Intraoral Pain Disorders










Odontogenic Pain
P
ain described by the patient as “toothache” may occasionally
confound the clinician during the diagnostic process because
perception of tooth sensitivity can be experienced due to den-
tal disease, or it can arise in other tissues, either adjacent to the
tooth or anatomically distant (ie, referred pain). Similarly challeng-
ing may be the fact that dental pathology may refer pain to other
teeth or distant locations in the maxillofacial area or the neck, which
can mimic other types of facial pain. In addition, regional pain from
adjacent structures, other orofacial pain disorders, and distant dis-
ease such as central nervous system (CNS) lesions (eg, tumors) may
refer pain to teeth and mimic the symptoms of toothache. Whereas
Key Points
Pain (both acute and chronic) in the oral cavity and adja-
cent craniofacial structures is a common complaint in both
healthy and medically complex patients.
Diagnosis of oral pain can be complicated by referred or
radiating pain and by proximity of multiple afferent nerve
bers.
Even though painful conditions of various etiologies may
overlap, there are typically distinguishing features that will
direct the clinician to the correct diagnosis.
Dental and periodontal pains generally have an infectious
or inammatory etiology but in rare instances may have
systemic or extraoral causes.
Mucosal (soft tissue) oral pain has a more varied etiology,
with traumatic, viral, fungal, autoimmune, and iatrogenic
causes predominating.
Intraoral Pain
Disorders
7

122
Intraoral Pain Disorders
7
the origin of most dental pain can be easily
located, the clinician must be aware of these
other possibilities, which become more likely
with chronic, intractable symptoms.
As a rst step in the diagnosis process,
the clinician must determine if the pain is truly
odontogenic in origin. If it can be attributed
to dental disease, it is then necessary to de-
termine if the pain is of pulpal or periodontal
origin (or both). Nonodontogenic sources of
pain that may mimic toothache are reviewed
at the end of this chapter, and the codes from
The International Classication of Diseases,
Tenth Edition (ICD-10) are presented for each
disorder.
Pulpal pain (ICD-10 K04.0)
The dental pulp is a visceral tissue, and pain
that originates there has characteristics similar
to other types of visceral pain, which tend to
be deep, dull, or aching pain that is of a thresh-
old nature and that may sometimes be difcult
to localize.
1
Pulpal pain can arise only from vital
teeth with functioning nerves. In these teeth,
pain may arise from pulpitis, which is revers-
ible or irreversible inammation of the tissue.
Reversible pulpitis
Reversible pulpitis is characterized by a short,
sharp, hyperalgesic response that subsides
soon (ie, seconds) after the stimulus is re-
moved. The pain must be provoked and typi-
cally does not occur spontaneously. Irritants
such as hypertonic solutions (eg, sugary food)
or thermal extremes may cause focal stimula-
tion, which produces a brief pain.
2
It is worth
noting that pain from reversible pulpitis is a
symptom, not a disease process.
Irreversible pulpitis
Irreversible pulpitis is characterized by pro-
longed pain, either spontaneous or provoked
by a stimulus. This type of pain tends to be
variable and may be intermittent or continu-
ous, moderate or severe, sharp or dull, local-
ized or diffuse, and affected by the time of
day or body position. The intensity of the pain
may also vary over time, and the tooth may
go through asymptomatic periods. Pulpal in-
ammation is typically more severe and more
widespread than in reversible pulpitis, and it
may progress to pulpal necrosis.
2
Nonvital tooth pain
Pulpal necrosis (ICD-10 K04.1) results from
untreated pulpitis, exposure of the pulp to oral
bacteria, traumatic injury, or other events that
cause long-term interruption of the blood sup-
ply to the tissue. Pulpal necrosis may be partial
or total. Partial necrosis may have some of the
symptoms associated with irreversible pul-
pitis, which is common in multirooted teeth.
Total necrosis is asymptomatic as long as no
other disease process (ie, infection) affects the
adjacent innervated tissues.
2
If pulpal disease
extends beyond the apex of the tooth, pain be-
comes both spontaneous and continuous and
can be exacerbated by percussion but not by
temperature changes.
Etiology of pulpal pain
Tooth sensitivity may occur when dentinal
tubules are exposed to the oral environment,
causing fluid movement that affects the
pulp.
3,4
Attrition (ICD-10 K03.0), abrasion (ICD-
10 K03.1), abfraction, erosion (ICD-10 K03.2),
dental caries (ICD-10 K02.9), gingival recession
(ICD-10 K06.0), toothbrush trauma, periodon-
tal diseases (ICD-10 K05.30), or periodontal
surgery may expose coronal and/or radicular
dentin. The factors leading to acute pulpal pain
can be grouped into three general categories:
bacterial, traumatic, and iatrogenic.
Bacterial. Bacteria or their metabolic byprod-
ucts are introduced into the pulp as a result of
dental caries, inadequate restorations, enamel
and/or dentin fractures, or anomalous tracts
from the periodontium or from the systemic
blood supply (bacteremia and retrograde
infection).
5–11
123
Traumatic (ICD-10 K03.8). Direct trauma to
a tooth can cause pulpitis, acute pulpalgia, in-
complete fracture, or complete fracture with
exposure of dentin or the pulp.
7
Trauma may
subluxate or completely avulse a tooth, with
consequent disruption of the apical blood sup-
ply and subsequent pulpitis or necrosis.
12
Re-
peated microtrauma, such as chronic awake or
sleep bruxism, may also cause pulpal inam-
mation or impact the blood ow to the pulp,
which may lead to necrosis.
Iatrogenic. The process of restoring teeth may
cause pulpitis and acute pulpalgia. Heat and
vibration from dental procedures, depth of
preparation, dehydration of dentin, insertion of
pin-retained restorations, and accidental pulp
exposure have been well documented. Pulpal
changes have also been reported following
impressions in which bacteria were forced
through the dentinal tubules. Furthermore,
many dental materials and chemicals have the
potential to irritate or injure the pulp.
Pathophysiology of pulpal pain
Myelinated (Aδ) and unmyelinated (C) afferent
nerve bers innervate the dental pulp. The Aδ
bers arborize in the coronal part of the tooth,
just below the odontoblasts, where they lose
their myelin sheath and form the plexus of
Raschkow.
4,13
This plexus sends free nerve
endings onto and through the odontoblastic
cell layer, where they contact the odontoblas-
tic processes at the pulpal end of the den-
tinal tubule.
14
The intimate association of Aδ
bers with the odontoblast is referred to as
the pulpo-dentinal complex.
15
If the cellular or
uid contents of the dentinal tubules are suf-
ciently disturbed to involve the odontoblastic
cell layer, the Aδ bers become excited.
16–18
These nociceptive signals are perceived as
sharp (bright), momentary pain that resolves
when the stimulus is removed.
15
If an exter-
nal irritant is of signicant magnitude to cause
pulpal inammation, a vascular response (hy-
peremia) can lead to an increase in tissue pres-
sure (perceived as pain), which increases as
inammation increases.
19
A tooth with localized inammation can also
produce Aδ ber pain with other types of exci-
tation. Inammatory mediators such as brady-
kinin, 5-hydroxytryptamine (5-HT, also known
as serotonin) and prostaglandin E2 can sensi-
tize the Aδ bers, heightening their response
to stimulants. As exaggerated Aδ ber pain
subsides, a dull throbbing ache remains, asso-
ciated with inammatory involvement of noci-
ceptive C-bers.
15
This type of pain occurs with
more severe tissue injury and is modulated
by chronic inammatory mediators, vascular
changes in blood volume and blood ow, and
increases in intrapulpal pressure. When C-ber
pain dominates over Aδ ber pain, the symp-
tom is more diffuse and poorly localized and
may be referred to other sites. C-ber pain typi-
cally signies irreversible tissue damage as the
inammation increases.
15
Pain may begin as a
short, lingering discomfort, which can escalate
to intense, prolonged episodes or constant,
throbbing pain. When a caries lesion contacts
the pulp, the cellular inammatory response
changes from mostly mononuclear to polymor-
phonuclear leukocytes (neutrophils), resulting
in microabscesses within the inammatory le-
sion, at which point pulpitis typically becomes
irreversible.
20–22
Complete necrosis of the pulp
may occur rapidly, or it may take years to de-
velop; symptomatology covers the spectrum
from severe pain to complete analgesia.
Clinical characteristics of pulpal pain
Pulpal pain usually presents as a visceral,
deep, dull, aching sensation.
22
This pain may
be superimposed with pulsing and throbbing,
or it may be sharp, burning, and lancinating
due to local nerve sensitization rather than to
vascular or neuropathic mechanisms. Clinical
symptoms correlate poorly with the histologic
status of the pulp.
23–25
Severe pain may be as-
sociated with early histopathologic changes,
while a tooth that is asymptomatic may be
necrotic. Pulpal pain can be modied by many
Odontogenic Pain

124
Intraoral Pain Disorders
7
factors including heat and cold, pressure from
occlusal contacts, head position, and the in-
tensity of the offending stimulus. In addition,
pain perception is complex and is affected by
pain signaling, the patient’s emotional state,
and sociocultural background.
4
When the pain is referred, it tends to fol-
low a laminated segmental pattern within the
trigeminal system. Maxillary teeth commonly
refer pain to maxillary and mandibular teeth
on the same side and to cutaneous locations
on the face, superior to the maxillary teeth.
Mandibular teeth tend to refer pain to maxil-
lary and mandibular teeth on the same side.
Anterior teeth may refer pain to both sides of
the face.
26–28
Cutaneous referral patterns start
at the level of the ear and project to locations
on the face inferior to the ear.
