Classification of oral lesions associated with HIV infection

Classification of oral lesions associated with HIV infection Jens J. Pindborg, DOS, Dr Odont, Dr Odont hc, Odont Dr hc, Hon ARCS, Hon Dr Sci, Hon LLD, Hon MD,” Copenhagen, Denmark ROYAL DENTAL COLLEGE, COPENHAGEN, AND UNIVERSITY HOSPITAL (“RIGSHOSPITALET”), COPENHAGEN, WHO COLLABORATIVE CENTRE FOR ORAL MANIFESTATIONS OF THE HUMAN IMMUNODEFICIENCY VIRUS, AND EEC CLEARINGHOUSE FOR ORAL PROBLEMS RELATED TO THE HIV INFECTION This article

proposes

a classification

for oral lesions

associated

classified into those with fungal, bacterial, or viral origin neurologic disturbances, and lesions of unknown cause. forwarded as a basis for epidemiologic surveys. (ORAL SURC ORAL MED ORAL PATHOL 1989;67:292-5)

n Sept. 16 and 17,1986, the European Economic 0Community sponsored a meeting in Copenhagen to

with HIV infection.

whereas other This proposal

subgroups is neither

The lesions

can be

include neoplasms, final nor exhaustive

and is

discuss oral problems related to human immunodeficiency virus (HIV) infection*. As a result of the meeting, a list of 30 diseases was generated, representing those lesions known to be associated with the HIV infection. Subsequently, several new lesions were reported to occur in the mouth or submandibular region, so it was thought necessary to propose a revision of the classification, which may serve as a guide for those examining patients infected with HIV. The revised list is shown in Table I. I have attempted to locate the first description of the disease process described herein yet am aware that this goal is difficult to achieve and therefore apologize for any oversight.

candidiasis may appear as four distinct clinical variants: pseudomembranous, erythematous, hyperplastic, and angular cheilitis. Because the four types occur with different frequency in patients with AIDS and AIDS-related complex (ARC) and in healthy seropositive persons, it is important to distinguish among the four types. Histoplasmosis. As far as I know, only one case of oral histoplasmosis related to HIV infection has been reported (Dr. David Lewis’s case, mentioned in the monograph by Greenspan and coworkers2). Cryptococcosis. Two cases of this rare disease with oral manifestations in patients with AIDS have been published.3v4 Geotrichosis. I am aware of only one case (personal communication by Dr. Deborah Greenspan).

FUNGAL

BACTERIAL

INFECTIONS

Candidiasis. Even the first report on the acquired immunodeficiency syndrome (AIDS) mentioned that patients had oral candidiasis.’ However, most if not all reports have referred to the pseudomembranous type (thrush). Later studies* demonstrated that oral ‘Professor, Department of Oral Pathology, Royal Dental College *The participants at the meeting were A. Angelopoulos, A. Baert, M. F. D’Agay, M. C. Em&o, D. and J. Greenspan, S. O.‘Hickey, W. H. van Palenstein Heldermann, G. Kayser, I. Loeb, B. Maeglin, J. J. Pindborg, S. Porter, P. Reichart, J. Rindum. and M. Schi#dt. 292

INFECTIONS

Necrotizing gingivitis and progressive periodontitis. Dennison and coworkers5 were the first to call

attention to the periodontal complications of HIV infection, Later studies have corroborated this initial description.6.7 Mycobacterium avium intracellulare. Seldom has a disease caused by this bacterium been reported in the oral cavity; one case has recently been published with respect to a patient with AIDS.’ Actinomycosis. A seropositive bisexual man had facial swelling and trismus after extraction of a maxillary molar. Culture was positive for Actinomyces israelii. 9

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Classification of oral lesions associated with HIV infection

Cat-scratch disease. In

1987, Cockerell and coworkers”’ described an unusual vascular neoplasm, distinct from Kaposi’s sarcoma, occurring in patients with AIDS or ARC. In one of five patients, there were oral lesions. However, in a subsequent article” it was pointed out by another group that the changes reported by Cockerell and coworkers’0 are an expression of cat-scratch disease; this was later confirmed by Cockerell. Klebsiella pneumoniae infection. This is a disease that seldom exhibits oral manifestations. A lingual lesion associated with HIV infection is illustrated in the monograph by Greenspan and coworkers.2 Enterobacter cloacae. Another disease that seldom shows oral manifestations is caused by Enterobatter cloacae. A mucosal lesion associated with an underlying osteitis in a homosexual man with reduced T4/Ts ratio is illustrated in the monograph by Greenspan and coworkers.* Escherichia coli. A disease that is seldom accompanied by oral manifestations is infection caused by Escherichia coli. Silverman’2 described a patient with AIDS with a lingual ulceration from which Escherichia coli could be cultured. Exacerbation of apical periodontitis. In 1984, Hurlen and Gerner13 reported on a patient with AIDS in whom repeated exacerbations of an endodontically involved tooth occurred. Sinusitis. In a report in 1985, Marcusen and Sooy14 mentioned that chronic sinusitis may occasionally be found in patients with AIDS. Submandibular cellulitis. In the Central African Republic, ten cases of diffuse cervical cellulitis have been observed. All of them resulted from untreated dental infection. Nine of the ten patients were positive for HIV antibody without any other symptoms or confirmation of AIDS.15 VIRAL

