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Home , Hairy leukoplakia, Oral candidiasis

HIV/AIDS; ORAL COMPLICATIONS AND CHALLENGES, THE NIGERIAN EXPERIENCE

*M UKPEBOR; **O.B BRAIMOH DEPARTMENT OF *ORAL MEDICINE, **PREVENTIVE UNIVERSITY OF BENIN TEACHING HOSPITAL, BENIN CITY, NIGERIA

ABSTRACT manifestations of HIV. In Nigeria, these So many oral complications of oral continue to occupy a place HIV/AIDS abound, these lesions can of importance because of its occur at any stage of the disease and significance in the prevention, diagnosis can be used for early recognition of the and management of HIV infection as a disease so that prompt treatment can be whole. commenced in order to prevent further The oral cavity is an important and complications. A number of work have frequently undervalued source of been done on oral lesions associated diagnostic and prognostic information in with HIV infection in Nigeria. patients with HIV disease2. A review is made of the possible oral Studies of oral conditions associated complications and challenges of with HIV infection in adult Nigerians HIV/AIDS in Nigeria, with special reported prevalence of oral lesions emphasis on some specific HIV- related ranging from 20% in 2001 to 84% in oral lesions which are easily identified, 2006. Similar studies carried out among for the purpose of diagnosis, prognosis HIV infected children reported prevalence and to reduce morbidity and mortality in of oral lesions to be 87.2%3-6. HIV/AIDS. A variety of conditions have been described affecting oral tissues in HIV KEYWORDS: HIV/AIDS, Complications, infection7. The most common oral Challenges, Nigeria. is oral , with pseudomembranous type the most frequent2,3,8. Historically, INTRODUCTION this was one of the first documented oral It has been estimated that 90% of features of AIDS and several studies people with HIV disease will present have confirmed its high prevalence9,10. with at least one oral manifestation at Oral lesions can appear at any stage of sometime during the course of their HIV infection with higher occurrence 1 infection . The ability to differentiate one associated with increasing immuno- manifestation from another, as well as suppression, and are more frequent in manage some of the more common women than in men, and the most conditions is fundamental to the overall common pathogen is albicans 8. health care of this patient population. Recognition of the oral manifestations Dentist as a key player in the primary of HIV disease is of great significance health care of patients have the ability to because they may represent the first positively affect the well being of signs of the disease. They have been patients. shown to be highly predictive markers of There have been a large number of severe immune deterioration and studies published over the years on oral disease progression and therefore serve

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Vol. 9 No. 1 December, 2007 HIV/AIDS; oral complications and challenges, the Nigerian experience as a clinical correlates of CD4+ They are indicators of progression to counts11,12. However, many respond to AIDS defining conditions. simple therapeutic measures13. Serve as universal component of HIV classification and staging scheme. FACTORS PREDISPOSING TO ORAL LESIONS ORAL COMPLICATIONS OF HIV/AIDS A number of factors have been Oral lesions associated with HIV documented to predispose to oral infection are classified as stated below: lesions in HIV infected individuals these COMMONLY ASSOCIATED INFECTIONS: include 3 Fungal: Candidiasis a) CD4 T cell counts <200cells/mm Erythematous b) High viral load Hyperplastic c) Poor Pseudomembranous d) Angular e) f) Low innate immunity Viral: g) Late presentation h) . Varicella zoster Hairy SIGNIFICANCE OF ORAL LESIONS IN HIV/AIDS Bacterial: Diagnosis: oral lesions may be the HIV-associated (LGE: first sign of the disease and therefore Linear gingival ). serve as a prompt for HIV screening and HIV- associated periodontitis (NUP: diagnosis. Necrotizig ulcerative periodontitis). Markers: may serve as markers for Necrotizing gingivitis early immune deterioration and disease 5 Tumours: progression . Kaposi's sarcoma Prognosis: clinical indicators of a Lymphadenopathy poor prognosis e.g. oral thrush, herpes zoster, . LESS COMMONLY ASSOCIATED Oral manifestations have been Atypical ulceration important entry criteria for clinical trials : as well as for vaccine studies. Xerostomia due to decreased Some of these lesions may salivary flow rate. compromise the patient’s appearance unilateral/bilateral swelling of e.g. herpes zoster and facial nerve major salivary gland especially palsy. the parotid glands. May be one of the earliest lesions of HIV infection and some of them herald Tumour Non-Hodgkin rapid deterioration and sometimes, death. Viral: Some of these lesion have a fatal human papilloma (warty-like outcome e.g. Kaposi's sarcoma. lesion) Some others are painful, cytomegalovirus compromising food intake and nutrition

