Phenytoin-Induced Gingival Over Growth: A Review

Context: Gingival overgrowth can be associated with pharmacotherapy. Among the offending medications of gingival overgrowth, phenytoin is the first reported and the most common agent. Evidence Acquisition: A literature search was performed with the relevant key words in different databases such as Scopus, Medline, Embase, and Google scholar. Results: About 50% of individuals receiving phenytoin may develop gingival overgrowth usually after 3-6 months of treatment. Poor oral hygiene and young age are two identified independent risk factors of phenytoin-induced gingival overgrowth. The possible relationship between this adverse drug reaction and dose, serum levels of phenytoin as well as other co-administered antiepileptic agents is equivocal. It may be associated with pain, tenderness, and bleeding of the gums. Phenytoin-induced gingival overgrowth can interfere with speech, mastication, nutrition, tooth eruption, and esthetics and may results in teeth shifting and malocclusion. Several cellular and molecular mechanisms have been suggested for phenytoin-induced gingival overgrowth including: 1) inducing local inflammatory responses; 2) stimulating angiogenesis, extracellular matrix, and collagen synthesis; 3) inhibiting extracellular matrix and collagen degradation; 4) inducing systemic as well as localized folate deficiency; and 5) development of bacterial biofilm. Avoiding local irritants, rigorous plaque control, chlorhexidine gluconate mouth rinse, and regular periodontal maintenance therapy at 3-month intervals are the suggested preventive measures against phenytoin-induced gingival overgrowth. Strategies for the management of phenytoin-induced gingival overgrowth can be categorized as surgical and non-surgical. Surgical approaches including gingivectomy, periodontal flap, electro surgery, and laser excision are generally reserved for severe and advanced stages of phenytoin-induced gingival overgrowth. In mild to moderate stages, non-surgical options such as oral hygiene measures, scaling and root surface instrumentation, discontinuing, dose de-escalation or the replacement of phenytoin with other antiepileptics (e.g. lamotrigine, gabapentin, sulthiame, and topiramate), and pharmacotherapy (e.g. oral folic acid supplementation) can be considered. Conclusions: Both pharmacoprophylaxis and pharmacotherapy of phenytoin-induced gingival overgrowth with potentially effective agents such as tamoxifen, finasteride, levamisole, celecoxib, and azithromycin has been largely overlooked and should be taken into account in future clinical investigations.