INFECTIONS

Herpetic stomatitis. Very early in the history of the syndrome, it became clear that patients with AIDS have a strong predilection for the development of herpetic lesions. In the dental literature,‘6,17 there are reports of a 9% to 10% prevalence of herpetic stomatitis in HIV-infected persons. Furthermore, herpetic lesions of the orofacial region are often extensive, severe, and prolonged. Cytomegalovirus. Infection with this virus is seldom associated with oral manifestations. However, in 1987, a report’* described a painful palatal gingival cytomegalovirus-associated ulcer in a patient with AIDS. Epstein-Barr virus. The most significant contribution in the area of oral manifestations of HIV

293

I. Oral lesions associated with HIV infection (as agreed at an EEC-sponsored meeting in Copenhagen, Sept. 16- 17, 1986, on “Oral problems related to the HIV infection”; revised edition as of Oct. 1, 1988, by J. J. Pindborg)

Table

Fungal infection Candidiasis Pseudomembranous Erythematous Hyperplastic Angular cheilitis Histoplasmosis Cryptococcosis Geotrichosis Bacterial infections HIV-necrotizing gingivitis HIV-gingivitis HIV-periodontitis Caused by: Mycobacterium avium intracellulare Klebsiella pneumoniae Enterobacter cloacae Escherichia coli

Actinomycosis Cat-scratch disease Sinusitis Exacerbation of apical periodontitis Submandibular cellulitis Viral infections Caused by: Herpes simplex virus Cytomegalovirus Epstein-Barr virus “Hairy” leukoplakia Varicella-zoster virus Herpes zoster Varicella Human papillomavirus Verruca vulgaris Condyloma acuminatum Focal epithelial hyperplasia

Neoplasms Kaposi’s sarcoma Squamous cell carcinoma Non-Hodgkin’s lymphoma Neurologic disturbances Trigeminal neuropathy Facial palsy Unknown cause Recurrent aphthous ulceration Progressive necrotizing ulceration Toxic epidermolysis Delayed wound healing Idiopathic thrombocytopenia Salivary gland enlargement Xerostomia Melanotic hyperpigmentation

infection was the report in 1984 on “hairy” leukoplakia by Greenspan and coworkers.‘9 The significance of this observation has been proven by the inclusion of hairy leukoplakia in the Centers for Disease Control classification system for HIV-associated disease.20 In a subsequent article,*’ the authors demonstrated electron microscopic evidence of papillomavirus-like particles in hairy leukoplakia; using southern blot DNA hybridization, they also demonstrated Epstein-Barr virus nucleic acid sequences in the epithelium. Later investigations have not been able to confirm the consistent presence of papillo-

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Pindborg

ORAL

mavirus but have identified Epstein-Barr virus in virtually all hairy leukoplakia lesionsz2* 23 Varicella-zoster virus. Schiddt and coworkersz4 have reported on a patient with varicella characterized by generalized skin eruption with attending oral manifestations. Although herpes zoster with skin manifestations is not a rare occurrence in HIV-infected patients, cases with oral manifestations are seldom reported.2 Severe facial zoster may indicate a poor prognosis.*j Papillomavirus lesions. A number of publications have described the presence of human papillomavirus (HPV) associated lesions in HIV-infected patients (e.g., verruca vulgaris, condyloma acuminaturn, and focal epithelial hyperplasia”). In this context, it should be mentioned that HPV infections are common in homosexuals as a group. Thus, it is possible that the aforementioned lesions could be attributed to sexual behavior.