Dierential diagnosis of pulpal pain
The rst step in the diagnostic process is to
determine whether the patient with a tooth-
ache is experiencing pain from an odontogenic
or a nonodontogenic source. The tooth caus-
ing the odontogenic pain is usually identied
by the presence of pathology to explain the
pain (eg, caries or large restoration, combined
with historic, clinical, and radiographic nd-
ings).
29
When a suspicious tooth is located,
diagnosis may be conrmed by increased pain
on application of a noxious stimulation (chemi-
cal, thermal, mechanical, or electric sources).
If the pain can be inuenced by local irritation,
the tooth should be anesthetized to determine
if the pain is blocked. If local anesthesia has
no effect, pain from a nonodontogenic source
should be considered. If administration of an-
esthesia decreases but does not eliminate the
pain, there may be an additional nonanesthe-
tized contributor to the pain.
Once a conclusion regarding the source has
been reached, the next step is to determine if
the pain is pulpal or periodontal in origin. Pain of
pulpal origin tends to respond to a stimulus at
a given threshold and may be difcult to local-
ize. Teeth that have only pulpal involvement are
generally not sensitive to percussion. Teeth that
have periodontal and/or periapical involvement
typically respond to percussion or pressure on
a graduated basis, and the pain is easier to lo-
calize.
29
Reversible pulpitis is characterized by
stimulated pain of brief duration that ceases
seconds after removal of the stimulus. Cold and
electric stimulation provoke a brief response,
and sensitivity to percussion is uncommon.
29
Ir-
reversible pulpitis is characterized by stimulated
pain of prolonged duration and/or by spontane-
ous pain. There may be no sensitivity to percus-
sion until the inammatory process extends to
the periapex.
29
A necrotic pulp is asymptomatic
until it becomes infected and inammation ex-
tends to periapical tissues. The tooth is not re-
sponsive to either cold or electric pulp testing;
however, there may be extreme sensitivity to
percussion if the periapex is inamed.
29
Management considerations for pulpal pain
Treatment for dentin sensitivity is directed at
reducing uid movement in the dentinal tu-
bules. Treatment modalities include (1) forma-
tion of a smear layer on the sensitive dentin by
burnishing the exposed surface; (2) application
of agents such as oxalate, arginine, or peptides
that form insoluble precipitates within the tu-
bules; (3) impregnation of the tubules with
plastic resins; and (4) application of dentin
bonding agents to seal the tubules.
30–33
Treatment for reversible pulpitis targets re-
moval of the pain-causing stimulus, such as
caries, and restoration of lost tooth structures.
Treatment of irreversible pulpitis or a necrotic
pulp requires root canal therapy or extraction
of the tooth. Systemic antibiotics are contrain-
dicated when disease is localized to the pulp. A
necrotic pulp is devoid of blood circulation, so no
systemic medication will penetrate the space.
Acute periodontal pain
The periodontium (ie, periodontal ligament
and alveolar bone) is of mesenchymal ori-
gin. Therefore, periodontal pain tends to be
125
more localized in comparison to visceral pain
of pulpal origin. Localization of the source of
pain is attributed to the proprioceptive and
mechanoreceptive sensation of the periodon-
tium.
34
Periodontal pain is generally dull and
aching. Inammatory uid may cause dis-
placement of the tooth in the socket with
a resulting acute malocclusion and typical
localization of the pain with biting or chew-
ing. The diseased site readily responds to
provocation proportionate to the stimulus.
1
At minimal levels of stimulation, the patient
may describe an innocuous sensation such
as itching or moderate dull aching; at severe
levels, the patient may describe unrelenting,
aching, and throbbing pain. Factors that may
increase periodontal pain include occlusal
contact, head position, the intensity of the
stimulus, and CNS modulation. Periodontal
pain, like pulpal pain, may stimulate second-
ary central excitatory activity, resulting in
regional pain referral around the head and
neck, to muscle overload with the potential
to develop myofascial trigger points, and to
autonomic effects such as sinus congestion,
conjunctival injection, and eyelid edema or
drooping. Sites of prior pain are more likely
to be sites of referred pain. Periodontal pain
localized to a single tooth is usually associ-
ated with a gingival or periodontal abscess or
a combined periodontal-endodontic lesion.
35
Gingival abscess (ICD-10 K05.00)
Clinical characteristics. The gingival abscess
is a relatively rare entity. It usually arises as a
result of foreign body impaction or trauma to
previously healthy tissue and is conned to the
marginal gingiva. It presents as a painful, pos-
sibly uctuant swelling. The surface may be
erythematous, smooth, and shiny. Spontane-
ous drainage may occur.
36
Etiology. The precipitating cause of a gingival
abscess is usually an impacted foreign object
(eg, popcorn kernel) or trauma followed by
infection.
Pathophysiology. The gingival abscess con-
sists of a purulent focus in the connective tis-
sue surrounded by an inammatory inltrate.
Management considerations. Treatment
is by incision and drainage, followed by oral
rinses with warm salt water, and may require
removal of the causative agent. On rare occa-
sions, irrigation and debridement of the soft
tissue lesion may be required.
Periodontal abscess (ICD -10 K05.20)
Clinical characteristics. Periodontal ab-
scesses arise as acute or recurrent inam-
matory swellings in periodontally diseased
dental sites. The classic periodontal abscess
is a localized swelling of the gingiva and/or the
alveolar mucosa. These lesions often have an
erythematous, violaceous, or cyanotic appear-
ance and may be uctuant. Pain is variable and
can range from a deep ache of low intensity
to severe discomfort. The pain is often exacer-
bated by chewing and percussion. The affected
tooth may be mobile and may be slightly ex-
truded. Fever and malaise may occur in more
severe cases, cases of cellulitis, and systemic
symptoms with lymphadenopathy.
36–39
Suppu-
ration may be noted from the pocket orice.
The tooth is usually vital.
36,37
Etiology. The infectious cause of the lesion
is the periodontal microbial ora, which is
usually composed of pathogens such as Por-
phyromonas gingivalis, Prevotella intermedia,
Fusobacterium nucleatum, Peptostreptococ-
cus micros, and Bacteroides forsythus.
40–42
It
may arise from chronic periodontitis that can-
not drain into the periodontal pocket or from
trauma or extension of pulpal inammation into
the periapical tissues.
29,43
A lateral pulp canal
may also cause an abscess in the periodontal
space, which technically is not a periodontal
abscess and requires root canal therapy.
Pathophysiology. A periodontal abscess is
usually an exacerbation of a preexisting chronic
Odontogenic Pain

126
Intraoral Pain Disorders
7
periodontal condition. More than 300 species
of microorganisms have been isolated from
periodontal pockets, but only a small number
are considered pathogenic.
44
Most of the tis-
sue destruction found in established periodon-
tal lesions is a result of the mobilization of the
host immunity via activation of monocytes,
lymphocytes, broblasts, and other host cells.
Engagement of these cellular elements by
bacterial factors, in particular bacterial lipopoly-
saccharide, is thought to stimulate production
of both catabolic cytokines and inammatory
mediators including arachidonic acid metabo-
lites such as prostaglandin E2. Cytokines
stimulate inammatory responses that cause
tissue destruction via activation of tissue me-
talloproteinases, a major pathway for connec-
tive tissue attachment loss and bone loss in
most forms of periodontitis.
45–47
Management considerations. Treatment con-
sists of establishing drainage (usually through
the pocket orice) and debridement of the
root surface and pocket wall under local an-
esthesia, accompanied by copious irrigation.
Occlusal adjustment is sometimes indicated.
Unless the tooth is beyond salvage, it is usu-
ally prudent to resolve the symptoms and then
reassess the periodontal status. The endodon-
tic status (ie, vitality) of the tooth should also
be determined.
Periradicular (periapical) abscess (ICD-10 K04.7)
Clinical characteristics. Pulpal infection may
induce an inammatory reaction that may lead
to periradicular abscess formation. Clinical
characteristics include rapid onset; spontane-
ous pain; and acute response to percussion,
purulence, and swelling.
2
It must be distin-
guished from the periodontal abscess, al-
though both processes may be operant in the
case of a combined periodontal-endodontic
lesion. One helpful element for differentiation
is that the periodontal abscess occurs in a set-
ting of periodontal attachment loss and pocket
formation. The initial pain associated with a
radicular abscess is intense when conned
to bone, and it subsides following formation
of a stulous tract (drainage) into the soft tis-
sues. The infection may drain in the oral cav-
ity or spread along fascial planes and result in
cellulitis. In addition, bacteremia may occur,
resulting in systemic infection. If the infection
localizes, it may progress to a uctuant swell-
ing that may eventually drain.
Etiology. A periradicular abscess usually devel-
ops from a necrotic pulp that becomes infected,
with spread of infection into the periradicular
tissues.
14
Occasionally, it may develop from ex-
acerbation of chronic periodontitis located near
the tooth apex (called phoenix abscess).
Pathophysiology. The periradicular abscess is
initiated by inltration of bacteria into the apical
periodontal ligament from an infection in the
pulp, causing an acute inammatory reaction.
Management considerations. Management
involves treating the cause of the abscess,
which is endodontic (root canal therapy), or
extraction of the offending tooth. Spread of
the infection may require drainage of exudates
and/or systemic antibiotics. Signs and symp-
toms such as fever, swelling of the infraorbital
region or other spaces due to extension along
fascial planes, trismus, stridor, elevation of the
oor of the mouth, or neck tracks may indicate
signicant danger and typically require urgent
intervention. In such cases, oral antibiotics are
insufcient, and the patient should be immedi-
ately referred to a hospital.
Pericoronitis (ICD -10 K05.20)
Clinical characteristics. Pericoronitis is a lo-
calized infection within the soft tissue that sur-
rounds the crown of an impacted or partially
erupted tooth, most commonly a third molar.
