Diagnosis and Management of Soft-Tissue Lesions
Free Online CME: HIV and Oral Health Care
Updated December 2001
I. INTRODUCTION
General Recommendations:
Oral lesions in patients infected with HIV should be evaluated and diagnosed in the same manner as lesions in all other dental patients.
An unexplained lesion that does not resolve following appropriate clinical management or empiric therapy warrants consideration of a biopsy and histologic examination of the tissue. If the decision is made not to obtain a biopsy, the reason for the decision should be documented.
As with any procedure, the risks involved in performing a biopsy should be weighed against the benefits. Patients with HIV infection may be at an increased risk for post-operative bleeding.6 Prior to biopsy procedures, the need for obtaining the patient’s platelet count, prothrombin time and/or international normalized ratio (INR), activated partial thromboplastin time, and bleeding time should be evaluated.
The need for patient referral to a dental or medical specialist for management of oral lesions or for assessment or management of underlying systemic disease should be individualized.
The patient’s primary care provider should be informed of the results of diagnostic procedures for all lesions as well as medications prescribed or any change in medications. Management of a patient with HIV infection often requires a multidisciplinary approach coordinated by the patient’s primary care provider or case manager.
Any patient not known to be HIV infected should be referred for HIV counseling and testing when he/she presents with an oral lesion that is associated with an immunodeficient status or a sexually transmitted disease and when the presence of the lesion cannot be explained by a confirmed underlying condition or by a medication.
In the era of antiretroviral (ARV) therapy, the incidence of oral lesions has decreased1; however, it remains important that oral health care providers recognize that certain oral lesions can be an early manifestation of HIV-associated immune deficiency or a clinical marker of disease progression in a patient known to be HIV infected. Studies have consistently shown that certain oral lesions are associated with decreased CD4 lymphocyte counts. Recent studies have also shown a relationship between the presence of some oral lesions and higher HIV viral load.2-5
Oral manifestations of HIV infection include candidiasis, hairy leukoplakia, Kaposi’s sarcoma, and several different types of oral ulcers, such as atypical herpes simplex ulceration, major aphthous-like ulcers, cytomegalovirus (CMV)-related oral ulceration, and ulcers caused by other conditions (e.g., histoplasmosis and lymphoma). HIV-associated mucosal melanin pigmentation, human papillomavirus (HPV) infection, and salivary gland lesions have been described, as have gingival and periodontal disease. Further discussion of gingival and periodontal disease in patients with HIV infection is included in Chapter 3: Clinical Manifestations and Management of HIV-Related Periodontal Disease. Because presentation of the lesions described in this chapter can be an early manifestation of HIV, a patient with such lesions should be referred for HIV counseling and testing and, if necessary, for medical care.
II. ORAL LESIONS
A. Oral Candidiasis
Oral candidiasis is caused by one of the Candida species, usually Candida albicans, a normal inhabitant of the oral cavity in many healthy individuals. In individuals infected with HIV, the development of oral candidiasis may be an indication of immune deterioration and has prognostic significance for the development of AIDS. Oral candidiasis may precede other signs of immune deficiency and is one of the clinical indicators for initiating and continuing prophylaxis for Pneumocystis carinii pneumonia (PCP).7,8
1. Diagnosis
Recommendation:
Diagnosis of oral candidiasis should be made by identification of clinically distinctive lesions, by microscopic examination of cytologic smears or biopsy tissue, or by response to antifungal therapy.
Oral candidiasis is the most prevalent oral lesion associated with HIV/AIDS. The following forms of oral candidiasis have been frequently associated with HIV infection: pseudomembranous, erythematous, and angular cheilitis. Chronic hyperplastic type has been described, but this finding is rare. The clinical appearance of each form is different, as are the criteria for diagnosis.
- Pseudomembranous type (thrush) is generally diagnosed on the basis of its characteristic clinical appearance: white curd-like material that may be easily wiped off and, when removed, reveals an erythematous mucosa. Examination of a cytologic smear of the pseudomembrane revealing hyphal forms confirms the diagnosis. This procedure may not be necessary if the lesions are clinically consistent with oral candidiasis and resolve with antifungal therapy (see Appendix 2-A for photographic example).
