Erythema multiforme (EM) is an inflammatory disorder that affects the skin or mucous membrane or both.[5
] According to von Hebra, who first described the disease in 1866, the patients with erythema multiforme should have acrally distributed typical target lesions or raised edematous skin papules with or without mucosal involvement.[6
] In 1968, Kenneth described an inflammatory oral disorder with oral lesions typical of EM but without any skin involvement. He reported nine cases seen at the East Man Dental hospital. The common sites involved were lips, cheeks, and tongue. These patients had irregular large ulcers with necrotic tags attached to the borders. When lips are involved the typical blood encrusted lesions were seen. In this series of cases, the typical target skin lesions were seen during the recurrences not in their initial attacks.[3
] Many investigators have suggested this as a third category of EM known as oral EM that are characterized by typical oral lesions of EM but no target skin lesions. Oral EM is a distinct but less well-recognized variant of EM. The diagnosis has to be established by excluding other oral inflammatory and vescicullobullous lesions.[2
Our two cases showed extensive irregular erythematous ulcerations in the buccal mucosa, labial mucosa, tongue, and palate along with blood encrusted lip ulcerations. Biopsies are advised only in early vesicular lesions of erythema multiforme not in ulcerated ones since histopathologic appearances are nonspecific and nondiagnostic.[3
] Our patients reported to us with advanced ulcerated lesions and hence the diagnosis had to be established based on the positive drug history, clinical appearance, and distribution of the lesion and exclusion of other ulcerative lesions.
We were able to establish a temporal relationship between the drug intake and occurrence of the oral mucosal lesions. The oral ulcerations in our cases started within a few days of the drug intake and were resolved upon cessation of the drug. Erythema multiforme is usually triggered by herpes simplex infections, but rarely by drug intake.
When the lesions are confined only to the oral cavity the different differential diagnosis that has to be considered are herpes, autoimmune vescicullobullous lesions such as pemphigus vulgaris or bullous pemphigoid and other patterns of drug reactions.
The most important of them is acute herpetic stomatitis. Herpetic lesions are more common in the keratinized mucosa especially the gingiva. Our cases did not have any gingival ulceration. Herpetic ulcers are smaller with regular borders than ulcers associated with EM. Extensive irregular ulcerations in the lining nonkeratinized mucosa as seen in our patients were typical of EM and are not a feature of herpes infection. The presence of a temporal relationship between the drug intake and onset of the disease excludes the possibility of any infectious aetiologies.[3
The positive drug histories associated with onset of ulcerations in our cases ruled out the possibility of other autoimmune vescicullobullous lesions like pemphigus vulgaris. Unlike pemphigus vulgaris oral EM have an acute onset and does not show any desquamative gingivitis.[4
] Bullous lichen planus lesions that may have similar ulcerations should have Wickham's striae, which were absent in our cases excluding it as the diagnosis.[3
Other patterns of drug reactions like lichenoid drug reactions, pemphigoid-like drug reactions that resemble their namesake can be easily differentiated based on the clinical patterns as above mentioned. Anaphylactic stomatitis often shows urticarial skin reactions with other signs and symptoms of anaphylaxis which were absent in our cases. In mucosal fixed drug eruptions the lesions are confined to localized areas of oral mucosa but in our cases there were wide spread lesions affecting labial, buccal, palatal, and tongue mucosa along with lip involvement.[1
Lesions of EM minor are characterized by single mucosal ulcerations and typical target lesions of skin. The oral mucosal ulcerations are usually irregular and large with necrotic tissue tags. Lip ulcerations are blood encrusted. Erythema multiforme major is considered to be a more aggressive form characterized by involvement of multiple mucosa accompanied by typical target skin lesions.[5
] The third category of EM, also described by many investigators as oral EM has the lesions confined to the oral mucosa and lips with no skin involvement.[2
] Since our cases were evidently triggered by drug intake and they had typical lesions of EM in the oral mucosa and lips with no skin involvement we came to a diagnosis of oral EM.
The most common drugs that trigger EM lesions are long acting sulfa drugs especially sulphonamides, co-trimoxazole, phenytoin, carbamazepine and nonsteroidal antiinflammatory drugs such as diclofenac, ibuprofen, and salicylates.
Management of oral EM involves identification of triggering agent. If it is found to be HSV infection patients have to be put on antiviral medications. If HSV is ruled out as a triggering agent and the culprit is an adverse drug reaction, the drug is immediately stopped. Usually lesions of oral EM can be treated palliatively with analgesics for oral pain, viscous lidocaine rinses, soothening mouth rinses, bland soft diet, avoidance of acidic and spicy food, systemic and topical antibiotics to prevent secondary infection.[2
] Lesions of EM usually respond to topical steroids, for more severe cases systemic corticosteroids are recommended.[8