Oral manifestations in HIV-infected patients: Diagnosis and management

Clinical review Oral manifestations in HIV-infected patients: Diagnosis and management Peter H. !tin, MD, Stephan Lautenschlager, MD, Ruedi Fluckiger, MD, and Theo Rutli, MD Basel, Switzerland Oral lesions have been observed since the beginning of the AIDS epidemic. The number of HIV-infected patientsis stillincreasing, especially in the heterosexual population. Oral diseases in HIV-infected patients are often more difficult to diagnose becausethe clinicalpresentations may differ from the samediseases in HIV-negative patients. HIV-associatedoral lesions havediagnostic, prognostic, and therapeutic impact. Approximately 10% of the HIVinfected population willhave oral manifestations as a first sign of their disease. In HIY-infected men oral hairy leukoplakia and oral candidiasis are useful markers for disease progression. This article summarizes the oral manifestations and the management of oral health in persons with HIV infection. (J AM ACAD DERMATOL 1993;29:749-60.)

The AIDSepidemic continues to growworldwide at an alarming rate. I Oral lesions are common signs of symptomatic infection withHIV and suspicion of HIV infection may be based exclusively on oral lesions. 2- 10 The rapid spread of the HIV epidemic makes an understanding of the signs and symptoms associated with AIDS important.I I The oral cavity is a typical site of involvement, although only few reviews on oral manifestations in HIV-infected patients have appeared in the dermatologic literature. 3, 4, 9, 12-14 It has been calculated in cumulative incidence studies that between 20% and 50% of HIV-infected patientshavean oral lesion during the diseaseprocess. 15 In a recentstudyit wasshown that suspicion ofHIV infection was basedentirely onoral changes in 10% of a study population of 160 patients," Prevalence seems to vary in the different risk groups studied," Barr et al.16 found in a well-designed studythat 36% of the 102 HIV-infected patients studied had oral lesions. In contrast, noneof the control population had oral lesions. Melnick et al. 17 found that in a group of homosexual men the likelihood of having serum antibodies against HIV was 5.7timeshigher if oneor more orallesions were found. Thirty percent of their HIV-infected homosexualpatients hadoneor moreorallesions. Laskaris

et al.7 documented oneor more oral manifestations in 90.6% of their HIV-infected study population. Moniaci et a1. 18 found HIV-related oral manifestations in 40.3% of 737 HIV-infected patients. The authors statedthat HIV-related oral manifestations were more prevalent in male homosexual patients than in the other risk groups. Nonspecific oral immunity in persons with HIV infection isreduced. Host defensemechanisms may be altered in the early course of HIV infection. In addition to the depletion of CD4 lymphocytes, a combined deficiency ofparotid lactoferrinand secretory IgA may contribute to the frequent oral infections.l" 20 Stomatologic manifestations, such as oral hairyleukoplakia (OHL) or candidiasis may be the initial clinical signs and may predict progression of the disease." It is now well documented that OHL and candidiasis are correlated with helper Tvlymphocyte depletion. 18,21-23 Oral manifestations of HIV infection may be classified asfungal, bacterial,andviralinfections, as well as neoplastic lesions and miscellaneous disorders, although more comprehensive categories exist. 24-30 In a recent study prevalence for these categories in 160 HIV-infected patients was 60.6% for fungal infections, 36.9% for bacterial infections, 32.5% forviralinfections, and 14.4% for neoplasms."

From the Department of Dermatology, University of Basel. Reprint requests: Peter H. Itin, Dermatologische Universitdtsklinik Basel,Petersgraben 4, 4031 Basel, Switzerland. Copyright O 1993 by the American Academy of Dermatology, Inc.

