# 29 - 38 Oral Manifestations of Disease

### 38 Oral Manifestations of Disease

Noninfectious causes of laryngitis include vocal trauma (e.g., due to 
yelling, screaming, or loud singing), inhalation injuries, allergies, gas­
troesophageal reflux disease (laryngopharyngeal reflux), asthma, and 
pollution. Immunosuppressed patients are at risk for infections with 
herpesvirus, HIV, and coxsackievirus. Smokers are at elevated risk for 
malignancy and other infections.

Laryngitis is characterized by a raspy, hoarse, or breathy voice, 
sometimes progressing to a complete loss of voice. Laryngitis can have 
associated dry cough and anterior throat pain; patients often feel a 
need to clear their throats. The physical examination in patients who 
may have laryngitis should focus on the head, neck, and lungs, but the 
diagnosis of laryngitis is generally based on history. If visualization 
of the vocal cords is necessary, indirect examination with a mirror or 
flexible laryngoscopy usually shows erythema and edema of the vocal 
cords and surrounding structures.
PART 2
Cardinal Manifestations and Presentation of Diseases
TREATMENT
Laryngitis
Laryngitis is generally self-limited, usually lasting 3–7 days, but may 
last up to 14 days. Vocal rest is crucial. Airway humidification and 
hydration should help. Patients likely to have laryngopharyngeal 
reflux should avoid gastroesophageal reflux–inducing foods and 
behaviors and should take antireflux medications. In randomized 
controlled trials, antibiotics were not effective in decreasing objec­
tive symptoms of laryngitis.
Red flags for emergency evaluation and monitoring include short­
ness of breath, stridor, dysphagia, odynophagia, drooling, and pos­
turing that could indicate epiglottitis. Referral to an otolaryngologist 
should be considered for patients who rely on their voice for work, such 
as singers and teachers. A history of smoking or weight loss should 
raise suspicion of malignancy. Symptoms lasting >3 weeks should 
prompt referral to an otolaryngologist or speech specialist.
■
■FURTHER READING
Centor RM, Linder JA: Web exclusive. Annals on call—Fusobacterium 
pharyngitis debate. Ann Intern Med 171:OC1, 2019.
Chua KP et al: Appropriateness of outpatient antibiotic prescribing 
among privately insured US patients: ICD-10-CM based cross sec­
tional study. BMJ 364:k5092, 2019.
Lieberthal AS et al: Clinical practice guideline: The diagnosis and 
management of acute otitis media. Pediatrics 131:e964, 2013.
Rowe TA, Linder JA: Novel approaches to decrease inappropriate 
ambulatory antibiotic use. Expert Rev Anti Infect Ther 17:511, 2019.
Sanchez GV et al: Antibiotic stewardship in outpatient telemedicine: 
Adapting Centers for Disease Control and Prevention core elements 
to optimize antibiotic use. Telemed J E Health 30:951, 2024. 
Samuel C. Durso

Oral Manifestations 

of Disease
Internists are often asked to evaluate patients with disease of the oral 
soft tissues, teeth, and pharynx. Knowledge of the oral milieu and its 
unique structures is necessary to guide preventive services and rec­
ognize oral manifestations of local or systemic disease (Chap. A3). 
Furthermore, internists frequently collaborate with dentists in the care 
of patients who have a variety of medical conditions that affect oral 

health or who undergo dental procedures that increase their risk of 
medical complications.
■
■DISEASES OF THE TEETH AND PERIODONTAL 
STRUCTURES
Tooth formation begins during the sixth week of embryonic life and 
continues through 17 years of age. Teeth start to develop in utero 
and continue to develop until after the tooth erupts. Normally, all 20 
deciduous teeth have erupted by age 3 and have been shed by age 13. 
Permanent teeth, eventually totaling 32, begin to erupt by age 6 and 
have completely erupted by age 14, though third molars (“wisdom 
teeth”) may erupt later.
The erupted tooth consists of the visible crown covered with enamel 
and the root submerged below the gum line and covered with bonelike 
cementum. Dentin, a material that is denser than bone and exquisitely 
sensitive to pain, forms the majority of the tooth substance, surround­
ing a core of myxomatous pulp containing the vascular and nerve 
supply. The tooth is held firmly in the alveolar socket by the peri­
odontium, supporting structures that consist of the gingivae, alveolar 
bone, cementum, and periodontal ligament. The periodontal ligament 
tenaciously binds the tooth’s cementum to the alveolar bone. Above 
this ligament is a collar of attached gingiva just below the crown. A few 
millimeters of unattached or free gingiva (1–3 mm) overlap the base 
of the crown, forming a shallow sulcus along the gum-tooth margin.
Dental Caries, Pulpal and Periapical Disease, and Complica­
tions 
Dental caries usually begin asymptomatically as a destructive 
infectious process of the enamel. Bacteria—principally Streptococ­
cus mutans—colonize the organic buffering biofilm (plaque) on the 
tooth surface. If not removed by brushing or by the natural cleansing 
and antibacterial action of saliva, bacterial acids can demineralize 
the enamel. Fissures and pits on the occlusal surfaces are the most 
frequent sites of early decay. Surfaces between the teeth, adjacent to 
tooth restorations and exposed roots, are also vulnerable, particularly 
as individuals age. Over time, dental caries extend to the underlying 
dentin, leading to cavitation of the enamel. Without management, the 
caries will penetrate to the tooth pulp, producing acute pulpitis. At this 
stage, when the pulp infection is limited, the tooth may become sensi­
tive to percussion and to hot or cold, and pain resolves immediately 
when the irritating stimulus is removed. Should the infection spread 
throughout the pulp, irreversible pulpitis occurs, leading to pulp necro­
sis. At this later stage, pain can be severe and has a sharp or throbbing 
visceral quality that may be worse when the patient lies down. Once 
pulp necrosis is complete, pain may be constant or intermittent, but 
cold sensitivity is lost.
Treatment of caries involves removing the softened and infected 
hard tissue and restoration of the tooth structure with silver amalgam, 
glass ionomer, composite resin, or gold. Once irreversible pulpitis 
occurs, root canal therapy becomes necessary; removal of the contents 
of the pulp chamber and root canal is followed by thorough clean­
ing and filling with an inert material. Alternatively, the tooth may be 
extracted.
Pulpal infection leads to periapical abscess formation, which can 
produce pain on chewing. If the infection is mild and chronic, a peri­
apical granuloma or eventually a periapical cyst forms, either of which 
produces radiolucency at the root apex. When unchecked, a periapical 
abscess can erode into the alveolar bone, producing osteomyelitis; 
penetrate and drain through the gingivae, producing a parulis (gum­
boil); or track along deep fascial planes, producing virulent cellulitis 
(Ludwig’s angina) involving the submandibular space and floor of the 
mouth (Chap. 182). Elderly patients, patients with diabetes mellitus, 
and patients taking glucocorticoids may experience little or no pain or 
fever as these complications develop.
Periodontal Disease 
Periodontal disease and dental caries are the 
primary causes of tooth loss. Like dental caries, chronic infection of the 
gingiva and anchoring structures of the tooth begins with formation of 
bacterial plaque. The process begins at the gum line. Plaque and calcu­
lus (calcified plaque) are preventable by appropriate daily oral hygiene, 
including periodic professional cleaning. Left undisturbed, chronic