SIJRG ORAL

Mm

PxrHoI. March 1989

ORAL

Trigeminal neuropathy. A case involving the mental nerve with associated odontalgia and anesthesia of the chin has been reported in a patient with AIDS.27 Facial palsy. Several case reports describing facial palsy as part of HIV infection have now appeared in the literature.**

monly encountered in most populations, it is difficult to evaluate whether the prevalence of RAU is truly heightened among patients with the HIV infection. Progressive necrotizing ulceration. Occasionally, oral mucosal ulcerations that are much larger than those encountered in recurrent aphthous ulcers develop in HIV-infected patients. Histologic examination does not provide any clue in regard to cause. Phelan and coworkers16 have urged future investigation of oral ulcers in this population. Toxic epidermolysis (Lyell’s syndrome). This has been more frequently observed in pediatric patients with AIDS with oral involvement (personal communication by Dr. I. Loeb, Brussels) but is also seen in adults.29 Delayed wound healing. After removal of teeth or osteotomies, a delay in wound healing has been observed among HIV-infected patients.29 Zdiopathic thrombocytopenia. HIV-infected patients may have idiopathic thrombocytopenia, which may lead to ecchymosis and/or petechiae of the oral mucosa.‘, 29 Salivary gland enlargement. There have been several reports on salivary gland enlargement in children with AIDS.30s3’ Recently, however, Colebunders and coworkers32 reported on parotid gland swelling in nine HIV-seropositive adult patients in Kinshasa. Xerostomia. In the sample (patients with AIDS and ARC, high-risk patients) of Silverman and coworkers,” 10% had xerostomia. In a sample from Copenhagen, xerostomia was observed in 6% of patients with AIDS and ARC and seropositive patients, Oral mucosal hyperpigmentation. Recently, melanin hyperpigmentation has been observed among HIV-infected patients (reference 33 and personal communication by Dr. G. Ficarra, Florence). The cause of this hyperpigmentation is unknown. I emphasize that this proposal for a classification is a suggestion only and does not represent a definitive classification inasmuch as more lesions will likely be seen in association with HIV infection. This preliminary tabulation may form a basis for further discussions and encourage readers to submit information on entities that should be included in future revisions of the classification.

UNKNOWN

REFERENCES

NEOPLASMS

Kaposi’s sarcoma. Although Kaposi’s sarcoma soon became identified with AIDS, it took several years before the oral lesions were thoroughly described.26 The majority of patients with Kaposi’s sarcoma have oral manifestations. In some rare cases, the oral lesions may be the first sign of the disease. Non-Hodgkin’s lymphoma. It has been known since 1982 that HIV infection predisposes to the development of non-Hodgkin’s lymphoma. Occasionally, the first sign of this malignant condition occurs as a swelling of the oral mucosa, most often the gingiva.‘j Squamous cell carcinoma. Oral carcinomas, most often involving the tongue, have been associated with HIV infection, occurring in a higher than expected number of young men.” NEUROLOGIC

DISTURBANCES

CAUSE

Recurrent aphthous ulceration (RAU). In a study by Silverman and coworkers,” 8% of 375 homosexuals (comprising AIDS, ARC, high-risk, contact, and healthy groups) had aphthae. Because RAU is com-

1. Gottlieb MS, Schanker HM, Fan PT, Saxon A, Weisman JO, Pozalski I. Pneumocystis pneumonia-Los Angeles. MMWR 1981;30:250-1. 2. Greenspan D, Greenspan J, Pindborg JJ, Schi$dt M. AIDS and the dental team. Copenhagen: Munksgaard, 1986.

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3. Lynch DP, Naftolin LZ. Oral Cryptococcus neoformans infection in AIDS. ORAL SURG ORAL MED ORAL PATHOL 1987;64:449-53.

