Oral Manifestations in An HIV+ Patients and Its Management
Oral Manifestations in An HIV+ Patients and Its Management
Oral Manifestations in An HIV+ Patients and Its Management
Abstract
Oral lesions are among the early signs of HIV infection and can predict its progression to acquired immunodeficiency syndrome
(AIDS). A better understanding of the oral manifestations of AIDS in both adults and children has implications for all health care
professionals. The knowledge of such alterations would allow for early recognition of HIV-infected patients. HIV-related oral
conditions occur in a large proportion of patients, and frequently are misdiagnosed or inadequately treated. Dental expertise is
necessary for appropriate management of oral manifestations of HIV infection or AIDS, but many patients do not receive
adequate dental care. Common or notable HIV-related oral conditions include xerostomia, candidiasis, oral hairy leukoplakia,
periodontal diseases such as linear gingival erythema and necrotizing ulcerative periodontitis, Kaposi's sarcoma, human papilloma
virus-associated warts, and ulcerative conditions including herpes simplex virus lesions, recurrent aphthous ulcers, and
neutropenic ulcers.
Oral manifestations of HIV disease are common and include oral lesions and novel presentations of previously known
opportunistic diseases Careful history taking and detailed examination of the patient's oral cavity are important parts of the
physical examination and diagnosis requires appropriate investigative techniques. Early recognition, diagnosis, and treatment of
HIV-associated oral lesions may reduce morbidity.
The present paper reviews epidemiology, relevant aspects of HIV infection related to the mouth in both adults and children, as
well as current trends in antiretroviral therapy and its connection with orofacial manifestations related to AIDS.
various stages of changes with respect to its epidemiology as absence of antiretroviral treatment, this period of clinical
well as its manifestations. latency may last 8–10 years or more [27]. However, the term
There are several ways in which someone can become “latency period” may be misleading, given the incredibly
infected with HIV, and some of these transmission routes are high turnover of the virus and the relentless daily destruction
well defined. HIV infection can be transmitted through of CD4+ T-cells At the end of the latency period, a number of
unprotected sexual intercourse with an infected partner The symptoms or illnesses may appear that do not fulfill the
HIV virus can be transmitted through unprotected oral sex, definition of AIDS. These symptoms include slight
both from fellatio and cunnilingus, although the precise immunological, dermatological, hematological, neurological,
degree of risk of disease transmission to and from the mouth and orofacial signs.
is difficult to establish as these practices often take place Oral manifestations are among the earliest and most
along with insertive sexual intercourse. Injection or important indicators of HIV infection. At present, three
transfusion of contaminated blood or blood products groups of oral manifestations of AIDS are defined based on
(infection through artificial insemination, skin grafts, and their intensity and features. Group 1 is composed of seven
organ transplants is also possible), sharing unsterilized cardinal lesions (oral candidosis, hairy leukoplakia, Kaposi
injection equipment that was previously used by an infected sarcoma, linear gingival erythema, necrotizing ulcerative
person, and maternal-fetal transmission (during pregnancy, at gingivitis, necrotizing ulcerative periodontitis, and non-
birth, and through breastfeeding) are other transmission Hodgkin lymphoma) that are strongly associated with HIV
routes. infection. The second group includes atypical ulcers, salivary
Occupational HIV infections of healthcare or laboratory glands diseases, viral infection such as cytomegalovírus
workers may occur, but this mode of infection is not frequent. (CMV), herpes simplex virus (HSV), papillomavirus (HPV),
Transmission of HIV from an infected patient to a health-care and herpes zoster virus (HZV). On group 3 are lesion rarer
worker has been documented after parenteral or mucous- than those on groups 1 and 2, such as diffuse osteomyelitis
membrane exposure to blood. However, this risk is less than and squamous cell carcinoma. The presence of oral lesions
1%, is limited to exposure to blood, and can be further can have a significant impact on health-related quality of life.
minimized through the availability of more effective Oral health is strongly associated with physical and mental
antiretroviral therapy (ART). health, and there are significant increases in oral health needs
There remains little evidence that HIV is transmitted via oral in people with HIV infection, especially in children, and in
fluids. However, saliva seems to play an important role in an adults particularly in relation to periodontal diseases. Thus,
individual’s protection from HIV infections. The saliva of physical and mental health measures of HIV patients should
non-HIV-infected persons contains non-immune endogenous incorporate indicators of oral functioning and well-being.