inflammation can ensue and produce hyperemia of the free and 
attached gingivae (gingivitis), which then typically bleed with brush­
ing. If this issue is ignored, severe periodontitis can develop, leading to 
deepening of the physiologic sulcus and destruction of the periodontal 
ligament. Gingival pockets develop around the teeth. As the periodon­
tium (including the supporting bone) is destroyed, the teeth loosen. 
A role for chronic inflammation due to chronic periodontal disease 
in promoting coronary heart disease and stroke has been proposed. 
Epidemiologic studies have demonstrated a moderate but significant 
association between chronic periodontal inflammation and atherogen­
esis, though a causal role remains unproven.
Acute and aggressive forms of periodontal disease are less common 
than the chronic forms described above. However, if the host is stressed 
or exposed to a new pathogen, rapidly progressive and destructive 
disease of the periodontal tissue can occur. A virulent example is 
acute necrotizing ulcerative gingivitis. The presentation includes sud­
den gingival inflammation, ulceration, bleeding, interdental gingival 
necrosis, and fetid halitosis. Localized juvenile periodontitis, which is 
seen in adolescents, is particularly destructive and appears to be asso­
ciated with impaired neutrophil chemotaxis. AIDS-related periodontitis 
resembles acute necrotizing ulcerative gingivitis in some patients and a 
more destructive form of adult chronic periodontitis in others. It may 
also produce a gangrene-like destructive process of the oral soft tissues 
and bone that resembles noma, an infectious condition seen in severely 
malnourished children in developing nations.
Prevention of Tooth Decay and Periodontal Infection 
Despite 
the reduced prevalences of dental caries and periodontal disease in the 
United States (due in large part to water fluoridation and improved 
dental care, respectively), both diseases constitute a major public 
health problem worldwide. The internist should promote preventive 
dental care and hygiene as part of health maintenance. Populations at 
high risk for dental caries and periodontal disease include those with 
hyposalivation and/or xerostomia, diabetics, alcoholics, tobacco users, 
persons with Down syndrome, and those with gingival hyperplasia. 
Furthermore, patients lacking access to dental care (e.g., due to low 
socioeconomic status) and patients with a reduced ability to provide 
self-care (e.g., individuals with disabilities, nursing home residents, and 
persons with dementia or upper-extremity disability) suffer dispropor­
tionately. It is important to provide counseling (to patients and/or their 
caregivers) regarding regular dental hygiene and professional cleaning, 
use of fluoride-containing toothpaste, professional fluoride treatments, 
and (for patients with limited dexterity) use of electric toothbrushes. 
Cost, fear of dental care, and differences in language and culture cre­
ate barriers that prevent some people from seeking preventive dental 
services.
Developmental and Systemic Disease Affecting the Teeth 
and Periodontium 
In addition to posing cosmetic issues, maloc­
clusion, the most common developmental oral problem, can interfere 
with mastication unless corrected through orthodontic and surgical 
techniques. Impacted third molars are common and can become 
infected or erupt into an insufficient space. Acquired prognathism due 
to acromegaly may also lead to malocclusion, as may deformity of the 
maxilla and mandible due to Paget’s disease of the bone. Delayed tooth 
eruption, a receding chin, and a protruding tongue are occasional 
features of cretinism and hypopituitarism. Congenital syphilis produces 
tapering, notched (Hutchinson’s) incisors and finely nodular (mulberry) 
molar crowns. Enamel hypoplasia results in crown defects ranging 
from pits to deep fissures of primary or permanent teeth. Intrauterine 
infection (syphilis, rubella), vitamin deficiency (A, C, or D), disorders 
of calcium metabolism (malabsorption, vitamin D–resistant rickets, 
hypoparathyroidism), prematurity, high fever, and rare inherited 
defects (amelogenesis imperfecta) are all causes. Tetracycline, given 
in sufficiently high doses during the first 8 years of life, may produce 
enamel hypoplasia and discoloration. Doxycycline does not cause 
permanent tooth staining in children despite warnings included for all 
tetracycline-class antibiotics. Worn enamel is seen with age, bruxism, 
or excessive acid exposure (e.g., chronic gastric reflux or bulimia). 

Celiac disease is associated with nonspecific enamel defects in children 
but not in adults.