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Benin Journal of Postgraduate Medicine M Ukpebor, O.B Braimoh

Bacterial: , labial mucosa, buccal mucosa, Mycobacterium tuberculosis gingival and the floor of the . It E. coli indicates declining immunity. Submandibular Approximately 50% of patients with Sinusitis HIV- associated thrush are likely to develop AIDS in 5 years. Deep mycoses: Sometimes it may be generalized, and this represents low immunity and must be vigorously treated to prevent systemic dissemination. It is usually Neurological disturbances: associated with Facial palsy Erythematous candidiasis usually Trigeminal neuropathy present on the dorsal surface of the tongue and/or roof of the mouth as a red Miscellaneous: flat lesion. It is probably the most Delayed wound healing underdiagnosed oral disease seen in people living with HIV infection .The Melanotic hyperpigmentation chief complain is burning sensation Recurrent aphthae associated with eating salty or spicy Progressive necrotising foods1. ulceration Angular Cheilitis: This lesion is more Osteomyelitis prevalent in HIV+ individuals when Drug reactions (ulceration, erythema compared to HIV- individuals, but does multiforme, lichenoid reaction). occur in both populations. Angular cheilitis, of itself is not diagnostic of HIV infection. It appears as cracks or Candida infections seen in HIV/AIDS fissures radiating from the corners of the patients include Pseudomembranous mouth which may or may not be candidiasis, Erythematous candidiasis, accompanied by intraoral "thrush"1,10. Hyperplastic candidiasis and Angular Hyperplastic Candidiasis: This type of cheilitis. It is the commonest oral candidiasis is unusual in persons with manifestation of HIV/AIDS. HIV infection. The lesions appear white In Nigeria, the prevalence of oral and hyperplastic. The white areas are candidiasis range between 36.4% and due to and, unlike the 80% (Onunu and Obuekwe 2002). The plaques of Pseudomembranous most commonly reported Candida candidiasis, cannot be removed by infection is Pseudomembranous candidiasis 3 scraping. These lesions may be (Thrush) , and has the following confused with hairy leukoplakia. features: Diagnosis of hyperplastic candidiasis is It is the most frequently encountered made from the histologic appearance of of the oral cavity. hyperkeratosis and the presence of (>70%) and appear as white soft creamy hyphae. Periodic acid-Schiff (PAS) stain patches on any which can is often used to demonstrate hyphae1,2. easily be wiped off, leaving an Most studies carried out in Nigeria, erythematous base. But most commonly reported Pseudom-embranous candidiasis found in the , followed by the to be the commonest variant followed by

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Vol. 9 No. 1 December, 2007 HIV/AIDS; oral complications and challenges, the Nigerian experience erythematous candidiasis. However, ml of amphotericin Oral Suspension on Taiwo et al8 reported Pseudomembranous the acrylic of their denture two to four candidiasis and angular cheilitis as the times per day before inserting the most common variants and all cases of prosthesis1,10. erythematous candidiasis reported in this study were exclusively seen in the VIRAL MUCOSAL INFECTIONS 8 female population . While candidiasis HAIRY LEUKOPLAKIA may suggest the possibility of HIV This is probably due to opportunistic infection, recurring candidiasis is a Epstein-Barr virus (EBV) infection of the pointer to HIV infection in Africa. epithelial cells. It may herald HIV disease in vast majority of cases, and TREATMENT also may be present after AIDS is Treatment varies according to the established. It is the second most degree of in the prevalent oral lesion in the world, patient. For minimally immuno- however, the reported incidence is lower in compromised patients, solution 3,14, 15 Nigeria with a range of 4.4%- 9.9% . swished and swallowed five times daily Hairy leukoplakia is highly is often successful1 . characteristic of HIV infection especially In moderate cases of immuno- in male homosexuals. It appears as a suppression, systemic agents soft, corrugated, painless plaques or are used, such as fluconazole white patches on lateral borders of (Diflucan), at 200 mg for the first dose, tongue and can extend to involve the then 100 mg once a day for several dorsum of tongue and buccal mucosa. days to several weeks, depending on The surface may be so thick as to the severity of disease and the response 16 produce -like projections. Fig 1 . of the patient to treatment. Prophylactic It is asymptomatic and rarely seen in use of antifungal agents is indicated in children. Most often it coexists with oral patients with frequent episodes (e.g., candidiasis and may be masked by it. It fluconazole in a dosage of 100 mg orally is an indication of advanced once a week). When patients present , a more rapid with symptoms of or progression to AIDS and a poor odynophagia, the should prognosis. also be evaluated to rule out It can be diagnosed by demonstration . Azole-resistant of EBV antigens in epithelial cell nuclei oropharyngeal or esophageal by in-situ hybridisation. Incisional candidiasis can be treated with is also useful in its diagnosis, this show fluconazole in a very high dosage (800 characteristic EBV nuclear inclusions in mg per day) or amphotericin B1,2 . upper-layer keratinocytes It is very important for people who Hairy leukoplakia rarely requires wear partial or complete to treatment, it may resolve spontaneously. treat these appliances when they have However can be treated with candidiasis. This can be done by (Retrovir) or high doses of acyclovir thoroughly cleaning the denture once a (800 mg four times per day) day and soaking it overnight in a 1:1 dilution of a solution. Patients are also instructed to place 1