inhibitors of HIV such as mucins, defensins, thrombospondin, Data obtained in the Coutler et al. study have shown that a
and various salivary proteins, in particular the secretory one-point increase in oral health was associated with a 0.05
leukocyte protease inhibitor. There is also evidence that the (p < 0.000) increase in mental health and a 0.02 increase in
hypotonicity of saliva itself exerts a significant inhibitory physical health (p = 0.031).
effect on cell-associated HIV replication.
The risk of transmission of HIV from a patient to a dental Discussion
health care worker remains very low, if not infinitesimal. Emerging and re-emerging diseases are having a profound
Transmission of HIV from an infected dental health care worldwide impact on society and on the delivery of medical
worker is also rare, although possible. Nevertheless, dental and oral health care. HIV infection leading to AIDS has been
health care workers are at risk of nosocomial acquisition of a major cause of illness and death among children, teens, and
HIV and other blood-borne viruses (BBVs), and these young adults worldwide. There remains little evidence that
individuals should be aware of, and follow available national supports transmission of HIV via oral fluids. However, saliva
guidelines on occupational exposure to BBVs. seems to play an important role in an individual’s protection
As in other virus infections, the individual course of HIV from HIV infections The risk of transmission of HIV from a
infection depends on both host and viral factors; however, the patient to a dental health care worker remains very low.
factors that may predispose one to or promote the Transmission of HIV from an infected dental health care
development of the AIDS syndrome are largely worker is also rare, although possible Although hundreds of
unknown. The clinical course of AIDS described in the millions of research dollars have been spent seeking
following sentences refers to HIV infection in the absence of successful treatment and eradication of HIV from infected
highly active antiretroviral therapy (HAART). Several individuals, that goal has yet to be achieved. A Preventive
factors, including immunological and virological variables, HIV vaccine is very technically challenging to construct,
have been reported to predict disease progression. The acute largely due to a high rate of spontaneous mutation and HIV
viral syndrome of primary HIV infection (which is defined as strain variation and, therefore is not available Undiagnosed or
the time period from initial infection with HIV to the untreated infection with HIV, results in progressive loss of
development of an antibody response) shows symptoms that immune function marked by depletion of the CD4+ T
often resemble those of mononucleosis [25]. These symptoms lymphocytes (CD4), leading to opportunistic infections and
appear within days to weeks of exposure to HIV. However, malignancies characteristic of Acquired Immunodeficiency
clinical signs and symptoms may not occur in all patients [26]. Syndrome (AIDS) Oral manifestations of HIV are common
After the acute infection, equilibrium between viral and have been important in identification of patients
replication and the host immune response is usually reached, harboring the HIV virus and in predicting the decline in their
and many infected individuals may have no clinical immune system. Early recognition, diagnosis, and treatment
manifestations of HIV infection for years. Even in the of HIV-associated oral lesions may reduce morbidity.
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International Journal of Medicine Research
Orofacial manifestations are among the earliest and most Hyperplastic candidiasis
common clinical signs of pediatric HIV disease too. Early Angular cheilitis is erythema and/or fissuring and cracks
diagnosis of perinatally exposed infants and children is of the corners of the mouth. Angular cheilitis can occur
especially important because the intervals between infection, with or without the presence of erythematous candidiasis
development of AIDS, and death are compressed in pediatric or pseudomembranous candidiasis.
patients. Early diagnosis allows prompt institution of both Hyperplastic or chronic candidiasis presents as white
multi-drug therapy, which appears to be most effective when nonremovable plaques over the mucosal surface; hence
instituted early, and prophylactic therapy to forestall life- they cannot be scraped off.
threatening opportunistic infections. Oral candidiasis can extend to involve the pharynx, larynx,
HIV disease has an effect over the entire body. It is not and esophagus as well. Treatment of oral candidiasis depends
practical in the present scenario for any health personnel on the clinical type, distribution, and severity of infection.