Total or partial tooth loss resulting from periodontitis is seen with 
cyclic neutropenia, Papillon-Lefévre syndrome, Chédiak-Higashi syn­
drome, and leukemia. Rapid focal tooth loosening is most often due 
to infection, but rarer causes include Langerhans cell histiocytosis, 
Ewing’s sarcoma, osteosarcoma, and Burkitt’s lymphoma. Early loss of 
primary teeth is a feature of hypophosphatasia, a rare congenital error 
of metabolism.
Pregnancy may produce gingivitis and localized pyogenic granu­
lomas. Severe periodontal disease occurs in uncontrolled diabetes 
mellitus. Drug-induced gingival overgrowth may be caused by anti­
convulsants, calcium channel blockers, and immunosuppressants, 
although excellent daily oral care can prevent or reduce its occurrence. 
Idiopathic familial gingival fibromatosis and several syndrome-related 
disorders cause similar conditions. Discontinuation of the medication 
may reverse the drug-induced form, although surgery may be needed 
to control both of the latter entities. Linear gingival erythema is variably 
seen in patients with advanced HIV infection and probably represents 
immune deficiency and decreased neutrophil activity. Diffuse or focal 
gingival swelling may be a feature of early or late acute myelomono­
cytic leukemia as well as of other lymphoproliferative disorders. A rare 
but pathognomonic sign of granulomatosis with polyangiitis is a redpurplish, granular gingivitis (strawberry gums).
Oral Manifestations of Disease 
CHAPTER 38
■
■DISEASES OF THE ORAL MUCOSA
Infections 
Most oral mucosal diseases involve microorganisms 
(Table 38-1).
Pigmented Lesions 
See Table 38-2.
Dermatologic Diseases 
See Tables 38-1, 38-2, and 38-3 and 
Chaps. 59–64.
Diseases of the Tongue 
See Table 38-4.
HIV Disease and AIDS 
See Tables 38-1, 38-2, 38-3, and 38-5; 
Chap. 208.
Ulcers 
Ulceration is the most common oral mucosal lesion. Although 
there are many causes, the host and the pattern of lesions, including 
the presence of organ system features, narrow the differential diagnosis 
(Table 38-1). Most acute ulcers are painful and self-limited. Recurrent 
aphthous ulcers and herpes simplex account for the majority. Persistent 
and deep aphthous ulcers can be idiopathic or can accompany HIV/
AIDS. Aphthous lesions are often the presenting symptom in Behçet’s 
syndrome (Chap. 376). Similar-appearing, though less painful, lesions 
may occur in reactive arthritis, and aphthous ulcers are occasionally 
present during phases of discoid or systemic lupus erythematosus 
(Chap. 372). Aphthous-like ulcers are seen in Crohn’s disease (Chap. 337), 
but, unlike the common aphthous variety, they may exhibit granuloma­
tous inflammation on histologic examination. Recurrent aphthae are 
more prevalent in patients with celiac disease and have been reported 
to remit with elimination of gluten.
Of major concern are chronic, relatively painless ulcers and mixed 
red/white patches (erythroplakia and leukoplakia) of >2 weeks’ dura­
tion. Squamous cell carcinoma and premalignant dysplasia should be 
considered early and a diagnostic biopsy performed. This awareness 
and this procedure are critically important because early-stage malig­
nancy is vastly more treatable than late-stage disease. High-risk sites 
include the lower lip, floor of the mouth, ventral and lateral tongue, 
and soft palate–tonsillar pillar complex. Significant risk factors for oral 
cancer in Western countries include sun exposure (lower lip), tobacco 
and alcohol use, and human papillomavirus infection. In India and 
some other Asian countries, smokeless tobacco mixed with betel nut, 
slaked lime, and spices is a common cause of oral cancer. Rarer causes 
of chronic oral ulcer, such as tuberculosis, fungal infection, granuloma­
tosis with polyangiitis, and midline granuloma, may look identical to 
carcinoma. Making the correct diagnosis depends on recognizing other 
clinical features and performing a biopsy of the lesion. The syphilitic

TABLE 38-1  Vesicular, Bullous, or Ulcerative Lesions of the Oral Mucosa
CONDITION
USUAL LOCATION
CLINICAL FEATURES
COURSE
Viral Diseases
Primary acute herpetic 
gingivostomatitis (HSV 
type 1; rarely type 2)
Lip and oral mucosa 
(buccal, gingival, lingual 
mucosa)
Labial vesicles that rupture and crust, and intraoral vesicles 
that quickly ulcerate; extremely painful; acute gingivitis, fever, 
malaise, foul odor, and cervical lymphadenopathy; occurs 
primarily in infants, children, and young adults
Recurrent herpes labialis
Mucocutaneous 
junction of lip, perioral 
skin
Eruption of groups of vesicles that may coalesce, then rupture 
and crust; painful to pressure or spicy foods
Recurrent intraoral herpes 
simplex
Palate and gingiva
Small vesicles on keratinized epithelium that rupture and 
coalesce; painful
PART 2
Cardinal Manifestations and Presentation of Diseases
Chickenpox (VZV)
Gingiva and oral 
mucosa
Skin lesions may be accompanied by small vesicles on oral 
mucosa that rupture to form shallow ulcers; may coalesce to 
form large bullous lesions that ulcerate; mucosa may have 
generalized erythema
Herpes zoster (VZV 
reactivation)
Cheek, tongue, gingiva, 
or palate
Unilateral vesicular eruptions and ulceration in linear pattern 
following sensory distribution of trigeminal nerve or one of its 
branches
Infectious mononucleosis 
(Epstein-Barr virus)
Oral mucosa
Fatigue, sore throat, malaise, fever, and cervical 
lymphadenopathy; numerous small ulcers usually appear 
several days before lymphadenopathy; gingival bleeding and 
multiple petechiae at junction of hard and soft palates
Herpangina 
(coxsackievirus A; also 
possibly coxsackievirus B 
and echovirus)
Oral mucosa, pharynx, 
tongue
Sudden onset of fever, sore throat, and oropharyngeal 
vesicles, usually in children <4 years old, during summer 
months; diffuse pharyngeal congestion and vesicles (1–2 mm), 
grayish-white surrounded by red areola; vesicles enlarge and 
ulcerate
Hand-foot-and-mouth 
disease (most commonly 
coxsackievirus A16)
Oral mucosa, pharynx, 
palms, and soles
Fever, malaise, headache with oropharyngeal vesicles that 
become painful, shallow ulcers; highly infectious; usually 
affects children under age 10
Primary HIV infection
Gingiva, palate, and 
pharynx
Acute gingivitis and oropharyngeal ulceration, associated 
with febrile illness resembling mononucleosis and including 
lymphadenopathy
Bacterial or Fungal Diseases
Acute necrotizing 
ulcerative gingivitis 
(“trench mouth”)
Gingiva
Painful, bleeding gingiva characterized by necrosis 
and ulceration of gingival papillae and margins plus 
lymphadenopathy and foul breath
Prenatal (congenital) 
syphilis
Palate, jaws, tongue, 
and teeth
Gummatous involvement of palate, jaws, and facial bones; 
Hutchinson’s incisors, mulberry molars, glossitis, mucous 
patches, and fissures at corner of mouth
Primary syphilis (chancre)
Lesion appearing where 
organism enters body; 
may occur on lips, 
tongue, or tonsillar area
Small papule developing rapidly into a large, painless ulcer 
with indurated border; unilateral lymphadenopathy; chancre 
and lymph nodes containing spirochetes; serologic tests 
positive by third to fourth weeks
Secondary syphilis
Oral mucosa frequently 
involved with mucous 
patches, which occur 
primarily on palate and 
also at commissures of 
mouth
Maculopapular lesions of oral mucosa, 5–10 mm in diameter 
with central ulceration covered by grayish membrane; 
eruptions occurring on various mucosal surfaces and skin, 
accompanied by fever, malaise, and sore throat
Tertiary syphilis
Palate and tongue
Gummatous infiltration of palate or tongue followed by 
ulceration and fibrosis; atrophy of tongue papillae produces 
characteristic bald tongue and glossitis
Gonorrhea
Lesions may occur 
in mouth at site 
of inoculation or 
secondarily by 
hematogenous spread 
from a primary focus
Most pharyngeal infection is asymptomatic; may produce 
burning or itching sensation; oropharynx and tonsils may be 
ulcerated and erythematous; saliva viscous and fetid
Tuberculosis
Tongue, tonsillar area, 
soft palate
Painless, solitary, 1- to 5-cm, irregular ulcer covered with 
persistent exudate; ulcer has firm undermined border
Cervicofacial 
actinomycosis
Swellings in region of 
face, neck, and floor of 
mouth
Infection may be associated with extraction, jaw fracture, 
or eruption of molar tooth; in acute form, resembles acute 
pyogenic abscess, but contains yellow “sulfur granules” 
(gram-positive mycelia and their hyphae)

