Ebook Textbook of oral pathology (2/E): Part 2

21

Acquired Immunodeficiency
Syndrome
Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe)

Chapter Outline
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Definition
AIDS related complex
Prevalence
Etiology
Characteristic of HIV virus
Mechanism of action
Transmission

Clinical features
Oral manifestations
Candidiasis
Kaposi’s sarcoma
Hairy leukoplakia
Periodontal disease associated with HIV
Non-Hodgkin lymphoma
Recurrent herpes labialis
Oral human papilloma virus lesions

Acquired immunodeficiency syndrome (AIDS) is a
devastating fatal disease, which is in epidemic form
throughout the world. It is an incurable viral STD caused
by human immunodeficiency virus (HIV). It stands for:
∙ A: Acquired, i.e. contagious not inherited
∙ I: Immune, i.e. power to receive disease
∙ D: Deficiency
∙ S: Syndrome, i.e. number of signs and complains
indicative of particular disease.
Four identified etiological agents are of substantially
lenti virus (HIV-I an HIV-II) that cause slow infection in
which sign and symptoms only appear after many months or
years of infection and two member of oncovirus (HTLV-I

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Herpes zoster
HIV associated salivary gland diseases
Idiopathic thrombocytopenic purpura
Mycobacterium infection
Hyperpigmentation
Histoplasmosis
Recurrent aphthous stomatitis
Molluscum contagiosum
Oral squamous cell carcinoma
Diagnostic tests
Screening test for AIDS
Enzyme-linked immunosorbant assay
The Western Blot method
Viral culture and polymerase chain reaction
Surrogate marker for progression of HIV-I infection
Management

and HTLV-II) that are capable of oncogenic transformation
and are usually associated with leukemia or lymphoma.

The case of AIDS was detected in June 1981 when
5 young homosexuals men came with the suffering
from rare lung infection due to microorganism called
Pneumocystis carinii. In India, the first description of
AIDS came in Madras where 6 women out of 125 who
were screened were HIV positive in high-risk group of
prostitutes.
The AIDS appear to be endemic in central and
equatorial Africa and it may be old disease of Africa that
has gone unrecognized. The HIV-1 infection has also
become the primary emphasis of effort at controlling


Acquired Immunodeficiency Syndrome

sexually transmitted diseases (STDs). Moreover, the
knowledge gain about sexual and other behavior associated
with transmission of HIV, as well as strategies that have
been effective in modifying those behaviors, is transferable
to other sexually transmittable and bloodborne infections
and has revolutionized standard approaches to the control
of these infections.
Oral and perioral lesions are common presenting
features in patient with human immunodeficiency virus
and may have deterioration of general health and a poor
prognosis.

DEFINITION
World Health Organization (WHO) has given following
definition of AIDS:

One or more opportunistic infections listed in clinical
features that are at least moderately indicative of underlying
cellular immune deficiency.
Absence of all known underlying causes of cellular
immune deficiency (other than HIV infection) and absence
of all other causes of reduced resistance reported to be
associated with at least one of those opportunistic diseases.

CLASSIFICATION
1st Classification (given in 1993) by Center for Disease Control (CDC)
CD4 + T-cell categories

A
Asymptomatic, acute HIV
and PGL

B
Symptomatic, not A or C
conditions

C
AIDS indicator condition

More 500/µL

A1

B1

C1

200 to 499/µL

A2

B2

C2

Less than 200/µL
AIDS indicator T-cell count

A3

B3

C3

Category A: In adolescent less than 13 years with
documented HIV infection:
∙ Persistence generalized lymphadenopathy
∙ Active condition.

∙
∙

Category B: Condition is attributed to HIV infection or
indicative of defect in the cell-mediated immunity.
∙ Bacillary angiomatosis
∙ Oropharyngeal and vulvovaginal candidiasis

∙ Cervical carcinoma in situ
∙ Constitutional symptoms like fever (38.5˚C) and
diarrhea
∙ Oral hairy leukoplakia and herpes zoster
∙ Idiopathic thrombocytopenic purpura.

∙
∙
∙
∙

Category C: AIDS indicative condition
∙ Candidiasis of bronchi, trachea or lung and esophageal
candidiasis

∙
∙
∙

Invasive cervical cancer
Disseminated or extrapulmonary coccidioidomycosis,
extrapulmonary cryptococcosis
Chronic intestinal cryptosporidiosis more than 1 month
duration
Cytomegalovirus retinitis with loss of vision
HIV related encephalopathy
Herpes simplex bronchitis, pneumonitis and esophagitis
Kaposi sarcoma, Burkitt’s lymphoma and immunoblastic
lymphoma
Mycobacterium tuberculosis infection at any pulmonary

or extrapulmonary sites
Pneumocystic carinii pneumonia and recurrent
pneumonia
Progressive multifocal leukoencephalopathy
Toxoplasmosis of brain and wasting syndrome
Recurrent Salmonella septicemia.

∙

∙
∙

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Textbook of Oral Pathology

2nd Classification by USPHS-CDC
526

∙
∙
∙
∙

Group I: Acute infection
Group II: Asymptomatic infection
Group III: Persistence generalized lymphadenopathy.
Group IV: Other disease
– Subgroup A: Constitutional diseases

– Subgroup B: Neurological diseases
– Subgroup C: Secondary infectious diseases
-

-

C1: Specified secondary infectious diseases
listed in CDC surveillance definition for
AIDS.
C2: Other specified secondary infectious
stages.

– Subgroup D: Secondary cancer
– Subgroup E: Other conditions.

AIDS RELATED COMPLEX
For clinical and research studies, persons exhibiting
complex clinical problems and immunological or
hematological abnormalities on the laboratory tests, have
been classified as having AIDS related complex (ARC).
The ARC requires any two or more symptoms and two or
more abnormal laboratory findings. It must be present for
at least 3 months.

Symptoms

Laboratory findings

• Lymphadenopathy
• Weight loss of 15 lbs or

10% of body weight
• Fever of 38.5˚C which is
intermittent or continuous
• Diarrhea, fatigue and
malaise
• Night sweats

•
•
•
•
•
•
•

Decreased number of T
helper cell
Decreased ratio of T helper
cells to T suppressor cells
Anemia or leukopenia
or thrombocytopenia or
lymphopenia
Increased serum globulin
level
Decreased blastogenic
response of lymphocytes to
mitogen
Increased level of
circulating immune
complex

Cutaneous anergy to
multiple the skin test
antigens

PREVALENCE
It is more common in Western countries particularly
in the United State. Largest population of AIDS is in
homosexuals, intravenous drug users and, heterosexuals
with sexual contact with AIDS patient. Patients who
received transfusion of blood or blood pigments donated by
the person with risk factors. Ninety-two percent of victims
are males, 6.5 percent female with 1 percent children. It is
common at the age of 25 to 49 years.

Etiology
T lymphocytes: There is quantitative and qualitative
deficiency of T4 helper cells in AIDS patients, which lead
to certain investigators to focus their efforts on determining
if etiologic agent was a virus that manifested a particular
tropism for T4 helper lymphocytes.
HTLV-III virus: Dr Robent C Galleo determined
that type C retrovirus was tropic for T4 lymphocytes in
adult T-cell leukemia/lymphoma. He named the virus,
Humans T-cell leukemia/lymphoma virus (HTLV–I). So
it is considered to be etiological agent for AIDS. But as
it causes lymphoproliferation in T-cell leukemia, where as
AIDS is a disease of lymphodepletion. The answer came in
the discovery of type D retrovirus of HTLV family that has
been termed as HTLV-III.
LAV virus: On the other hand, virus called lymphadenopathy associated virus (LAV), was being isolated from the

AIDS patient in Europe.
HTLV-III and LAV is closely related members of same
class of virus. Finally, it is proved that HTLV and LAV
are cytopathic human T–lymphocytotropic viruses that
manifested selective infectivity for the helper/inducer
subset of T-cells that as phenotypically designated
reactivity with monoclonal antibody T4 or Leu3.
HIV: In order to avoid different nomenclatures
retrovirus responsible for the AIDS are named ‘Human
immunodeficiency virus’ which belong to family of
retroviruses.
Risk person: Six groups are at risk of developing AIDS.
These are homosexuals or bisexuals—71.4 percent,
intravenous drug users—18.4 percent, hemophilia,
recipient of multiple blood transfusion, infant born of
parents belonging to first three high-risk groups and
heterosexual contacts of high-risk group.


Acquired Immunodeficiency Syndrome

CHARACTERISTIC OF HIV VIRUS
The HIV is a spherical enveloped virus, about 90 to
120 nm in size (Fig. 21.1). The nucleocapsid has an outer
icosahedral shell and inner cone shaped core, enclosing the
ribonucleoproteins. The genome is diploid, composed of
two identical single stranded, positive sense RNA copies.
Inside the envelope is a protein core, which contain enzymes
reverse transcriptase, intregrase, protease, etc. all essential for
viral replication and maturation. When the virus infects a cell,

the viral RNA is transcribed by the enzymes, first into single
stranded DNA and then to double stranded DNA (provirus),
which is integrated into the host cell chromosomes. The virus
is extremely sensitive to heat, thus boiling and autoclaving are
very effective measure of inactivating the virus.