- Erythematous type presents as flat, clinically red, sometimes painful macules that may first appear on the soft palate and oropharynx. This type of candidiasis can appear as areas of mucosal erythema or on the dorsal tongue as irregular, depapillated, erythematous, sometimes painful areas. It may occur independently of or simultaneously with pseudomembranous candidiasis. Erythematous candidiasis is less well recognized than the pseudomembranous type, and its clinical appearance is not specific to candidiasis. Therefore, the identification of hyphal forms on a mucosal smear or biopsy and/or response to antifungal therapy is important for confirmation of this diagnosis (see Appendix 2-A for photographic example).
- Angular cheilitis is diagnosed on the basis of its clinical appearance. It appears as erythema or fissures of the labial commissures and frequently accompanies intra-oral candidiasis. In patients with deeply pigmented skin, depigmentation may occur at the site of angular cheilitis. Cytologic smears of angular cheilitis are often negative for fungal hyphae. Angular cheilitis is quite common among dental patients, regardless of HIV status. It has been associated with certain anemias and nutritional deficiencies as well as decreased vertical dimension of occlusion. Observation of the response of the lesions to antifungal therapy is important in confirming the role of Candida in the etiology of this lesion (see Appendix 2-A for photographic example).
2. Treatment
Recommendations:
Topical and systemic medications outlined in this section should be used to treat HIV-associated candidiasis (see Tables 2-1 through 2-4).
Because significant interactions between systemic antifungal medications and ARV agents occur, the primary care provider and/or pharmacist should be consulted before prescribing these medications concurrently. Any change of medications should be discussed with the patient’s health care provider.
Patients should be instructed in proper oral hygiene to prevent caries that may result from the high sugar content in nystatin and clotrimazole. The use of topical fluoride therapy should be considered for patients taking such medication.
When oropharyngeal candidiasis cannot be controlled with topical medication alone, systemic therapy should be initiated. It may be necessary to continue topical medication use in addition to systemic medication use to control oral candidiasis.
A typical antifungal treatment course is 10 to 14 days, with use of the antifungal agent continued even after clinical signs and symptoms of oral candidiasis have been resolved.
Because patients with reduced salivary flow are more susceptible to oral candidiasis, salivary flow should be stimulated to help reduce the incidence and severity of oral candidiasis. Chewing sugarless gum or dissolving sugarless lozenges in the mouth can accomplish salivary flow stimulation.
| Table 2-1: Topical Medications for Oral Candidiasis | |||||||||||||||
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| * Adherence to this regimen is often poor because of the time requirement.
† Used for the treatment of oral candidiasis refractory to nystatin and imidazole preparations. ‡ Although this preparation is not designed for oral use, clinicians have found it useful for treatment of oral candidiasis when the sugar content of other topical anticandidal medications is a concern. The prescription can be written as “nystatin vag. tabs.” A sugarless, flavored lozenge may be dissolved simultaneously in the mouth to mask the taste of nystatin. Adherence with this regimen is often poor because of the time requirement. |
| Table 2-2: Topical Medications for Angular Cheilitis | |||||||||
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| * For the treatment of angular cheilitis, some clinicians have found combination creams more effective than antifungal medications alone. These include combination preparations of topical hydrocortisone, antifungal agents, and hydrocortisone-iodoquinol cream, which combines an antifungal-antibacterial medication with an anti-inflammatory antipruritic. |
| Table 2-3: Systemic Antifungal Medications | ||||||
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| * Because these medications are easier for patients to use than topical preparations, adherence often improves. |
| Table 2-4: Special Considerations for Systemic Antifungal Medications | ||||||||||||||
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3. Prophylaxis of Recurrent Oropharyngeal Candidiasis
Many experts do not recommend routine chronic prophylaxis to prevent recurrent oropharyngeal candidiasis. However, if recurrences are frequent or severe, intermittent or chronic administration of fluconazole, ketoconazole, or itraconazole may be considered. Frequent recurrences of oropharyngeal candidiasis may be a marker of HIV disease progression.
B. Hairy Leukoplakia
1. Presentation
Hairy leukoplakia most commonly presents as a white, ragged, corrugated, or irregular lesion involving the lateral and dorsolateral tongue. Lesions may be unilateral or bilateral. Hairy leukoplakia involving other mucosal surfaces also has been reported. Hairy leukoplakia is caused by infection of the lesional epithelial cells with Epstein-Barr virus (EBV) and is associated with immune deterioration (see Appendix 2-A for photographic example).
