# Non-Plaque Induced Diffuse Gingival Overgrowth: An Overview
## 3 Drug-Influenced Gingival Overgrowth (DIGO)  
Excessive gingival growth can be induced by a number of frequently used drugs, including antiepiletics, immunosuppressants and calcium channel blockers [2; 5; 11]. Among the antiepiletics, phenytoin, valpro acid, phenobarbital and carbamazepine are the most frequently involved. Immunosuppressants are reported to cause gingival enlargement too: both cyclosporine and tacrolimus are well documented as possible triggers [2; 5]. Among the calcium antagonist drugs, in addition to nifedipine and diliazem, amlodipine, felodipine and verapamil may induce gingival overgrowth [2; 5]. As previously reported, the incidence of DIGO varies according to the drug analyzed, ranging from 4% for some antihypertensives to 70% for antiepiletics such as phenytoin [5; 12]. In the United States of America, approximately 1,000,000 people suffer from DIGOs [12]. DIGOs usually manifest as a diffuse increase in gingival volume, visible from 1 to 3 months after the first drug consumption [2; 5; 11; 13]. These clinical data differ from hereditary gingival fibromatosisis, in which there is a slow and progressive growth of the gingival tissues [5]. The extent of gingival growth can be mild to severe forms, in relation to the amount of medications taken [2; 5; 11]. Furthermore, the combined use of these drugs often has a synergistic action in generating more severe forms of gingival overgrowth compared to those triggered by a single drug [2; 5]. Clinically, the gingival tissues show a granular appearance or a \"cobble stones\" aspect. The enlarged gingival tissues often cover the teeth, hindering oral hygiene practices and causing the accumulation of plaque [2; 14]. These patients often present with chewing difficulties and aesthetic problems [2]. Overgrown gingiva may present with normal or erythematas discoloration [5]. These lesions can be associated with periodontal disorders such as bleeding and bone loss [2]. These problems are due to excessive gingival tissue which causes the formation of pseudo pockets with plaque accumulation [2; 5; 11; 15]. Difficulty in carrying out normal oral hygiene maneuvers increases this vicious circle [2; 5]. In Table 1, the clinical features of all drug-induced gingival overgrowth are listed. Although the clinical manifestations of DIGOs seem similar, the cellular and tissue characteristics vary according to the type of drug involved [5; 13]. From histological and cytological analyses reported in literature, it emerges that the lesions induced by phenytoin are characterized by an important fibrotic tissue component. The lesions induced by cyclosporine, on the other hand, present tissues with a predominant inflammatory component and few fibrotic outcomes. The lesions caused by nifedipine histologically show both the above-mentioned features [12]. Furthermore, cyclosporine, acting on cyclophilin and IL-2, attenuates the adaptive immune response, breaking the balance between adaptive and innate immune responses, and causing their enhancement [12]. Another element that has been documented is the attenuation of the apoptotic mechanisms induced by inflammation in all drug-induced lesions [12]. All these studies emphasize the hyperplastic nature of DIGOs and suggest that the amounts of inflammatory cells in these tissues differ according to the drug used [12].