Mechanism of Action
The HIV attacks the immune system of the body. Due
to that an individual is not able to protect himself from
potentially harmful organism.
Normal mechanism: Pathogenic viruses → identified
by macrophage → it activates T lymphocytes → it get
differentiated into effecter cell like T helper cell or T4
and T suppresser cell or T8 → T4 cells secrete various
lymphokines which induce lymphocyte to differentiated
into plasma cell → it secrete specific antibodies against
viral antigen → it destroy the virus.
Mechanism in AIDS: HIV virus is lymphotropic virus
→ its primary target is T4 cell → when the virus enters the
bloodstream, it integrates into gene into DNA of some primary

T4 lymphocyte → this viral DNA then becomes integrated
into the host chromosomes → the chromosomal integration
is prerequisite for replication of retroviruses, but also for the
latency → once the viral genes are integrated into cells of own
DNA, they can apparently remain dormant for an indefinite
period of time, without causing its affects. This is called
‘incubation period’ → once the viral gene is activated, virus
particles convert T4 lymphocytes into AIDS virus factory →
when the number of T4 lymphocyte is severely depleted, the

immune system collapses and variety of infections occur → at
this stage patient is said to have AIDS.

Transmission
Repeated intimate contact: It is in 90 percent of cases.
It depends upon number of sexual partners, receptive anal
intercourse and presence of other STDs. All these are in
high-risk group. Prostitution is a major heterosexual factor
associated with AIDS.
Use of contaminated blood products: Intravenous drug
users, HIV contaminated blood transfusion, blood clotting
concentrate and organ transplantation.
Perinatal transmission: It occurs in 13 percent among
children born to HIV seropositive mother.
Other nosocomial routes: Transmission from patient to
patient due to reuse of contaminated and shared needles.
Professional hazards: The risk of transmission from HIV
infected patient to health care workers is more than health
care workers to patient.

CLINICAL FEATURES (FIG. 21.2)
Protozoan and helminthes infection: Cryptosporidiosis
(intestinal) causing diarrhea for over one month. The
most common opportunistic infection is by Pneumocystis
carinii which causes pneumonia. CNS infection or other
disseminated infections and toxoplasmosis.
Fungal infection: Candidiasis causing esophagitis,
cryptococcosis causing CNS infection, disseminated
histoplasmosis and bronchial or pulmonary candidiasis.
Bacterial infections: Mycobacterium avium intracellulare

causing infection disseminated beyond lung and lymph
node. Mycobacterium tuberculosis will cause tuberculosis.

Figure 21.1 HIV virus

Viral infections: Cytomegalovirus causing infection in the
internal organs other than liver, spleen and lymph nodes.
Herpes simplex virus, causing chronic mucocutaneous
infection with ulcers persisting more than one month.

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Figure 21.2 Features of HIV infection

Malignancy: Kaposi’s sarcoma and squamous cell
carcinoma. Lymphoma limited to bronchi and nonHodgkin’s lymphoma.
AIDS dementia complex: This occur in patient with HIV
infection and causes progressive encephalopathy.

ORAL MANIFESTATIONS
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 HIVassociated oral lesions may reduce morbidity. The
presence of these lesions may be an early diagnostic
indicator of immunodeficiency and HIV infection may
change the classification of the stage of HIV infection and
is a predictor of the progression of HIV disease. Around 95
percent of AIDS patients have head and neck lesions and
about 55 percent have important oral manifestation. They
are described below.

Oral Disorders in HIV Disease
∙ Fungal
More common
– Candidiasis
Less common
– Aspergillosis
– Histoplasmosis
– Cryptococcus neoformans
– Geotrichosis
∙ Bacterial
More common
– HIV gingivitis
– HIV periodontitis
– Necrotizing gingivitis
Less common
– Mycobacterium avium intracellulare
– Klebsiella pneumoniae
– Enterobacter cloacae
– E. coli

– Salmonella enteritidis
– Sinusitis
– Exacerbation of apical periodontitis
– Submandibular cellulitis


Acquired Immunodeficiency Syndrome

∙

∙

∙
∙

∙

Viral
More common
– Herpes simplex
– Varicella zoster
– Epstein-Barr virus including hairy leukoplakia
Less common
– HPV virus
– CMV virus
Neoplasm
More common
– Kaposi’s sarcoma
Less common
– Non-Hodgkin lymphoma

– Squamous cell carcinoma
Lymphadenopathy
Neurologic disorders
Less common
– Paresthesia
– Facial palsy
– Hyperesthesia
– Dysphagia
Miscellaneous
Less common
– Recurrent apthous ulceration
– Progressive necrotizing ulceration
– Toxic epidermolysis
– Delayed wound healing
– Thrombocytopenia
– Xerostomia and sicca type syndrome
– HIV embryopathy
– Hyperpigmentation
– Granuloma annulare
– Exfoliative cheilitis
– Lichenoid and other drug reaction.

EC-Clearinghouse
Classification
of
Oral
Manifestation of HIV
Group I—strongly associated with HIV infection
∙ Candidiasis
∙ Hairy leukoplakia

∙ Kaposi’s sarcoma
∙ Non-Hodgkin’s lymphoma
∙ Periodontal disease (linear gingival erythema,
necrotizing gingivitis and necrotizing periodontitis).

Group II—less commonly associated with HIV
infection
∙ Bacterial infection (Mycobacterium)
∙ Melanotic hyperpigmentation
∙ Necrotizing ulcerative stomatitis
∙ Salivary gland disease
∙ Thrombocytopenia purpura
∙ Oral ulceration NOS (not otherwise specified)
∙ Viral infections like herpes simplex, zoster,
papillomavirus.
Group III—seen in HIV infection
∙ Bacterial infection (Actinomyces israelii, E. coli,
Klebsiella pneumonia)
∙ Cat scratch disease
∙ Epithelioid angiomatosis
∙ Drug reaction
∙ Fungal infection other than candidiasis
∙ Neurologic disturbance
∙ Recurrent aphthous stomatitis
∙ Viral infection like cytomegalovirus, molluscum
contagiosum.

Candidiasis
Oral candidiasis is most commonly associated with Candida
albicans, although other species, such as C. glabrata and

C. tropicalis, are frequently part of the normal oral flora.
A number of factors predispose patients to develop candidiasis: infancy, old age, antibiotic therapy, steroid and other immunosuppressive drugs, xerostomia, anemia, endocrine
disorders and primary and acquired immunodeficiency.
Candidiasis is a common finding in people with HIV
infection. Reports describe oral candidiasis during the
acute stage of HIV infection, but it occurs most commonly
with falling CD4+ T-cell count in middle and late stages of
HIV disease.
Several reports indicate that most persons with HIV
infection carry a single strain of Candida during clinically
apparent candidiasis and when candidiasis is quiescent.

Clinical Features
Location: Patient with a HIV usually has lesion of hard
palate and soft palate.
Appearance: The clinical appearances of oral candidiasis vary. The most common presentations include

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clinical lesions are examined using potassium hydroxide
(KOH), PAS, or Gram’s stain.
Smear shows candidal organism embedded in
superficial keratin.

530

Management

Topical clotrimazole is treatment option in case of
candidiasis associated with HIV infection.
Systemic fluconazole is given if the CD4+ count is below
50 cell/mm3. In some patient itraconazole and intravenous
amphotorecin B are given to combat severe infection.
Points to Remember
Figure 21.3 Candidiasis in AIDS patient

pseudomembranous, hyperplastic, angular, and erythematous candidiasis, which are equally predictive of the
development of AIDS and angular cheilitis (Fig. 21.3).
Symptoms: These lesions may be associated with a variety
of symptoms, including a burning mouth, problems in
eating spicy food and changes in taste. All three of these
common forms may appear in one individual.
Pseudomembranous candidiasis (Thrush): Characteristic creamy white, removable plaques on the oral
mucosa are caused by overgrowth of fungal hyphae mixed
with desquamated epithelium and inflammatory cells. The
mucosa may appear red when the plaque is removed. This
type of candidiasis may involve any part of the mouth or
pharynx.
Erythematous candidiasis: Erythematous candidiasis
appears as flat, red patches of varying size. It commonly
occurs on the palate and the dorsal surface of the tongue.
Erythematous candidiasis is frequently subtle in appearance
and clinicians may easily overlook lesions, which may
persist for several weeks if untreated.
Angular cheilitis: Angular cheilitis appears clinically
as redness, ulceration and fissuring, either unilaterally or
bilaterally at the corners of the mouth. It can appear alone
or in conjunction with another form of candidiasis.

Histopathological Features
Candida is a commensal organism in the oral cavity.
Candidiasis is diagnosed by its clinical appearance and
by detection of organisms on smears. Smears taken from

C. glabrata and C. tropicalis, falling CD4+ T-cell count,
pseudomembranous, hyperplastic, angular, and erythematous candidiasis, burning mouth, smears, embedded
in superficial keratin, topical clotrimazole, systemic fluconazole, itraconazole and intravenous amphotorecin B.