2. Diagnosis
Recommendations:
Diagnosis of oral hairy leukoplakia in patients known to be HIV infected should be confirmed by identification of distinct clinical lesions. If the lesions are clinically consistent with hairy leukoplakia and the patient is known to be HIV infected, no further diagnostic procedure is necessary.
As in all patients, when an HIV-infected patient presents with a white lesion on the lateral border of the tongue, which cannot be diagnosed on the basis of its clinical appearance, biopsy and microscopic examination should be considered.
Histologically, hairy leukoplakia exhibits hyperparakeratosis, often with hair-like projections, epithelial hyperplasia, vacuolated epithelial cells (koilocyte-like), and little or no inflammatory infiltrate in the underlying connective tissue. Changes have been reported in the nuclei of epithelial cells infected with EBV, which can be seen by light microscopic examination. Hybridization techniques also have been used to identify EBV in biopsy specimens. When a patient’s HIV status is unknown, a biopsy and identification of EBV in the epithelial cells of the lesion may be considered before recommending HIV testing.
3. Treatment
Recommendation:
Hairy leukoplakia generally does not require treatment.
For some patients, hairy leukoplakia lesions may be cosmetically objectionable. Hairy leukoplakia has been treated successfully with systemic acyclovir, although it usually recurs when treatment is discontinued. Hairy leukoplakia also has been reported to resolve with zidovudine, podophyllin, and interferon. Regardless of treatment, the lesions may spontaneously resolve and recur.
C. Oral Ulcers
The most commonly reported oral ulcers seen in patients with HIV are herpes simplex ulcers and aphthous ulcers. Oral ulcers also may develop due to other opportunistic diseases, including CMV infection, histoplasmosis, herpes zoster, and lymphoma. Ulcers associated with zalcitabine (dideoxycytidine or ddC) and foscarnet also have been noted. With accurate diagnosis and appropriate treatment, most oral ulcers resolve in a short time.
1. Evaluation and General Management
Recommendations:
Diagnosis of oral ulcers should be based on characteristic clinical appearance; the results of cytologic smear, viral culture (isolation), and biopsy and microscopic examination; or response to therapy (see Figure 2-1).
If an ulcer does not respond to treatment within 2 weeks, a biopsy and histologic examination should be performed.
If the decision is made not to obtain a biopsy of an ulcer that is non-responsive to treatment, the provider should document the reason for the decision.
2. Herpes Simplex Ulcers
In immunocompetent patients, oral ulcers caused by the herpes simplex virus (HSV) occur in primary infection form (primary herpetic gingivostomatitis) and recurrent forms (herpes labialis and recurrent intra-oral herpes simplex ulceration). The primary infection most commonly occurs in children but also may occur in adults. Recurrent ulcers occur due to reactivation of latent infection.
a. Presentation
Herpes labialis appears as a crop of vesicles that coalesce and form an irregular ulcer on the vermilion of the lips or peri-oral skin. Intra-oral recurrent herpes simplex infection presents as a localized crop of vesicles that characteristically form only on keratinized mucosa. In immunocompetent individuals, these ulcers follow a predictable course and usually resolve spontaneously in 7 to 10 days.
In patients with HIV infection who have marked immune deficiency, ulcers caused by herpes simplex infection tend to be persistent, superficial (infecting the epithelium and not connective tissue), and painful. In HIV-infected patients, persistent herpetic lesions that do not resolve after 4 weeks fulfill the Centers for Disease Control and Prevention (CDC) criteria for a diagnosis of AIDS.9 These ulcers do not have a characteristic clinical appearance and may appear to be similar to ulcers caused by other agents or circumstances. These ulcers differ from herpes simplex ulceration in immunocompetent individuals in that they are larger, can occur anywhere in the oral cavity, present for longer periods, and are non-responsive to routine therapy (see Appendix 2-A for photographic example). Atypical herpetic ulcers may be the first sign of immunosuppression and may signal a need for HIV counseling and testing in patients no known to be HIV infected.
| Figure 2-1: Diagnosis and Treatment of Mucosal Ulcers | |
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| * Possible diagnoses and treatments: Atypical herpes simplex ulceration (see Table 2-5); major aphthous-like ulcer (see Table 2-6); cytomegalovirus ulceration; ulceration due to other infectious agents; lymphoma (refer to an HIV Specialist for treatment recommendations). |
b. Diagnosis
Recommendations:
Diagnosis of typical recurrent herpes simplex ulceration should be made by recognizing the typical clinical appearance on the labial vermilion border or intra-orally on keratinized mucosa attached to bone.