ORAL CANDIDIASIS

0190-9622/93 $1.00 +.10

16/1/47997

Severalclinical variants of oral candidiasis exist, such as thrush (pseudomembranous candidiasis), erythematous (atrophic) type, hyperplastic type,

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Fig. 1. Pseudomembranous candidiasis. Fig. 2. Erythematous (atrophic) variant of candidiasis together with pseudomembranous type.

median rhomboid glossitis, and angular cheilitis. Oral candidiasis classifies as AIDS group IV C2.31 The same patient may initially have several variants of candidiasis. Progression to AIDS is increased in patients with oral candidiasis compared with HIVinfected men with normal findings .P' This is true for all variants of cand idiasis including pseudomembranous and erythematous types. 16, 32 In a pediatric HIV-infected population, the median time from oral fungal manifestation to death was 3.4 years, compared with 5,4 years for pediatric patients with parotid enlargement. 33 It has been reported recently that recurrent oral candidiasis is often caused by a single strain unique to each patient. 34 Defective salivary antifungal activity may contribute to the oral candidiasis seen in patients with AIDS.35 Muller et aL36 found low levels of parotid calprotectin in HIV-infected patients with oral candidiasis. Xerostomia was an independent and statistically significant predictor of HIV-related oral candidiasis.3?, 38 In HIV-infected patients candidiasis appears in multiple sites and on large areas of oral mucosa. Candida albicans is most common , although other types such as Candida glabrata, Candida parapsilosis, and Candida tropicalis may be isolated in special cases.39,40 N ca-albicans strains may have reduced susceptibility to azole antifungals. Thrush or pseudomembranous candidiasis is the

most obvious type, characterized by yellow-white plaques that are removable by scraping, leaving a red and slightly bleeding surface (Fig. I). This type most often affectsthe tongue, although every area of the oral mucosa may be affected. Erythematous candidiasis shows red macular patches on mucosal surfaces. Occurrence on the dorsal aspect of the tongue corresponds to the atrophic variant associated with depapillation or the median rhomboid glossitis (Fig. 2). Because the redness of the mucosa may be caused by increased vascularity with or without atrophy of the epithelium, the term erythematous candidiasis is now preferred to atrophic cendidiasis.I? Before the AIDS epidemic erythematous candidiasis was rarely observed. Increasing evidence shows that erythematous candidiasis is the most common variety in HIV-infected patients. It seems that the erythematous type of candidiasis does precede the pseudomembranous type.39 Hyperplastic oral candidiasis occurs often on the buccal mucosa and has white plaques that are unremovable by scraping. Differential diagnosis between OHL and erythematous candidiasis may be difficult. Angular cheilitis in candidiasis is characterized by fissures and ulceration at the corners of the mouth. Before the AIDS epidemic angular cheilitis was most commonly seen in elderly persons, and the disease was

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relatively uncommon in younger people. Angular cheilitis and hyperplastic candidiasis are the least common variants. A review of 23 surveys suggests that oral candidiasis develops in 30% to 50% of HIV-infected patients, although variable data are available." Phelan et a1. 2 reported that 94 of 103 patients with AIDS had oral candidiasis. Candidiasiswas found in 62 of 103 Zairian patients with HIV infection.v' Laskaris et al.? found candidiasis in 60.6% of their study population. There is some evidence that candidiasis may enhance immunosuppression and oral candidiasis may predict the development of serious opportunistic infections.21, 42, 43 Management of oral candidiasis may be performed topically with polyenes (nystatin, amphotericin) or imidazoles, although HIV-infected patients respond only partially and relapses are common. For these reasons systemic antifungal agents have been proposed for HIV-related oral candidiasis. Ketoconazole is recommended in a daily dosage of 200 mg, although doses up to 400 mg have been administered.t" Treatment failures occurred because ofdrug malabsorption and ketoconazole-resistant strains of C. albicans. Fluconazole and itraconazole are watersoluble systemic antifungals with reliable absorption, fewer drug interactions than under ketoconazole, and mild toxicity. Fluconazole has proved to be more effective than ketoconazole in the treatment of oral candidiasis in patients with HIV infection." Fluconazole is administered 50 mg a day or as a single dose, 150 mg. AlSO mg dosage once a week may be effective as prophylaxis after treatment of acute candidiasis. Itraconazole, 100 mg orally once daily, is another effective choice, although it might be slightly less effective than fluconazole for oral candidiasis (Table I) . Unusual fungal infections of the mouth have been observed in the HIV-positivepopulation. Geotrichosis , cryptococcosis, and histoplasmosis are such examples. 46-51 Simultaneous oral infection with herpes simplex virus, cytomegalovirus, and histoplasmosis has been reported recently. 52 HIV-ASSOCIATED GINGIVITIS AND PERIODONTITIS