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Benin Journal of Postgraduate Medicine M Ukpebor, O.B Braimoh

with oral acyclovir. In severely immunocompromised patients with frequent recurrence of oral herpetic lesions, prophylaxis with acyclovir is indicated. Foscarnet can be used in cases of acyclovir-resistant oral herpetic lesions.

Fig. 1: Hairy Leukoplakia16

HERPES SIMPLEX It is caused by Herpes simplex virus type 1, common in childhood with a prevalence of 10% in Nigerian children infected with HIV/AIDS6. The 2006 report from Nigeria noted a prevalence of 5.5% in adults8. It is characterised by vesicles, which rupture to form ulcers which are the most common form of infectious oral Fig. 2: Herpetic Ulceration in HIV ulcers affecting any part of the oral 16 mucosa Fig 2. In immunocompetent patient individual it affects only the gingiva and HERPES ZOSTER INFECTION hard palate Herpes zoster or results Usually a prolonged or severe from reactivation of the varicella zoster infections and herpetic ulceration virus previously dormant in cranial persisting for more than a month is an nerves in 30% of cases. There is a AIDS defining illness predilection for the opthalmic nerve and represents a its incidence increase with age and recurrent infection which presents with immunosupression17,18. It presents as a multiple grouped, fragile vesicles or painful unilateral intraoral, facial or ulcers on the vermillion border of the ocular vesicular, pustular, and ulcerative or adjacent skin. The vesicles may lesions which are distributed along the coalesce to form larger vesicles which area supplied by the different branches heal slowly. In HIV/AIDS lesion may of the trigeminal nerve occur in any oral sites and are more The vesicles often confluent form on severe and prolonged. one side of the face and in the mouth up Treatment of herpetic lesions in HIV- to the midline. positive persons consists of acyclovir (or This can be an early complication of a similar antiviral agent) in a dosage of AIDS, where it is 5 times more common 200 mg five times a day. This treatment than in HIV-negative persons, and is effective only if started early in the potentially lethal course of the lesion. Mild to moderate Complications of varicella zoster oral herpetic lesions should be treated infection include post herpetic neuralgia,

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Vol. 9 No. 1 December, 2007 HIV/AIDS; oral complications and challenges, the Nigerian experience middle ear infections, motor paralysis, progress to HIV-associated periodontitis paraesthesia ocular inflammation, and if not vigorously treated. excessive scarring leading to facial disfigurement. HIV-ASSOCIATED PERIODONTITIS Treatment is with topical acyclovir This include necrotising ulcerative cream and gentian violet. Systemic periodontitis (NUP) characterised by acyclovir, valcyclovir, famciclovir, extensive destruction of soft tissue and forscarnet can also be used bone simultaneously leading to mobility A case of unusual facial scarring and exfoliation of teeth, typically secondary to herpes zoster infection, intensely painful and are usually sharply confined to the area of the generalised. It is highly prevalent distribution of the maxillary division of amongst HIV infected children and the trigeminal nerve,not crossing the young adults in Africa and may progress midline which was preceeded by itching to cancrum oris as a result of and a vesicular rash, affecting a 32 yr malnutrition and poor oral hygiene. old Nigerian female was reported in HIV-associated UBTH. (Obuekwe et al, 2002)19. Fig 3 also include necrotising gingivitis and accelerated periodontitis. Necrotizing ulcerative periodontitis could be intractable and life threatening and early and aggressive treatment is necessary for its resolution20. In addition to the microbial and host factors, the role of local irritants should be considered as smoking has been identified as a strong aetiologic factor21. This condition could lead to halitosis, and is associated with a low CD4 cell count /poor prognosis.