4. Glick M, Cohen SG, Cheney RT, Crooks GW, Greenberg MS. Oral manifestations of disseminated Cryptococcus neoformans in a patient with acquired immunodeficiency syndrome. ORAL SURG ORAL MED ORAL PATHOL 1987;64:4549. 5. Dennison DK, Smith B, Newland JR. Immune responsiveness and ANUG. J Dent Res 1985;64: spec. issue, abstr. no. 204. 6. Winkler JR, Murray RA, Greenspan D, Greenspan JS. AIDS virus associated periodontal disease. J Dent Res 1986;65: spec. issue, abstr. no. 139. 7. Pindborg JJ, Holmstrup P. Necrotizing gingivitis related to human immunodeficiency virus (HIV) infection. Afr Dent J 1987;1:5-8. 8. Volpe F, Schwimmer A, Barr C. Oral manifestations of disseminated Mycobacterium avium intracellulare in a patient with AIDS. ORAL SURG ORAL MED ORAL PATHOL 1985;60:567-70. 9. Yeager BA, Hoxie J, Weisman RA, Greenberg MS, Bilaniuk LT. Actinomycosis in the acquired immunodeficiency syndrome-related complex. Arch Otolaryngol Head Neck Surg 1986;112:1293-5. 10. Cockerell CJ, Whitlow MA, Webster GF, Friedman-Kien AE. Epithelioid angiomatosis: a distinct vascular disorder in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Lancet 1987;2:654-6. 11. LeBoit PE, Berger TG, Egbert BM, et al. Epithelioid haemangiomalike vascular proliferation in AIDS: manifestations of cat-scratch disease. Lancet 1988;1:960-3. 12. Silverman Jr S. AIDS update: oral findings, diagnosis, and precautions. J Am Dent Assoc 1987;115:559-63. 13. Hurlen B, Gerner NW. Acquired immune deficiency syndrome (AIDS)&omplications in dental treatment. Int J Oral Surg 1984;13:148-50. 14. Marcusen DC, Sooy CD. Otolaryngologic and head and neck manifestations of acquired immunodeficiency syndrome (AIDS). Laryngoscope-1985;95:401-5. 15. Vuillecard E. Mathiot CC. Georzes-Courbot MC. Georzes HJ. Diffuse cervical celluli& associated with HIV-1 infectyon in Central Africa. Third International Conference on AIDS, Washington, 1987. Abstract No. MP 164. 16. Phelan JA. Saltzman BR. Friedland GH. Klein RS. Oral findings in’ patients with ‘acquired immuhodeficiency syndrome. ORAL SURG ORAL MED ORAL PATHOL 1987;64:50-6. 17. Silverman Jr S, Migliorati CA, Lozada-Nur F, Greenspan D, Conant M. Oral findings in people with or at high risk for AIDS: a study of 375 homosexual males. J Am Dent Assoc. 1986;112:187-92. 18. Kanas RJ, Jensen JL, Abrams AM, Wuerker RB. Oral mucosal cytomegalovirus as a manifestation of the acquired immune deficiency syndrome. ORAL SURG ORAL MED ORAL PATHOL 1987;64:183-9.

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19. Greenspan D, Greenspan J, Conant M, Petersen V, Silverman Jr S, de Souza Y. Oral “hairy” leukoplakia in male homosexuals: evidence of association with both papillomavirus and a herpes-group virus. Lancet 1984;2:831-4. 20. Centers for Disease Control. Classification system for HIVassociated disease. MMWR 1986;35:334-9. 2 1. Greenspan J, Greenspan D, Lennette ET, et al. Replication of Epstein-Barr virus within the epithelial cells of oral “hairy” leukoplakia, an AIDS-associated lesion. N Engl J Med 1985;313:1564-71. 22. Belton CM, Eversole LR. Oral hairy leukoplakia: ultrastructural features. J Oral Path01 1986;15:493-9. 23. Eversole LR, Stone CE, Beckman AM. Detection of EBV and HPV DNA in hairv leukonlakia. J Med Virol (in mess). 24. Schiddt M, Rindum J, Bygbjert I. Chicken&x -with’oral manifestations in an AIDS patient. Dan Dent J 1987;91:3169. 25. Melbye M, Grossman RJ, Goedert JJ, Eyster ME, Biggar RJ. Risk of AIDS after herpes zoster. Lancet 1987;1:728-31. 26. Lozada F, Silverman Jr S, Migliorati CA, Conant MA, Volberding PA. Oral manifestations of tumor and opportunistic infections in the acquired immunodeficiency syndrome (AIDS): findings in 53 homosexual men with Kaposi’s sarcoma. ORAL SURGORAL MED ORAL PATHOL 1983;56:491-4. 27. Milan SB, Rees TD, Leiman HI. An unusual case of bilateral mental neuropathy in an AIDS patient. J Periodontol 1986;57:753-5. 28. Wiselka MJ, Nicholson KG, Ward SC, Flower AJE. Acute infection with human immunodeficiency virus associated with facial nerve palsy and neuralgia. J Infect 1987;15:189-94. 29. Reichart P, Gelderblom HR, Becker J, Kuntz A. AIDS and the oral cavity. The HIV-infection: virology, etiology, origin, immunology, precautions and clinical observations in 110 patients. Int J Oral Maxillofac Surg 1987;16:129-53. 30. Rubinstein A, Sicklick M, Gupta A, et al. Acquired immunodeficiency with reversed TI/T8 ratio in infants born to promiscuous and drug-addicted mothers. JAMA 1983;249~2350-7. 31. Amman AJ. Is there an acquired immune deficiency syndrome in infants and children? Pediatrics 1983;72:430-2. 32. Colebunders R, Francis H, Mann J, et al. Parotid swelling during human immunodeficiency virus infections. Arch Otolaryngol Head Neck Surg 1988;114:330-2. 33. Langford AA, Reichart P, Pohle HD. Oral manifestations associated with HIV-infection. Abstract No. 7578 from Fourth International Conference on AIDS, Stockholm, 1988. Reprint

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Dr. Jens J. Pindborg Royal Dental College 20, Nr. Alle DK-2200 Copenhagen N Denmark