Kaposi’s Sarcoma
It is also called angioreticulo-endothelioma. It is the most
common tumor associated with AIDS and occurs in 1/3rd
of AIDS patients.

Etiology
There is higher incidence of Kaposi’s sarcoma is in
homosexual men with AIDS as compared to heterosexuals
with AIDS. It has been suggested that there is transmissible
agent prevalence in homosexual population, which
stimulate certain factor such as angiogenesis protein that
may be critical in the pathogenesis of neoplasm.
The patient with AIDS often shows clustered lesion
in the oral cavity, which suggests direct inoculation of
mucosa with sexually transmitted agent.
Some theories suggests role of cytomegalovirus in
the pathogenesis of Kaposi’s sarcoma, but studies on
prevalence of antibodies to cytomegalovirus in patient
with classic and epidemic Kaposi’s sarcoma have failed to
demonstrate role of cytomegalovirus.

Nowadays, it has been stated that Kaposi’s sarcoma is
associated with human herpes virus (HHV 8). The HHV 8
is detected in oral epithelial cells and in oropharynx.
Types
•
•
•
•

Classic
African (cutaneous variant)
African (lymphadenopathy variant)
Kaposi’s sarcoma associated with AIDS.


Acquired Immunodeficiency Syndrome

Epidemiology and Form
Kaposi’s sarcoma appears in various forms like classic,
African (cutaneous variant), African (lymphadenopathy
variant) and Kaposi’s sarcoma associated with AIDS.
Classic type is a rare neoplasm and occurs in the older
man. Usually, it appears as blue-black macule on the lower
extremities. It is slow growing and rarely involves the
lymph nodes and visceral organs.
African Kaposi’s sarcoma is considered an endemic
disease and affects children, 10-year-old or younger
patients, more common in men than women. It appears as
exophytic growth located in legs and arms. This form is
locally aggressive and lymph nodes involvement is rare.

The lymphadenopathic form occurs in children of 10 years
age and younger with same frequency in men and women.
The visceral and massive nodal involvement is common.
Kaposi’s sarcoma is observed in patients with kidney
transplantation and in patients who receive the immunosuppressive drugs for variety of diseases. Drugs such as
prednisolone, cyclosporine and cyclophosphamide have
been associated with development of Kaposi’s sarcoma.
It usually affects legs, arms, lymph nodes and visceral
organs.

Clinical Features
Age and sex distribution: It is more common in male as
compared to female in ratio of 20:1. It can occur at any age
but most common in 5th, 6th, 7th decade except in Africa
where it more common in children.

on any part of the oral mucosa including the gingiva, soft
palate, buccal mucosa and in the oropharynx. It can involve
either alone or in association with skin and disseminated
lesions. It may be the first symptom of AIDS.
Appearance: It can appear as a red, blue, or purplish lesion.
It may be flat or raised solitary or multiple. Occasionally,
yellowish mucosa surrounds the lesion. The lesions may
enlarge, ulcerate and become infected. Good oral hygiene
is essential to minimize these complications.
Sign: It may vary in size from few millimeter to a centimeter
or more in diameter and are tender and painful.

Histopathological Features
It consists of interweaving band of spindle shaped and

or plump endothelial cell and atypical vascular channels,
enmeshed in reticular or collagen fibers.
It consists of numerous, small capillary type blood
vessels, which may or may not contain blood. Inflammatory
cell infiltration is common (Fig. 21.4).
In late stage, lesion consists of well defined nodules or
lesions with diffuse involvement of the lamina propria.
Histopathological Stages
• P
atch stage (macular): In this proliferation of
miniature vessels
• Plaque stage: It shows further proliferation of
vascular channels with development of spindle cells
• Nodularstage: Spindle cell increase to form nodular
tumor like mass.

Site: Commonly affects skin, oral and visceral organs. It
occurs commonly in head and neck region. Tip of nose is
peculiar and frequent location of it. It can involve lymph
nodes, soft tissue, extremities, GIT, lung, liver, pancreas,
spleen and adrenal gland.
Appearance: It begins as multinucleated neoplastic
process that manifests as multiple red or purple macules
and in more advanced stage, a nodule occurring on the skin
or mucosal surface.
Sign: Size of it ranges from a few millimeters to a centimeter
or more in diameter and are usually tender on palpation. It
is slow growing but can behave as a very aggressive lesion
with rapid visceral involvement.

Oral Manifestations
Location: It has tendency to involve the oral cavity, with
hard palate as the most common site. But lesions may occur

Figure 21.4 Capillary blood cell seen in Kaposi’s sarcoma

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Management

Clinical Features

Treatment is determined on the basis of the number, size
and location of the oral lesions. The choice of therapy
depends on the effect of treatment on the adjacent mucosa,
pain associated with treatment, interference with eating
and speaking and the patient’s preference.
It is important to perform thorough dental prophylaxis
before initiating therapy for lesions involving the gingiva.
Response to therapy is improved if all local plaque and
calculus are removed. Local application of sclerosing
agents may reduce the size of oral lesions.
Local treatment is appropriate for large oral lesions that
interfere with eating and talking. Oral lesion can be treated
surgically or with localized intralesional chemotherapy.

Intralesional vinblastine, radiation therapy, intravenously interferon alpha and sclerotherapy with 3 percent
sodium tetradecyl sulfate.

Location: It is unique and significant lesion which
primarily occurs unilaterally or bilaterally on the lateral
border of tongue. It can also occur on dorsum of the tongue,
buccal mucosa, floor of mouth, retromolar area and soft
palate. Many time lesion start on lateral border and spread
to entire dorsum of tongue.

Points to Remember
Angioreticulo-endothelioma, affects skin, multinucleated neoplastic process that manifests as multiple red or
purple macules, hard palate, most common site, red, blue,
or purplish lesion, yellowish mucosa surrounds the lesion,
spindle shaped and or plump endothelial cell, numerous,
small capillary type blood vessels, Inflammatory cell
infiltration, thorough dental prophylaxis, intralesional
vinblastine, radiation therapy, intravenously.

Hairy Leukoplakia
Oral hairy leukoplakia, which presents as a non-movable,
corrugated or “hairy” white lesion on the lateral margins
of the tongue occurs in all risk groups for HIV infections,
although less commonly in children than in adults.
It occurs in about 20 percent of persons with
asymptomatic HIV infection and becomes more common
as the CD4+ T-cell count falls.

Appearance: There is characteristic corrugated and
white appearance. It does not rub off and may resemble

the keratotic lesion. The surface is irregular and may
have prominent folds or projections, sometimes markedly
resembling hairs. Occasionally, however, some areas may
be smooth and flat (Fig. 21.5).
Pseudo hairy leukoplakia: Sometimes, the white lesion
satisfies many criteria for diagnosis of hairy leukoplakia,
but if EBV not present this is called ‘pseudo hairy
leukoplakia’. Presence of hairy leukoplakia is fairly
indicator of HIV pro-sensitivity and is predictor of
deficiency immunocompetence.

Histopathological Features
Histologically lesion shows hyperkeratosis, acanthosis,
contain Epstein-Barr virus and no or minimum inflammation.
Balloon cells: The epithelial exhibits band-like zone of
lightly stained cells with abundant cytoplasm in the upper
spinous layer.
Nuclear beading: There is presence of scattered cells with
nuclear clearing with pattern of peripheral margination of

Etiology
Exact etiology is not known but Epstein-Barr virus has
identified in these lesions.
One hypothesis is that basal epithelial cells of lateral
margin of tongue normally harbors EBV in majority of
adult population, who are EBV sero-positive and carrier of
that disease.
It is found primarily in homosexual male. Direct
infection of Langerhans cell due to HIV induced loss of
factor essential for their integrity and function, permit

reactivation of EBV with frequent epithelial hyperplasia.

Figure 21.5 Hairy leukoplakia showing characteristic

corrugated appearance


Acquired Immunodeficiency Syndrome

chromatin on superficial epithelium. This is called nuclear
beading.
Immunochemistry tissue in situ hybridization, noninvasive tissue in situ hybridization, or electron microscopy
does demonstrate of Epstein-Barr virus. The lesion of
leukoplakia consists of Langerhans cells.