Viral culture, mucosal smear, biopsy, and response to acyclovir are recommended options to accurately diagnose HSV-associated ulcers.
As atypical herpetic ulcers may be the first sign of immunosuppression, patients with these ulcers who are not known to be HIV infected should be referred for HIV counseling and testing.
c. Treatment
Recommendation:
While awaiting confirmation of the diagnosis, oral health care providers should consider initiation of systemic acyclovir treatment if atypical HSV ulceration is suspected (see Table 2-5). Response to this medication may be helpful in confirming the diagnosis.
| Table 2-5: Treatment Regimen for Atypical HSV | ||||||
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| * Valacyclovir is the prodrug of acyclovir and is commonly used.
† Acyclovir-resistant herpes simplex ulcerations should be considered when ulcers with a confirmed diagnosis of HSV infection do not respond to acyclovir. Treatment with foscarnet is recommended for such lesions. |
3. Aphthous Ulcers
a. Diagnosis
Recommendation:
Diagnosis of aphthous ulcers should be based on the characteristic clinical appearance of painful, round-to-oval, yellow-white ulcers surrounded by a halo of erythema (see Figure 2-1). For all ulcers not exhibiting these characteristic clinical features or when empiric therapy has failed, viral culture (isolation), mucosal smear, or biopsy may be necessary to rule out ulcers caused by opportunistic infections.
Increased frequency and severity of episodes of typical minor aphthous ulcers have been reported in patients with HIV. Major aphthous-like ulcers, also called ulcerative stomatitis, present as persistent, deep, crater-like lesions that extend through the epithelium into the connective tissues.
Although much less common, the herpetiform type of aphthous stomatitis also has been reported in patients with HIV. As in non–HIV-infected patients, these ulcers generally occur on non-keratinized oral mucosa but can present in any location (see Appendix 2-A for photographic example).
b. Treatment
Recommendation:
The management of aphthous ulcers should include the use of topical corticosteroids; however, the provider should be aware that steroid use may result in candidal overgrowth.
The agents listed in Table 2-6 are used to treat aphthous ulcers.
Some clinicians have found systemic corticosteroids useful for the treatment of ulcers not easily accessible for application of topical medications or for patients not able to adhere to topical regimens; however, systemic corticosteroids are usually not necessary in the treatment of localized oral aphthous ulcerations.
Thalidomide has been shown to be effective for the treatment of non-resolving aphthous ulcers in HIV-infected patients10; however, there are serious documented teratogenic effects associated with thalidomide in pregnant women. Because of these severe side effects, thalidomide should only be used when all other options have been exhausted. In adolescent and adult women capable of bearing children, thalidomide should only be used when the woman is known not to be pregnant and is using effective methods of birth control.
| Table 2-6: Treatment of Aphthous Ulcers | |||||||||||||||
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| * Used for multiple ulcers or ulcers not easily accessible for topical application. |
4. Cytomegalovirus Oral Ulceration
CMV is a herpes-type virus. Serologic evidence of a history of CMV infection is present in up to 80% of HIV-infected adults studied. Cases of CMV-related oral ulceration have been reported in patients with HIV infection. The presence of CMV suggests immunosuppression.
a. Presentation
Oral ulcers due to CMV may occur anywhere in the oral cavity; characteristic clinical features have not been identified.
b. Diagnosis
Recommendation:
Diagnosis of an oral ulcer due to CMV should be established by biopsy and histologic examination.
Cells exhibiting characteristic intranuclear and intracytoplasmic inclusions are seen on microscopic examination.
c. Treatment
Recommendation:
Patients with a diagnosis of CMV oral ulceration should be referred to a physician for further evaluation and treatment.
5. Other Ulcers
a. Diagnosis
Recommendation:
Diagnosis of oral ulceration due to other infectious agents, such as Histoplasma capsulatum (histoplasmosis), Cryptococcus neoformans (cryptococcosis), and Aspergillus organisms, should be made by biopsy and histologic examination.