Clinical features may include an erythematous,
swollen, suppurating gingival lesion that is ten-
der and may cause radiating pain to the ear,
throat, and oor of the mouth. The patient may

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Odontogenic PainPain described by the patient as “toothache” may occasionally confound the clinician during the diagnostic process because perception of tooth sensitivity can be experienced due to den-tal disease, or it can arise in other tissues, either adjacent to the tooth or anatomically distant (ie, referred pain). Similarly challeng-ing may be the fact that dental pathology may refer pain to other teeth or distant locations in the maxillofacial area or the neck, which can mimic other types of facial pain. In addition, regional pain from adjacent structures, other orofacial pain disorders, and distant dis-ease such as central nervous system (CNS) lesions (eg, tumors) may refer pain to teeth and mimic the symptoms of toothache. Whereas Key Points◊ Pain (both acute and chronic) in the oral cavity and adja-cent craniofacial structures is a common complaint in both healthy and medically complex patients.◊ Diagnosis of oral pain can be complicated by referred or radiating pain and by proximity of multiple afferent nerve bers.◊ Even though painful conditions of various etiologies may overlap, there are typically distinguishing features that will direct the clinician to the correct diagnosis.◊ Dental and periodontal pains generally have an infectious or inammatory etiology but in rare instances may have systemic or extraoral causes.◊ Mucosal (soft tissue) oral pain has a more varied etiology, with traumatic, viral, fungal, autoimmune, and iatrogenic causes predominating.Intraoral Pain Disorders7 122Intraoral Pain Disorders7the origin of most dental pain can be easily located, the clinician must be aware of these other possibilities, which become more likely with chronic, intractable symptoms.As a rst step in the diagnosis process, the clinician must determine if the pain is truly odontogenic in origin. If it can be attributed to dental disease, it is then necessary to de-termine if the pain is of pulpal or periodontal origin (or both). Nonodontogenic sources of pain that may mimic toothache are reviewed at the end of this chapter, and the codes from The International Classication of Diseases, Tenth Edition (ICD-10) are presented for each disorder.Pulpal pain (ICD-10 K04.0)The dental pulp is a visceral tissue, and pain that originates there has characteristics similar to other types of visceral pain, which tend to be deep, dull, or aching pain that is of a thresh-old nature and that may sometimes be difcult to localize.1 Pulpal pain can arise only from vital teeth with functioning nerves. In these teeth, pain may arise from pulpitis, which is revers-ible or irreversible inammation of the tissue.Reversible pulpitisReversible pulpitis is characterized by a short, sharp, hyperalgesic response that subsides soon (ie, seconds) after the stimulus is re-moved. The pain must be provoked and typi-cally does not occur spontaneously. Irritants such as hypertonic solutions (eg, sugary food) or thermal extremes may cause focal stimula-tion, which produces a brief pain.2 It is worth noting that pain from reversible pulpitis is a symptom, not a disease process.Irreversible pulpitisIrreversible pulpitis is characterized by pro-longed pain, either spontaneous or provoked by a stimulus. This type of pain tends to be variable and may be intermittent or continu-ous, moderate or severe, sharp or dull, local-ized or diffuse, and affected by the time of day or body position. The intensity of the pain may also vary over time, and the tooth may go through asymptomatic periods. Pulpal in-ammation is typically more severe and more widespread than in reversible pulpitis, and it may progress to pulpal necrosis.2Nonvital tooth painPulpal necrosis (ICD-10 K04.1) results from untreated pulpitis, exposure of the pulp to oral bacteria, traumatic injury, or other events that cause long-term interruption of the blood sup-ply to the tissue. Pulpal necrosis may be partial or total. Partial necrosis may have some of the symptoms associated with irreversible pul-pitis, which is common in multirooted teeth. Total necrosis is asymptomatic as long as no other disease process (ie, infection) affects the adjacent innervated tissues.2 If pulpal disease extends beyond the apex of the tooth, pain be-comes both spontaneous and continuous and can be exacerbated by percussion but not by temperature changes.Etiology of pulpal painTooth sensitivity may occur when dentinal tubules are exposed to the oral environment, causing fluid movement that affects the pulp.3,4 Attrition (ICD-10 K03.0), abrasion (ICD-10 K03.1), abfraction, erosion (ICD-10 K03.2), dental caries (ICD-10 K02.9), gingival recession (ICD-10 K06.0), toothbrush trauma, periodon-tal diseases (ICD-10 K05.30), or periodontal surgery may expose coronal and/or radicular dentin. The factors leading to acute pulpal pain can be grouped into three general categories: bacterial, traumatic, and iatrogenic.Bacterial. Bacteria or their metabolic byprod-ucts are introduced into the pulp as a result of dental caries, inadequate restorations, enamel and/or dentin fractures, or anomalous tracts from the periodontium or from the systemic blood supply (bacteremia and retrograde infection).5–11 123Traumatic (ICD-10 K03.8). Direct trauma to a tooth can cause pulpitis, acute pulpalgia, in-complete fracture, or complete fracture with exposure of dentin or the pulp.7 Trauma may subluxate or completely avulse a tooth, with consequent disruption of the apical blood sup-ply and subsequent pulpitis or necrosis.12 Re-peated microtrauma, such as chronic awake or sleep bruxism, may also cause pulpal inam-mation or impact the blood ow to the pulp, which may lead to necrosis.Iatrogenic. The process of restoring teeth may cause pulpitis and acute pulpalgia. Heat and vibration from dental procedures, depth of preparation, dehydration of dentin, insertion of pin-retained restorations, and accidental pulp exposure have been well documented. Pulpal changes have also been reported following impressions in which bacteria were forced through the dentinal tubules. Furthermore, many dental materials and chemicals have the potential to irritate or injure the pulp.Pathophysiology of pulpal painMyelinated (Aδ) and unmyelinated (C) afferent nerve bers innervate the dental pulp. The Aδ bers arborize in the coronal part of the tooth, just below the odontoblasts, where they lose their myelin sheath and form the plexus of Raschkow.4,13 This plexus sends free nerve endings onto and through the odontoblastic cell layer, where they contact the odontoblas-tic processes at the pulpal end of the den-tinal tubule.14 The intimate association of Aδ bers with the odontoblast is referred to as the pulpo-dentinal complex.15 If the cellular or uid contents of the dentinal tubules are suf-ciently disturbed to involve the odontoblastic cell layer, the Aδ bers become excited.16–18 These nociceptive signals are perceived as sharp (bright), momentary pain that resolves when the stimulus is removed.15 If an exter-nal irritant is of signicant magnitude to cause pulpal inammation, a vascular response (hy-peremia) can lead to an increase in tissue pres-sure (perceived as pain), which increases as inammation increases.19A tooth with localized inammation can also produce Aδ ber pain with other types of exci-tation. Inammatory mediators such as brady-kinin, 5-hydroxytryptamine (5-HT, also known as serotonin) and prostaglandin E2 can sensi-tize the Aδ bers, heightening their response to stimulants. As exaggerated Aδ ber pain subsides, a dull throbbing ache remains, asso-ciated with inammatory involvement of noci-ceptive C-bers.15 This type of pain occurs with more severe tissue injury and is modulated by chronic inammatory mediators, vascular changes in blood volume and blood ow, and increases in intrapulpal pressure. When C-ber pain dominates over Aδ ber pain, the symp-tom is more diffuse and poorly localized and may be referred to other sites. C-ber pain typi-cally signies irreversible tissue damage as the inammation increases.15 Pain may begin as a short, lingering discomfort, which can escalate to intense, prolonged episodes or constant, throbbing pain. When a caries lesion contacts the pulp, the cellular inammatory response changes from mostly mononuclear to polymor-phonuclear leukocytes (neutrophils), resulting in microabscesses within the inammatory le-sion, at which point pulpitis typically becomes irreversible.20–22 Complete necrosis of the pulp may occur rapidly, or it may take years to de-velop; symptomatology covers the spectrum from severe pain to complete analgesia.Clinical characteristics of pulpal painPulpal pain usually presents as a visceral, deep, dull, aching sensation.22 This pain may be superimposed with pulsing and throbbing, or it may be sharp, burning, and lancinating due to local nerve sensitization rather than to vascular or neuropathic mechanisms. Clinical symptoms correlate poorly with the histologic status of the pulp.23–25 Severe pain may be as-sociated with early histopathologic changes, while a tooth that is asymptomatic may be necrotic. Pulpal pain can be modied by many Odontogenic Pain 124Intraoral Pain Disorders7factors including heat and cold, pressure from occlusal contacts, head position, and the in-tensity of the offending stimulus. In addition, pain perception is complex and is affected by pain signaling, the patient’s emotional state, and sociocultural background.4When the pain is referred, it tends to fol-low a laminated segmental pattern within the trigeminal system. Maxillary teeth commonly refer pain to maxillary and mandibular teeth on the same side and to cutaneous locations on the face, superior to the maxillary teeth. Mandibular teeth tend to refer pain to maxil-lary and mandibular teeth on the same side. Anterior teeth may refer pain to both sides of the face.26–28 Cutaneous referral patterns start at the level of the ear and project to locations on the face inferior to the ear.Dierential diagnosis of pulpal painThe rst step in the diagnostic process is to determine whether the patient with a tooth-ache is experiencing pain from an odontogenic or a nonodontogenic source. The tooth caus-ing the odontogenic pain is usually identied by the presence of pathology to explain the pain (eg, caries or large restoration, combined with historic, clinical, and radiographic nd-ings).29 When a suspicious tooth is located, diagnosis may be conrmed by increased pain on application of a noxious stimulation (chemi-cal, thermal, mechanical, or electric sources). If the pain can be inuenced by local irritation, the tooth should be anesthetized to determine if the pain is blocked. If local anesthesia has no effect, pain from a nonodontogenic source should be considered. If administration of an-esthesia decreases but does not eliminate the pain, there may be an additional nonanesthe-tized contributor