Management
Hairy leukoplakia usually is asymptomatic and does not
require treatment. Hairy leukoplakia is almost always a
manifestation of HIV infection and clinicians should arrange
evaluation of HIV disease and appropriate treatment for
patients with hairy leukoplakia.
Hairy leukoplakia has disappeared in patients receiving
high-dose acyclovir for herpes zoster, presumably because
of the anti-EBV activity of acyclovir. Doses of acyclovir
(2.5–3 mg per day for 2–3 weeks) usually eliminate HL, but
the lesion usually recurs with cessation of treatment.
Elimination or almost complete clinical resolution of
the lesion has occurred in patients treated with agents such
as desciclovir (an analog of acyclovir), phosphonoformate,
Retin A and podophyllin resin, although lesions tend to

recur within few months. Occasionally, Candida albicans
may be found in HL lesions.
Antifungal medications like topical clotrimazole,
topical nystatin 10000 unit/g 5 times a day can be given.
Systemic agent like ketoconazole 200 mg BD a day,
acyclovir, azidothymidine and retinoid acid podophyllin
resin can also be given.
Points to Remember

Clinical Features
Site: It often occur in clean mouths, where there is very
little plaque or calculus to account for the gingivitis.
Sign: The onset is often sudden, with rapid loss of bone and
soft tissue. Patients sometimes complain of spontaneous
bleeding.
Linear gingival erythema: In this condition gingiva may
be reddened involving the free gingival margin. There is
linear band of erythema which can extend 3 mm apically.
The diagnosis of this should be done if gingivitis does not
respond to improved plaque control (Fig. 21.6).
Necrotizing ulcerative gingivitis: In these ulcers
occurs at the tips of the interdental papilla and along the
gingival margins and often elicits complaints of severe
pain. The ulcers heal, leaving the gingival papillae with a
characteristic cratered appearance.
Necrotizing ulcerative periodontitis may present as
rapid loss of supporting bone and soft tissue. Typically,
these losses occur simultaneously with no formation of
gingival pockets, sometimes involving only isolated areas
of the mouth. Teeth may loosen and eventually fall out, but

uninvolved sites can appear healthy. There is loss of more
than 6 mm attachment.
Necrotizing stomatitis may develop and areas of
necrotic bone may appear along the gingival margin. The
bone may eventually sequestrate. Patients with necrotizing
ulcerative periodontitis and necrotizing stomatitis
frequently complain of extreme pain and spontaneous
bleeding.

Nonmovable, corrugated or hairy white lesion on the
lateral margins of the tongue, Epstein-Barr virus, does
not rub off, pseudo hairy leukoplakia, hyperkeratosis,
acanthosis, balloon cells, nuclear beading, demonstrate
of Epstein-Barr virus, Langerhans cells, high-dose
acyclovir, desciclovir, phosphonoformate, Retin A,
podophyllin resin, antifungal medications like topical
clotrimazole, topical nystatin 10000.

Periodontal Disease Associated with HIV
Periodontal disease is a fairly common problem in both
asymptomatic and symptomatic HIV-infected patients.
Form
•
•
•

Linear gingival erythema
Necrotizing ulcerative gingivitis
Necrotizing ulcerative periodontitis.

Figure 21.6 Linear gingival erythema

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Textbook of Oral Pathology

Management

534

Appearance: Herpes labialis occurs as characteristic lip
lesion consisting of vesicles on an erythematous base that
Clinicians should refer patients to a periodontist or dentist
heals within 7 to 10 days. The recurrent herpes labialis
for management.
(RHL) are small, shallow, irregular and erosive-like lesion
The following protocol has achieved reasonable
that may coalesce and seen to occur only on keratinized
success: plaque removal, local debridement, irrigation
epithelium like that of gingiva, hard palate or dorsal surface
with povidine-iodine, scaling and root planning and
of tongue.
maintenance with a chlorhexidine mouth rinse once or
Diagnosis is made by isolation of virus from ulcer.
twice daily.
Antiviral drugs like acyclovir 30 mg/kg/day should be
The use of systemic antibiotics like metronidazole has
given. In case of resistant infection foscarnet is preferred.
been given in patient which has got extensive involvement.

Points to Remember
Linear gingival erythema, necrotizing ulcerative
gingivitis, necrotizing ulcerative periodontitis, necrotizing stomatitis, plaque removal, local debridement,
irrigation with povidine-iodine, scaling and root
planning, metronidazole.

Non-Hodgkin Lymphoma
This is the second most common malignancy in HIV
infection. It may cause by EBV virus infection and HHV 8.

Clinical Features
Site: It is seen in extranodal location. CNS is the most
common site of involvement. Intraorally, it can be seen on
gingiva, palate, tongue, tonsil, and maxillary sinus.
Sign: There is loss of periodontal attachment and loosening
of teeth.
Appearance: There is erythematous and soft tissue
enlargement seen in oral cavity.

Management
Combination of chemotherapy and radiotherapy is
effective.
Points to Remember
EBV virus infection and HHV 8, CNS involvement,
gingiva, loss of periodontal attachment, erythematous and
soft tissue enlargement, chemotherapy, radiotherapy.

UNCOMMON ORAL MANIFESTATION
OF HIV
Recurrent Herpes Labialis

Recurrent herpes labialis mainly appears as herpes labialis
and recurrent intraoral herpes. It is cause by HSV.

Points to Remember
HSV, vesicles on an erythematous base, antiviral drugs.

Oral Human Papilloma Virus Lesions
It is cause by human papilloma virus. Oral warts,
papillomas, skin warts and genital warts are associated
with the human papilloma virus (HPV) lesions. Because
the HPV types found in oral lesions in HIV-infected
persons are different from the HPV types associated with
anogenital warts, clinicians should probably not use the
term condyloma acuminate to describe oral HPV lesions.
Location: Lesions caused by HPV are common on the skin
and mucous membranes of persons with HIV disease. Anal
warts have frequently been reported among homosexual
men. It can be found on any mucosal surface and are
contagious to both host and sex partner.
Appearance: HPV lesions in the oral cavity may appear
as solitary or multiple nodules. They may be sessile or
pedunculated and appear as multiple, smooth-surfaced
raised masses resembling focal epithelial hyperplasia or as
multiple, small papilliferous or cauliflower-like projections.
Histopathologically lesion is sessile or papillary
which is covered by acanthotic or hyperplastic stratified
squamous epithelium. Affected epithelium demonstrated
vacuolization of numerous epithelial cells which is called
‘koilocytosis’.

Management
Simultaneous irradiation of all lesions and care of infected
partner. Local excision and cauterization of base.
Points to Remember
Oral warts, papillomas, skin warts, homosexual men,
solitary or multiple nodules, small papilliferous,
cauliflower-like projection, koilocytosis, acanthotic or
hyperplastic stratified squamous epithelium.


Acquired Immunodeficiency Syndrome

Herpes Zoster
It occurs more frequently in HIV infected patients and
carries poor prognosis.
The occurrence of unilateral vesicles that break and
scab is characteristic of this infection. They are selflimiting. When herpes zoster infection involvements occur
intraorally, it will lead to sequestrationofbone with loss of
teeth.
Main complication is neuropathy after inflammation.
Diagnosis is made by cytological smear and finding of
multinucleated giant cells.

Management
Systemic acyclovir 800 mg orally or 15 to 30 mg/kg/day
IV 8 hourly for 10 to 15 days.
Points to Remember
Occurrence of unilateral vesicles, sequestration of bone,
loss of teeth, neuropathy, systemic acyclovir.

HIV Associated Salivary Gland Diseases
Salivary gland disease associated with HIV infection (HIVSGD) can present as xerostomia with or without salivary
gland enlargement. Reports describe salivary gland
enlargement in children and adults with HIV infection
usually involving the parotid gland.
The etiology of HIV-SGD is as yet unknown. It has
been postulated that cytomegalovirus infection has got
predilection for salivary glands. Cytomegalovirus infection
produces inflammation which causes reduced salivary
production.
Sign: The enlarged salivary glands are soft but not
fluctuant, but the enlarged parotid glands can be a source
of annoyance and discomfort.
Xerostomia is sometimes seen in individuals with
HIV-SGD. HIV-infected patients may also experience dry
mouth.
Diffuse infiltrative lymphocytosis syndrome: It is seen
in HIV infected salivary gland disease. There is salivary
gland enlargement. The glandular involvements result from
infiltration of CD8 lymphocytes.

Management
Antiretroviral therapy is useful in this case. Removal of
the enlarged parotid glands is rarely recommended. For

individuals with xerostomia, the use of salivary stimulants
such as sugarless gum or sugarless candies may provide
relief. Candies that are acidic should be avoided as
frequent use may lead to loss of tooth enamel. The use
of salivary substitutes may also be helpful. An increase

in caries can occur, so fluoride rinses (that can be bought
over the counter) should be used daily and visits to the
dentist should occur two to three times per year.
Points to Remember
Xerostomia, parotid gland, cytomegalovirus infection,
enlarged salivary glands, diffuse infiltrative lymphocytosis
syndrome, antiretroviral therapy.

Idiopathic Thrombocytopenic Purpura
Reports have described idiopathic thrombocytopenic
purpura (ITP) in HIV-infected patients. It can be cause by
direct infection by HIV, immune dysfunction, alteration of
platelet production and drug reaction.
Oral lesions may be the first manifestation of this
condition. Petechiae, ecchymosis and hematoma can occur
anywhere on the oral mucosa.
Spontaneous bleeding from the gingiva can occur and
patients may report finding blood in their mouth on waking.

Management
HAART has reduced the prevalence of thrombocytopenia.
Other approach like splenectomy, intravenous immunoglobulin, platelet transfusion is given.
Points to Remember
Infection by HIV, immune dysfunction, alteration of
platelet production, petechiae, ecchymosis and hematoma,
spontaneous bleeding.

Mycobacterium Infection
It can results in tuberculosis which is cause by
Mycobacterium tuberculosis.

It involves tongue, gingiva, and buccal mucosa, floor of
mouth, lip and palate.
Appearance: There is chronic ulceration, exophytic
proliferation
Diagnosis: It is difficult as maximum cases do respond
to tuberculin skin test. Confirmative diagnosis is done by
AFB stained section of biopsy material.

