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

In some diseases applying lateral pressure to an area of normal appearing skin or mucosa may cause formation of a blister. This phenomenon is known as a Nikolsky sign. A Nikolsky sign may be present in epidermolysis bullosa, pemphigus, mucous membrane pemphigoid, lichen planus and lupus erythematosus. Not all patients with these diseases demonstrate a Nikolsky sign.

A thorough history should be obtained from patients with vesicular-ulcerative diseases and should include the following questions:

1. How long have the lesions been present? This helps distinguish between acute and chronic diseases. Genetic diseases are often present from birth or early childhood.
2. Are the lesions recurrent? If yes:
   
   1. How often do they recur?
   2. How long does it take for each lesion to heal? Recurrent oral ulcers that heal in the same amount of time for a particular patient are characteristic of aphthous ulcers and recurrent herpes.
   3. Do they recur in the same locations? Recurrent herpetic lesions typically recur in the same location.


3. Has the patient noticed blisters? If blisters are seen, the following diseases can be excluded from the differential diagnosis: aphthous ulcers, ulcers of infectious mononucleosis, traumatic ulcers, and ulcers due to bacteria.
4. Has the patient noticed lesions on the skin, eyes, or genitals? Some systemic diseases may occur with extraoral lesions.
5. Has the patient had fever, malaise, lymphadenopathy in association with the lesions? A positive response may indicate an infectious agent, usually viral, caused the lesion.
6. What medications does the patient take? Medications may cause oral ulcers.
7. Have other family members had similar lesions? Epidermolysis bullosa is usually a familial disease.

Vesicular-ulcerative-erythematous lesions are categorized based on their cause, if known. Lesions are classified as hereditary, autoimmune, viral, mycotic (candidosis or candidiasis), and idiopathic (unknown cause). Bacteria rarely cause oral ulcers and are not discussed here.