to the pain.Once a conclusion regarding the source has been reached, the next step is to determine if the pain is pulpal or periodontal in origin. Pain of pulpal origin tends to respond to a stimulus at a given threshold and may be difcult to local-ize. Teeth that have only pulpal involvement are generally not sensitive to percussion. Teeth that have periodontal and/or periapical involvement typically respond to percussion or pressure on a graduated basis, and the pain is easier to lo-calize.29 Reversible pulpitis is characterized by stimulated pain of brief duration that ceases seconds after removal of the stimulus. Cold and electric stimulation provoke a brief response, and sensitivity to percussion is uncommon.29 Ir-reversible pulpitis is characterized by stimulated pain of prolonged duration and/or by spontane-ous pain. There may be no sensitivity to percus-sion until the inammatory process extends to the periapex.29 A necrotic pulp is asymptomatic until it becomes infected and inammation ex-tends to periapical tissues. The tooth is not re-sponsive to either cold or electric pulp testing; however, there may be extreme sensitivity to percussion if the periapex is inamed.29Management considerations for pulpal painTreatment for dentin sensitivity is directed at reducing uid movement in the dentinal tu-bules. Treatment modalities include (1) forma-tion of a smear layer on the sensitive dentin by burnishing the exposed surface; (2) application of agents such as oxalate, arginine, or peptides that form insoluble precipitates within the tu-bules; (3) impregnation of the tubules with plastic resins; and (4) application of dentin bonding agents to seal the tubules.30–33Treatment for reversible pulpitis targets re-moval of the pain-causing stimulus, such as caries, and restoration of lost tooth structures. Treatment of irreversible pulpitis or a necrotic pulp requires root canal therapy or extraction of the tooth. Systemic antibiotics are contrain-dicated when disease is localized to the pulp. A necrotic pulp is devoid of blood circulation, so no systemic medication will penetrate the space.Acute periodontal painThe periodontium (ie, periodontal ligament and alveolar bone) is of mesenchymal ori-gin. Therefore, periodontal pain tends to be 125more localized in comparison to visceral pain of pulpal origin. Localization of the source of pain is attributed to the proprioceptive and mechanoreceptive sensation of the periodon-tium.34 Periodontal pain is generally dull and aching. Inammatory uid may cause dis-placement of the tooth in the socket with a resulting acute malocclusion and typical localization of the pain with biting or chew-ing. The diseased site readily responds to provocation proportionate to the stimulus.1 At minimal levels of stimulation, the patient may describe an innocuous sensation such as itching or moderate dull aching; at severe levels, the patient may describe unrelenting, aching, and throbbing pain. Factors that may increase periodontal pain include occlusal contact, head position, the intensity of the stimulus, and CNS modulation. Periodontal pain, like pulpal pain, may stimulate second-ary central excitatory activity, resulting in regional pain referral around the head and neck, to muscle overload with the potential to develop myofascial trigger points, and to autonomic effects such as sinus congestion, conjunctival injection, and eyelid edema or drooping. Sites of prior pain are more likely to be sites of referred pain. Periodontal pain localized to a single tooth is usually associ-ated with a gingival or periodontal abscess or a combined periodontal-endodontic lesion.35Gingival abscess (ICD-10 K05.00)Clinical characteristics. The gingival abscess is a relatively rare entity. It usually arises as a result of foreign body impaction or trauma to previously healthy tissue and is conned to the marginal gingiva. It presents as a painful, pos-sibly uctuant swelling. The surface may be erythematous, smooth, and shiny. Spontane-ous drainage may occur.36Etiology. The precipitating cause of a gingival abscess is usually an impacted foreign object (eg, popcorn kernel) or trauma followed by infection.Pathophysiology. The gingival abscess con-sists of a purulent focus in the connective tis-sue surrounded by an inammatory inltrate.Management considerations. Treatment is by incision and drainage, followed by oral rinses with warm salt water, and may require removal of the causative agent. On rare occa-sions, irrigation and debridement of the soft tissue lesion may be required.Periodontal abscess (ICD -10 K05.20)Clinical characteristics. Periodontal ab-scesses arise as acute or recurrent inam-matory swellings in periodontally diseased dental sites. The classic periodontal abscess is a localized swelling of the gingiva and/or the alveolar mucosa. These lesions often have an erythematous, violaceous, or cyanotic appear-ance and may be uctuant. Pain is variable and can range from a deep ache of low intensity to severe discomfort. The pain is often exacer-bated by chewing and percussion. The affected tooth may be mobile and may be slightly ex-truded. Fever and malaise may occur in more severe cases, cases of cellulitis, and systemic symptoms with lymphadenopathy.36–39 Suppu-ration may be noted from the pocket orice. The tooth is usually vital.36,37Etiology. The infectious cause of the lesion is the periodontal microbial ora, which is usually composed of pathogens such as Por-phyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococ-cus micros, and Bacteroides forsythus.40–42 It may arise from chronic periodontitis that can-not drain into the periodontal pocket or from trauma or extension of pulpal inammation into the periapical tissues.29,43 A lateral pulp canal may also cause an abscess in the periodontal space, which technically is not a periodontal abscess and requires root canal therapy.Pathophysiology. A periodontal abscess is usually an exacerbation of a preexisting chronic Odontogenic Pain 126Intraoral Pain Disorders7periodontal condition. More than 300 species of microorganisms have been isolated from periodontal pockets, but only a small number are considered pathogenic.44 Most of the tis-sue destruction found in established periodon-tal lesions is a result of the mobilization of the host immunity via activation of monocytes, lymphocytes, broblasts, and other host cells. Engagement of these cellular elements by bacterial factors, in particular bacterial lipopoly-saccharide, is thought to stimulate production of both catabolic cytokines and inammatory mediators including arachidonic acid metabo-lites such as prostaglandin E2. Cytokines stimulate inammatory responses that cause tissue destruction via activation of tissue me-talloproteinases, a major pathway for connec-tive tissue attachment loss and bone loss in most forms of periodontitis.45–47Management considerations. Treatment con-sists of establishing drainage (usually through the pocket orice) and debridement of the root surface and pocket wall under local an-esthesia, accompanied by copious irrigation. Occlusal adjustment is sometimes indicated. Unless the tooth is beyond salvage, it is usu-ally prudent to resolve the symptoms and then reassess the periodontal status. The endodon-tic status (ie, vitality) of the tooth should also be determined.Periradicular (periapical) abscess (ICD-10 K04.7)Clinical characteristics. Pulpal infection may induce an inammatory reaction that may lead to periradicular abscess formation. Clinical characteristics include rapid onset; spontane-ous pain; and acute response to percussion, purulence, and swelling.2 It must be distin-guished from the periodontal abscess, al-though both processes may be operant in the case of a combined periodontal-endodontic lesion. One helpful element for differentiation is that the periodontal abscess occurs in a set-ting of periodontal attachment loss and pocket formation. The initial pain associated with a radicular abscess is intense when conned to bone, and it subsides following formation of a stulous tract (drainage) into the soft tis-sues. The infection may drain in the oral cav-ity or spread along fascial planes and result in cellulitis. In addition, bacteremia may occur, resulting in systemic infection. If the infection localizes, it may progress to a uctuant swell-ing that may eventually drain.Etiology. A periradicular abscess usually devel-ops from a necrotic pulp that becomes infected, with spread of infection into the periradicular tissues.14 Occasionally, it may develop from ex-acerbation of chronic periodontitis located near the tooth apex (called phoenix abscess).Pathophysiology. The periradicular abscess is initiated by inltration of bacteria into the apical periodontal ligament from an infection in the pulp, causing an acute inammatory reaction.Management considerations. Management involves treating the cause of the abscess, which is endodontic (root canal therapy), or extraction of the offending tooth. Spread of the infection may require drainage of exudates and/or systemic antibiotics. Signs and symp-toms such as fever, swelling of the infraorbital region or other spaces due to extension along fascial planes, trismus, stridor, elevation of the oor of the mouth, or neck tracks may indicate signicant danger and typically require urgent intervention. In such cases, oral antibiotics are insufcient, and the patient should be immedi-ately referred to a hospital.Pericoronitis (ICD -10 K05.20)Clinical characteristics. Pericoronitis is a lo-calized infection within the soft tissue that sur-rounds the crown of an impacted or partially erupted tooth, most commonly a third molar. Clinical features may include an erythematous, swollen, suppurating gingival lesion that is ten-der and may cause radiating pain to the ear, throat, and oor of the mouth. The patient may 127experience a bad taste and inability to open or fully close the jaws. Swelling of the cheek in the region of the angle of the mandible is common, as is lymphadenopathy. The patient may also experience signs and symptoms of systemic complications such as fever, leuko-cytosis, and malaise.Etiology. The typical process involves bacterial colonization of the pericoronal space, which triggers inammation. Food debris or foreign objects may also become trapped under the gingival tissue covering the crown, thereby contributing to the inammatory process.Pathophysiology. Streptococci are common in the oral cavity and can produce hyaluroni-dase, which makes these organisms the typi-cal cause of pericoronitis. Cellulitis may follow the spread of the infection posteriorly into the oropharyngeal area and medially to the base of the tongue, making it difcult for the patient to swallow. Depending on the severity of the infection, lymph node involvement of the sub-mandibular, posterior cervical, deep cervical, and retropharyngeal regions may occur.48Management considerations. An irrigat-ing syringe should be used to perform la-vage under the gingiva with sterile saline or chlorhexidine solution. Removal of the tooth is