Heals spontaneously in 10–14 days; unless 
secondarily infected, lesions lasting >3 weeks 
are not due to primary HSV infection
Lasts ∼1 week, but condition may be prolonged 
if secondarily infected; if severe, topical or oral 
antiviral treatment may reduce healing time
Heals spontaneously in ∼1 week; if severe, 
topical or oral antiviral treatment may reduce 
healing time
Lesions heal spontaneously within 2 weeks
Gradual healing without scarring unless 
secondarily infected; postherpetic neuralgia 
is common; oral acyclovir, famciclovir, 
or valacyclovir reduces healing time and 
postherpetic neuralgia
Oral lesions disappear during convalescence; 
no treatment is given, though glucocorticoids 
are indicated if tonsillar swelling compromises 
the airway
Incubation period of 2–9 days; fever for 

1–4 days; recovery uneventful
Incubation period 2–18 days; lesions heal 
spontaneously in 2–4 weeks
Followed by HIV seroconversion, 
asymptomatic HIV infection, and usually 
ultimately by HIV disease
Debridement and diluted (1:3) peroxide lavage 
provide relief within 24 h; antibiotics in acutely 
ill patients; relapse may occur
Tooth deformities in permanent dentition 
irreversible
Healing of chancre in 1–2 months, followed by 
secondary syphilis in 6–8 weeks
Lesions may persist from several weeks to a 
year
Gumma may destroy palate, causing complete 
perforation
More difficult to eradicate than urogenital 
infection, though pharyngitis usually resolves 
with appropriate antimicrobial treatment
Autoinoculation from pulmonary infection 
is usual; lesions resolve with appropriate 
antimicrobial therapy
Typically, swelling is hard and grows 
painlessly; multiple abscesses with draining 
tracts develop; penicillin first choice; surgery 
usually necessary
(Continued)

TABLE 38-1  Vesicular, Bullous, or Ulcerative Lesions of the Oral Mucosa
CONDITION
USUAL LOCATION
CLINICAL FEATURES
COURSE
Bacterial or Fungal Diseases (Continued)
Histoplasmosis
Any area of the mouth, 
particularly tongue, 
gingiva, or palate
Nodular, verrucous, or granulomatous lesions; ulcers are 
indurated and painful; usual source hematogenous or 
pulmonary, but may be primary
Candidiasisa
 
 
 
Dermatologic Diseases
Mucous membrane 
pemphigoid
Typically produces 
marked gingival 
erythema and 
ulceration; other 
areas of oral cavity, 
esophagus, and vagina 
may be affected
Painful, grayish-white collapsed vesicles or bullae of fullthickness epithelium with peripheral erythematous zone; 
gingival lesions desquamate, leaving ulcerated area
EM minor and EM major 
(Stevens-Johnson 
syndrome)
Primarily oral mucosa 
and skin of hands and 
feet
Intraoral ruptured bullae surrounded by inflammatory area; lips 
may show hemorrhagic crusts; “iris” or “target” lesion on skin 
is pathognomonic; patient may have severe signs of toxicity
Pemphigus vulgaris
Oral mucosa and skin; 
sites of mechanical 
trauma (soft/hard 
palate, frenulum, lips, 
buccal mucosa)
Usually (>70%) presents with oral lesions; fragile, ruptured 
bullae and ulcerated oral areas; mostly in older adults
Lichen planus
Oral mucosa and skin
White striae in mouth; purplish nodules on skin at sites of 
friction; occasionally causes oral mucosal ulcers and erosive 
gingivitis
Other Conditions
Recurrent aphthous ulcers
Usually on nonkeratinized 
oral mucosa (buccal and 
labial mucosa, floor of 
mouth, soft palate, lateral 
and ventral tongue)
Single or clustered painful ulcers with surrounding 
erythematous border; lesions may be 1–2 mm in diameter in 
crops (herpetiform), 1–5 mm (minor), or 5–15 mm (major)
Behçet’s syndrome
Oral mucosa, eyes, 
genitalia, gut, and CNS
Multiple aphthous ulcers in mouth; inflammatory ocular 
changes, ulcerative lesions on genitalia; inflammatory bowel 
disease and CNS disease
Traumatic ulcers
Anywhere on oral 
mucosa; dentures 
frequently responsible 
for ulcers in vestibule
Localized, discrete ulcerated lesions with red border; 
produced by accidental biting of mucosa, penetration by 
foreign object, or chronic irritation by dentures
Squamous cell carcinoma
Any area of mouth, most 
commonly on lower 
lip, lateral borders of 
tongue, and floor of 
mouth
Red, white, or red and white ulcer with elevated or indurated 
border; failure to heal; pain not prominent in early lesions
Acute myeloid leukemia 
(usually monocytic)
Gingiva
Gingival swelling and superficial ulceration followed 
by hyperplasia of gingiva with extensive necrosis and 
hemorrhage; deep ulcers may occur elsewhere on mucosa, 
complicated by secondary infection
Lymphoma
Gingiva, tongue, palate, 
and tonsillar area
Elevated, ulcerated area that may proliferate rapidly, giving 
appearance of traumatic inflammation
Chemical or thermal burns
Any area in mouth
White slough due to contact with corrosive agents (e.g., 
aspirin, hot cheese) applied locally; removal of slough leaves 
raw, painful surface
aSee Table 38-3.
Abbreviations: CNS, central nervous system; EM, erythema multiforme; HSV, herpes simplex virus; VZV, varicella-zoster virus.
chancre is typically painless and therefore easily missed. Regional 
lymphadenopathy is invariably present.
Disorders of mucosal fragility often produce painful oral ulcers 
that fail to heal within 2 weeks. Mucous membrane pemphigoid and 
pemphigus vulgaris are the major acquired disorders. While their 
clinical features are often distinctive, a biopsy or immunohistochemi­
cal examination should be performed to diagnose these entities and to 
distinguish them from lichen planus and drug reactions.
Hematologic and Nutritional Disease 
Internists are more likely 
to encounter patients with acquired, rather than congenital, bleeding 