Prevalence of HIV-associated gingivitis and conventional periodontal disease is high, according to the report of Masouredis et al. 53 HIV-associated gingivitis was found in 42 of L36 patients. HIV-associated gingivitis features a diffuse or punctate erythematous gingival band, often extending from marginal gingiva to alveolar mucosa. 53-55 Gingivitis

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Table I. Management of oral lesions in patients with HIV infection Lesions

Drug anddosage

Oral

Amphotericin, topical (3 x/day, 2 wk) Nystatin, topical (3 X/day, 2 wk) Miconazole, topical (3 X/day, 2 wk) Fluconazole (50 mg/day, for 2 wk; 150 mg/wk for prophylaxis) Ketoconazole (200-400 trig/day, 2 wk) Itraconazole (100 mg/day, 2 wk) Acyclovir (200-400 mg orally Herpes 5 X/day for 10-14 days, or simplex intravenously 5-10 mg/kg virus 3 X/day) Acyclovir (800 mg orally Herpes zoster 5 X/day for 10-14 days, or 10 mg/kg intravenously 3 X/day) Cytomegalovirus Ganciclovir (7.5-15 mg/kg/day intravenously for 10-14 days) Erythromycin (500 mg 4X/day, Epithelioid weeks to months) angiomatosis Doxycycline (l00 mg 2X/day, weeks to months) (Cave: J arisch-Herxheimer reaction) candidiasis

often involves all quadrants and bleeding with pain is often noted. In a recent study by Laskaris et a1. 56 necrotizing gingivitis was found in 10.1% of 178 HIV-infected patients, gingivitis in 5.0%, and periodontitis in 18.5%. Rowland et al. lO stated that necrotizing ulcerative gingivitis may be an early sign of HIV infection. Thompson et al. 23 found a significant correlation with necrotizing ulcerative gingivitis and depletion of helper T cells. Riley et a1. 57 did not find unique characteristic changes in periodontitis of patients infected with HIY. Reports about the presence of periodontal diseases in HIV-infected patients have come primarily from institutions where patients had gone for treatment; therefore the study group is often biased and not representative of HIV-infected patients in general. Although prevalence of periodontal disease has ranged from 3% to 69%, Winkler et al.58 did not find a significant increase in periodontal disease among HIV-infected men.

