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Clinical
p r a c t i c EH
IV is a retrovirus carried by more than 40 million people worldwide.1 HIV in- fection leads to gradual deterioration of the immune system and to the development of AIDS. As of June 2006, 61,423 people in people in Canada had been infected with HIV; 20,493 of them had been diagnosed with AIDS, and at least 13,326 people with AIDS had died.2 Notwithstanding extraordinary progress in understanding and managing HIV pathogen- esis, there is no cure for HIV-related disease and the treatment of choice is to target HIV viral replication with the expectation of de- laying further immune suppression. With dis- ease progression, the deleterious effect of HIV on the immune system results in an escalating incidence of widely recognized and extensively described opportunistic infections and dis- eases, among which are the oral manifestations of HIV (OMHs).3–5 A summary of the most common OMHs and their recommended treat- ment is presented in Table 1.Since the onset of the HIV pandemic, OMHs have been well documented as early markers of HIV infection7 and as predictors
of HIV disease progression.8 Oral candidiasis (Fig. 1) and oral hairy leukoplakia (Fig. 2)9 are lesions associated with fungal and viral patho- gens, respectively, and are the most frequently occurring OMHs. Others, such as human pap- illomavirus (HPV) related warts (Fig. 3), aph- thous-like ulcers and Kaposi’s sarcoma have also been reported extensively. OMHs con- tribute to HIV-related morbidity and are be- lieved to serve as important markers of HIV infection and disease progression even in those on modern HIV therapy.
The therapeutic breakthrough associated with the introduction of HIV-specific pro- tease inhibitors more than 10 years ago has significantly improved the prognosis of HIV disease.10,11 The use of HIV protease inhibitors combined with therapy targeting the HIV re- verse transcriptase enzyme (highly active an- tiretroviral therapy or HAART) is associated with a sustained decrease in viral replication and stabilization or even an increase in the peripheral CD4+ T-helper cell count,12 a subset of lymphocytes targeted by HIV. It is generally accepted that the risk of developing an OMH
For citation purposes, the electronic version is the definitive version of this article: www.cda-adc.ca/jcda/vol-73/issue-10/949.html
Dr. Epstein
Email: jepstein@uic.edu �ontact ��uthor
Changes in the Pattern of Oral Lesions Associated with HIV Infection: Implications for Dentists
Herve Y. Sroussi, DMD, PhD; Joel B. Epstein, DMD, MSD, FRCD(C), FDS RCSE
ABSTRACT
Broad access to better HIV treatment has resulted in a significant reduction in the preva- lence of HIV-associated oral lesions in western industrialized countries. However, a pos- sible increased prevalence of oral warts and a potential dissociation between CD4+ T-cell counts and oral manifestations of HIV require continued vigilance by oral health care providers. Head and neck and oral examination coupled with a careful consideration of the complications associated with hyposalivation remain essential components of a comprehensive oral health care program.
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Table 1 Most commonly observed oral manifestations of HIV and recommended treatment
Oral manifestations of HIV Treatment �omments
Oropharyngeal candidiasis Clotrimazole: 10-mg troches, orally, 5 times a day for 7–14 days
Fluconazole: 100 mg, orally, once daily for 7–14 days
Refer when refractory to fluconazolea
• CDC guidelines do not recommend prophylaxis except for exceptional cases of severe or frequent recurrences.
• Consider drug–drug interactions and liver status when choosing a systemic or topical treatment.
Oral hairy leukoplakia In-office application of podophyllum
resin (25%) • There are insufficient data to support evidence-based treatment recommen- dations. Considering the inconsequen- tial nature of the lesion, systemic antiviral medication may not be warranted.
Oral warts Surgical excision and biopsy; refer for
extensive/recurrent lesionsa • There are insufficient data to support evidence-based treatment recommen- dations other than surgical excision.
• Consideration should be given to the possibility of spreading HPV to other surfaces during surgery, and potential cancer risk.
Oral herpes simplex Acyclovir: 800 mg, 4 times a day for 7 days
Valacyclovir: 500 mg twice daily for 7 days
Refer those with severe, persisting or recurrent lesionsa
• Topical antiviral medication should be considered for patients with
CD4+ counts above 0.2 × 109/L and herpes labialis.
Recurrent aphthous-like ulcerations High-potency topical steroids, such as fluocinonide and clobetasol
Refer severe casesa; systemic steroids, thalidomide or immunosuppresives may be considered
• The use of topical steroids may result in increased incidence of oral pharyngeal candidiasis.
• Systemic therapy should be limited to those experienced in the use of these medications.
Gingival and periodontal disease Oral hygiene, prophylaxis, scaling/
curettage, chlorhexidine rinse; may be combined with systemic antibiotics.