Oral lesions due to these organisms are signs of disseminated disease. Once a diagnosis has been made, the patient should be referred to a physician for evaluation and treatment.
b. Treatment
Recommendation:
Treatment should be based on identification of the causative organism.
D. Kaposi’s Sarcoma
Kaposi’s sarcoma has been the most common malignant tumor associated with HIV infection. Since the introduction of ARV agents, the occurrence seems to be rare. Herpes virus (HHV-8) has been implicated in the etiology of Kaposi’s sarcoma. Kaposi’s sarcoma oral lesions may interfere with function, be cosmetically objectionable, and proliferate uncontrollably.
1. Presentation
The palate is by far the most commonly affected oral site, followed by the maxillary gingiva. The lesions are often multifocal and usually present as flat purple plaques or raised nodules (see Appendix 2-A for photographic example).
2. Diagnosis
Recommendation:
The diagnosis of Kaposi’s sarcoma should be confirmed by either biopsy or identification of distinct clinical appearance.
Clinical appearance may be sufficient to diagnose Kaposi’s sarcoma, especially if the patient has a previous biopsy-confirmed diagnosis of Kaposi’s sarcoma at another site.
3. Treatment
There is no consistently effective management for Kaposi’s sarcoma. Systemic chemotherapy is used, and intralesional injections of vincristine, vinblastine, or interferon-alpha have been used with some success. Intralesional injections with sodium tetradecyl sulfate, a sclerosing solution, also have been effective. Radiation therapy has been successful for treatment of oral Kaposi’s sarcoma lesions. Surgical excision of a portion of the lesion may be helpful to allow restoration of teeth or to prevent interference with function. Patients who are successfully treated with ARV medications usually experience remission of Kaposi’s sarcoma lesions. Kaposi’s sarcoma should be treated in conjunction with the primary care provider.
E. Lymphoma
Lymphoma is a common malignancy occurring in patients with HIV. Most AIDS patients with lymphoma develop lesions in sites other than the lymph nodes. Most AIDS-related lymphomas are of B-lymphocyte origin, and EBV has been found in the lesions. The development of lymphoma in a patient with HIV is an AIDS-defining event.
1. Presentation
The clinical appearance of oral lymphoma varies from irregular, necrotic, ulcerated masses to non-ulcerated masses covered by normal or erythematous mucosa. The lesions may be painful.
2. Diagnosis
Recommendation:
Diagnosis of oral mucosal lymphoma should be made by biopsy and histologic examination.
3. Treatment
Recommendation:
Patients with a diagnosis of oral lymphoma should be referred to a physician for further evaluation and treatment.
F. Salivary Gland Disease Associated With HIV Infection
Recommendation:
For patients with xerostomia, additional measures should be employed to prevent dental caries and periodontal disease. Such measures include topical fluoride therapy, chlorhexidine oral rinse, decreased sugar consumption, and meticulous oral hygiene. The use of saliva substitutes should also be considered.
Xerostomia has been associated with HIV infection.12 Although its prevalence and cause are not clear, xerostomia may be due to medications or to HIV-related salivary gland disease. The presence of xerostomia increases the risk of the development of dental caries and periodontal disease. Bilateral parotid gland enlargement can occur in both children and adults who are HIV positive, but the clinical significance is unclear.13 In some patients, a complex similar to Sjögren’s syndrome has been described, and the histologic appearance of cystic benign lymphoepithelial lesions has been reported.
G. Human Papillomavirus Infection
1. Presentation
Lesions caused by human papillomavirus (HPV) present as papillary lesions that may be of normal mucosal color, slightly erythematous, or hyperkeratotic. In patients with HIV, these lesions may be florid with numerous small papillomas, or they may present with fewer and larger papillary projections.
2. Diagnosis
Recommendation:
Diagnosis of HPV lesions should be made by routine biopsy and histologic examination.
Immunofluorescence or immunoperoxidase staining for papillomavirus can be performed to determine the strain of HPV infecting the tissue.
3. Treatment
Surgical excision of the lesions is the most widely used treatment for oral papillomas; however, recurrence of HPV lesions is common. Some clinicians believe that cauterization of the base of the lesion following excision helps minimize reinfection from the surgical site. Intralesional interferon and topical application of podophyllin are other approaches to treatment of these lesions.