(Continued)
Systemic antifungal therapy necessary
Protracted course with remissions and 
exacerbations; involvement of different 
sites develops slowly; glucocorticoids may 
temporarily reduce symptoms but do not 
control disease
Oral Manifestations of Disease 
CHAPTER 38
Onset very rapid; usually idiopathic, but may be 
associated with trigger such as drug reaction; 
condition may last 3–6 weeks; mortality rate for 
untreated EM major is 5–15%
With repeated occurrence of bullae, toxicity 
may lead to cachexia, infection, and death 
within 2 years; often controllable with oral 
glucocorticoids
White striae alone usually asymptomatic; 
erosive lesions often difficult to treat, but may 
respond to glucocorticoids
Lesions heal in 1–2 weeks but may recur 
monthly or several times a year; protective 
barrier with benzocaine and topical 
glucocorticoids relieve symptoms; systemic 
glucocorticoids may be needed in severe cases
Oral lesions often first manifestation; persist 
several weeks and heal without scarring
Lesions usually heal in 7–10 days when irritant 
is removed, unless secondarily infected
Invades and destroys underlying tissues; 
frequently metastasizes to regional lymph 
nodes
Usually responds to systemic treatment 
of leukemia; occasionally requires local 
irradiation
Fatal if untreated; may indicate underlying HIV 
infection
Lesion heals in several weeks if not 
secondarily infected
disorders. Bleeding should stop 15 min after minor trauma and within 
an hour after tooth extraction if local pressure is applied. More pro­
longed bleeding, if not due to continued injury or rupture of a large 
vessel, should lead to investigation for a clotting abnormality. In addi­
tion to bleeding, petechiae and ecchymoses are prone to occur at the 
vibrating line between the soft and hard palates in patients with platelet 
dysfunction or thrombocytopenia.
All forms of leukemia, but particularly acute myelomonocytic leuke­
mia, can produce gingival bleeding, ulcers, and gingival enlargement. 
Oral ulcers are a feature of agranulocytosis, and ulcers and mucositis 
are often severe complications of chemotherapy and radiation therapy

TABLE 38-2  Pigmented Lesions of the Oral Mucosa
CONDITION
USUAL LOCATION
CLINICAL FEATURES
COURSE
Oral melanotic macule
Any area of mouth
Discrete or diffuse, localized, brown to black macule
Remains indefinitely; no growth
Diffuse melanin pigmentation
Any area of mouth
Diffuse pale to dark-brown pigmentation; may be 
physiologic (“racial”) or due to smoking
Nevi
Any area of mouth
Discrete, localized, brown to black pigmentation
Remains indefinitely
Malignant melanoma
Any area of mouth
Can be flat and diffuse, painless, brown to black; or can 
be raised and nodular
Addison’s disease
Any area of mouth, but 
mostly buccal mucosa
Blotches or spots of bluish-black to dark-brown 
pigmentation occurring early in disease, accompanied 
by diffuse pigmentation of skin; other symptoms of 
adrenal insufficiency
PART 2
Cardinal Manifestations and Presentation of Diseases
Peutz-Jeghers syndrome
Any area of mouth
Dark-brown spots on lips, buccal mucosa, with 
characteristic distribution of pigment around lips, nose, 
and eyes and on hands; concomitant intestinal polyposis
Drug ingestion (neuroleptics, 
oral contraceptives, 
minocycline, zidovudine, 
quinine derivatives)
Any area of mouth
Brown, black, or gray areas of pigmentation
Gradually disappears following cessation of 
drug intake
Amalgam tattoo
Gingiva and alveolar 
mucosa
Small blue-black pigmented areas associated with 
embedded amalgam particles in soft tissues; may show 
up on radiographs as radiopaque particles in some 
cases
Heavy metal pigmentation 
(bismuth, mercury, lead)
Gingival margin
Thin blue-black pigmented line along gingival margin; 
rarely seen except in children exposed to lead-based 
paint
Black hairy tongue
Dorsum of tongue
Elongation of filiform papillae of tongue, which become 
stained by coffee, tea, tobacco, or pigmented bacteria
Fordyce spots
Buccal and labial mucosa
Numerous small yellowish spots just beneath mucosal 
surface; no symptoms; due to hyperplasia of sebaceous 
glands
Kaposi’s sarcoma
Palate most common, but 
may occur at any other site
Red or blue plaques of variable size and shape; often 
enlarge, become nodular, and may ulcerate
Mucous retention cysts
Buccal and labial mucosa
Bluish, clear fluid–filled cyst due to extravasated mucus 
from injured minor salivary gland
TABLE 38-3  White Lesions of Oral Mucosa
CONDITION
USUAL LOCATION
CLINICAL FEATURES
COURSE
Lichen planus
Buccal mucosa, tongue, 
gingiva, and lips; skin
Striae, white plaques, red areas, ulcers in mouth; purplish 
papules on skin; may be asymptomatic, sore, or painful; 
lichenoid drug reactions may look similar
White sponge nevus
Oral mucosa, vagina, 
anal mucosa
Painless white thickening of epithelium; adolescence/early 
adulthood onset; familial
Smoker’s leukoplakia 
and smokeless tobacco 
lesions
Any area of oral mucosa, 
sometimes related to 
location of habit
White patch that may become firm, rough, or red-fissured 
and ulcerated; may become sore and painful but is usually 
painless
Erythroplakia with or 
without white patches
Floor of mouth commonly 
affected in men; tongue 
and buccal mucosa in 
women
Velvety, reddish plaque; occasionally mixed with white 
patches or smooth red areas
Candidiasis
Any area in mouth
Pseudomembranous type (“thrush”): creamy white curdlike 
patches that reveal a raw, bleeding surface when scraped; 
found in sick infants, debilitated elderly patients receiving 
high-dose glucocorticoids or broad-spectrum antibiotics, and 
patients with AIDS
Erythematous type: flat, red, sometimes sore areas in same 
groups of patients
Candidal leukoplakia: nonremovable white thickening of 
epithelium due to Candida
Angular cheilitis: sore fissures at corner of mouth
Responds to topical antifungal therapy
Hairy leukoplakia
Usually on lateral 
tongue, rarely elsewhere 
on oral mucosa
White areas ranging from small and flat to extensive 
accentuation of vertical folds; found in HIV carriers (all risk 
groups for AIDS)
Warts (human 
papillomavirus)
Anywhere on skin and 
oral mucosa
Single or multiple papillary lesions with thick, white, 
keratinized surfaces containing many pointed projections; 
cauliflower lesions covered with normal-colored mucosa or 
multiple pink or pale bumps (focal epithelial hyperplasia)