dealing with diagnosis and treatment in humans to not Topical treatment is effective for limited and accessible
encounter this dreaded disease and its manifestations. Thus it lesions. Clotrimazole troches, nystatin pastilles, and nystatin
becomes imperative to be aware of the various forms of HIV oral suspension are effective for mild-to-moderate
manifestations. erythematous and pseudomembranous candidiasis. However,
Oral health is an important component of the overall health prolonged use of these agents can result in significant dental
status in HIV infection. Awareness of the variety of oral caries due to the fermentable carbohydrate substrates present
disorders which can develop throughout the course of HIV in the formulations. Increased risk of caries can be avoided
infection and coordination of health care services between a by using a nystatin oral suspension (100,000 units/5 ml,
physician and a dentist may improve the overall health of the rinsing mouth, and expectorating 3 times/day). Chlorhexidine
patient. The spectrum of oral manifestations is very vast in 0.12% oral rinses do not contain a cariogenic substrate and
HIV-AIDS. may be similarly effective.
Oral manifestations of HIV infection occur in 30–80% of the Topical amphotericin B can also be used in the treatment for
affected patient population The overall prevalence of oral resistant candidiasis and can be prepared by dissolving 50 mg
manifestations in HIV disease has changed since the advent in 500 ml of sterile saline (0.1 mg/ml). Clotrimazole 1%
of HAART. cream, miconazole or ketoconazole 2% cream, and nystatin
The various oral manifestations can be categorized into ointment are useful medications for angular cheilitis and for
Infections: bacterial, fungal, viral application to a removable denture base when there is
Neoplasms: Kaposi's sarcoma, non-Hodgkin's lymphoma candidal infection involving the underlying mucosa.
Immune mediated: major aphthous, necrotizing stomatitis Systemic treatment for oral candidiasis involves the use of
Others: parotid diseases, nutritional, xerostomia imidazole (ketoconazole) and triazole (fluconazole and
Oral manifestations as adverse effects of antiretroviral itraconazole) antifungal medications. Fluconazole is given in
therapy. the dose of 100–200 mg/day. The duration of treatment with
There is no particular oral lesion which is associated only oral imidazoles usually is around 7–10 days but in cases of
with HIV-AIDS but there are certain manifestations like oral suspicion of esophageal involvement, the duration can be
candidiasis, oral hairy leukoplakia (OHL) which are extended to 21 days. As per the recent guidelines there is no
associated very frequently and are considered AIDS-defining role of prophylaxis for candidiasis in HIV patients.
diseases and have also been included in the clinical
classification of HIV by CDC in category B Histoplasmosis: Histoplasmosis is a granulomatous fungal
disease caused by Histoplasma capsulatum. The clinical
Fungal Infections presentation ranges from an asymptomatic or mild lung
Candidiasis: Oral or pharyngeal candidiasis are the infection to an acute or chronic disseminated form. Oral
commonest fungal infections observed as the initial histoplasmosis appears as chronic ulcerated areas located on
manifestation of symptomatic HIV infection Many patients the dorsum of the tongue, palate, floor of the mouth, and
can have esophageal candidiasis as well. It is usually vestibular mucosa. Focal or multiple sites can be involved. In
observed at CD4 counts of less than 300/μl. The commonest AIDS patients, histoplasmosis is rarely curable, but it can be
species of candida involved are Candida albicans although controlled with long-term suppressive therapy consisting of
nonalbicans species have also been reported. There are four the administration of amphotericin B and ketoconazole.
frequently observed forms of oral candidiasis: erythematous
candidiasis, pseudomembranous candidiasis, angular cheilitis, Cryptococcosis: Oral manifestations are quite unusual and
and hyperplastic or chronic candidiasis only two cases have been reported in the literature The
Erythematous candidiasis presents as a red, flat, subtle lesions consist of ulcerations of the oral mucosa, but the
lesion either on the dorsal surface of the tongue and/or the clinical diagnosis of oral cryptococcus may be difficult since
hard/soft palates. Patients complain of a burning sensation other microbial infections and trauma may show similar
in the mouth more so while eating salty and spicy food. appearances. Tissue biopsy may be required for the diagnosis
Diagnosis is made on the basis of clinical examination, a and treatment involves use of amphotericin B.