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Textbook of Oral Pathology

Management
536

Triple drug regimen is used. It includes rifampicin,
isoniazid, and pyrazinamide with ethambutol.
Points to Remember
Chronic ulceration, exophytic proliferation, triple drug
regimen.

Hyperpigmentation
Hyperpigmentation of skin, nail and mucosa is seen in HIV
patient.
There is increase melanin pigmentation occur in basal
layer of affected epithelium.
In some cases, adrenocortical destruction occur due to
HIV resulting in addisonian pattern of pigmentation.

Histoplasmosis
It is cause by Histoplasma capsulatum. It is most common
type of fungal infection seen in patient with HIV other than
candidiasis.
Sign: There is fever, splenomegaly and pulmonary
infiltrate.
Appearance: Orally, it is presented as indurated mucosal
ulceration with raised border.
Histopathologically, fungal organism are visible within
the cytoplasm of histiocytes and multinucleated giant cells.

Management
Intravenous amphotericin B is useful in this case.

Recurrent Aphthous Stomatitis
In HIV infection all three forms of aphthous ulceration like
minor, major and herptiform is seen.
There is well defined ulceration seen in the oral cavity.

Management
It is done with the help of topical and intralesional
corticosteroids.

Molluscum Contagiosum
It is infection of skin cause by pox virus.
Location: It is seen on genital, trunk and facial region.
Appearance: Lesion are small, waxy, dome-shaped
papules with center depressed crater. In HIV infection, this
are hundred in number.

Histopathologically surface epithelium forms several
hyperplastic down growth. There is presence of molluscum
bodies which are large intracytoplasmic inclusion.

Management
There is resolution of lesion after giving HAART therapy.

Oral Squamous Cell Carcinoma
Squamous cell carcinoma of oral cavity, pharynx, and
larynx has been seen in the HIV infected patients. The HIV
infection accelerated the development of squamous cell
carcinoma due to impaired immune surveillance.

Management
It is same as that of squamous cell carcinoma.

DIAGNOSTIC TESTS
Diagnosis of AIDS can be made by history and medical
examination for symptoms and signs. Individual is
generally young and in high risk group. There are several
circumstances in which, it is important for dentist to know
HIV antibody status.
To ensure accurate differential diagnosis and appropriate treatment of the oral lesions those are associated
with development of AIDS.
To assess the risk to dental health care worker (HCW)
after needle stick or other injury from contaminated once
by contact with patients blood and saliva.
To convey with communicable disease control (CDC)
guideline that all HCW engaging in invasive dental practice
should be aware of HIV antibody status.

SCREENING TEST FOR AIDS
Enzyme-linked Immunosorbent Assay
(Fig. 21.7)
Enzyme-linked immunosorbent assay (ELISA) is a color
reaction test in which prepared whole HTLV III virus
particle which acts as antigen, will bind with antibodies to
HTLV III in an infected human serum.
Then this complex is added to goat antihuman antibody
labeled with chemical enzymes, which gives color reaction
with particular chemicals e.g. orange color with peroxides
labeled goat antihuman antibody.
ELISA test is simple and convenient to perform; it is
very sensitive for small amount of HTLV III antibodies
and in initial screening tests.


Acquired Immunodeficiency Syndrome

antigen or reverse transcriptase assay provide method that
specifically demonstrates the presence of virus in given
patient or specimen.
The variable amount of virus present in peripheral
blood monocytes at different stage of infection and degree
of immunosuppression both influence the extent HIV-I
viremia.
Polymerase chain reaction technique has provided
an opportunity for detection of very small amount of an
infectious agent like HIV-I based on reported cycle of
enzymatic duplication of number of copies of either DNA

or RNA specific for microorganism.
Figure 21.7 ELISA kit for detection of AIDS

It is not 100 percent reliable because it is not completely
specific only for HTLV II antibodies and reacts with other
related viral antibodies and other nonspecific chemicals
giving false positive result of about 5 to 25 per 1000
patients.
In case of positive test, there is strong indication of past
exposure and infection with virus but this does not show
whether the patient is infectious because it does not show
whether virus is still active or has been destroyed.

The Western Blot Method
The prepared HTLV III virus particles consists of specific
HTLV III specific proteins separated by a process called
electrophoresis and subsequent transfer of nine protein
bands to nitrocellulose membrane strip, which are reacted
with patient’s serum followed by an enzyme linked
antihuman antibody and enzyme substance.
Positive test is indicated when the treated, i.e. HTLVIII specific nitrocellulose strip are exposed to infected
human serum and a goat antihuman antibody strip display
the characteristic band detected for each of three (env, pol
and gag) group of viral protein on exposure to X-ray film.
Those that react with only one of these three groups
of antigens are termed indeterminate and those react with
only non viral proteins are negative.
It is more specific for HTLV III antibodies and is used
to eliminate false positive result.

Viral Culture and Polymerase Chain Reaction
Cultivation of HIV from blood and other body fluids and
tissues with detection of the increased filter by either HIV

Surrogate Marker for Progression of
HIV-I Infection
The absolute CD4+ T-cell lymphocyte count correlate best
with progression of HIV-I related immune dysfunction.
Other serum neoprotein beta-2-microreceptor HIV P24
antigen interleukin-2 receptor IgA and impaired delayed
type of sensitivity are also used.

MANAGEMENT
Various drugs are used for immunotherapy are as follows:
Interferon: It is a useful therapeutic agent in this
syndrome of infection and neoplasms in view of their
antiviral antiproliferative and immunomodulater activity.
The interferon is a glycoprotein produced by a number of
different types cells. Type I interferon (alpha and beta) are
produced by leukocytes and fibroblasts. Type II interferon
(gamma) is produced by lymphocytes and monocytes.
Low doses of interferon enhance the antibody formation
and lymphocyte blastogenesis. They also prolong cell
cycle and cause inhibition of intracellular enzyme system
(antineoplastic effect). The gamma interferon stimulate
macrophage oxidative metabolism and have antimicrobial
effect.
Thymic replacement therapy: The thymic epithelium
plays an important role in transformation of blood borne
precursor cell into mature T-cells. Thymic hormones or

factor mediates this effect, since the immune system in
AIDS is characterized by numerical and functional defects
of T-cell lymphocytes, it will correct the immune defect.
Transplant of fetal thymus of cultural thymic epithelium
and injection of thymic hormone have been successfully
utilized in treatment of AIDS.

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Textbook of Oral Pathology

538

Lymphokines and cytokines: Lymphokines are materials
produced by lymphocyte. Interleukin-I is macrophage
product. In in vitro system interleukin-I enhance plague
forming cells responses and the generation of cytotoxic
T-cell alloantigen. In the presence of macrophage,
interleukin-1 stimulates the production of interleukin-2,
which stimulates and maintains the growth of T-cell
activated by antigens. Various studies have conformed
that purified interleukin-2 (which stimulate and maintain
growth of T-cell activated by antigen), preparation in
in vitro system can normalize lymphocyte reaction
in high percentage of individuals with unexplained
lymphadenopathy and immunologic abnormalities, but the
result are not significant in patients with AIDS.
Bone marrow transplantation: Syngeneic (identical
twin) allogenic (HLA/NHC matched) bone marrow

transplantation has been successful in reconstituting
immune function in the patients with severe congenital
immune defects. If this could be therapeutic in patient with
AIDS that have appropriate marrow donor.
Monoclonal antibodies therapy: In this, antibodies are
directed against T-cell differentiation antigens as a result
of that number of circulating leukemic cells are decreased
in patients with adult T-cell active lymphoblastic
leukemia.
Pharmacological
immunomodulation:
Amitidine,
isoprinosine and retinoid are also used but results are
insignificant.
Intravenous immunoglobulin therapy: It reduces
incidence of bacterial and viral infection. Infusion of
hyperimmune gamma globulin enriched for neutralizing
antibodies for LAV/HTLV-III could prove beneficial
for individuals with AIDS or ARC who have inadequate
specific antibodies.
Antiviral drug HPA–23: It is an oraganometallic
compound of tungsten and antimony, azidothymidine. It is
analogs of thymidine. It appears to inhibit multiplication
of HTLV-III virus and cyclosporine. It shows marked
increase in T lymphocyte population.
HAART therapy—nowadays introduction of highly
active antiretroviral therapy (HAART) results in long
survival of the patient. The HAART includes two
nucleoside analog reverse transcriptase inhibitor, at least
one protease inhibitor and/or one non-nucleoside analog

reverse transcriptase inhibitor. Nucleoside analogue

reverse transcriptase inhibitors, which are used are abacavir,
didanosine, emtricitabine, lamivudine, stavudine. Nonnucleosides used are capravirine, delavirdine, efavirenz
and nevirapine. Protease inhibitor used is amprenavir,
darunavi, indianvir, tipranvir.

PREVENTION
∙
∙
∙
∙
∙
∙

Educational counseling of general public
Avoid sexual contact with suspect and in high-risk
group
Use of disposable syringes and needles
Blood donor should be properly screened
Avoid multiple sex partners, intimate kissing and oral
contact
Educate healthcare workers on safety measures.