Remains indefinitely
Expands and invades early; metastasis leads 
to death
Condition controlled by adrenal steroid 
replacement
Oral pigmented lesions remain indefinitely; 
gastrointestinal polyps may become malignant
Remains indefinitely
Indicative of systemic absorption; no 
significance for oral health
Improves within 1–2 weeks with gentle 
brushing of tongue or (if due to bacterial 
overgrowth) discontinuation of antibiotic
Benign; remains without apparent change
Usually indicative of HIV infection or nonHodgkin’s lymphoma; rarely fatal, but may 
require treatment for comfort or cosmesis
Benign; painless unless traumatized; may be 
removed surgically
Protracted; responds to topical glucocorticoids
Benign and permanent
May or may not resolve with cessation of habit; 
2% of patients develop squamous cell carcinoma; 
early biopsy essential
High risk of squamous cell cancer; early biopsy 
essential
Responds favorably to antifungal therapy and 
correction of predisposing causes where possible
Course same as for pseudomembranous type
Responds to prolonged antifungal therapy
Due to Epstein-Barr virus; responds to high-dose 
acyclovir but recurs; rarely causes discomfort 
unless secondarily infected with Candida
Lesions grow rapidly and spread; squamous cell 
carcinoma must be ruled out with biopsy; excision 
or laser therapy; may regress in HIV-infected 
patients receiving antiretroviral therapy

TABLE 38-4  Alterations of the Tongue
TYPE OF CHANGE
CLINICAL FEATURES
Size or Morphology
Macroglossia
Enlarged tongue that may be part of a syndrome 
found in developmental conditions such as Down 
syndrome, Simpson-Golabi-Behmel syndrome, or 
Beckwith-Wiedemann syndrome; may be due to 
tumor (hemangioma or lymphangioma), metabolic 
disease (e.g., primary amyloidosis), or endocrine 
disturbance (e.g., acromegaly or cretinism); may 
occur when all teeth are removed
Fissured (“scrotal”) tongue
Dorsal surface and sides of tongue covered by 
painless shallow or deep fissures that may collect 
debris and become irritated
Median rhomboid glossitis
Congenital abnormality with ovoid, denuded area 
in median posterior portion of tongue; may be 
associated with candidiasis and may respond to 
antifungal treatment
Color
“Geographic” tongue 
(benign migratory glossitis)
Asymptomatic inflammatory condition of tongue, 
with rapid loss and regrowth of filiform papillae 
leading to appearance of denuded red patches 
“wandering” across surface
Hairy tongue
Elongation of filiform papillae of medial dorsal 
surface area due to failure of keratin layer of 
papillae to desquamate normally; brownish-black 
coloration may be due to staining by tobacco, food, 
or chromogenic organisms
“Strawberry” and 
“raspberry” tongue
Appearance of tongue during scarlet fever due 
to hypertrophy of fungiform papillae as well as 
changes in filiform papillae
“Bald” tongue
Atrophy may be associated with xerostomia, 
pernicious anemia, iron-deficiency anemia, 
pellagra, or syphilis; may be accompanied by 
painful burning sensation; may be an expression 
of erythematous candidiasis and respond to 
antifungal treatment
for hematologic and other malignancies. Plummer-Vinson syndrome 
(iron deficiency, angular stomatitis, glossitis, and dysphagia) raises 
the risk of oral squamous cell cancer and esophageal cancer at the 
postcricoidal tissue web. Atrophic papillae and a red, burning tongue 
may occur with pernicious anemia. Deficiencies in B-group vitamins 
produce many of these same symptoms, as well as oral ulceration and 
cheilosis. Consequences of scurvy include swollen, bleeding gums; 
ulcers; and loosening of the teeth.
NONDENTAL CAUSES OF ORAL PAIN
Most, but not all, oral pain emanates from inflamed or injured tooth 
pulp or periodontal tissues. Nonodontogenic causes are often over­
looked. In most instances, toothache is predictable and proportional to 
the stimulus applied, and an identifiable condition (e.g., caries, abscess) 
is found. Local anesthesia eliminates pain originating from dental 
or periodontal structures, but not referred pains. The most common 
nondental source of pain is myofascial pain referred from muscles of 
mastication, which become tender and ache with increased use. Many 
sufferers exhibit bruxism (grinding of the teeth) secondary to stress and 
anxiety. Temporomandibular joint disorder is closely related. Features 
include pain, limited mandibular movement, and temporomandibular 
joint sounds. The etiologies are complex; malocclusion does not play 
the primary role once attributed to it. Osteoarthritis is a common 
cause of masticatory pain. Anti-inflammatory medication, jaw rest, 
soft foods, and heat provide relief. The temporomandibular joint is 
involved in 50% of patients with rheumatoid arthritis and is usually a 
late feature of severe disease.
Migrainous neuralgia may be localized to the mouth. Episodes of 
pain and remission without an identifiable cause and a lack of relief 
with local anesthesia are important clues. Trigeminal neuralgia (tic 
douloureux) can involve the entire branch or part of the mandibular 