potassium hydroxide preparation which demonstrates the
fungal hyphae can be used for confirmation. Viral Infections
Pseudomembranous candidiasis appears as creamy white Oral hairy leukoplakia: These lesions are usually seen on
curd-like plaques on the buccal mucosa, tongue, and other the lateral surface of the tongue, but may extend to the dorsal
oral mucosal surfaces that can be wiped away, leaving a and ventral surfaces Lesions may be variably sized and may
red or bleeding surface appear as vertical white striations, corrugations, or as flat
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International Journal of Medicine Research
plaques, or raised, shaggy plaques with hair-like keratin usually affects children and young adults and is spread by
projections. In most cases, OHL is bilateral and direct and indirect contact. The typical lesion is an
asymptomatic. When it leads to discomfort it is usually umbilicated papule that may itch, leading to autoinoculation.
associated with superimposed candidal infection. OHL has Lesions may persist for years and eventually regress
been shown to be associated with a localized Epstein–Barr spontaneously. The occurrence of disseminated molluscum
virus (EBV) infection and occurs most commonly in contagiosum has been reported in HIV-infected patients.
individuals whose CD4 lymphocyte count is less than 200/μl. These lesions usually subside with immune reconstitution
Histological investigations reveal typical epithelial when patients are started on HAART.
hyperplasia suggestive of EBV infection. This condition
usually does not require treatment but use of oral acyclovir, Bacterial Infection
topical podophyllum resin, retinoids, and surgical removal The most common oral lesions associated with bacterial
have all been reported as successful treatments infection are linear erythematous gingivitis, necrotizing
ulcerative periodontitis, and, much less commonly, bacillary
Herpes simplex and varicella zoster virus infections: epithelioid angiomatosis and syphilis. In the case of the
Herpes simplex virus (HSV) is responsible for both primary periodontal infections, the bacterial flora is no different from
and recurrent infections of the oral mucosa. These infections that of a healthy individual with periodontal disease. Thus,
are acquired in childhood and after initial pustular lesions. the clinical lesion is a manifestation of the altered immune
The virus remains dormant, but in later stages of response to the pathogens.
immunosuppresion the virus can be activated and can lead to
various manifestations. Oral manifestations, represented by Linear erythematous gingivitis: This entity appears as a
diffuse mucosal ulcerations, are accompanied by fever, band of marginal gingival erythema, often with petechiae. It
malaise, and cervical lymphadenopathy. Ulcerations that is typically associated with no symptoms or only mild
follow the rupture of vesicles are painful and may persist for gingival bleeding and mild pain. Histological examination
several weeks. Recurrent HSV usually appears in keratinizing fails to reveal any significant inflammatory response,
oral mucosa (i.e., palate, dorsum of tongue, and gingiva) as suggesting that the lesions represent an incomplete
ulcerations but in most HIV-seropositive patients, this rule is inflammatory response, principally with only hyperemia
not followed. In these patients, the lesions may show unusual present. Oral rinsing with chlorhexidine gluconate often
clinical aspects and persist for many weeks. Contact with the reduces or eliminates the erythema and may require
varicella zoster virus (VZV) may result in varicella (chicken prophylactic use to avoid recurrence.
pox) as a primary infection and herpes zoster (shingles) as a
reactivated infection. In HIV infection, herpes zoster Necrotizing ulcerative periodontitis (NUP): This
frequently presents with early cranial nerve involvement and periodontal lesion is characterized by generalized deep
carries a poor prognostic significance. There may be osseous pain, significant erythema that is often associated
involvement of multiple dermatomes and these lesions might with spontaneous bleeding, and rapidly progressive
get secondarily infected as well. The lesions are usually destruction of the periodontal attachment and bone. The
associated with severe postherpetic neuralgias. destruction is progressive and can result in loss of the entire
alveolar process in the involved area. It is a very painful
Cytomegalovirus: CMV-related oral ulcerations, although lesion and can adversely affect the oral intake of food,
infrequent, are a recognized complication of HIV infection. resulting in significant and rapid weight loss. Patients also
The diagnosis of oral CMV is based upon the presence of have severe halitosis. Because the periodontal microflora is
large intranuclear and smaller cytoplasmic CMV inclusions no different from that seen in healthy patients, the lesion
in the endothelial cells at the base of the ulcerations. These probably results from the altered immune response in HIV
infections usually manifest in stage IV of the infection when infection. More than 95% of patients with NUP have a CD4
there is advanced immunosuppression with a CD4 count lymphocyte count of less than 200/mm3. Treatment consists
below 50. Presently, the drug of choice for CMV infection is of rinsing twice daily with chlorhexidine gluconate 0.12%,
intravenous gancyclovir. metronidazole (250 mg orally four times daily for 10 days),
and periodontal debridement, which is done after antibiotic
Human papilloma virus: In some patients with HIV therapy has been initiated.