BIBLIOGRAPHY
1. Baccaglini L, Atkinson JC, Patton LL, et al. Management
of oral lesion in HIV positive patients: Oral Surg Oral Med
Oral Pathol Oral Radiol. 2007;103(Supp 1);S50.e1-23.
2. EC:Clearinghouse on oral problems related to HIV infection
and WHO collaborating center on oral manifestation of

immunodeficiency virus: classification and diagnostic
criteria for oral lesion in HIV infection. J Oral Pahtol Med;
1993;22:289-91.
3. Epstein JB, Cabay RJ, Glick M. Oral malignancies in
HIV disease: change in disease presentation, increasing
understanding of molecular pathogenesis and current
management. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod. 2005;100:571-8.
4. Frezzini C, Leao JC, Porter S. Current trends in HIV disease
of mouth. J Oral Pathol Med. 2005;34:513-31.
5. Greenspan D, Greenspan JS. Significance of oral hairy
leukoplakia: Oral Surg Oral Med Oral Pathol. 1992;73:1514.
6. Holmstrup P, Westergaard J. HIV infection and periodontal
disease: periodontal. 1998;18:37-46.
7. Lager I, Altini M, Coleman H. Oral Kaposi’s sarcoma: a
clinicopatholgoic study from south Africa. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 2003;96:701-10.
8. Miziara ID, Weber R. Oral candiadisis and oral hairy
leukoplakia as predictor of HAAAT failure in Brazilian
HIV infected patients. Oral Dis. 2006;12:402-7.
9. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and
maxillofacial pathology, 3rd edn, Saunder Elsevier; 2009.
10. Piluso S, Ficarra G, Lucatorto FM, et al. Cause of oral ulcer
in HIV infected patients: a study on 19 cases. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 1996;82:166-72.


Acquired Immunodeficiency Syndrome

MULTIPLE CHOICE QUESTIONS

1. HIV is:
a. 90–120 nm
c. 70–120 nm

b.
d.

80–120 nm
50–100 nm

2. AIDS dementia complex causes:
a. Progressive encephalopathy
b. Regressive encephalopathy
c. Both a and b
d. None of the above
3. Most common fungal oral manifestation of HIV is:
a. Kaposi’s sarcoma
b. Candidiasis
c. RAS
d. Dysphagia
4. Most common tumor associated with AIDS is:
a. Squamous cell carcinoma
b. Hodgkin’s lymphoma
c. Non-Hodgkin’s lymphoma
d. Kaposi’s sarcoma

5. Causative organism for hairy leukoplakia is:
a. EBV
b. HPV
c. Rota virus

d. None of the above
6. ELISA is a:
a. Color reaction test
c. PCR

b.
d.

Electrophoresis test
None of the above

7. Balloon cells and nuclear beading are seen in:
a. Hairy leukoplakia
b. Pseudo hairy leukoplakia
c. Non-Hodgkin’s lymphoma
d. All of the above
8. The following are the histopathological stages of
Kaposi’s sarcoma except:
a. Patch stage
b. Plaque stage
c. Nodular stage
d. Bullous stage

539


22

Odontogenic Infection
and Pulp Pathology

Anil Govindrao Ghom, Shubhangi Mhaske (Jedhe), Seema Vaidya

Chapter Outline
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Effect of infection on host
Pathophysiology of infection
Pulp
Classification of pulpitis
Pulpitis
• Reversible pulpitis
• Chronic hyperplastic pulpitis
• Irreversible pulpitis

Pulp degeneration
Pulp calcifications
Necrosis of pulp
Cracked tooth syndrome
Periapical abscess
Periodontal abscess
Acute exacerbation of a chronic lesion
Periapical granuloma
Periapical scar
Osteomyelitis
Acute suppurative osteomyelitis
Chronic suppurative osteomyelitis

Infection is a clinicopathological entity involving invasion
of the body by pathogenic microorganisms and reaction of
the tissues to microorganisms and their toxins.
Soft tissue infections of head and neck are commonly
encountered in routine practice in dentistry. These
infections may be odontogenic or nonodontogenic in
origin. Once the infection extends past the apex of the
tooth the pathophysiology of the infectious process
can vary, depending upon the number and virulence of

Infantile osteomyelitis
Diffuse sclerosing osteomyelitis
Primary chronic osteomyelitis
Chronic tendoperiostitis
SAPHO syndrome
CRMO
Focal sclerosing osteomyelitis (condensing osteitis)

Osteomyelitis with proliferative periostitis
Radiation osteomyelitis
Cellulitis
Ludwig’s angina
Fatal complications of oral infection
• Bacterial meningitis
• Brain abscess
• Cavernous sinus thrombosis
• Odontogenic infection of orbit
• Mediastinitis
• Necrotizing fascitis
 Oral foci of infections
 Dry socket
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the microorganisms, the host resistance and anatomic
geography.
These odontogenic infections can become severe, lifethreatening facial space infections. These infections have
the potential to spread through facial planes of head and

neck there by compromise the vital structures in these
regions, e.g. intracranial odontogenic infection leading to
necrotizing fascitis of head and neck. Most odontogenic
infections can be managed successfully with minimal


Odontogenic Infection and Pulp Pathology

complications. The key to successful management is sound
surgical principles.
The relationship between the host and microbes is a
dynamic one. Usually, host resistance is the dominant
factor. On the other hand, when the host resistance is
lowered, microbes predominate and clinical infection
occurs. In establishing the presence of infection there is
interaction between three viz factors host, environment and
microbes.
A compromised patient is more likely to have infection
and this infection can rapidly acquire a serious form. Hence,
patient history is more important so as to recognize the
patient ability to defend himself against the infection. The
adverse relationship between the host and the infectious
microorganism can be best understood by imagining a
balance on which the pathologic attribute of microbes are
weighed against the protective mechanisms of the host.
Body defends against the microbial invasion by three
major defenses local defense, cellular defense and humoral
defense. The microorganisms on the other hand use
two weapons in this battle, i.e. virulence and number of
microbes.

occur due to neutralization of host defence. There is
fever, endotoxic shock and intravascular coagulation.
The pathogen or its products, in certain situations, may
combine with antibodies or sensitized mononuclear
leukocytes to produce harmful immunologic effects called
hypersensitivity reaction.
Compromised host: It is a person whose defense
mechanisms have been lowered as a result of diabetes,
tuberculosis, rheumatic fever, malignancy, radiation
therapy, use of therapeutic immunosuppressive drug or
antibiotics, extensive skin burns, genetic deficiency of
immune system and malnutrition.
Spread of Infection
• Directinvasionorextension
• Spreadbylymphaticsystem
• Spreadbybloodvessels.

PATHOPHYSIOLOGY OF INFECTION

The body’s response to infectious agent is inflammatory,
which is essentially a protective phenomenon. Hence, the
cardinal signs of inflammation are present, to some degree,
Factors for Host Defense
in nearly all patients with infection.
Local defense
Redness (rubor) is seen when the infection is close
to
the
tissue surface, which is secondary to the intense

• Epitheliallining
hyperemia
caused by increased vasodilation of arterioles.
• Secretoryanddrainagesystem
Calor or heat is due to inflow of relatively warm blood
• Microbialfloralinterference
from deeper tissues, increased velocity of blood flow and
• Mucosalimmunesystem
increased rate of metabolism.
Humoral factor
Dolor or pain results from pressure on sensory nerve
• Immunoglobulin
endings, from distension of tissues caused by edema or
• Complementsystem
spread of infection. Release of substance like kinins,
Cellular component
histamines or bradykinin is also responsible for pain. It is
the most universal sign of infection.
• Polymorphonuclearleukocytes
Swelling accompanies infection, unless the infection
• Lymphocyte.
is confined to bone which cannot swell. It is due to the
accumulation of fluid, exudate or pus.
EFFECT OF INFECTION ON HOST
Loss of function is another sign of infection. A patient
Infectious agents initiate, in the host, a series of reactions immobilizes the painful part in the most comfortable
that are collectively called inflammatory reaction. This position he can find. Hence, when the masticatory muscles
response results in generation and release of mediators, are involved, there is limitation of jaw movement.
Fever occurs in some cases, which reflect a nonmicrovascular changes and mobilization and activation
of leukocytes, all designed to eliminate the infectious specific physiologic response of host to tissue injury.

pathogens and repair tissue injury. Therefore, these This injury results in increase of substance called pyrogen
from endogenous (injured tissue) and exogenous source
reactions are protective in nature.
Direct injury to the host cells, enhancement of the (infecting agent). In clinical fever, it appears that the
parasite’s invasiveness and amplification of these effects hypothalamic regulating center is stimulated by endogenous

541


Textbook of Oral Pathology

pyrogen, which is activated by bacterial endotoxin release
from granulocytes, monocytes and macrophages.
542

Cardinal Sign of Inflammation
•
•
•
•
•
•

Redness(rubor)
Calororheat
Dolororpain
Swelling
Lossoffunction
Fever.