752 Itin et al.

The predominant microflora of sites with HIVassociated gingivitis includes C. albicans, Porphyromonas gingivalis and Bacteroides intermedius, Actinobacillus actinomycetemcomitans, Lactobacillus, Streptococcus sanguis, Staphylococcus epidermidis, Actinomyces, Enterococcus avium and faecalis, Clostridium, Klebsiella, Fusobacterium, and Wolinella recta.55, 59, 60 The etiologic significance of periodontal microorganisms in HIV-related periodontitis is not clear. HIV-associated necrotizing periodontitis produces severe destructive lesions, deep pain, gingival bleeding, and soft tissue necrosis with rapid destruction of the periodontal attachment apparatus appears.55 Winkler and Robertson55 suggest that HIV-associatedperiodontitisis the later evolutionof HIV -associatedgingivitis. The most important points in the treatment are removal of etiologic factors such as dental plaques and calculus. In addition, debridement of the surrounding necrotic tissue is important. Local antimicrobial therapy with cWorhexidine mouth rinseor povidoneiodine rinse and metronidazole 250 mg four times a day for 4 to 5 days is helpful in reducing the pain and promoting rapid healing.v' Loose bone fragments should be removed. Follow-up care and long-term maintenance are important. 55 Postscaling bacteremia in HIV-associated gingivitis was found in 6 of 22 patients and in two fever developed (> 38.5° C) within 24 hours.62 Six of 19 patients with HIV-associated periodontitis had bacteremia and three had fever. 62 No significantdifferencewasfound between the absolute CD4 T-cell counts of nonbacteremic versus bacteremic patients. Routine antibiotic prophylaxiswas believedto be unnecessary because no singlecase of sepsisresulted in the treatment of more than 400 patients with HIV-associated gingivitis or HIV-related periodontitis.61 Patients shouldbe given the appropriate knowledge for achieving successful oral hygiene, and they should be advisedto have periodontal assessment at three monthly intervals.t" Necrotizing stomatitis is characterized by destructive ulcerative and necrotizing processes of the gingiva that extends to mucosal and osseous tissues. Margins are undermined and specific laboratory studies and biopsy specimens are not helpful in identifying etiologic agents. Management is similar to the treatment for HIV -associated gingivitis and periodontitis. EPITHELIOID ANGIOMATOSIS

Epithelioid angiomatosis is a recently reported vascular lesion, probably induced by Rochalimea

Journal of the American Academy of Dermatology November 1993

species. Those cutaneousvascular proliferationsare most often described in HIV-infected patients, althoughcasereports onotherwise immunosuppressed patients exist. Often the lesions are widespread and affectthe oral mucosa.s- 64 The red or duskypapules develop in a short time, affecting especially the face and the upper part of the body. They may progress to dome-shaped nodules. Sometimes crusts and scales may develop. In long-standing lesions of the face pedunculatedtypes may evolve.v' Isolated oral manifestation is rare but has been observed.F Differentialdiagnosis fromKaposi'ssarcoma isdifficult by clinical and histologic methods. Lesionalbacteria can be documentedbysilver stain (Warthin-Starry), and the infection can be treated successfully with antibiotics. The treatment of choiceiserythromycin, 500mg fourtimes a day,or doxycycline, twicea day, for several weeks. 64, 66 VIRAL INFECfIONS

HI V-infected patients often have locallydestructive and persistent herpes simplex infection but rarely generalizedmanifestations.v? Herpes simplex infectionoccursas an intraoral and perioralvariant. Most oral herpes simplex manifestationsin HIV-infected patients are caused by herpes simplextype 1. Prevalence of herpes simplex in HIV-infected patients is about 10%to 20%.2,68 Recurrent intraoral herpes simplex and herpes labialis are seen in patients with HIV infection. Solitary or numerous vesicles appear on the hard palate or gingiva and dorsum of the tongue, which develop painful coalescing erosions and ulcers. The perioral form is characterized by single or multiple vesicles or erosions with crusts. Clinical diagnosis may be confirmed by culture or immunohistochemical methods. Intraoral herpes simplex may be self-limiting but occasionally progresses to a large nonhealingulcer. The treatment of choice is acyclovir, 1000 to 2000 mg a day.69 In resistantcasesfoscarnet may be given70,71 (Table I). Cytomegalovirus is a DNA virus that belongsto the herpesvirus family and has a high prevalencein the general population. In immunocompetent persons, this infection is almost always latent without clinical symptoms. Cytomegalovirus infection in immunocompromised patients is rarely associated with oral lesions, although painful cytomegalovirusassociated ulcers have been reported on lips,tongue, pharynx, and buccal mucosa.72, 73 The oral ulcers have a punched-out appearance without surrounding edema. Clinically apparent cytomegalovirus in-

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Fig. 3. Major aphthous ulcers.