generally indicated when the acute episode has resolved. Removal of the operculum is sometimes advocated in lieu of extraction; however, the soft tissue frequently regrows, resulting in the same local conditions that lead to infection. Abscess formation is common and leads to the need for surgical drainage and appropriate antibiotic therapy. Patients pre-senting with trismus, fever greater than 101°F, and facial swelling are candidates for referral to an oral and maxillofacial surgeon.49 Celluli-tis that extends along fascial planes to involve other anatomical spaces requires aggressive treatment due to the potential for morbidity and—rarely—mortality.Combined periodontal-endodontic lesionsThese lesions may be of primary pulpal origin or of periodontal origin.50 They may occur in a patient with preexisting periodontitis or in a setting of relatively good periodontal health. If the lesion is primarily endodontic in origin, root canal treatment alone may lead to resolution; however, this can only occur if the lesion is of recent onset.Clinical characteristics. The clinical presenta-tion includes pain to pressure and percussion, increased tooth mobility, probing depth and attachment loss, and swelling of the marginal gingiva, simulating a periodontal abscess. The suppurative process may cause the formation of a narrow, deep pocket that may be traced to the apex with a gutta-percha cone or a peri-odontal probe. Pulp testing is negative, or in a multirooted tooth it may show an abnormal response.51 All these signs, including radio-graphic ndings, are somewhat variable.Etiology and pathophysiology. The etiology and pathophysiologic processes are detailed in the preceding sections on periodontal and periradicular abscess.Management considerations. The periodon-tal component of the combined lesion may resolve subsequent to root canal therapy, and therefore it is preferable to perform this treat-ment rst and allow for a suitable period of healing. If the periodontal lesion persists, fur-ther treatment will be required.52 Of note is that vertical root fractures (see following sec-tion) may show similar signs and symptoms. Electric pulp testing may help separate these two lesions.Pulpal and periodontal pain secondary to fractured teethTooth fractures occur in approximately 5% of adults annually.53 In most cases, the fracture of a cusp or a split tooth are readily diagnosed. Odontogenic Pain 128Intraoral Pain Disorders7Surface cracks, or craze lines, are considered incomplete tooth fractures. These incomplete fractures are usually asymptomatic but when painful, they may be due to “cracked tooth syndrome,” which can be difcult to diagnose.2Clinical characteristics. Patients with a cracked tooth may have complaints of spo-radic, sharp, momentary pain on biting or re-leasing, along with occasional pain from cold stimuli. Sometimes, patients may indicate the pain occurs minutes after chewing.2 In con-trast with other tooth-related pains, the pain of a cracked tooth is usually easily located.54Etiology. A fracture rarely occurs in teeth that are without caries or have no or small resto-rations. Predisposing factors include loss of support due to caries or large restorations, inadequate cusp protection by restorations, developmental weaknesses of the tooth, a his-tory of local trauma, and clenching or bruxing habits.55–57Pathophysiology. The pain associated with a cracked tooth occurs when occlusal forces spread portions of the crown, exposing the underlying dentin. Momentary hydrostatic movement of uid within the dentinal tubules causes pain.Differential diagnosis. The diagnosis of a cracked tooth is usually made from history and clinical tests. Generally, percussion, palpation, mobility, and probing are within normal limits if the crack is conned to the crown. The most useful test is biting on successive cusps with a rm object such as a wood stick or Tooth Slooth (Professional Results) until the pain is reproduced. Staining and transillumination may also disclose subtle fractures. In addition, the use of a microscope greatly facilitates the observation of fractures.58 Electric pulp test-ing will produce normal responses unless the pulp is involved. Cold testing may be produc-tive, whereas heat may not be helpful. Frac-ture lines are not visible on radiographs when they run mesiodistally and are not in the plane of the x-ray beam. If the fracture extends into the root, a periodontal defect may be observed adjacent to the fracture. At this point, the pulp may have become necrotic. Sharp pain and cold sensitivity are not common. Typically, a dull ache on biting might be present when the periodontal ligament is inamed, resulting in tenderness on percussion.14,59Management considerations. Early detec-tion of cracked teeth is essential, and therapy depends on the severity of symptoms and lo-cation of the crack.54,56–59 Temporary stabiliza-tion can be achieved with an orthodontic stain-less steel band or a provisional crown until an overlay or full crown can be fabricated.60 Root canal therapy with or without stabilization has been advocated. In cases with extensive cracks, extraction may be necessary.2Systemic factors associated with dental infectionSystemic conditions that may modify host re-sponse to infection include diabetes, anemia, diseases causing altered neutrophil count and function, immunosuppression (pathologic or medically induced), tobacco use, nutrient and caloric deciencies, hormone abnormalities, and emotional stress.61–64 Additionally, patho-logic conditions and/or medications that affect exocrine secretions may inuence oral homeo-stasis through effects on saliva. Rheumatic diseases such as arthritis, Sjögren syndrome, systemic lupus, and systemic sclerosis (sclero-derma) are counted among the most common inducers of pathologic changes in salivary glands. Dehydration, alcoholism, and a large variety of medications induce hyposalivation without signicant change in glandular tissues. In addition, genetic diseases that affect calci-cation may interfere in mineralization of teeth. Most common among these are osteogenesis imperfecta and the related dentinogenesis and amelogenesis imperfecta. Patients affected by these conditions are generally more prone to 129cariogenic, periodontal, or other oral infectious processes where pain is a prominent feature. Both diagnosis and treatment of these pa-tients involve unusual complexity.Nonodontogenic ToothacheThe clinician should never assume that all patient-reported tooth pain is caused by pulpal or periodontal disease. When the pa-tient reports toothache, the clinician must determine if the pain has its origin in dental structures or if pain is referred from other sites. Effective treatment can only be provided following a correct diagnosis. Because dental pain is so commonly treated in the dental of-ce and nonodontogenic tooth pain is rare, these latter cases are often inappropriately treated with dental therapy before appropriate diagnosis of the cause. The appropriate diag-nosis is often made after multiple treatment failures that may include invasive and irrevers-ible procedures such as root canal therapy and tooth extractions.65,66Potential identifiers of nonodontogenic toothache include:• Spontaneous multiple-tooth pain• Inadequate dental cause for the pain• Stimulating, burning, electric/lancinating pain, nonpulsatile toothaches• Constant/persistent, unremitting toothaches• Persistent, recurrent toothaches• Failure of local anesthesia to signicantly reduce pain• Failure of the toothache to respond to reasonable dental therapy• Pain referral to region of tooth from mus-cle trigger points• Associated autonomic symptoms such as tearing, conjunctival injection, regional sweating, and other vascular phenomena• Regional pain and paresthesia• Severe headache• Recent cold, allergy, stuffiness, and coughing with pain on maxillary teethNonodontogenic toothache may be differ-entiated from odontogenic toothache by local provocation. Pulpal and periodontal pains are increased by local stimulation such as percus-sion, hot, cold, or bite forces. When the pain is not increased by provocation, the clinician should be suspicious of a nondental etiology. Local anesthetic may be helpful in differentiat-ing true dental pain from pain referred to the teeth. Local anesthetic placed at the site of the nonodontogenic toothache often will be ineffective because the site of pain report is not the true source.67,68 Pain can be referred to the teeth from multiple sources including myo-fascial trigger points in the masseter (most common muscle source), temporalis, medial pterygoid, lateral pterygoid, and anterior digas-tric muscles. Maxillary sinusitis or a regional tumor may be a source of maxillary tooth pain.69–72 Nonodontogenic toothache may also result from continuous neuropathic pain (ie, deafferentation, neuritis, neuroma, persistent dentoalveolar pain), episodic neuropathic pain disorders (ie, neuralgias), and other neoplas-tic or neurovascular disorders.73 CNS disease and cardiac pain may also be experienced as toothache.74,75 In some instances, psychogenic conditions may also present as tooth pain. Knowing the pain characteristics and referral patterns for each of these sources is essential for differential diagnosis.Oral Mucosal PainLocal mucogingival and glossal painsLocalized mucosal pain is often associated with a detectable lesion resulting from physi-cal, chemical, or thermal trauma; infection; in-ammation; neoplasia; immune dysfunction; or other origin. The pain experienced is typi-cally localized to the site of mucosal change. Oral Mucosal Pain 130Intraoral Pain Disorders7A response to stimulation (eg, eating spicy or acidic foods or contact with toothpaste) is representative in intensity and location, and topical anesthetic at the site modulates the pain. By contrast, for diffuse mucosal pain, it may be difcult to identify the specic cause unless widespread lesions are obvious. This type of pain may result from a direct insult to the tissues due to local or CNS lesions that require special studies or bacterial, viral, or fungal infection, which can be identied by the characteristic appearance of the oral mucosa and conrmed with diagnostic testing. Diffuse pain may also be due to radiation therapy and cytotoxic or targeted chemotherapy, which may result in acute mucositis with severe generalized pain that may persist past heal-ing of the lesions as chronic mucosal pain. Burning sensation of the oral mucosa, particu-larly the tongue, may result from neuropathy/ neuralgia, hyposalivation, use of certain medi-cations, and in some cases, nutrient deciency diseases. Generalized diffuse pain with a sym-metric distribution in the oral mucosa, with a burning quality that may be accompanied by a change in taste, may represent burning mouth syndrome (see chapter 6).39Necrotizing diseaseNecrotizing mucosal conditions are generally characterized by severe pain, and they often hemorrhage on slight provocation. The term necrotizing periodontal diseases includes the somewhat