PULP

2nd Classification
According to involvement
• Focal or subtotal or partial pulpitis: In it
inflammatory process is confined to a portion of the
pulp, usually a portion of the coronal pulp.
• Total or generalized pulpitis: In it most of the pulp is
involved.
According to severity
• Acute
• Chronic
According to presence or absence of direct communication
between the dental pulp and oral environment
• Pulpitis aperta (open pulpitis): In it pulp is
communicated with the oral cavity.
• Pulpitis clausa (closed pulpitis): No communication
exists.

The pulp is the formative organ of the tooth. It builds
primary dentin during the development of the tooth,
secondary dentin after tooth eruption and reparative dentin
in response to stimulation as long as the odontoblasts
remain intact. The pulp has been described as both a
highly resistant organ and as an organ with little resistance
or recuperating ability. It is a delicate connective tissue
liberally interspersed with tiny blood vessels, lymphatics,
myelinated and unmyelinated nerves, and undifferentiated
connective tissue cells.

The initial response to injury to pulp is same as that of other
tissue, but the end results is different due to rigid dentinal
wall of pulp chamber.

CLASSIFICATION OF PULPITIS

Pathogenesis

1st Classification
Pulpitis (Inflammation)
Reversible
• Symptomatic(acute)
• Asymptomatic(chronic)
Irreversible
• Acute
– Abnormally responsive to cold
– Abnormally responsive to heat
• Chronic
– Asymptomatic with pulp exposure
– Hyperplastic
– Internal resorption
Pulp degeneration
• Calcific
• Others
Necrosis

PULPITIS

Some stimuli of short duration, such as cutting dentin may
cause short-term vasodilation and a reversible increase in

vessel wall permeability.
More severe stimuli and a greater degree of cell
damage cause more marked vasodilatation and the
movement of polymorphonuclear leukocytes into the
injured tissues.
These acute inflammatory reactions are usually limited
to the odontoblast and subodontoblastic regions adjacent to
the dentinal tubules involved.
Odontoblastic nuclei may be displaced into the tubules,
due to either increased local tissue pressure or dentinal fluid
during the injury. It is reversible, if the etiological factors
are removed. Repair involves the return to normal tissue
fluid dynamics, exit of polymorphonuclear leukocytes
from the area and the re-differentiation of odontoblasts
if they have damaged. The pulpal tissue after repair is
usually less vascular, more fibrous and less cellular than
before and may be less able to withstand a subsequent
insult.


Odontogenic Infection and Pulp Pathology

If stimuli are not removed, pulpal damage can
overwhelm the system and spread progressively to apical
portion of pulp. This will result in pulpal necrosis.

Causes
Mechanical cause: It includes traumatic accident,
iatrogenic damage for dental procedure, attrition, abrasion.
Thermal cause: It may cause through uninsulated metallic

restoration, during cavity preparation, polishing.
Chemical cause: It arises from erosion or inappropriate
use of acidic dental material.
Bacterial cause: It can damage the pulp through the toxins
secreted by bacteria from caries.

Clinical Features
Reversible Pulpitis
It is a mild-to-moderate inflammatory condition of the pulp
caused by noxious stimuli in which the pulp is capable of
returning to un-inflamed state following removal of the
stimuli.
Pulp hyperemia: It is the earliest form which is sometimes
known as pulp hyperemia. There is excessive accumulation
of the blood within the pulp tissue leading to vascular
congestion.
Symptoms: It is characterized by sharp pain lasting for a
moment. It is more often brought on by cold than hot food or
beverages and by cold air. It does not occur spontaneously
and does not continue when the cause has been removed.
Tooth responds to electric pulp testing at lower current.

i.e. change of position, exacerbates the pain which is due to
change in intrapulpal pressure.
Referred pain:Patientmaycomplainofpainreferredto
adjacent teeth to the temporal region or sinuses when an
upper posterior tooth is involved, or to the angle, when
lower posterior tooth is affected.
In later stages, pain is more severe and is generally
described as boring, gnawing or throbbing or as if tooth is

under constant pressure. Patient is often awake at night due
to pain.Painisincreasedbyheatandissometimesrelieved
by cold, although continued cold may intensify the pain.

Chronic Hyperplastic Pulpitis
It is also called pulp polyp or pulpitis aperta. It is essentially
an excessive, exuberant proliferation of chronically
inflamed dental pulp tissue. It occurs due to long standing
low grade infection. Mechanical irritation from chewing
and bacterial infection often provides the stimuli.
Teeth involved: Teeth most commonly involved are
deciduous molars and first permanent molars as they have
an excellent blood supply because of a large root opening,
and this coupled with high tissue resistance and reactivity
in young person’s accounts for unusual proliferative
properties of the pulp tissue. It is asymptomatic and it is
seen only in teeth of children and young adults.
Appearance:Polypoidtissueappearsasafleshy,reddish
pulpal mass filling most of the pulp chamber or cavity
or even extending beyond the confines of the tooth (Fig.
22.1). Sometimes, mass if large enough interferes with

Irreversible Pulpitis
It is a persistent inflammatory condition of the pulp, which
may be symptomatic or asymptomatic and is caused by a
noxious stimulus.
Symptoms: In early stages of irreversible pulpitis, a
paroxysm of pain may be caused by the following: sudden
temperature changes like cold, sweet and acid foodstuffs.
The pain often continues when the cause has been removed

and it may come and go spontaneously.
Nature of pain: Pain is sharp, piercing or shooting and
is generally severe. It may be intermittent or continuous,
depending on the degree of pulpal involvement and
depending on whether it is related to an external stimulus. Figure 22.1 Chronic hyperplastic candidiasis showing reddish
The patient may also state that bending over or lying down
pulpal mass

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Textbook of Oral Pathology

comfortable closure of teeth. Polypoid tissue is less
sensitive than normal pulp tissue and more sensitive than
the gingival tissue.
544

Signs and symptoms: It may cause discomfort during
mastication, due to pressure of food bolus. This tissue
bleeds easily because of rich network of blood vessels.
The tooth may respond feebly or not at all to the thermal
test. There is presence of squamous covering as a result
of grafting of exfoliated epithelial cells from adjacent oral
mucosa.

Histopathological Features (Figs 22.2 to 22.4)
It may range from hyperemia to mild-to-moderate
inflammatory changes to the area of the involved dentinal
tubules such as dentinal caries.

Microscopically one sees involved reparative dentin,
disruption of the odontoblastic layer, dilated blood
vessels, extravasation of fluid (edema) and the presence
of immunological response. Chronic inflammatory cells
predominate. In some cases acute inflammatory cells can
also be seen.
In irreversible pulpitis the postcapillary venules
become congested and affect the circulation within the
pulp, causing pathologic changes such as necrosis. These
necrotic areas attract polymorphonuclear leukocytes by
chemotaxis and start an acute inflammatory reaction.
After phagocytosis, the polymorpho-nuclear leukocytes,
which have a short life span, die and release lysosomal
enzymes. The lysosomal enzymes lyse some of the pulpal
stroma and together with the cellular debris of the dead
polymorphonuclear leukocytes form purulent exudates
(pus).
The inflammatory reaction produces micro-abscess
(acute pulpitis). The pulp trying to protect itself walls off
the areas of the micro-abscess with fibrous connective
tissue. The surrounding pulp tissue exhibits fibrosis and
mixture of plasma cells, lymphocytes and histiocytes.
In some cases within a few days, the acute inflammation
spreads to involve most of the pulp so that neutrophilic
leukocytes fill the pulp. The entire odontoblastic layer
degenerates. As pulp is closed, there is rise in pressure
and the entire pulp tissue undergoes rapid disintegration,
forming numerous small abscesses. Eventually the entire
pulp undergoes liquefaction and necrosis which is called
acute suppurative pulpitis.

Figure 22.2 Necrosis of pulp in pulpitis

Figure 22.3 Pulp hyperemia showing cellular infiltrate and

inflammatory cells

Figure 22.4 Pulp hyperemia showing many dilated blood

vessels and necrotic area in the center


Odontogenic Infection and Pulp Pathology

In chronic hyperplastic pulpitis the surface of the
pulp polyp is covered by stratified squamous epithelium.
Such epithelium may be derived from gingiva or freshly
desquamate epithelial cells of the oral mucosa or tongue.
The tissue in the pulp chamber is often transformed into
granulation tissue which projects from the pulp into the
carious lesion.
The granulation tissue is a young vascular tissue
containing polymorphonuclear neutrophils, lymphocytes
and plasma cells. The granulation tissue may become
epithelized as a result of implantation of epithelial
cells on its surface. Granulation tissue is made up of
delicate connective tissue fibers interspersed with a
variable number of small capillaries. Inflammatory cell
infiltration chiefly lymphocytes and plasma cells are also
seen.

Points to Remember
Stimuli of short duration, mechanical cause, thermal
cause, chemical cause, bacterial cause:
•
•

•

•
Clinical Differences between Reversible and
Irreversible Pulpitis
The pain of irreversible pulpitis is more severe and
lasts longer. In reversible pulpitis, the cause of pain is
generally traceable to a stimulus such as cold water or
air whereas in irreversible pulpitis, the pain may come
without any apparent stimulus.

