A Guide to Clinical Differential Diagnosis of Oral Mucosal Lesions
Table 3. Vesicular-Ulcerated-Erythematous Surface Lesions of Oral Mucosa

Course Author(s): Michael W. Finkelstein, DDS, MS;Emily Lanzel, DDS, MS;John W. Hellstein, DDS, MS

Table 3. Vesicular-Ulcerated-Erythematous Surface Lesions of Oral Mucosa

HEREDITARY – EPIDERMOLYSIS BULLOSA
Skin lesions are always present; Nikolsky’s sign often present; mouth opening may be restricted due to scarring. Lesions are congenital or begin at an early age; patient frequently has a familial history.
MYCOTIC – CANDIDOSISv(CANDIDIASIS)
Diffuse mucosal erythema; burning or pain may be present; ulcers are rarely present; lymphadenopathy is rare. Patient often has predisposing factors: antibiotics, immunosuppression.
AUTOIMMUNE
Slow onset; chronic lesions; exacerbations & partial remissions; lesions do not heal in a predictable period of time; lymphadenopathy is rare.
Mucous membrane pemphigoid (cicatricial pemphigoid; benign mucous membrane pemphigoid)Erythematous attached gingiva; vesicles sometimes observed; Nikolsky sign may be present; skin vesicles & ulcers may be present.
Bullous pemphigoidSkin vesicles, bullae & ulcers are always present; occasional oral vesicles & ulcers.
PemphigusMucosal vesicles & ulcers in any location usually precede skin lesions; Nikolsky sign may be present.
Lupus erythematosusNonspecific mucositis & ulcers are sometimes present but are associated with skin lesions.
Oral lesions: white epithelial striae with submucosal erythema (lichenoid lesions).
Multiple organ system disorders: erythematous skin
rash, photosensitivity, arthritis, nephritis, neurologic disease; anemia, leukopenia, thrombocytopenia.
VIRAL
Acute onset; multiple lesions; systemic manifestations (malaise, fever, diarrhea, lymphadenopathy, lymphocytosis) often present; vesicle stage is present in all except mononucleosis.
Primary herpesVesicles & ulcers may be present anywhere in the oral cavity, pharynx, lips or perioral skin; gingiva is edematous & erythematous; lymphadenopathy is common; malaise, fever & diarrhea in some cases.
Recurrent herpesOccurs on sun-exposed surfaces of lips; intraorally occurs on keratinized mucosa (dorsum of tongue, hard palate, attached gingiva); usually recurs in same location; heals in a predictable period of time for each patient.
Varicella (chickenpox)Crops of pruritic papules, vesicles, ulcers on trunk spreading to arms, legs & face; mild malaise, fever & lymphadenopathy; occasional oral ulcers.
Herpes zoster (shingles)Prodromal pain followed by vesicles & ulcers in the distribution of a sensory nerve; unilateral lesions; postherpetic neuralgia may occur.
Herpangina (Coxsackievirus A)Vesicles & ulcers in posterior oral cavity & pharynx; may have mild systemic manifestations.
Hand, foot and mouth disease
(Coxsackievirus A)
Vesicles & ulcers of oral & pharyngeal mucosa; vesicles & macules on hands and feet; mild systemic manifestations.
Rubeola (measles)Fever, conjunctivitis, photophobia, cough, nasal discharge; oral vesicles (Koplik spots); erythematous maculopapular skin rash on face spreading to trunk & extremities.
Epstein-Barr virusInfectious mononucleosis Generalized lymphadenopathy; splenomegaly; hepatomegaly; palatal petechiae; erythematous oral & pharyngeal mucosa; occasionally mucosal ulcers; no vesicular stage.
IDIOPATHIC
Each disease must be considered as a separate entity.
Aphthous ulcersAbrupt onset of recurrent ulcers on nonkeratinized mucosal surfaces; individual ulcers heal in a predictable period of time which is variable for each patient; may be menstrually related; familial history common; “herpetiform” aphthae refer to multiple crops of small aphthous ulcers; “major” aphthae are deeper, longer lasting and more frequent ulcers which often heal with scarring.
Erosive lichen planusErythematous mucosal lesions usually with areas of ulceration; often bilateral distribution; white epithelial striae at edge of erythematous areas; atrophy of filiform papillae may be seen; chronic course.
Medication-induced mucositisA variety of drugs cause mucosal lesions that do not appear to be allergic in nature; mucosal lesions consists of ulcers and erosions occurring on both keratinized & nonkeratinized mucosal surfaces.
Contact stomatitisBurning, pain, ulcers, erosions, erythema sometimes covered with shaggy hyperkeratosis. Most commonly secondary to cinnamon flavoring.
Erythema multiformeSudden onset of diffuse mucosal ulcers involving buccal & labial mucosa; sometimes recurrent with variable periods of remission; skin lesions present “iris” or “target” appearance on palmar & plantar surfaces; lymphadenopathy is rare.
Erythroplasia (erythroplakia): epithelial dysplasia, carcinoma in situ, superficially-invasive squamous cell carcinomaAsymptomatic, persistent, erythematous, velvety, focal to diffuse mucosal areas; more common in heavy consumers of alcohol.