manifestations of HIV infection are a fundamental component of disease
progression and occur in approximately 30 to 80 percent of the affected patient
population. 1, 2, 3 Factors which predispose expression of oral
lesions include CD4 counts less than 200 cells/mm3, viral load
greater than 3000 copies/mL, xerostomia, poor oral hygiene and smoking. 4,5
Oral lesions are differentiated as fungal, viral and bacterial infections,
neoplasms such as Kaposi’s sarcoma and non-specific presentations such as
aphthous ulcerations and salivary gland disease.
prevalence of the oral manifestations of HIV disease has changed since the
advent of highly active antiretroviral therapy (HAART). One study noted a
reduction of oral lesions from 47.6% pre-HAART to 37.5% during the HAART era 3.
The details of this study included a significant reduction in oral hairy
leukoplakia and necrotizing ulcerative periodontitis, yet there was no
significant change in the incidence of oral candidiasis, oral ulcers and
Kaposi’s sarcoma. This population did, however, see an increase in salivary
gland disease. Other published reports show a markedly increased incidence of
oral warts in the HAART era. 6,7
of the oral diseases seen in association with HIV disease is reportedly very
low. A study of 1424 adults who participated in the AIDS Cost and Utilization
Study revealed that only 9.1% reported treatment for oral manifestations.
After adjusting for CD4 count and other variables, African-Americans and
Hispanics were significantly less likely to receive treatment. Factors which
were significant in regards to receiving care for oral disease included more
than a high school education, participation in clinical trials and utilization
of counseling services.8 The ability to differentiate one
manifestation from another, and to manage some of the more common conditions are
fundamental to the overall health care of this patient population. The following
discussion will cover the most commonly seen oral manifestations seen in
association with HIV infection.
most common fungal infection seen in association with HIV infection is
oropharyngeal candidiasis. There are three frequently observed forms of oral
candidiasis: erythematous candidiasis, pseudomembranous candidiasis and angular
cheilitis. Erythematous candidiasis (EC) presents as a red, flat, subtle
lesion either on the dorsal surface of the tongue and/or the hard/soft palates.
EC tends to be symptomatic with patients complaining of oral burning, most
frequently while eating salty or spicy foods or drinking acidic beverages.
Clinical diagnosis is based on appearance, taking into consideration the
person’s medical history and virologic status. The presence of fungal hyphae
or blastospores can be confirmed by performing a potassium hydroxide
preparation. Although EC has been identified as one of the more common oral
manifestations seen in association with HIV disease, this presentation is
frequently under-diagnosed. 4 Due to the limited nature of this
infection, treatment involves the use of topical antifungal therapies.
(PC) appears as creamy white curd-like plaques on the buccal mucosa, tongue and
other oral mucosal surfaces that will wipe away, leaving a red or bleeding
underlying surface. The most common organism involved with the presentation of
candidiasis is Candida albicans, however there are increasing reports of
the increased incidence of non-albicans species. 9 Like EC, diagnosis
of PC is based on clinical appearance taking into consideration the person’s
medical history. Potassium hydroxide preparation, fungal culture or biopsy, may
be useful in obtaining an accurate diagnosis. There has been a decline in the
occurrence of PC in patients who are on successful highly active retroviral
regimens containing protease inhibitors. A review of the literature suggests
that immune reconstruction alone does not account for this reduction, but rather
the added effect of protease inhibitors on candidal virulence factors such as
aspartyl protease.10 Whereas there has been a decline in the
prevalence of PC in the HAART era, this is still one of the most common oral
manifestations seen in HIV disease. Treatment should be based on the extent of
the infection with topical therapies (nystatin, clotrimazole) utilized for mild
to moderate cases and systemic therapies (fluconazole) used for moderate to
severe presentations. Antifungal therapy should last for two weeks to reduce the
colony forming units to the lowest level possible to prevent recurrence.
HIV disease progresses and immunosuppression becomes more severe, the incidence
and severity of oropharyngeal candidiasis increase. The introduction of oral
azoles, most notably fluconazole, has led to the increased incidence of azole
resistant Candida albicans as well as the emergence of non-albicans
species such as Candida glabrata, which are inherently resistant to this
class of drug.11 Factors that increase the probability of
azole resistant strains of Candida presenting in the oral cavity include
previous exposure to azoles, low CD4 count and the presence of non-albicans
species.12, 13 To minimize the risk of resistance, topical
therapies should be considered for first-line treatment of initial or recurrent
cases of mild to moderate oropharyngeal candidiasis.11 Systemic
therapies should be utilized for moderate to severe cases.
clinical presentation of Angular cheilitis (AC) is erythema and/or
fissuring of the corners of the mouth. AC can occur with or without the presence
of EC or PC. Angular cheilitis can exist for an extensive period of time if left
untreated. Treatment involves the use of a topical antifungal cream directly
applied to the affected areas four times a day for the two-week treatment period.