Management
Prevention is the best management for it. It is done by
periodic care, early insertion of a filling if a cavity has
developed. Removal of noxious stimuli should be done.
In early stages pulpotomy (removal of the coronal
pulp) and placing material that favors calcification such as
calcium hydroxide over the entrance of root canals. Root
canal filling with inert material like gutta percha should be
done.
Complete removal of the pulp or pulpectomy and
placement of an intracanal medicament to act as a
disinfectant or obtundent such a cresatin, eugenol or

formacresol is carried out in irreversible pulpitis.
In case of hyperplastic pulpitis elimination of
polypoid tissue, followed by extirpation of the pulp is
done. After removing the hyperplastic tissue bleeding
can be controlled by pressure. Extraction of tooth can
also be done.

•

Reversible pulpitis: Mild noxious stimuli, pulp
hyperemia, sharp pain lasting for a moment, brought
on by cold
Irreversible pulpitis: Paroxysm of pain, sudden
temperature changes like cold, pain often continues
cause has been removed and it may come and pain
is sharp, piercing or shooting, referred pain, later
stages, pain is more severe, patient is often awake at
night due to pain
Chronic hyperplastic pulpitis: Pulp polyp, pulpitis
aperta, polypoid tissue appears as a fleshy, reddish
pulpal mass filling most of the pulp chamber,
discomfort during mastication
Histopathological features: Hyperemia, mildto-moderate inflammatory changes, disruption
of the odontoblastic layer, dilated blood vessels,
extravasation of fluid (edema), chronic inflammatory
cells predominate, polymorphonuclear leukocytes by
chemotaxis, lysosomal enzyme, microabscess, chronic
hyperplastic pulpitis, stratified squamous epithelium,
delicate connective tissue fibers interspersed with a
variable number of small capillaries

Management: Removal of noxious stimuli, pulpotomy,
pulpectomy, elimination of polypoid tissue.

PULP DEGENERATION
Degeneration is usually present in older aged people. It
is a result of persistent, mild irritation in teeth of younger
people.

Clinical Features
In early stages, there are no symptoms and no clinical
findings. As degeneration progresses, the tooth may
become discolored and the pulp within does not respond
to stimuli.

Types
Calcific degeneration: A part of pulp tissue is replaced
by calcific material that is pulp stones and denticles are
formed. The calcific material has a laminated structure like

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546

the skin of an onion and lies unattached within the body of
pulp. In another type of calcification the calcified material
is attached to the wall of the pulp cavity and is an integral
part of it which is called diffuse calcification.

Atrophic degeneration: It is observed in older people.
The pulp tissue is less sensitive than normal.
Fibrous degeneration: It is characterized by replacement
of the cellular element by fibrous connective tissue. On
removal from the root canal, the pulp has the characteristic
appearanceofaleatheryfiber(Fig.22.5).
Pulp artifacts: Vacuolization of the odontoblasts was once
thought to be a type of pulp degeneration characterized by
empty spaces formally occupied by odontoblasts. It is an
artefact caused by poor fixation of the tissue specimen.
Tumor metastasis: It is rare except possibly in the terminal
stages. It may occur due to direct local extension from the
jaw.
Points to Remember
No symptoms, no clinical findings, calcific degeneration,
atrophic degeneration, fibrous degeneration, pulp
artifacts, tumor metastasis.

PULP CALCIFICATIONS
Various forms of pulp calcifications are found within the
pulp which may be located in the pulp chamber or in the
root canals. It can occur in any sex and in any teeth in the
dental arch.

Figure 22.5 Fibrosis of pulp seen as replacement of cellular

element by fibrous connective tissue

Etiology
There is no clear-cut etiology. There is strong association

between chronic pulpitis and presence of pulpal
calcification. But pulp calcification can be found in
unerupted teeth.
Extremely high percentage of pulp stones yield pure
growth of streptococci on culture but often the affected
teeth are normal.
Sundell Schematic Presentation
Localmetabolicdysfunction=trauma=hyalinizationof
injuredcells=vasculardamage=thrombosis=vessels
walldamage=fibrosis=minerlization(nidusformation)
=growth=pulpstone
Classification of Pulp Stone
• Denticle
• Pulpstones
– True
- Free
- Attached
– False
- Free
- Attached
• Interstitial

Classification
There are of following types:
Denticle: It occur due to epitheliomesenchymal interaction
within developing pulp. They develop during the formation
and root and form before completion of primary dentin. So
denticle will become attached to or embedded in the dentin.
Pulp stone: Also called pulp nodules. It is of following
types:

∙ True: They are made of localized masses of calcified
tissue that resembles dentin due to their tubular
structure. Tubules are irregular and few in number. It is
more common in pulp chamber than root canals. They
are subdivided into:
– Free: It lies entirely within pulp tissue and is not
attached to the dentinal wall.
– Attached: These are continuous with the dentinal
wall.
∙ False: It is composed of localized mass of calcified
material and they do not exhibit dentinal tubules.
Nodule appears to be made up of concentric layers


Odontogenic Infection and Pulp Pathology

∙

or lamellae deposited around a central nidus. It is
composed of cells around which laid down is a layer
of reticular fibers that subsequently calcifies. They are
again classified as free or attached. They are larger
than true denticles and they may fill nearly the entire
pulp chamber.
Interstitial: As the concentric deposition of calcified
material continues it approximates and finally is in
apposition with the dentinal wall where it may be
surrounded by secondary dentin then it is called an
interstitial pulp stone.

Diffuse linear calcification: It is also called calcific
degeneration. It is amorphous unorganized linear strands
or columns parallel with blood vessels and nerves of pulp.
It contains fine fibrillar irregular calcification.

547

Figure 22.6 Radiopaque pulp stone seen in the pulp chamber

Clinical and Radiographic Significance
As such they have very little clinical significance. Usually
it is discovered on the radiograph only as radiopacity.
Sometimes, it may cause pain from mild pulpal
neuralgia to severe excruciating pain resembling that of tic
douloureux as the denticle can impinge on the nerve of the
pulp.
Difficulty may be encountered in extirpating the pulp
during root canal therapy.
In some cases pulp calcification may become large
enough to interfere with root formation which may lead to
periodontal destruction and tooth loss.
In some condition like dentin dysplasia (type II),
tumoral calcinosis, calcinosis universalis and Ehlers
Danlos syndrome you may observe calcification.
Radiographic features: It is radiopaque on the resultant
radiograph. It can be seen hanging in pulp chamber or it is
attachedtowallofpulpchamber(Fig.22.6).

Histopathological Features (Figs 22.7 to 22.9)
Denticle consists of tubular dentin which surround central

nest of epithelium. After some time it degenerated and
tubules undergo necrosis.
Pulp stone shows central amorphous mass of
calcification which is surrounded by concentric lamellar
rings. In some cases fibrillar irregular calcified material
can be seen at the periphery of pulp stone.
Diffuse calcification consists of fine fibrillar and
irregular calcification which developed in pulp chamber
and canals. This is deposited in linear fashion.

Figure 22.7 Pulp calcification

Management
Notreatmentisnecessaryastoothisasymptomatic.Care
should be taken while undergoing root canal therapy for
tooth having pulp stone.
Points to Remember
Discovered on the radiograph, difficulty during root
canal therapy, periodontal destruction, radiopaque on the
resultant radiograph, denticle consists of tubular dentin,
pulp stone, central amorphous mass of calcification,
diffuse calcification consists of fine fibrillar and irregular
calcification.


Textbook of Oral Pathology

Liquefaction necrosis: It results when proteolytic enzymes
convert the tissue into softened mass, liquid or amorphous
debris.

548

Clinical Features
It causes no painful symptoms.
Sign:Discolorationofthetoothisthefirstindication
that the pulp is dead (Fig. 22.10). The tooth with partial
necrosis can respond to thermal changes owing to presence
of vital nerve fibers passing through the adjacent inflamed
tissue.
History of severe pain lasting from a few minutes to a
few hours, followed by complete and sudden cessation of
pain.
Figure 22.8 Pulp calcification (Courtesy: Dr Sangamesh

Halawar, Reader, Department of Oral Pathology, VPDC and
H, Kavalapur, Sangli, Maharashtra, India)

Histopathological Features
Necrotic pulp tissue, cellular debris and microorganisms
may be seen in the pulp cavity.
The periapical tissue may be normal or slight evidence
of inflammation of the apical periodontal ligament may be
seen.

Management
Preparationandobturationofrootcanalsshouldbecarried
out.
Points to Remember
Discoloration of the tooth, history of severe pain,
necrotic pulp tissue, cellular debris, microorganisms,

obturation of root canals.
Figure 22.9 Diffuse calcification presented as linear strands

NECROSIS OF PULP
It is the death of pulp. It may be partial or total depending
on whether a part or the entire pulp is involved.
It is sequelae of inflammation and can also occur
following trauma, in which the pulp is destroyed before an
inflammatory reaction.

Types
Coagulation necrosis: The soluble portion of tissue is
precipitatedorisconvertedintoasolidmaterial.Caseation
is a form of coagulation necrosis in which the tissue
is converted into a cheesy mass consisting chiefly of
coagulated proteins, fats, and water.

Figure 22.10 Necrotic pulp showing discoloration of tooth