Drug-Induced Gingival Overgrowth—a Review

Abstract

Drug-induced gingival overgrowth is a side effect associated with 3 types of drugs: anticonvulsants (phenytoin), immunosuppressive agents (cyclosporine A), and various calcium channel blockers for cardiovascular diseases. Gingival overgrowth is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components with various degrees of inflammation. Although the mechanisms of these disorders have not been elucidated, recent studies suggest that these disorders seem to be induced by the disruption of homeostasis of collagen synthesis and degradation in gingival connective tissue, predominantly through the inhibition of collagen phagocytosis of gingival fibroblasts. The integrins are a large family of heterodimeric transmembrane receptors for extracellular matrix molecules. a a 2b b1 integrin serves as a specific receptor for type I collagen on fibroblasts, and a a 2 integrin has been shown to play a crucial role in collagen phagocytosis. Actin filaments, which are assembled from monomers and oligomers, are involved in collagen internalization after binding to integrins. Furthermore, the implication of intracellular calcium in the regulation of integrin-mediated binding activity and gelsolin activity, known as a calcium-dependent actin-severing protein, is also described. In this review, we focus on collagen metabolism in drug-induced gingival overgrowth, focusing on the regulation of collagen phagocytosis in fibroblasts.

Oral findings in 58 adults with tuberous sclerosis complex

“…In one patient, gingival overgrowth was associated with mouth breathing. Another patient was taking nifedipine, a drug associated with gingival overgrowth 14 .…”

“…Gingival overgrowth, the term currently preferred over gingival hyperplasia or gingival hypertrophy 14 , can be drug induced in TSC 8 , especially by phenytoin which causes gingival overgrowth in 10-50% of non-TSC patients 14 . However, gingival overgrowth in TSC may occur in the absence of phenytoin treatment 4,24 , and four patients in the current study had never been treated with anticonvulsants.…”

Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages

“…Whether pathological fibrosis occurs simply due to overwhelming collagen production or a combination of persistent collagen production coupled with impaired collagen degradation has yet to be determined. Interestingly, in some forms of pharmaceutically induced fibrosis, the phagocytic capacity of fibroblasts is severely reduced, suggesting that collagen turnover pathways can be inhibited (49,50). As we learn more about the pathways responsible for remodeling and removal of collagen from the extracellular matrix, we can begin to dissect out the relative contribution of increased collagen production and impaired collagen degradation to fibrotic disease.…”

REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis

“…1 GF may also develop from environmental exposure such as a side effect of medications including anticonvulsants (i.e., phenytoin), immunosuppressants (i.e., cyclosporine), or calcium channel blockers (i.e., nifedipine, diltiazem, and verapamil). 2,3 The initial differential diagnosis for GF also includes chronic hyperplastic gingivitis, leukemic infiltrate, and some systemic diseases such as Crohn disease (MIM: 266600), neurofibromatosis (MIM: 162200), primary amyloidosis (MIM: 204850), sarcoidosis (MIM: 181000), scurvy (MIM: 240400), and Wegener granulomatosis (MIM: 608710) that have been associated with gingival overgrowth. 4 HGF is the most common genetic form of GF which is usually transmitted as an autosomal-dominant trait.…”