fection puts the patient into the AIDS classification group IV Cl. Cytomegalovirus in intraoral Kaposi's sarcoma has been documented.I" Although the authors discuss the concept that the presence of cytomegalovirus may playa role in the neoplastic transformation of endothelial cells, cytomegalovirus is not believed to be related to the pathogenesis of Kaposi's sarcoma any longer. Diagnosis can be established by light microscopy that reveals granulation tissue with "owl's eye"-like inclusions, in situ hybridization, electron microscopy, and immunohistochemical and cultural procedures.F: 73, 75 , 76 Treatment with acyclovir may be beneficial, although for life-threatening cytomegalovirus infections ganciclovir has to be applied. Ganciclovir is available only for intravenous infusion71 (Table 1). Herpes zoster is provoked by reactivation of the varicella-zoster virus. Varicella-zoster virus reactivation in oral mucosa leads to unilateral erosive eruptions accompanied by severe pain. Oral treatment with acyclovir 5 X 800 mg a day for 10 days should be started promptly. For intravenous therapy 10 rng/kg every 8 hours is recommendedsv " (Table I). Oral manifestations of chickenpox in AIDS have been observed rarely. ORAL PAPILLOMA

Papillary outgrowth of oral mucosa caused by infection with human papillomavirus is not common in HIV-infected patients. Verruca vulgaris, condyloma acuminatum, and focal epithelial hyperplasia are the clinical variants to be observed. Lesions in HIVinfected patients are associated especially with human papillomavirus type 7, although types 13, 18, and 32 have been reported. 27, 77 Management can be successful with cryosurgery, surgical excision, and laser therapy.

APHTHOUS-LIKE ULCERS

Aphthous-like ulcers can be classified by size, duration, and number into minor and major aphthous ulcers as well as herpetiform types." These lesions may first appear during the acute disease state associated with HIV seroconversion. 79, 80 Minor aphthous ulcers are well circumscribed and painful small ulcers measuring 0.2 to 0.5 em. They occur on nonkeratinized mucosal tissue and last for about 1 to 2 weeks. The typical sites of involvement are labial and buccal mucosa and the tongue. Major aphthous ulcers are solitary or multiple and larger than 1 ern. Prevalence of major aphthous-like ulcers is about 1.1%81 (Fig. 3). Duration is often prolonged (2 weeks to months) and they generally heal with scarring.8! They are usually located at the tonsillar area and the tongue. In general, they are painful, and no infectious agent can be recovered either from the minor or from the major type. Herpetiform aphthous ulcers are less than 0.2 em in diameter and may have from five to about 100 small lesions, which may coalesce. They are localized on the soft palate, tonsillar area, buccal mucosa, and tongue. Diagnosis of HIV-associated aphthous ulcers should be considered negative after negative cultures for infectious agents such as herpes simplex virus, Mycobacterium avium-intracellulare, cytomegalovirus, Cryptococcus neoformans, Histoplasma capsulatum, Klebsiella pneumoniae, and Enterobacter cloacae and after ruling out neoplastic processes. 81-84 In addition, oral ulceration should be excluded as an iatrogenic disease (e.g., after chemotherapy or irradiation in HIV infeetion).85 Once the diagnosis of recurrent aphthous ulcers is established, patients should be instructed to begin topical corticoid therapy as soon as new lesions appear.I'' In recalcitrant cases thalidomide seems to have a place in treat-

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754 [tin et al.

Fig. 4. Oral hairy leukoplakia.

ment, but women of childbearing age should not take it because of teratogenic effects, especially phocomelia. 86-89 Doses between 100 and 300 mg daily are recommended.i? HAIRY LEUKOPLAKIA