These patients should be referred to Fig. 3: Herpes Zoster an oral surgeon for debridement, scaling and curettage of the involved areas. This treatment is followed by BACTERIAL INFECTION administration of metronidazole (Flagyl), HIV-ASSOCIATED GINGIVITIS: in a dosage of 200 mg four times a day HIV-associated gingivitis which is for five to six days, irrigation with now known as povidone iodine and daily mouth rinsing (LGE) happened to be the most frequent with chlorhexidine gluconate (Peridex). presentation of periodontal disease Because it may potentiate peripheral (16.6%), it is more common than HIV- neuropathy, metronidazole should not associated periodontitis (11.7%)3. be given to patients taking didanosine Linear gingival erythema presents as (ddI; Videx) or zalcitabine (ddC; Hivid). a bright red line characterised by In these patients, clindamycin (Cleocin), intense, asymptomatic erythema of the one 300-mg tablet three times daily, or marginal gingival not proportional to amoxicillin, 250 mg three times daily, is accumulated plaque present. This may prescribed.

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Benin Journal of Postgraduate Medicine M Ukpebor, O.B Braimoh

MYCOBACTERIUM TUBERCULOSIS Kaposi’s sarcoma is significantly The high prevalence of HIV co- associated with death in HIV disease. infection with tuberculosis in developing Kaposi's sarcoma in the mouth, countries including Nigeria has changed particularly in a young male who is not the picture of oral lesions associated receiving immunosuppressive treatment with HIV infection as opposed to what is is virtually pathognomonic of AIDS16. observed in the developed countries. It is usually associated with a low This has led to the development of oral CD4 lymphocyte count of < tuberculous lesions or ulcerations of 200cells/mm3 and frequently associated which the common site is the posterior with other lesions such as candidiasis, aspect of the dorsum of the tongue. hairy leukoplakia. It is very aggressive and has a poor prognosis. It is an ORAL ULCERATION indicator for profound immuno- Oral ulceration is frequently seen in suppression. Lesion is usually 21 HIV infection . In a Nigerian study, the asymtomatic unless when infected. minor and major variants of recurrent Therapy for patients with oral aphthous ulcers accounted for 10.0%. Kaposi's sarcoma ranges from no The non-recurrent type was 3.3%. intervention for asymptomatic lesions to However, since recurrent aphthous radiation, surgical removal and ulceration is commonly encountered in in patients with 22 most population , it is difficult to symptomatic lesions. evaluate whether its prevalence is heightened among patients with HIV NON-HODGKIN LYMPHOMA infection3, 23. Has a reported prevalence of about 5% in developing countries. Non- TUMOURS Hodgkin's lymphoma, in contrast to Kaposi’s sarcoma is the most Kaposi's sarcoma, occurs most common oral malignancy associated commonly in intravenous drug abusers with HIV infection and it accounts for with AIDS. After Kaposi's sarcoma, this 24,25 90% of all in HIV+ patients . is the most common neoplasm in In Nigeria, it accounts for about 3.1%- patients with AIDS. The lesions of non- 3 ,6,15 11.6% in adults and 10% in children . Hodgkin's lymphoma are red and It is a tumour of vascular endothelium exophytic, and commonly involve the and presents as a flat purplish or alveolar ridge, the gingiva and the reddish macule or nodule. The tumour is palate. The disease can also present as usually multifocal, with lesions affecting a rapidly enlarging neck mass. Most skin, lymph nodes and viscera. Within lesions are of large B-cell origin and the mouth the palate and gingival are originate extranodally. Non-Hodgkin's the most frequent sites, Fig 4. lymphoma can be diagnosed by tissue Symptoms include increasing pain, biopsy. The diagnosis carries a poor odynophagia, dysphagia and difficulty in prognosis. Treatment varies from mastication. chemotherapy to radiotherapy or Occasionally, it could be of normal surgical excision, according to the site mucosal colour and in the early stage and extent of involvement26,27,28. could be confused with other lesions.

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Vol. 9 No. 1 December, 2007 HIV/AIDS; oral complications and challenges, the Nigerian experience

LYMPHADENOPATHY MISCELLANEOUS ORAL This is characteristic of AIDS and its COMPLICATIONS prodromes. Cervical lymphadenopathy Autoimmune disease e.g. seen in HIV infection is a part of the Thrombocytopenic purpura, it gives rise generalized lymphadenopathy and could to oral purple patches which may be be the most prevalent orofacial mistaken for Kaposi's sarcoma, and manifestation. It is probably the most petechiae. common site of lymph node involvement Oral hyperpigmentation in HIV infection. A prevalence of 5.1% in Neurological disease such as facial females and 4.3% in males was palsy and trigeminal neuralgia reported in Nigeria15. Adverse drug reactions or side effects of antiviral drugs: toxic epidermal necrosis syndrome (TENS), , lichenoid reactions. Oral mucosal cytomegalovirus: this presents clinically as a large painful ulceration on any part of the oral mucosa that is non-healing and non- specific.