TABLE 38-5  Oral Lesions Associated with HIV Infection
LESION MORPHOLOGY
ETIOLOGIES
Papules, nodules, plaques
Candidiasis (hyperplastic and pseudomembranous)a
Condyloma acuminatum (human papillomavirus 
infection)
Squamous cell carcinoma (preinvasive and 
invasive)
Non-Hodgkin’s lymphomaa
Hairy leukoplakiaa
Ulcers
Recurrent aphthous ulcersa
Oral Manifestations of Disease 
CHAPTER 38
Angular cheilitis
Squamous cell carcinoma
Acute necrotizing ulcerative gingivitisa
Necrotizing ulcerative periodontitisa
Necrotizing ulcerative stomatitis
Non-Hodgkin’s lymphomaa
Viral infection (herpes simplex, herpes zoster, 
cytomegalovirus infection)
Infection caused by Mycobacterium tuberculosis or 
Mycobacterium avium-intracellulare
Fungal infection (histoplasmosis, cryptococcosis, 
candidiasis, geotrichosis, aspergillosis)
Bacterial infection (Escherichia coli, Enterobacter 
cloacae, Klebsiella pneumoniae, Pseudomonas 
aeruginosa)
Drug reactions (single or multiple ulcers)
Pigmented lesions
Kaposi’s sarcomaa
Bacillary angiomatosis (skin and visceral lesions 
more common than oral)
Zidovudine pigmentation (skin, nails, and 
occasionally oral mucosa)
Addison’s disease
Miscellaneous
Linear gingival erythemaa
aStrongly associated with HIV infection.
or maxillary branch of the fifth cranial nerve and can produce pain 
in one or a few teeth. Pain may occur spontaneously or may be trig­
gered by touching the lip or gingiva, brushing the teeth, or chewing. 
Glossopharyngeal neuralgia produces similar acute neuropathic 
symptoms in the distribution of the ninth cranial nerve. Swallowing, 
sneezing, coughing, or pressure on the tragus of the ear triggers pain 
that is felt in the base of the tongue, pharynx, and soft palate and 
may be referred to the temporomandibular joint. Neuritis involv­
ing the maxillary and mandibular divisions of the trigeminal nerve 
(e.g., maxillary sinusitis, neuroma, and leukemic infiltrate) is distin­
guished from ordinary toothache by the neuropathic quality of the 
pain. Occasionally, phantom pain follows tooth extraction. Pain and 
hyperalgesia behind the ear and on the side of the face in the day or 
so before facial weakness develops often constitute the earliest symp­
tom of Bell’s palsy. Likewise, similar symptoms may precede visible 
lesions of herpes zoster infecting the seventh nerve (Ramsy-Hunt 
syndrome) or trigeminal nerve. Postherpetic neuralgia may follow 
either condition. Coronary ischemia may produce pain exclusively 
in the face and jaw; as in typical angina pectoris, this pain is usually 
reproducible with increased myocardial demand. Aching in several 
upper molar or premolar teeth that is unrelieved by anesthetizing the 
teeth may point to maxillary sinusitis.
Giant cell arteritis is notorious for producing headache, but it may 
also produce facial pain or sore throat without headache. Jaw and 
tongue claudication with chewing or talking is relatively common. 
Tongue infarction is rare. Patients with subacute thyroiditis often 
experience pain referred to the face or jaw before the tenderness of the 
thyroid gland and transient hyperthyroidism are appreciated.
“Burning mouth syndrome” (glossodynia) occurs in the absence of 
an identifiable cause (e.g., vitamin B12 deficiency, iron deficiency, dia­
betes mellitus, low-grade Candida infection, food sensitivity, or subtle

xerostomia). The etiology may be neuropathic. Clonazepam, α-lipoic 
acid, and cognitive-behavioral therapy benefit some patients. Some 
cases associated with an angiotensin-converting enzyme inhibitor have 
remitted when the drug was discontinued.