OHL was first seen in 1981 in young homosexual men in the San Francisco area, often associated with persistent generalized lymphadeaopathy.i'v?' In 1984 Greenspan et al. made a first report on 37 homosexual men with white lesions of the tongue. In 1985 the same authors found Epstein-Barr virusDNA (EBV-DNA) in all of 13 specimens investigated. 92 In 1986 they expanded the risk group for Hl'V-infected patients in whom OHL may develop.93 OHL in an HIV-negative kidney transplant recipient was reported in 1988 for the first time." In 1990 Kratochvil et a1. 95 and Sugihara et a1. 96 reported an elegant method for diagnosis of 0 HL by ultrastructural examination of exfoliative cytologic specimens. By polymerase chain reaction, sequences of EBV-DNA were found in all biopsy specimens from patients with OHL,97 In patients with hairy leukoplakia, viremia was statistically significantly correlated.l'' Prevalence of OHL is variable in different studies. 98 Today it can be concluded that OHL is found in about one fourth of HIV-infected persons.P' OHL classifies as AIDS group IV C2. OHL is a white, corrugated, nonremovable patch, usually occurring on the lateral margins of the tongue (Fig. 4).99 The lesion may appear either unilaterally or bilaterally and may also be present on the ventral surface of the tongue.F" Occasionally the floor of the mouth, soft palate, and tonsilar pillar are involved.lv' Potassium hydroxide (KOH) preparations demonstrated candidal hyphae in half of the

cases. Although the clinical features of OHL are characteristic, they are not diagnostic. In questionable cases the presence of EBV is required for diagnosis. Greenspan et al.' 02 established the relation of OHL to infection with HIV and the risk of developing AIDS. Its presence in HIV-infected persons usually predicts a rapid progression of the disease. 21, 43, 103 However, Lau et al. 104 identified 4 of 35 patients with OHL, who have been observed for more than 36 months and who have not had further signs of AIDS. OHL in children is rare; only four cases have been reported.l- 105, 106 Topical or systemic antifungal agents, local treatment with 0.1 % vitamin A acid twice daily, and systemic acyclovir are effective.90, 107 There was improvement after desciclovir, azidothymidine, and topical therapy with podophyllin resin; surgical excision was effective.IOS-l11 Remission occurs spontaneously in approximately 10.8% of cases.112 HIV SALIVARY GLAND DISEASE

HIV-infected patients may report xerostomia and parotid gland enlargement. Salivary gland disease in HIV-infected patients is associated with high suppressor T-cell counts and lymphocytosis. 113 This subset of HIV-infected patients has the HLA-DR5 antigen phenotype. The natural history shows a favorable prognosis.F': 114 Normal salivary function is essential to maintain oral homeostasis. The function of the salivary glands may be impaired by HIV infection. ll3- 117 Chloride, lysozyme, and peroxidase were significantly higher in HIV-infected patients. 117 Conflicting results among studies on the effect on IgA secretion exist. 19,20,117 Extensive squamous metaplasia with cyst formation seems to be typical. l i S Salivary glands affected by HIV infection are

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Fig. 5. Oral Kaposi's sarcoma.

characterized by enlargement and symptoms of dry mouth. Salivary gland enlargements are much more common in HIV-infected children than in adults.'!" Neoplasms such as Kaposi's sarcoma of the parotid and lymphoma of parotid are unusual. F? The cause of HIV-associated salivary gland disease remains unknown. A viral cause has been suggested, but no evidence of cytomegalovirus, EBV, or HIV in the glands has been found. If Sjogren syndrome-like condition is suspected, measurement of salivary flow rates and labial salivary biopsy are recommended. In addition, examination for keratoconjunctivitis sicca and antinuclear antibodies such as SS-A, SS-B, and rheumatoid factor should be undertaken. I 14 These serologic markers, usually positive in true Sjogren's syndrome, are absent in the HIV-associated cases. Fine-needle biopsy of salivary gland swellingsshould be performed to rule out neoplastic lesions. HIV-associated salivary gland disease gives a typical picture on computed tomography and magnetic resonance imaging. The salivary swellings appear as multicentric cystic lesions. Specific treatment is not yet established. Good oral hygiene, stimulation of salivary flow by sugarless chewing gum, and topical use of fluoride should be maintained. Azidothymidine may produce regression of the symptoms and of parotid swelling. ORAL KAPOSI'S SARCOMA