arbitrary terms necrotizing ulcera-tive gingivitis (NUG) and necrotizing ulcerative periodontitis (NUP), which have been used to distinguish necrotizing conditions that pre-sent with or without attachment loss.76 Tissue necrosis of gingiva or periodontium may run a short course or may become chronic; there-fore, the term acute has been deleted.Spontaneous or, more commonly, trauma- and/or extraction-associated soft tissue and jaw bone necrosis has been described in asso-ciation with antiresorptive bone medications or osteolytic inhibitors such as bisphosphonates and receptor activator of nuclear factor κB li-gand inhibitors (eg, denosumab) and antivascu-lar drugs. Cases related to other biologic thera-pies have also been reported.77 Antiresorptive agent-related bone necrosis is dened as a his-tory of bone exposure in the mandible or max-illa of more than 8 weeks’ duration, though this concept has been challenged.78Clinical characteristics. NUG/NUP is charac-terized by painful, hyperemic, ery red gingiva and punched-out ulceration of the interdental papilla. The lesions bleed easily and are often covered with a gray necrotic pseudomem-brane. The patient may complain of bad breath and inability to eat. Occasionally, systemic symptoms are seen, such as malaise and low-grade fever. The lesions may occasionally involve other areas of the oral mucosa (nec-rotizing ulcerative stomatitis), which is usually seen in debilitated or immunocompromised individuals (also known as noma, gangrenous stomatitis, and cancrum oris).79–81 When the condition occurs in immunocompetent indi-viduals, which is usually the case, the patient is often a young adult with poor hygiene who is also a heavy frequent smoker. Patients who do not t this prole should be evaluated for po-tential predisposing immunosuppressive con-ditions including blood dyscrasia and HIV/AIDS.Etiology. Vascular changes associated with emotional stress, tobacco use, poor oral hy-giene, local trauma, fatigue, and impaired host defense predispose the individual to infection and tissue necrosis.79Pathophysiology. NUG was originally referred to as a fusospirochetal disease. More recently, P intermedia has been implicated, along with various Treponema spp, Fusobacterium spp, and Selenomonas spp.82Management considerations. Treatment of NUG/NUP consists of mechanical debride-ment; systemic antibiotic therapy with met- 131ronidazole, tetracycline, or doxycycline; and 0.12% chlorhexidine mouthrinse.Aphthous stomatitis (ICD-10 K12.0)Aphthous stomatitis is the most common oral mucosal disease affecting the general popu-lation. Aphthae may present in three clinical forms: minor, major, and herpetiform. Aph-thous minor is the most widespread form with a prevalence of 17.7% of the general popula-tion (80% of the cases of aphthous stomatitis). The prevalence of the major form ranges from 10% to 15%.83 Herpetiform cases comprise 7% to 10%.84–88Clinical characteristics. Aphthous minor ap-pears as discrete, painful, shallow, recurrent ul-cers, covered by a yellowish-gray pseudomem-brane, that are surrounded by an erythematous halo. Ulcers typically number one to ve at any one time and measure less than 10 mm in di-ameter. These lesions are painful and usually heal within 10 to 14 days without scar forma-tion.89 Aphthous major produces ulcers that are usually larger than 10 mm in diameter, may persist for weeks, and may be recurrent or present continuously for extended periods. They appear as very painful, large, deep-based ulcers containing a yellow-gray necrotic cen-ter, and they may develop raised, rolled bor-ders with a predilection for the lips, soft palate, posterior aspect of the tongue, and tonsillar fauces. These lesions may heal with scarring. Herpetiform aphthae occur in crops of 10 to 100 at a time, usually in the posterior part of the mouth.89 The ulcers measure 1 to 3 mm in diameter but sometimes coalesce, creating a look reminiscent of a herpetic infection. In all types of aphthae, ulcers predominantly involve nonkeratinized mucosa of the mouth: the labial and buccal mucosae, maxillary and mandibular sulci, nonattached gingiva, oor of the mouth, ventral surface of the tongue, soft palate, and tonsillar fauces. Ulcers of this type typically spare the keratinized mucosa of the dorsum of the tongue, the attached gingiva, and the hard palate. While patients may develop sub-mandibular lymphadenopathy, fever is rare.90Etiology. Factors that play a role in triggering the development of aphthous stomatitis in-clude hormonal changes, trauma, stress, and food allergies. Foods associated with aphthous stomatitis include bovine milk protein, glu-tens, chocolate, nuts, cinnamon, spices, and preservatives.90,91 A number of medications are known to cause aphthous-like lesions, in-cluding nonsteroidal anti-inammatory drugs (NSAIDs) and “targeted” cancer therapies (eg, mammalian target of rapamycin [mTOR] inhibitors).92 Deciencies of ferritin and vitamin B12 have also been associated with this con-dition.93 Nevertheless, the complete etiology remains unknown.Pathophysiology. Causative microorganisms have not been identied. Rather, the disease is considered to result from immune dysfunction with overexpression of tumor necrosis factor α (TNF-α). Blood studies from otherwise healthy persons with aphthous stomatitis have found various immune abnormalities: depressed or reversed CD4:CD8 cell ratios (especially in persons with severe stomatitis), increased T-cell receptor d+ cells in patients with active aphthae compared with controls, and patients with inactive aphthous stomatitis.88,94,95Management considerations. Therapeutic agents such as topical steroids, topical tetra-cyclines, and amlexanox 5% oral paste have been effective in decreasing the symptoms and healing time, but nothing has been effec-tive in decreasing the recurrence rate unless a trigger or a serum deciency can be identi-ed.96–100 Other treatments for minor aphthae include topical anesthetics, mouthrinses, caustic agents, and laser ablation. In cases of major aphthous stomatitis where the healing process may be prolonged and topical cortico-steroids have not been effective, therapy may include systemic and/or intralesional steroids Oral Mucosal Pain 132Intraoral Pain Disorders7or thalidomide. Other drugs that have been ad-vocated are lysine, dapsone, azathioprine, and etanercept. Interventions with anti-TNF effects may have a future role.101,102InfectionsViral infectionHerpes family viruses often cause oral mucosal and salivary gland infection in either primary or reactivated form.103 The most common patho-gens affecting the oral mucosa are the herpes simplex virus (HSV) members (HSV 1 and 2, primarily the former), but recent research iden-tied a relatively high prevalence of human her-pes virus (HHV) 6, 7, and 8 in the oral mucosa. The varicella zoster virus (VZV) is present in all patients with a history of chicken pox, whereas cytomegalovirus (CMV) or Epstein-Barr virus (EBV) may be latent in those patients with a history of mononucleosis. Common to all her-pes viruses is the fact that after primary ex-posure (which may or may not produce overt disease), the virus achieves a dormant state and is subject to episodic reactivation.Primary herpetic gingivostomatitis. Primary herpetic gingivostomatitis occurs in individuals without prior exposure to the virus. These in-fections are seen mostly in children and young adults. When symptomatic, the clinical mani-festations include diffuse oral lesions and pos-sible systemic involvement. The initial presen-tation has rapid onset of generalized prodromal signs and symptoms, including erythema, pru-ritus, fever, malaise, headache, irritability, and regional lymphadenopathy, followed by the de-velopment of frank oral lesions that consist of severe generalized inammation and vesicles primarily involving keratinized mucosa of the lips, gingiva, tongue, and palate. The vesicles rupture rapidly, forming shallow, ragged, pain-ful ulcerations with a yellowish center and erythematous borders. The lesions begin as clustered, punctate (1- to 2-mm rounded) ul-cerations that may coalesce to form irregular lesions that usually heal within 2 weeks. In some cases, extraoral ulcerations develop on the skin and vermillion borders of the lips, with resultant crusting and oozing. Severe pain, foul odor, and increased salivation may accom-pany the oral lesions. Diagnosis is most often based on the history and clinical presentation. Laboratory diagnosis is not usually necessary except in the setting of immunosuppression or atypical presentation.104 Diagnosis can be conrmed by direct viral culture, uorescence or peroxidase stain, or by assessing acute and convalescent viral serology.Secondary (recurrent) herpetic gingivosto-matitis. The prevalence of secondary or recur-rent HSV has been estimated at 20% to 40% of the population worldwide and 35% to 38% in the United States.105 Recurrent infections are caused by reactivation of the virus, which is latent in the trigeminal ganglion.Clinical characteristics. Recurrent herpes infection is characterized by mostly unilateral vesicular eruptions surrounded by erythema, followed by crusting and healing. The eruptions are often preceded by a prodromal tingling sensation. Oral mucosal lesions are rare and usually restricted to small clusters of vesicles (1 to 3 mm in size) that rupture, resulting in punctate ulcers, typically on the palatal gin-giva (occasionally elsewhere on the gingiva) unilaterally. The lesions may be triggered by ultraviolet light exposure, stress, immunosup-pression, or dental procedures. The lesions are usually self-limiting, resolving within several days.106 Extraoral lesions may appear on the skin, genitalia, anal and perianal areas, eyes (keratitis, keratoconjunctivitis), and nervous system (encephalitis, meningitis).107,108Etiology. The typical route of HSV transmis-sion is physical contact with an infected indi-vidual by someone who has not been previ-ously exposed to the virus. During the primary 133infection, only about 50% of individuals show clinical signs and symptoms, while most ex-perience a subclinical course. This latter group becomes seropositive and can be identied through laboratory evaluation of circulating antibodies to HSV.109 Approximately 90% of adults are seropositive for HSV 1 and about 35% for HSV 2, which are the most common agents for mucosal lesions.Pathophysiology. The incubation period for primary infection ranges from several days to 2 weeks after exposure to the virus. The clini-cal picture consists of a vesiculo-ulcerative eruption on the mucosal tissues at the site of inoculation. Following resolution of primary herpetic gingivostomatitis, the virus becomes latent in the trigeminal ganglia. Reactivation of the virus is not fully understood but may follow exposure to ultraviolet light, trauma and stress, or immunosuppression, causing a secondary or recurrent infection. Virions as-semble and migrate along the nerve and enter epidermal cells, causing vesicles that ulcerate at the epithelial surface. Because