infection, human papilloma virus (HPV) causes a focal
epithelial and connective tissue hyperplasia, forming an oral Bacillary Epithelioid Angiomatosis (BEA): This lesion
wart. In HIV-infected patients, oral HPV-related lesions have appears to be unique to HIV infection and is often clinically
a papillomatous appearance, either pedunculated or sessile, indistinguishable from oral Kaposi's sarcoma (KS). Since
and are mainly located on the palate, buccal mucosa, and both may present as an erythematous, soft mass which may
labial commissure. The most common genotypes found in the bleed upon gentle manipulation, biopsy and histological
mouth of patients with HIV infection are 2, 6, 11, 13, 16, and examination are required to distinguish bacillary epithelioid
32. Surgical removal, with or without intraoperative irrigation angiomatosis (BEA) from KS. The presumed etiological
with podophyllum resin, is the treatment of choice pathogen, Rochalimaea henselae, can be identified using
Warthin–Starry staining. Both KS and BEA are histologically
Molluscum contagiosum: Molluscum contagiosum is caused characterized by atypical vascular channels, extravasated red
by an unclassified DNA virus of the poxvirus family. Lesions blood cells, and inflammatory cells. However, prominent
appear as single or multiple papules on the skin of the spindle cells and mitotic figures occur only in KS.
buttocks, back, face, and arms. Molluscum contagiosum Erythromycin is the treatment of choice for BEA.
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International Journal of Medicine Research
Syphilis: While the prevalence of syphilis infection has risen mg/kg) in the case of large multiple ulcers and those not
significantly over the past decade, it is an uncommon cause responding to topical preparations. Alternative therapies such
of intraoral ulceration, even in HIV infection. Its appearance as dapsone 50–100 mg daily and thalidomide 200 mg daily
is no different from that observed in healthy individuals; it is for 4 weeks should be considered in recalcitrant cases. When
a chronic, nonhealing, deep, solitary ulceration; often immunosuppressant drugs are used in order to prevent
clinically indistinguishable from that due to tuberculosis, superadded fungal or bacterial infection, concurrent
deep fungal infection, or malignancy. Dark field examination antifungal medications such as fluconazole, itraconazole, and
may demonstrate treponema. Positive reactive plasma reagin antibacterial medications such as chlorhexidine gluconate
(RPR) and histological demonstration of Treponema oral rinse may be required.
pallidum is diagnostic. Combination treatment with
penicillin, erythromycin, and tetracycline is the treatment of Necrotizing stomatitis: It is an acute, painful ulceration
choice, the dosage and duration of the treatment depending which often exposes the underlying bone and leads to
on the presence or absence of neurosyphilis. considerable tissue destruction. This lesion may be a variant
of major aphthous ulceration, but occurs in areas overlying
Neoplasms the bone and is associated with severe immune deterioration.
Kaposi's sarcoma: It is the most common intraoral These lesions can also occur in edentulous areas. Like in
malignancy associated with HIV infection. The lesion may major aphthous ulceration, systemic corticosteroid
appear as a red-purple macule, an ulcer, or as a nodule or medication or topical steroid rinse is the treatment of choice.