■
■DISEASES OF THE SALIVARY GLANDS
Saliva is essential to oral health. Its absence leads to dental caries, 
periodontal disease, and difficulties in wearing dental prostheses, 
masticating, and speaking. Its major components, water and mucin, 
serve as a cleansing solvent and lubricating fluid. In addition, saliva 
contains antimicrobial factors (e.g., lysozyme, lactoperoxidase, secre­
tory IgA), epidermal growth factor, minerals, and buffering sys­
tems. The major salivary glands secrete intermittently in response 
to autonomic stimulation, which is high during a meal. Hundreds 
of minor glands in the lips and cheeks secrete mucus continuously 
throughout the day and night. Consequently, oral function becomes 
impaired when salivary function is reduced. The sensation of a dry 
mouth (xerostomia) is perceived when salivary flow is reduced by 
50%. The most common etiology is medication, especially drugs with 
anticholinergic properties but also alpha and beta blockers, calcium 
channel blockers, and diuretics. Other causes include Sjögren’s syn­
drome, chronic parotitis, salivary duct obstruction, diabetes mellitus, 
HIV/AIDS, and radiation therapy that includes the salivary glands 
in the field. Management involves eliminating or limiting drying 
medications, preventive dental care, and supplementation with oral 
liquid or salivary substitutes. Sugarless mints or chewing gum may 
stimulate salivary secretion if dysfunction is mild. When sufficient 
exocrine tissue remains, pilocarpine or cevimeline can increase secre­
tions. Commercial saliva substitutes or gels relieve dryness. Fluoride 
supplementation is critical to prevent caries.
PART 2
Cardinal Manifestations and Presentation of Diseases
Sialolithiasis presents most often as painful swelling but in some 
instances as only swelling or only pain. Conservative therapy consists 
of local heat, massage, and hydration. Promotion of salivary secretion 
with mints or lemon drops may flush out small stones. Antibiotic treat­
ment is necessary when bacterial infection is suspected. In adults, acute 
bacterial parotitis is typically unilateral and most commonly affects 
postoperative, dehydrated, and debilitated patients. Staphylococcus 
aureus (including methicillin-resistant strains) and anaerobic bacteria 
are the most common pathogens. Chronic bacterial sialadenitis results 
from lowered salivary secretion and recurrent bacterial infection. 
When suspected bacterial infection is not responsive to therapy, the 
differential diagnosis should expand to include benign and malignant 
neoplasms, lymphoproliferative disorders, Sjögren’s syndrome, sar­
coidosis, tuberculosis, lymphadenitis, actinomycosis, and granuloma­
tosis with polyangiitis. Bilateral nontender parotid enlargement occurs 
with diabetes mellitus, cirrhosis, bulimia, HIV/AIDS, and drugs (e.g., 
iodide, propylthiouracil).
Pleomorphic adenoma composes two-thirds of all salivary neo­
plasms. The parotid is the principal salivary gland affected, and the 
tumor presents as a firm, slow-growing mass. Although this tumor is 
benign, its recurrence is common if resection is incomplete. Malignant 
tumors such as mucoepidermoid carcinoma, adenoid cystic carcinoma, 
and adenocarcinoma tend to grow relatively fast, depending upon 
grade. They may ulcerate and invade nerves, producing numbness and 
facial paralysis. Surgical resection is the primary treatment. Radiation 
therapy (particularly neutron-beam therapy) is used when surgery is 
not feasible and after resection for certain histologic types with a high 
risk of recurrence. Malignant salivary gland tumors have a 5-year sur­
vival rate of 94% when the stage is local, 70% with regional spread, and 
43% when distant.
Dental Care for Medically Complex Patients 
Routine dental 
care (e.g., uncomplicated extraction, scaling and cleaning, tooth resto­
ration, and root canal) is remarkably safe. The most common concerns 
regarding care of dental patients with medical disease are excessive 
bleeding for patients taking anticoagulants, infection of the heart valves 
and prosthetic devices from hematogenous seeding by the oral flora, 
and cardiovascular complications resulting from vasopressors used 

with local anesthetics during dental treatment, although the risk of any 
of these complications is very low.
Patients undergoing tooth extraction or alveolar and gingival 
surgery rarely experience uncontrolled bleeding when warfarin 
anticoagulation is maintained within the therapeutic range currently 
recommended for prevention of venous thrombosis, atrial fibrilla­
tion, or mechanical heart valve. Embolic complications and death, 
however, have been reported during subtherapeutic anticoagulation. 
Therapeutic anticoagulation should be confirmed before and contin­
ued through the procedure. Likewise, low-dose aspirin (e.g., 81–325 mg) 

can safely be continued. For patients taking aspirin and another 
antiplatelet medication (e.g., clopidogrel), continuation of the second 
antiplatelet medication should be based on individual consideration 
of the risks of thrombosis and bleeding. Target-specific oral antico­
agulants (dabigatran, apixaban, rivaroxaban, and edoxaban) are in 
increasingly common use. Simple extractions of one to three teeth, 
periodontal surgery, abscess drainage, and implant positioning do 
not typically require interruption of therapy. More extensive surgery 
may necessitate delaying or holding a dose of the anticoagulant 
or more elaborate measures to manage the risk of thrombosis and 
bleeding.
Patients at risk for bacterial endocarditis (Chap. 133) should main­
tain optimal oral hygiene, including flossing, and regular professional 
cleanings. Currently, guidelines recommend that prophylactic antibiot­
ics be restricted to patients at high risk for bacterial endocarditis who 
undergo dental and oral procedures involving significant manipulation 
of gingival or periapical tissue or penetration of the oral mucosa. If 
unexpected bleeding occurs, antibiotics given within 2 h after the pro­
cedure provide effective prophylaxis.
Hematogenous bacterial seeding from oral infection can produce 
late prosthetic-joint infection and therefore requires removal of the 
infected tissue (e.g., drainage, extraction, root canal) and appropriate 
antibiotic therapy. However, evidence that late prosthetic-joint infec­
tion follows routine dental procedures is lacking. For this reason, anti­
biotic prophylaxis is generally not recommended before oral surgery 
or oral mucosal manipulation for patients who have undergone joint 
replacement surgery. Exceptions to this may be considered for patients 
who have experienced joint replacement complications.
Concern often arises regarding the use of vasoconstrictors to 
treat patients with hypertension and heart disease. Vasoconstrictors 
enhance the depth and duration of local anesthesia, thus reducing 
the anesthetic dose and potential toxicity. If intravascular injection is 
avoided, 2% lidocaine with 1:100,000 epinephrine (limited to a total of 
0.036 mg of epinephrine) can be used safely in patients with controlled 
hypertension and stable coronary heart disease, arrhythmia, or con­
gestive heart failure. Precautions should be taken with patients taking 
tricyclic antidepressants and nonselective beta blockers because these 
drugs may potentiate the effect of epinephrine.
Elective dental treatments should be postponed for at least 1 month 
and preferably for 6 months after myocardial infarction, after which the 
risk of reinfarction is low provided the patient is medically stable (e.g., 
stable rhythm, stable angina, and no heart failure). Patients who have 
suffered a stroke should have elective dental care deferred for 9 months. 
In both situations, effective stress reduction requires good pain control, 
including the use of the minimal amount of vasoconstrictor necessary 
to provide good hemostasis and local anesthesia.
Bisphosphonate therapy is associated with osteonecrosis of the jaw. 
However, the risk with oral bisphosphonate therapy is very low. Most 
patients affected have received high-dose aminobisphosphonate ther­
apy for multiple myeloma or metastatic breast cancer and have under­
gone tooth extraction or dental surgery. Intraoral lesions, of which 
two-thirds are painful, appear as exposed yellow-white hard bone 
involving the mandible or maxilla. Screening tests for determining risk 
of osteonecrosis are unreliable. Patients slated for aminobisphospho­
nate therapy should receive preventive dental care that reduces the risk 
of infection and the need for future dentoalveolar surgery.
Halitosis 
Halitosis typically emanates from the oral cavity or nasal 
passages. Bacterial decay of food and cellular debris account for the