Kaposi's sarcoma is an endothelial cell multicentric malignant neoplasm. 121 The oral cavity may be the first and only localization of Kaposi's sarcoma. Kaposi's sarcoma in an HIV-infected patient classifies him into AIDS group IV D. The oral manifestation of Kaposi's sarcoma typically appears as red, blue, or purple macules or nodules (Fig. 5). Predi-

lection sites are the hard palate and gingiva, but Kaposi's sarcoma may progress to any mucosal site.121 Ulceration, bleeding, pain and difficulties in mastication, as well as dysphagia are possible symptoms and signs of progressive oral Kaposi's sarcoma. Differential diagnosis inc1udeslymphoma. 122- t25 Kaposi's sarcoma has been observed especially in homosexual patients, although all risk groups for AIDS can be affected. Management has included radiation, surgery, systemic and intralesional chemotherapy, and intralesional interferon treatment. 121, 126-1 28 Carbon dioxide or argon laser can be effective in treatment of Kaposi's sarcoma. ORAL LYMPHOMAS

Non-Hodgkin's lymphoma is the second most common malignancy in HIV infection. Hodgkin's disease and T-cell lymphoma have also been reported in HIV-positive patients and the occurrence of such a malignancy indicates AIDS group IVD. Non-Hodgkin's lymphoma associated withHIV infection appears in 4.4% with an oral Iesion.P! NonHodgkin's lymphoma in the oral cavity appears as a growing mass. This appears mainly on the palate and gingiva. Lymphomas in AIDS are highly aggressive, and survival is measured in months from the diagnosis. It may be the initial sign ofthe infection,129 and differential diagnosis from Kaposi's sarcoma may be difficult. 124 An association of oral lymphomas in HIV-infected patients with EBVDNA has been discussed. 123 Management requires chemotherapy or radiotherapy. SQUAMOUS CELL CARCINOMA Silverman et a1. 68 found oral squamous cell carcinoma in 1.9% of their large series of HIV-infected

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Fig. 6. Oral hyperpigrnentation. Fig. 7. Syphilitic oral condyloma.

patients. Laskaris et al. 7 recorded squamous cell carcinoma in 1 of 160 HIV-infected patients. Squamous cell carcinoma in AIDS is seen in younger patients than in the general noninfected population. 130 Oncogenic human papillomaviruses, as already documented in HIV-infected patients, may be important. MISCELLANEOUS DISORDERS

Pigmentary changes during the course of HIV infection are well documented.P! Oral pigmented macules in HIV-infected patients have been described by Langford et al. 132 in 1989. These authors described six HIV-infected patients with oral hyperpigmentation. A recent review lists the systemic drugs that may produce mucocutaneous hyperpigmentation.P" In AIDS the lesions were related to c1ofazimine, ketoconazole, and azidothymidine, although in some patients no explanation for the oral pigmentation could be found. 132. 134-136 In one patient, who was taking azidothymidine, the lesions faded after withdrawal of the drug. No signs or

symptoms of adrenal insufficiency were found. The lesions show increased melanin deposition in the basal cell layer and normal melanocyte count. No ultrastructural alterations of the melanocytes were found. Ficarra et al. 136 found that in 6.4% of 217 patients who tested seropositive for HIV, such lesions developed during an I8-month period. In a control population of 210, hyperpigmentation was also found in 3.6%. The lesions may be circumscribed or diffuse and are asymptomatic (Fig.

6). Ectopic geographic tongue in AIDS,137 necrotizing vasculitis with oral involvement, l38 as well as granuloma annulare of the buccal mucosa--? have been described recently. Mucocutaneous syphilitic manifestations in patients with AIDS are a diagnostic challenge.It? We have seen specific cheilitis angularis, luetic tonsillitis, and syphilitic condylomas leading to loss of teeth (Fig. 7). In patients with HIV infection Reiter's syndrome and psoriasis have a different clinical appearance. Painless oral ulcers may be seen in some cases.v"

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