Gingival Erythema (LGE), a
periodontal disease, presents as a red band along the gingival margin, which may
or may not be accompanied by occasional bleeding and discomfort. LGE is seen
most frequently in association with anterior teeth, but commonly extends to the
posterior teeth. LGE can also present on attached and non-attached gingiva as
petechia-like patches. Research has
indicated there may be a relationship between sub-gingival colonization of
Candida species and HIV-related periodontal conditions including LGE.14
The most recent classification of periodontal diseases by the American Academy
of Periodontology grouped LGE under “gingival disease of fungal origin”.15
Treatment for this condition would include debridement by a dental professional
followed by twice daily rinses with a 0.12% chlorhexidine gluconate suspension
for two weeks and improved oral hygiene home care.
chronic adult periodontal disease occurs frequently in persons living with HIV
disease, three unique presentations of periodontal disease have also been
reported in this patient population: the previously discussed linear gingival
erythema, necrotizing ulcerative gingivitis (NUG) and necrotizing ulcerative
periodontitis (NUP). The demarcation between necrotizing gingivitis and
necrotizing periodontitis was created to define the difference between the rapid
destruction of soft (NUG) and hard (NUP) tissues. It has not been determined
whether or not NUG and NUP are the same or unique entities and both have been
classified as “Necrotizing Periodontal Diseases” by the American Academy of
Periodontology. Due to the lack of significant differences in the microbial
profile of these two conditions and similarity in treatment, this discussion
will focus on NUP, which is a marker of severe immune suppression.16
This condition is characterized by severe pain, loosening of teeth, bleeding,
fetid odor, ulcerated gingival papillae and rapid loss of bone and soft tissue.
Patients often refer to their pain as “deep jaw pain.” Prompt referral to a
dental professional for removal of dental plaque, calculus and necrotic soft
tissues utilizing a 0.12% chlorhexidine gluconate or 10% povidone iodine lavage
will alleviate symptoms. Patients should be placed on antibiotic therapy
effective against gram-negative flora such as metronidazole or Augmentin.
The healthcare team should address pain management, nutritional
supplementation and stress the importance of oral hygiene. Timely referral to
the primary care team is indicated to rule out other systemic opportunistic
is widespread and oral manifestations of herpes lesions are common. Seventeen
percent of the US population over age 12 experienced an oral herpetic lesion
over a 1-year period.17 Recurrent intraoral herpes simplex starts as
a small crop of vesicles that rupture to produce small, painful ulcerations
which may coalesce. Although these herpetic ulcerations are often self-limiting,
the use of an antiviral medication such as acyclovir is sometimes necessary to
control the outbreak. Medications such as acyclovir stop viral replication and
allow the affected area to heal.
Zoster, a reactivation of
the varicella zoster virus, can occur along any branch of the trigeminal nerve;
therefore an intraoral or extraoral presentation along branches of this nerve is
possible. The external lesions will start as vesicles, break open and then crust
over. The intraoral lesions will start as vesicles, burst and then present as
oral ulcerations. Since both of these presentations are along the trigeminal
nerve, the patient’s chief complaint may be toothache of unknown origin.
Treatment options include higher doses of acyclovir (800 mg, five times a
day for 7 to 10 days) or famciclovir 500 mg three times a day for 7 days.).
hairy leukoplakia (OHL) is caused by the Epstein-Barr virus and presents as a
white corrugated, nonremovable lesion on the lateral borders of the tongue.