mass. Intraoral KS occurs on the heavily keratinized mucosa,
the palate being the site in more than 90% of reported cases. Xerostomia: Xerostomia is common in HIV disease, most
KS is especially common among homosexual and bisexual often as a side effect of antiviral medications or other
males and is rarely found in HIV-infected women. Human medications commonly prescribed for patients with HIV
herpes virus (HHV8) has been demonstrated to be an infection, like angiolytics, antifungals, etc. The oral dryness
important cofactor in the development of KS. A histological is a significant risk factor for caries and can lead to rapid
examination is warranted for the definitive diagnosis of KS. dental deterioration. Xerostomia also can lead to oral
There is no cure for KS. Therapy for intraoral KS should be candidiasis, mucosal injury, and dysphagia, and is often
instituted at the earliest sign of the lesion, the goal being local associated with pain and reduced oral intake of food. Patient
control of the size and number of lesions. When only a few who has residual salivary gland function which is determined
lesions exist and the lesions are small (< 1 cm), intralesional by gustatory challenge, oral pilocarpine often provides
chemotherapy with vinblastine sulfate or sclerotherapy with improved salivary flow and consistency. Oral hygiene should
3% sodium tetradecyl sulfate is usually effective. Radiation be scrupulously maintained along with the use of dental floss.
therapy (800–2,000 cGy) is required for larger or multiple
lesions; stomatitis and glossitis are common side effects of Parotid gland disease
radiation. Although this entity has been reported in the HIV infection is associated with parotid gland disease. There
western literature but its incidence in Indian patients is quite can be gland enlargement and diminished flow of secretions.
low with only nine cases been reported till date Histologically, there may be lymphoepithelial infiltration and
benign cyst formation. The enlargement typically involves
Non-Hodgkin's lymphoma: NHL is the most common the tail of the parotid gland or, less commonly, the
lymphoma associated with HIV infection and is usually seen submandibular gland, and it may present uni- or bilaterally
in late stages with CD4 lymphocyte counts of less than with periods of increased or decreased size. The enlargement
100/mm3. It appears as a rapidly enlarging mass, less can be mistaken for a malignancy but in such cases a needle
commonly as an ulcer or plaque, and most commonly on the aspiration with yellow secretions in aspiration would help in
palate or gingivae. A histological examination is essential for making the diagnosis and in such cases further biopsy is
diagnosis and staging. Prognosis is poor, with mean survival unnecessary. Occasional swelling can be managed simply by
time of less than 1 year, despite treatment with multidrug repeated aspiration and rarely is radical removal of the gland
chemotherapy. necessary. The pathophysiological mechanism is not known,
though cytomegalovirus has been suggested to play a role.
Immune mediated oral diseases
In HIV there is immune suppression of cell-mediated Side effects of Anti Retrovial Therapy as oral
immunity as the disease progresses but at the same time there presentations
is abnormal activation of B-cell immunity. These disorders of With the widespread availability and usage of antiretroviral
the immune system also lead to various oral manifestations. therapy for the management of HIV, the clinical picture now
has shown a paradigm shift. The manifestations due to
Aphthous ulcers: They are the most common immune- adverse effects of the HAART are also observed along with
mediated HIV-related oral disorder, with a prevalence of the above-mentioned features of immunosuppresion. Thus
approximately 2–3%. These ulcers are either large solitary or one should be aware about them as well. Oral
multiple, chronic, deep, and painful often lasting much longer hyperpigmentation can be observed if a patient is on
in the seronegative population and are less responsive to zidovudine.
therapy. Treatment requires the use of a potent topical steroid Erythema multiformes is a known side effect of NNRTIs.
such as clobetesol when the lesions are accessible or Xerostomia is also observed in patients on lamivudine,
dexamethasone oral rinse when not accessible. Systemic didanosine, indinavir and ritonavir. Lipodystrophy with loss
glucocorticosteroid therapy may be required (prednisone 1 of subcutaneous fat has been reported extensively in patients
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International Journal of Medicine Research
on stavudine. Other oral effects like paresthesias, lip edema, the response to the HIV/AIDS epidemic include the support
chelitis, and taste disturbances have been observed in patients of the World Universal Public Health System, the provision
on protease inhibitors. of universal access to highly active antiretroviral therapy, and
The above-mentioned list is not the complete panorama of the creation of harm reduction projects that are politically and
manifestations which can be observed in an HIV patient but financially supported by federal governments
only an illustration of important lesions. It is thus essential Hence the prevention, diagnosis, treatment, and control of
that oral healthcare professionals recognize the hallmarks of these oral manifestations should be part of the objectives of
the illness and provide timely management for better survival every dental health professional.
of these patients.
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