the humoral and cell-mediated arms of the immune sys-tem have been sensitized to HSV antigens, the lesions typically remain localized, and sys-temic symptoms are rare. As the secondary lesion resolves, the virus returns to its latent state.109 It is worth noting that viral shedding occurs commonly in infected individuals, from oral and genital sites, without clinical symp-toms or overt lesions. Hence, contagion can occur even in the absence of clinical lesions. In immunosuppressed patients, recurrent le-sions may spread, persist for longer periods, and present atypical appearances including ulceration of attached and unattached mucosa in contrast to those of nonimmunosuppressed patients.Varicella zoster infection. Primary infection with VZV (chicken pox) is also a disease with recurrent episodes (shingles or herpes zoster). It is estimated that in the United States, more than 90% of adults are susceptible to VZV re-activation.110 With an estimated 30% chance of reactivation over the lifetime, about one million cases of shingles occur in the United States annually. Common causes of reactiva-tion include age over 60 years, immunosup-pression, or trauma. Reactivation of VZV has a typical onset with pain that can be severe, followed by segmental distribution of lesions that may involve the head, neck, and oral cav-ity. Herpes zoster may run its course, and the virus becomes latent in immunocompetent pa-tients but may spread locoregionally or cause systemic infection in immunosuppressed indi-viduals. Postherpetic neuralgia is quite com-mon after shingles and may result in persisting chronic neuropathic pain following resolution of active infection. Other herpes viruses may occasionally cause oral lesions, including CMV and HHV 8, which are responsible for ulcer-ations in immunocompromised patients, and Kaposi sarcoma. Acute infection by CMV and the EBV may cause mononucleosis-like symp-toms. CMV may become latent in salivary gland tissue and has been associated with cancer at that location. EBV is associated with nasopharyngeal cancer, B-cell lymphoma, and posttransplant lymphoproliferative disorder. HHV 6 (A and B) and 7 are commonly found in the salivary glands and tonsils and contribute to the reactivation of CMV and EBV.Management considerations. Treatment of primary herpetic gingivostomatitis focuses on supportive care to prevent dehydration by en-suring adequate uid intake and oral nutrition. Systemic analgesics may be required for pain management. Systemic antiviral agents such as acyclovir and valacyclovir may be indicated and are mandatory in immunocompromised patients or those with ocular involvement.110 Treatment of recurrent herpetic gingivostoma-titis is early prescription of acyclovir or one of its congeners (eg, famciclovir, valacyclovir).111 A recent systematic review on the safety of nucleoside antiviral drugs for the treatment Oral Mucosal Pain 134Intraoral Pain Disorders7of recurrent herpes labialis, including 25 ran-domized controlled trials, found that systemic administration was more effective than topical administration. In addition, it was found that valacylcovir was more effective than acyclovir. The study also found that famciclovir and pen-ciclovir did not prevent the development of le-sions, although the use of penciclovir reduced time to heal as effectively as valacyclovir and acyclovir.112 Lysine supplements have not been subjected to rigorous trials.102 Active herpetic lesions should be considered infectious until complete reepithelialization. Patients should be warned of the possibility of transmission to others, especially infants and the immuno-compromised.111 Autoinoculation of the virus into other receptive mucosal sites (eg, the eye) is also possible. For dental professionals, herpetic whitlow and herpetic conjunctivitis is a professional risk. Management of herpes zoster includes use of antivirals (eg, acyclovir 800 mg three times daily) early after reactiva-tion and consideration for systemic cortico-steroid use to prevent possible progression to postherpetic neuralgia. There is a vaccine (Zostavax, Merck) that is currently approved for the prevention of herpes zoster (51% ef-fective) and postherpetic neuralgia (66% effec-tive). Additionally, vaccination has been shown to reduce the incidence of postherpetic neu-ralgia by 39% among patients who develop herpes zoster. The Centers for Disease Control and Prevention recommend that patients aged 60 years and older be vaccinated regardless of their prior exposure to VZV. However, the vac-cine is approved for patients as young as 50 years of age.113,114Candidiasis (ICD-10 B37.0)Candidiasis encompasses a group of mucosal and cutaneous conditions most commonly caused by the yeast Candida albicans. Other members of the Candida genus such as C tropicalis, C krusel, C parapsilosis, C guillier-mondi, and C dubliniensis are rarely the cause of disease; however, continuing overuse of antifungals has led to an increase in the preva-lence of strains that are resistant to common drugs, particularly in immunosuppressed indi-viduals.115,116 Candida species are opportunistic pathogens that may lead to clinical overgrowth and frank, local, and—rarely—systemic infec-tion due to changes in oral conditions, oral ora, and systemic status of the host.117Pseudomembranous candidiasis. The pseu-domembranous form occurs most commonly in infants, elderly patients, or those with white cell or immune deciencies. The lesions pre-sent as supercial, curd-like white plaques that wipe off, leaving an erythematous, eroded, or ulcerated surface. Plaques are composed of fungal organisms, keratotic debris, inamma-tory cells, desquamated epithelial cells, bac-teria, and brin. The lesions commonly affect the palate, buccal mucosa and mucobuccal folds, lateral and dorsal aspects of the tongue, and oropharynx. Patients may have no symp-toms or may complain of tenderness, mucosal burning, taste change, and odynophagia. Pre-disposing factors include a history of medica-tion with broad-spectrum antibiotics or cortico-steroids, hyposalivation, wearing of removable dentures, tobacco use, nutritional deciency, diabetes, malignancy, chemotherapy, radiation therapy, and cell-mediated immune dysfunc-tion, including that induced by HIV.Erythematous (atrophic) candidiasis. Ery-thematous lesions are most often seen on the middorsal tongue (median rhomboid glossitis) and on denture-bearing areas of the palate. Oral tenderness, burning, taste change, and odynophagia are common. Predisposing fac-tors are the same as those listed above. Ery-thematous candidiasis may also occur under dentures, presenting with erythema and edema on a velvety or pebbly surface (ie, pap-illary hyperplasia). Chronic candida infections are also capable of producing a hyperplastic tissue response with inter- and intracellular invasion of the epithelium. White lesions may 135include palpable thickness and irregular sur-face texture with or without erythema. These lesions are mostly asymptomatic. Predispos-ing factors include inherited or acquired altered cellular immunity and general local risk factors for candidiasis. Angular cheilitis presents as localized erythema and/or ulcerations, uni- or bilaterally at the commissures of the lips. The lesions may be painful, eroded, and crusted when extending onto the skin surface. Angular cheilitis is often associated with intraoral forms of candidiasis. Predisposing factors include overclosure of the jaw, drooling at the corners of the mouth, lip-licking and/or thumb- or digit-sucking habits, and risk factors common to all other forms of candidiasis. Angular cheilitis is often a mixed infection of Candida and salivary species of streptococci and staphylococci. The diagnosis of candidiasis may be made from the patient history and the clinical appearance and distribution of the mucosal lesions. When necessary, especially in an immunocompro-mised individual, identication of the organism is made in a culture or smear from the lesion. For hyperplastic lesions, biopsy followed by microscopy with fungal stain is necessary.118Management considerations. The underlying risk factors for candidiasis should be identied and managed when possible, or recoloniza-tion and recurrence of infection is likely, as the yeast can rarely be completely eliminated. Oral candidiasis is most often treated with an-tifungal agents such as topical polyenes (ny-statin) and azoles (clotrimazole, miconazole). Oral preparations in the form of troches or adherent patches provide the advantage of prolonged contact of the medication with the lesions.101 The angular cheilitis lesions respond well to broad-spectrum antimicrobials or com-bination therapy containing an antifungal and a topical steroid (miconazole with betameth-asone dipropionate or nystatin with triam-cinolone acetonide). Persistent lesions may require addition of antibacterial creams, such as mupirocin (Bactro ban, GlaxoSmithKline), and treatment of oral infection/colonization. Recurrence is common if the underlying risk factors are not managed. In cases of refractory candidiasis in immunosuppressed patients and for chronic mucocutaneous candidiasis, a sys-temic antifungal from the azole family such as uconazole is a common choice. For per-sisting cases, next-generation antifungals are available.Mucosal traumaTrauma is a common cause of irritation and ulceration of the oral mucosa. Traumatic oral lesions may be accidental, factitial, or iatro-genic and may result from physical, chemical, or thermal insults to the tissue.119 Hyposali-vation may predispose a patient to traumatic lesions of the mucosa. Chemical and ther-mal burns are rare because the oral mucosa is quite resistant to heat and acid or alkaline compounds. Thermal burns usually affect the hard palate and are most commonly caused by ingestion of hot liquids or hot melted cheese (pizza-palate). Electrical burns are almost ex-clusively seen in children who may bite elec-tric cords. Mucositis due to cancer therapies, including radiation and/or chemotherapy for head and neck cancer or other solid tumors, and hematopoietic malignancies, are common signicant and treatment-limiting complica-tions (see below). Chemical burns can be a consequence of deliberate or accidental inges-tion of caustic agents; prolonged contact with aspirin or vitamin C tablets; use of undiluted oral antiseptics; contamination of prosthesis with denture cleaners; or accidental contact with phosphoric, chromic, or trichloroacetic acid during dental treatment. As the offend-ing cause or agent is usually quickly discon-tinued or deleted, most traumatic injuries to the oral mucous membranes will be acute in nature. Management includes identication of the cause, discontinuing the offending agent, management of risk factors (eg, hyposaliva-tion), and symptomatic care.119Oral Mucosal Pain 136Intraoral Pain Disorders7Cancer painApproximately 3% of all malignancies in the United States are oral and oropharyngeal, with 90% of these being oral squamous cell carcinomas (OSCCs). Annually in the United