Can look like condyloma 

-condyloma have broader base, more blunted papilla, look like cauliflower

HPV diagnosis

*Koilocyte – clear cytoplasm, enlarged and crinkled nucleus

HPV treatment

*Excision 

*Trichloroacetic acid- caustic in mouth

HIV-associated periodontal disease types

*Linear Gingival Erythema

*Necrotizing ulcerative gingivitis 

*Necrotizing ulcerative periodontitis

HIV-associated periodontal disease oral manifestations

*Linear Gingival Erythema

-Etiology = candida

-Can be confused with marginal gingivitis 

*Necrotizing ulcerative gingivitis 

-Punched out gingival papillae

*Necrotizing ulcerative periodontitis

-Gingiva affected AND bone loss
*Necrotizing ulcerative stomatitis

HIV-associated periodontal disease treatment

*Linear gingival erythema: antifungal 

*NUG and NUP: debridement, antimicrobial therapy, follow up and long term maintenance

aphthous ulcers pathophysiology

*Aka canker sores

*Exact cause not completely understood, but involves a T-cell mediated immune response triggered by a variety of factors

*Very common, affecting about 20% of general population 

*Not contagious 

*Appear on NON-keratinized mucosa (i.e. anywhere except attached gingiva, hard palate, dorsum of tongue)- can be on keratinizing surfaces in more severe forms 

*Ulcers occur periodically and typically heal in 7-10 days in healthy patients

aphthous ulcer types

*Minor aphthous 

-most common 

-lesions are 2-3 mm in diameter and affect non-keratinized mucosal surfaces 

-1 to several can appear at the same time 

-heal in 7-10 days without scarring 

*Major aphthous 

-10% of cases 

->10 mm in diameter 

-healing takes longer and can leave scar

*Herpetiform 

-lesions resemble HSV infection, however they are not caused by HSV

-<1mm in diameter, up to 100 at a time 

-adjacent ulcers merge to form larger areas of ulceration 

-healing occurs within 15 days without scarring 

-can affect keratinized mucosa 

*RAS type ulceration or aphthous like ulcers

-recurrent oral ulcerations associated with systemic conditions

aphthous ulcer oral manifestations

*Ulcers with peripheral erythema

*In immunosuppressed – looks larger

aphthous ulcers treatment

*No cure 

*Treatments aim to manage pain, reduce healing time, reduce frequency of episodes of ulceration

mollusum contagiosum pathophysiology

*Infection of skin caused by Poxvirus 

-self-limiting in healthy pts (trunk and genital regions) 

-pts with AIDS 100’s may be present (face common) 

*Immunosuppressed patients can develop lesions that spread, last a long time, very difficult to treat  

*Molluscum itself not serious

mollusum contagiosum epidemiology

*20% of people with AIDS will develop molluscum

mollusum contagiosum oral manifestations

*Most are <1/2 inch in diameter with a, center has indentation 

-same color as normal skin but appear waxy 

-usually asx

mollusum contagiosum diagnosis

*Millions of virions proliferate in cytoplasm of affected epithelial cells resulting in characteristic intracytoplasmic bodies 

-these viral inclusions are the largest in all of the human body

mollusum contagiosum treatment

*Treated the same as cutaneous warts – frozen with liquid nitrogen, laser ablated, chemically treated with caustic agents i.e. TCA, podophyllin or podofilox, surgically excised, application of antiviral meds directly onto lesions 

*Resolution with HAART documented

cancer epidemiology

*Significant cause of morbidity and mortality in HIV patients 

-30-40% will develop malignancy during lifetime 

-Majority of cancer affects HIV+ patients are those established as AIDS defining: Kaposi’s sarcoma, non-Hodgkin’s lymphoma, invasive cervical ca

cancer oral manifestations- Kaposi’s sarcoma

-multifocal endothelial cell neoplasm of skin or oral mucosa (HHV-8) 

-skin: trunk, arms, H and N

-oral cavity: hard palate, gingiva, tongue 

-lesions: brown/red/purple flat patch -> plaques -> nodules 

-pain, bleeding, necrosis necessitates tx

-microscopically looks like proliferation of spindle cells

cancer oral manifestations- NHL

-2^nd most common malignancy in HIV+ 

-in AIDS, it is high grade and aggressive (EBV and HHV-8 detected, usually in extra-nodal sites such as CNS and oral cavity) 

-gingiva, palate, tongue, tonsils most frequent sites 

-survival is often only months from time of dx 

-diffuse sheet of inflammatory cells

cancer oral manifestations- plasmablastic lymphoma

-B cell lymphoma with plasmablastic morphology predominantly associated with HIV infection 

-arises in 2 settings: most cases involve oral cavity or jaw, some cases associated with multi-centric Castleman disease 

-nearly all cases in HIV+ patients

cancer oral manifestations- squamous cell carcinoma

-same risk factors as general population

-red patch with exophytic nodule, feels firm on palpation 

-atypical stratified squamous epithelium of surface that invades into connective tissue -> tumor islands, atypical epithelial cells and mitotic figures

Karposi’s and NHL treatment

*Karposi: no specific treatment, use HAART therapy to get AIDS under control 

 *NHL: HAART has only reduced some cases