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

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

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

Skin lesions are always present; Nikolsky 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.
Diffuse mucosal erythema; burning or pain may be present; ulcers are rarely present; lymphadenopathy is rare. Patient often has predisposing factors: antibiotics, immunosuppression.
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 pemphigoid Skin vesicles, bullae & ulcers are always present; occasional oral vesicles & ulcers.
Pemphigus Mucosal vesicles & ulcers in any location usually precede skin lesions; Nikolsky sign may be present.
Lupus erythematosus Nonspecific 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.
Acute onset; multiple lesions; systemic manifestations (malaise, fever, diarrhea, lymphadenopathy, lymphocytosis) often present; vesicle stage is present in all except mononucleosis.
Herpes simplex virus:
Primary herpes Vesicles & 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 herpes Occurs 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 virus Infectious mononucleosis: Generalized lymphadenopathy; splenomegaly; hepatomegaly; palatal petechiae; erythematous oral & pharyngeal mucosa; occasionally mucosal ulcers; no vesicular stage.
Each disease must be considered as a separate entity.
Aphthous ulcers Abrupt 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 planus Erythematous 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 mucositis A 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 stomatitis Burning, pain, ulcers, erosions, erythema sometimes covered with shaggy hyperkeratosis. Most commonly secondary to cinnamon flavoring.
Erythema multiforme Sudden 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 carcinoma Asymptomatic, persistent, erythematous, velvety, focal to diffuse mucosal areas; more common in heavy consumers of alcohol.