States, there are nearly 45,000 new cases and more than 9,000 deaths due to head and neck cancers. Improved survival rates have been re-ported in the recent past, reecting change in cancer etiology involving human papilloma virus and changes in cancer therapy. Unfortunately, the improvement does not appear related to early detection, as approximately two-thirds of OSCC are diagnosed in advanced stages.120,121 Discomfort is common at diagnosis, and man-agement remains difcult because the neural mechanisms underlying cancer pain are poorly understood and because of lack of adequate pharmacologic management options.122 Oral involvement by hematologic cancers and oro-facial spread of metastatic cancer frequently cause oral pain. Pain from cancer may be due to the malignant disease itself or to antican-cer therapy. Pain from OSCC may be due to ulceration; pressure on nerves; invasion of nerves, vessels, muscle, and periosteum; or secondary infection. When intraoral neoplasms become large, patients may complain of pares-thesia or hypoesthesia that may be accompa-nied by loose teeth; mass or swelling; and/or restriction of tongue, lip, or jaw movement.123 Also, as with other painful conditions involving the orofacial structures, pain from cancer may be felt at the primary site, may be referred to another site, or both.Symptoms from metastatic lesions to the jaw may be the rst indication of a distant tumor or may occur during the course of the disease, most commonly breast, prostate, colon, or lung, frequently causing unilateral pain, paresthesia, or anesthesia. Hematologic cancers may involve gingival tissues directly and may be associated with intraoral infection (eg, pericoronitis). Lymphoma commonly in-volves lymphatic tissues of the head and neck and can present with cervical adenopathy and/or inltration of gingival tissues with or with-out discomfort. Solitary tumors may appear on the palate. Cancers may also produce in-ammatory cytokines and release nociceptive and sensitizing molecules that stimulate nerve pain, such as bradykinin, 5-HT, substance P, and endothelin-1.Pain due to cancer treatmentHead and neck cancer treatment may in-clude surgery, radiation therapy, chemo-therapy, targeted agents, and immunother-apy. Treatment-induced acute pain occurs due to surgery or due to mucositis induced by ra-diation or chemotherapy. The most distressing side effect of head and neck cancer therapy is pain due to mucositis. In radiation therapy, mu-cositis develops following release of reactive oxygen species, proinammatory cytokines, and sensitizing and nociceptive molecules (eg, bradykinin, 5-HT, prostaglandins, substance P). When ulcerative mucositis is present, the condition is aggravated by secondary micro-bial irritation, resulting in further upregulation of proinammatory cytokines and nociceptive molecules. In cycled chemotherapy, mucositis and associated pain may occur in up to 25% of patients; it is more common in patients with mucositis in prior courses of chemotherapy and is more common in later cycles. In hema-topoietic stem cell transplant (SCT), symptom-atic mucositis occurs in more than half of the patients, and as in radiation therapy, it may be the most signicant acute symptom these pa-tients experience. Current mucositis manage-ment frequently requires use of opiate/opioid analgesics and possible adjuvant medications. In radiation therapy, mucositis may persist for a few weeks following completion of therapy; with chemotherapy alone, mucositis may per-sist for 1 to 2 weeks; and in combined chemo-therapy and radiation therapy, it may continue for 1 to 2 months or even longer periods. Se-vere ulcerative mucositis may also be associ-ated with chronic mucosal sensitivity that has 137been reported to persist for months to years, and possibly indenitely in many patients fol-lowing cancer therapy.Other mucosal pain-inducing mechanisms may be at work in patients undergoing can-cer therapy. In immunosuppressed and my-elosuppressed patients, herpes viruses are common causes of mucosal lesions and pain. Following SCT, oral graft versus host disease (GVHD) may be a cause of symptomatic mu-cosal lesions (see immune-mediated mucosal lesions). Lastly, many cytotoxic agents (eg, platinum and taxane agents) may affect nerve cells, producing neurogenic pain that can man-ifest in the orofacial region (see below). All of these mechanisms can induce mucosal pain and taste change that can affect oral function, nutrient and energy intake, and quality of life. Post–cancer treatment muscle brosis can occur with surgical intervention and radiation therapy and may be increased in patients with chemotherapy. Head and neck cancer patients may have brosis, limiting movement of the tongue and lips and limiting jaw movement. Neuropathy following head and neck can-cer treatment and radiation therapy– and/or chemotherapy-induced neuropathy is common and may result in orofacial pain.Management of cancer-related oral pain is dependent on its cause: tumor-induced symp-toms will regress with anticancer treatment, while therapy-induced mucositis requires topical and/or systemic analgesics because no effective therapy has been described. Sev-eral prevention methods of cancer therapy– induced mucositis have been described, in-cluding cryotherapy (cooling of the mouth during infusion of cytotoxic agents), the drug Kepivance (Biovitrum; keratinocyte growth fac-tor 2), and low-level laser therapy. Oral pain of infectious etiology requires the use of the ap-propriate antimicrobial agent.Geographic tongue (benign migratory glossitis, erythema migrans) (ICD-10 K14.1)Clinical characteristics. Geographic tongue is a benign inammatory disorder that is charac-terized by multiple, well-demarcated zones of erythema located on the dorsum and lateral borders of the tongue. Lesions may be present in the buccal mucosa and lip (stomatitis areata migrans) and rarely other oral surfaces.124–126 The condition is not usually symptomatic but may occasionally present with a burning sensation, often related to the consumption of food (particularly spicy, hot food, or foods and drinks high in acid content), likely related to tissue inammation. Fissured tongue is frequently observed. Lesions vary in size and shape and may have episodic occurrence.109Etiology. The etiology of geographic tongue remains unclear. The lesion has not been linked to stress and/or infection. It has been suggested that it may represent a manifesta-tion of psoriasis.109,124Pathophysiology. Loss of adhesion molecules may underlie the clinical ndings of red areas (atrophic tongue) surrounded by a white bor-der of less attached epithelium.Management considerations. Reassurance and education is generally the only treatment indicated. When symptomatic, topical steroids and/or analgesics may be helpful.125,126Immune-mediated inammatory conditionsPainful oral conditions may occur due to drug-induced reactions or subsequent to hyposalivation induced by many medications, Oral Mucosal Pain 138Intraoral Pain Disorders7including tricyclic antidepressants, antipsy-chotics, muscle relaxants, antihistamines, anti-convulsants, diuretics, anxiolytics, opioid anal-gesics, and antihypertensive agents. A number of inammatory/immune disorders may pre-sent only in the oral cavity or associated with clinical extraoral manifestations, including lichen planus, aphthous stomatitis, erythema multiforme, mucous membrane (cicatricial or bullous) pemphigoid, pemphigus vulgaris, and lupus erythematosus. Pain is common with these lesions. Oral lichen planus is the most common immune-mediated condition and can cause pain due to inammation, including neu-rogenic inammation/sensitization and muco-sal ulceration. Pain is commonly aggravated by spicy, acidic, and highly avored foods or oral care products. A number of other systemic dis-eases are known to present with erythema-tous, erosive, ulcerative or hemorrhagic, and generally painful lesions in the oral cavity. These include discoid and systemic lupus ery-thematosus, uncontrolled diabetes mellitus, uremia, Crohn disease, and blood dyscrasias, such as leukemia and pancytopenia, agranu-locytosis, cyclic neutropenia, and sickle cell anemia. GVHD is an inammatory condition that may follow allogeneic bone marrow (he-matopoietic) SCT that may affect oral tissues, resulting in lichenoid or lupus-like lesions.Clinical signs and symptoms are rarely pathognomonic, so diagnosis of systemic and/or immune-mediated oral lesions requires lab-oratory testing, including specic blood com-ponents and biopsy specimen immunouores-cence studies. Therefore, these lesions should be referred to specialists or hospital practices for appropriate evaluation. Management of di-agnosed immune-mediated lesions requires therapy that involves local and/or systemic immune modulation, with initial treatment often consisting of corticosteroids. Pain relief is typically rapid after inception of appropriate therapy and can be further managed with topi-cal anesthetics or systemic analgesics. Lack of response to immunoactive drugs should increase suspicion of primary or secondary infection of the lesions. Complete remission of the disease is a rare outcome, and these conditions generally require chronic treatment and frequent follow-ups.Mucosal pain secondary to HIVThe number of oral lesions in HIV-infected indi-viduals has decreased considerably since the introduction of effective antiretroviral therapy. Nevertheless, painful lesions persist in this population and are directly related to immune incompetence.127 Orofacial pain may be due either directly to HIV infection or to comor-bid conditions, including mucosal infection and necrotizing diseases.128 Causes of oral pain in this population may include herpetic gingivostomatitis, recurrent zoster, candidia-sis, progressive gingival and periodontal dis-ease, necrotizing gingivitis or periodontitis, or Kaposi sarcoma or other malignant disease (eg, OSCC, lymphoma), among others. Pain may also be due to HIV-associated peripheral neuropathy. As with all patients, a proper diag-nostic evaluation and identication of disease processes must precede treatment (other than palliation). Painful oral ulcerative conditions are often seen and may be caused by a variety of pathogens, including fungi, viruses, parasites, and bacteria, or they could represent aphthous lesions or tumor.129–135 Nonulcerative lesions can occur with nonspecic mucositis, hypo-salivation, and nutritional deciencies.27 The treatment of oral pain in the patient with HIV/AIDS will depend on the specic diagnosis. Symptom management employing analgesics including NSAIDs or acetaminophen to control mild to moderate pain is generally indicated. If the pain is not adequately controlled, an opioid may be prescribed. Various chemotherapeutic or analgesic mouthrinses or topical agents may also be useful in some cases. 139139ReferencesReferences1. Okeson J. Bell’s Oral and Facial Pain, ed 7. Chicago: Quintessence, 2014.2. Berman LH, Rotstein I. Diagnosis. 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