HIV/AIDS; CHALLENGES FACED BY THE DENTIST The ever increasing number of people with HIV/AIDS re-emphasizes

the need for proper cross infection Fig. 4: Kaposi’s Sarcoma16 control in clinical practice. HIV can easily spread in the dental clinic if SALIVARY GLAND DISEASE proper infection control practices are not Salivary gland disease in HIV followed due to the limited available infection can occur as xerostomia or as facilities and lack of disposable glandular enlargement. Xerostomia may instruments especially in the developing be seen in 10-15% of patients with HIV countries of the world. Also, the infection. This is usually the result of increasing number of asymptomatic HIV gland disease or secondary to HIV-positive patients that might attend medications which may produce dry for routine treatment re-emphasizes the 29 mouth symptoms . The frequency of need for adequate infection control salivary gland enlargement in Nigerian measures in dental practice3. studies were reported to be 25.6% in Upsurge in the number of cases has 5,15 children and 1.0 -1.3% in adults .The put pressure on available facilities which parotid gland is the most commonly in actual sense are not adequate and affected salivary gland in HIV infection the dentist. and one, or both glands could be Stigmatization is another very involved, with a presentation of bilateral important challenge in our environment. parotid gland swelling. The glands are Stigma is a mark of shame and to soft, painless with diffuse swelling which stigmatize is to label as shameful. This enlarges slowly. is a major problem for the victims of the

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Benin Journal of Postgraduate Medicine M Ukpebor, O.B Braimoh disease. The consequences of CONCLUSION stigmatization is denial of or refusal to Orofacial lesions are common in disclose HIV status, and this result in people infected with HIV. These lesions unmet treatment needs of these patients are easily accessible and may be as some of them may shy away from predictive of disease progression. seeking treatment5. In developing countries like Nigeria Other challenges include recurrence were sophisticated diagnostic apparatus and persistence of orofacial infections used to monitor the immunologic status due to immune depression and poor of HIV/AIDS patients is not readily access to drugs for related opportunistic available, early recognition of the infections. commonest and specific HIV-related Removing barriers to care: The risk oral lesions can be used for diagnosis of transmission of HIV infection to the so that prompt treatment can be dentist through accidental needle-stick provided to reduce morbidity. injuries may lead to reluctance of the dentist to treat once the HIV status of REFERENCES the patient is known. 1. Greenspan D, Schiodt M, Greenspan The inability of attending physicians JS, Pindborg JJ. AIDS and the or medical examiners in the recognition Mouth, Diagnosis and Management of oral lesions in HIV infection in order to of Oral Lesions. Copenhagen: fit into the role of an early detector of Munksgaard; 1990 HIV infection, and their failure to refer patient for dental care or include regular 2. Chapple Lain LC, Hamburger J. The dental checkups in their routine significance of oral health in HIV management of HIV positive patient30. A disease. Sex Transm Inf 2000; 76: study conducted by Cruz et al (1996) 236-243. noted that medical examiners were significantly less able to identify oral 3. Onunu AN, Obuekwe ON. HIV- lesions than dental examiners. These Related oral disease in Benin City, have management import because with Nigeria. WAJM 2002 Jan-Mar; the increasing number of HIV- infected 21(1):9-11. individuals in the population, a thorough 4. Arotiba JT, Adebola RA, Iliyasu Z, intraoral examination is necessary to Babashan M. Oral manifestations of substantiate other clinical findings that HIV infection in Nigerian patients might lead to screening of such seen in Kano. Nigerian J of Surgical patients3. research 2005;7(1&2):176-181. The challenge of providing relevant and sophisticated counselling intervention 5. Agbelusi GA, Wright AA. Oral lesions to people with HIV/AIDS in order to as indicators of HIV infection among bring healing to the emotional situation routine dental patients in Lagos, of the patient demoralized by the news Nigeria. Oral Dis 2005 Nov; of the infection and finally the late 11(6):370-376. presentation of patient to the dental clinic with full blown HIV/ AIDS infection where little or nothing can be done to salvage the situation.

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