• Some studies report linear gingival erythema with a band-like pattern of erythema and increased intensity of bone and soft tissue loss
Malignant lesions: oral Kaposi’s sarcoma, squamous cell carcinoma, lymphoma
Intralesional injection of vinblastine or sodium tetradecyl sulfate 3% and/or low-dose radiation therapy
• Patient with biopsy-confirmed disease should be referred to physician for evaluation of the involvement of other organs.
• Intralesional treatment should be lim- ited to those experienced in the use of these medications.
Hyposalivation Stimulation of gland function: taste, chewing and sialogogues
Prevention of oral complications (caries, candidiasis)
Source: Reference 6
aRefer to an appropriate specialist
CDC = US Centers for Disease Control and Prevention; HPV = human papillomavirus.
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increases with decreasing CD4 count and higher HIV load.13,14 However, this observation may be less accurate in patient populations with long histories of HIV infection.15 Because CD4+ counts are not a direct measure of immune function, opportunistic infections, such as OMHs, may be a more accurate reflection of HIV disease status. A disconnect between opportunistic infections and CD4+
counts could also be explained by a paradoxical transient deterioration of immune function during initial response to HIV medication, referred to as the immune reconstitu- tion syndrome.16
Although the treatment of specific OMHs has been ef- fective,6 it is evident that the most successful treatment is to prevent or reverse the underlying primary immunodefi- ciency disease.17 Accordingly, the introduction of HAART is associated with a significant decrease in the prevalence of opportunistic diseases including OMHs. For example, HAART is associated with a significant decrease in the prevalence of oral candidiasis and oral hairy leukoplakia coupled with an improved CD4 count.18
Seemingly in contradiction with those findings, an increased prevalence of oral warts has been noted by some investigators despite a marked improvement in CD4cell count.19 This observation may not reflect true increased prevalence in the population. However, because of the link between HPV and cancer, it suggests that, with increased life expectancy of HIV-infected patients, oral cancer may become a clinically significant long-term complication.
The prevalence of OMHs is declining in populations in industrialized countries with the introduction of better HIV therapies. However, an increase in salivary gland disease, xerostomia and oral warts has been seen.20 This should be of utmost interest to the dental profession be- cause saliva is an essential contributor to oral health.
Xerostomia in HIV patients, either triggered by HIV dis- ease directly or as a side effect of medications, represents an additional risk factor for caries and periodontal disease
as well as OMHs, especially oral candidiasis, the most commonly diagnosed OMH.
Finally, in addition to poor response or adherence to HIV treatment, low CD4 counts or high HIV load, to- bacco use is confirmed as a risk factor for OMHs.21–23 Furthermore, the effect of tobacco use in addition to in- creased HPV disease may result in a dramatic increase in the incidence of oral cancer in HIV patients.
Taken together, the epidemiology of OMHs in the post- HAART era indicates that OMHs are less frequent, but new and poorly understood paradigms are emerging. Those paradigms include a possible upsurge in the prevalence of oral warts and the possibility that, with time, CD4+ T-cell counts and the prevalence of OMHs may not correlate.
The practical significance of those 2 emerging paradigms is that oral health care providers have to continue to be vigilant in their examination and treatment of their HIV- infected patients. To deliver an optimal level of care, oral health clinicians should emphasize the early detection of oral cancer. They should remain vigilant in the diagnosis of OMHs traditionally associated with low CD4+ counts (i.e., Kaposi’s sarcoma) even in patients with high CD4+
counts. In addition, clinicians must address the complica- tions of hyposalivation and must offer an effective tobacco smoking cessation program either by referral or by the oral health care provider directly. a
THE AUTHORS
Dr. Sroussi is assistant professor and director of oral medi- cine, department of oral medicine and diagnostic sciences and Chicago Cancer Center, University of Illinois at Chicago, Chicago, Illinois.
Dr. Epstein is professor and head, department of oral medi- cine and diagnostic sciences, College of Dentistry, and dir- ector, interdisciplinary program in oral cancer, College of Medicine, Chicago Cancer Center, University of Illinois at Chicago, Chicago, Illinois.
Figure 2: Hairy leukoplakia, a condition associated with Epstein-Barr virus, presents as a painless corrugated lesion on the right lateral tongue.
Figure 3: Multiple and recalcitrant oral warts presenting as sessile and pedunculated lumps on the lower lip.
Figure 1: Pseudomembranous candi- diasis on the hard and soft palate presents as white removable plaque.
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Clinical
p r a c t i c ECorrespondence to: Dr. Joel Epstein, UIC College of Dentistry, Oral Medicine, MC-838, 801 South Paulina St., Chicago, IL 60091, USA.
The authors have no declared financial interests.
This article has been peer reviewed.
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