Studies have shown a significant decrease in the incidence of OHL in the HAART
era.3,4 This condition is normally asymptomatic and does not require
therapy unless there are cosmetic concerns. Patients, who present with this
condition while on HAART may be experiencing a failure in their present
warts due to Human
papillomavirus (HPV) have dramatically increased in the HAART era.6,7
One study noted the risk of oral warts
was associated with a
one-log10 decrease in HIV RNA in the 6 months prior to oral HPV
diagnosis, which suggests that this may in part be related to immune
reconstitution.6 Oral warts may appear cauliflower-like, spike or
raised with a flat surface. Treatment, which may involve surgery, laser surgery
or cryotherapy, is problematic, as these lesions tend to recur.
is still the most frequent oral malignancy seen in association with HIV
infection, although the incidence has dramatically decreased in the HAART era.4
For homosexual men with AIDS, incidence of all presentations of KS is highest in
the 30 – 39 age group with 5 cases/100 person-years.18 Kaposi's
sarcoma-associated herpesvirus (KSHV) has been implicated as a co-factor in the
presentation of KS in persons living with HIV disease. The overall prevalence of
KSHV in Texas blood donors proved to be 15%, which is higher than studies
performed in other states.19
clinical appearance of KS can be macular, nodular, or raised and ulcerated; the
color can range from red to purple. Early lesions tend to be flat, red and
asymptomatic, with the color becoming darker as the lesion ages. As lesions
progress they can interfere with the normal functions of the oral cavity and
become symptomatic secondary to trauma or infection. A biopsy is necessary for a
definitive diagnosis. Treatment of oral lesions ranges from localized injections
of chemotherapeutic agents, such as vinblastine sulfate, to surgical removal.
For persons who present with extraoral and intraoral KS, systemic chemotherapy
may be the treatment of choice. It is important that the entire primary health
care team, including the primary care provider, dentist and oncologist work
closely together in order to facilitate the best possible outcome. Oral hygiene
should be stressed for people with oral KS.
is an AIDS defining condition that, on occasion, presents in the oral cavity.
This lesion tends to present as a large, painful, ulcerated mass on the palate
or gingival tissues. A biopsy is necessary for a definitive diagnosis. The oral
health care team should refer patients with a diagnosis of non-Hodgkin’s
lymphoma to an oncologist for treatment.
Gland Disease and xerostomia
is clinically apparent by an increase in the size of the major salivary glands,
most notably the parotids. Biopsy of suspect enlarged parotid salivary glands
has revealed an increase in lymphocytic infiltrates, more specifically, CD8
condition usually presents as a bilateral enlargement of the parotid salivary
glands and is often times accompanied by symptoms of dry mouth. There has been a
reported increase in the presentation of salivary gland disease in the HAART
era, which may be related to a reconstitution syndrome.3
or dry mouth is common complaint among people living with HIV disease.
Approximately 29% of those participating in the HIV Cost and Utilization Study
cohort reported symptoms of xerostomia. Factors which proved to be significant
in the presentation of xerostomia included the previously referenced salivary
gland disease, use of medications to manage HIV and other conditions, smoking,
and a viral load of > 100,000/mm3. 20
of dry mouth can be temporarily alleviated by sucking on sugar-free hard
candies, chewing sugar-free gum and by using oral moisturizers. The change in
the quantity and quality of saliva may lead to increased dental decay and
therefore meticulous oral hygiene should be stressed and use of prescription
topical fluoride preparations encouraged.
aphthous ulcerations (RAU) are a common occurrence with approximately 17 percent
of the U.S. population reporting an episode within a twelve-month period of time17.
RAU present on non-keratinized or non-fixed tissues such as labial and buccal
mucosa, the floor of the mouth, ventral surface of the tongue, posterior
oropharynx and the maxillary and mandibular vestibules.
RAU are characterized by a halo of inflammation and a yellow-gray
pseudomembranous covering. RAU, which last between 7 and 14 days in the general
population, may last longer and be more painful in immunocompromised
individuals. Pain is noted to increase upon eating salty, spicy or acidic foods
and beverages as well as due to trauma when consuming hard or rough foods.
Treatment involves the use of topical corticosteroids such as dexamethasone
elixir (0.5mg/5ml) 5 ml swished for one minute then expectorated, or for more
severe occurrences, systemic corticosteroids such as prednisone.
While the use of immunoactive agents contributes to a reduction in
inflammation and therefore speeds healing, they do not immediately address pain
resulting from due to RAU is typically managed by using topical anesthetics or
systemic analgesics. Whereas topical anesthetics do offer some relief from the
pain associated with these lesions, such relief is usually of short duration.
Another consequence of use of anesthetic mouthrinses is the numbing effect on
the taste buds, which results in decreased desire to eat. Diminished nutritional
intake further negatively impacts patients’ overall well-being. Systemic
analgesics are somewhat effective, but do not specifically address localized
pain associated with oral ulcerative disease.
A new over-the-counter oral formulation of 2-octyl cyanoacrylate (Orabase
Soothe-N-Seal) has shown promise as a barrier product for managing localized
oral pain due to ulcerative disease.21
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