H. Mucosal Melanin Pigmentation
1. Presentation
Mucosal melanin pigmentation occurs as newly emerging single or multiple oral mucosal melanotic (brown) macules. These macules are attributed to an increase in the amount of melanin pigment in the basal cell layer of the epithelium and the underlying connective tissue. The prevalence of this condition has not been determined. Melanin pigmentation has been associated with zidovudine therapy in some patients.
2. Diagnosis
Recommendation:
For newly emerging or changing mucosal pigmented lesions, biopsy and histologic examination should be considered. However, most of these lesions can be presumptively diagnosed by appearance and observation over time.
3. Treatment
There is no treatment for mucosal melanin pigmentation at this time.
REFERENCES
1. Ceballos-Salobrena A, Gaitan-Cepeda LA, Ceballos-Garcia L, Lezama-Del Valle D. Oral lesions in HIV/AIDS patients undergoing highly active antiretroviral treatment including protease inhibitors: A new face of oral AIDS? AIDS Patient Care STDS 2000;14:627-635.
2. Patton LL. Sensitivity, specificity, and positive predictive value of oral opportunistic infections in adults with HIV/AIDS as markers of immune suppression and viral burden. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:182-188.
3. Margiotta V, Campisi G, Mancuso S, Accurso V, Abbadessa V. HIV infection: Oral lesions, CD4+ cell count and viral load in an Italian study population. J Oral Pathol Med 1999;28:173-177.
4. Patton LL, McKaig RG, Eron JJ Jr, Lawrence HP, Strauss RP. Oral hairy leukoplakia and oral candidiasis as predictors of HIV viral load. AIDS 1999;13:2174-2176.
5. Greenspan D, Komaroff E, Redford M, Phelan JA, Navazesh M, Alves ME, et al. Oral mucosal lesions and HIV viral load in the Women’s Interagency HIV Study (WIHS). J Acquir Immune Defic Syndr 2000;25:44-50.
6. Patton LL. Hematologic abnormalities among HIV-infected patients: Associations of significance for dentistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:561-567.
7. Centers for Disease Control and Prevention. 1997 USPHS/ISDA guidelines for the prevention of opportunistic infections in persons infected with the human immunodeficiency virus. MMWR Morb Mortal Wkly Rep 1997;46(RR-12):19.
8. Kaplan JE, Hanson DL, Navin TR, Jones JK. Risk factors for primary Pneumocystis carinii pneumonia in human immunodeficiency virus-infected adolescents and adults in the United States: Reassessment of indications for chemoprophylaxis. J Infect Dis 1998;178:1126-1132.
9. Centers for Disease Control and Prevention. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep 1992;41(RR-17):1-19.
10. Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. N Engl J Med 1997;336:1487-1493.
11. Lozada-Nur F, Miranda C, Maliksi R. Double-blind clinical trial of 0.05% clobetasol propionate in orabase and 0.05% fluocinonide ointment in orabase in the treatment of patients with oral vesiculoerosive disease. Oral Surg Oral Med Oral Pathol 1994;77:598-604.
12. Navazesh M, Mulligan R, Komaroff E, Redford M, Greenspan D, Phelan J. The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV-positive and at-risk women. J Dent Res 2000;79:1502-1507.
13. Mulligan R, Navazesh M, Komaroff E, Greenspan D, Redford M, Alves M, et al. Salivary gland disease in human immunodeficiency virus-positive women from the WIHS study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89:702-709.
FURTHER READING
American Dental Association and American Academy of Oral Medicine. Dental management of the HIV-infected patient. J Am Dent Assoc 1995;(Suppl):34-39.
Greenspan JS, Greenspan D, eds. Oral Manifestations of HIV Infection. Chicago, IL: Quintessence Publishing Co, Inc; 1995.
Greenspan JS, Barr CE, Sciubba JJ, Winkler JR, for the USA Oral AIDS Collaborative Group. Oral manifestations of HIV infection: Definitions, diagnostic criteria and principles of therapy. Oral Surg Oral Med Oral Pathol 1992;73:142-144.
APPENDIX 2-A
ILLUSTRATIONS OF ORAL LESIONS ASSOCIATED WITH HIV-INFECTION
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