This type of gingival enlargement is sometimes termed "drug induced gingival enlargement" or "drug influenced gingival enlargement", abbreviated to "DIGO". Gingival enlargement may also be associated with the administration of three different classes of drugs, all producing a similar response: Gingival overgrowth is a common side effect of phenytoin, termed "Phenytoin-induced gingival overgrowth" (PIGO).

- anticonvulsants (such as phenytoin, phenobarbital, lamotrigine, vigabatrin, ethosuximide, topiramate and primidone NOT common for valproate)

- calcium channel blockers (antihypertensives such as nifedipine, amlodipine, and verapamil). The dihydropyridine derivative isradipidine can replace nifedipine and does not induce gingival overgrowth.

- cyclosporine, an immunosuppresant.

Of all cases of DIGO, about 50% are attributed to phenytoin, 30% to cyclosporins and the remaining 10-20% to calcium channel blockers.

Drug-induced enlargement has been associated with a patient's genetic predisposition, and its association with inflammation is debated. Some investigators assert that underlying inflammation is necessary for the development of drug-induced enlargement, while others purport that the existing enlargement induced by the drug effect compounds plaque retention, thus furthering the tissue response. Careful attention to oral hygiene may reduce the severity of gingival hyperplasia. In most cases, discontinuing the culprit drug resolves the hyperplasia.

This condition occurs in association with denture wearing, and so those affected tend to be middle aged or older adults. 66-75% are estimated to occur in women. Epulis fissuratum is the third most common reactive lesion that occurs in the mouth, after peripheral giant cell granuloma and pyogenic granuloma.

Many systemic diseases can develop oral manifestations that may include gingival enlargement, some that are related to conditions and others that are related to disease:

- Conditioned enlargement

- pregnancy

- puberty

- vitamin C deficiency

- nonspecific, such as a pyogenic granuloma

- Systemic disease causing enlargement

- leukemia

- granulolomatous diseases, such as granulomatosis with polyangiitis, sarcoidosis, or orofacial granulomatosis.

- neoplasm

- benign neoplasms, such as fibromas, papillomas and giant cell granulomas

- malignant neoplasms, such as a carcinoma or malignant melanoma

- false gingival enlargements, such as when there is an underlying bony or dental tissue lesion

If the causative factor persists, tissue will become more fibrous over time.

Treatment usually involves surgical removal of the lesion down to the bone. If there are any adjacent teeth, they are cleaned thoroughly to remove any possible source of irritation. Recurrence is around 16%.

Also termed a "pregnancy tumor" or "granuloma gravidarum", this lesion is identical to a pyogenic granuloma in all respects apart from the fact that it occurs exclusively in pregnant females. There is usually pregnancy gingivitis also. Pregnancy epulis commonly occurs during the third trimester of pregnancy.

Epulis (; plural "epulides") is any tumor like enlargement (i.e. lump) situated on the gingival or alveolar mucosa. The word literally means "(growth) on the gingiva", and describes only the location of the mass and has no further implications on the nature of the lesion. There are three types: fibromatous, ossifying and acanthomatous. The related term parulis (commonly called a gumboil) refers to a mass of inflamed granulation tissue at the opening of a draining sinus on the alveolus over (or near to) the root of an infected tooth. Another closely related term is gingival enlargement, which tends to be used where the enlargement is more generalized over the whole gingiva rather than a localized mass.

Peripheral ossifying fibroma “a gingival nodule which is composed of a cellular fibroblastic connective tissue stroma which is associated with the formation of randomly dispersed foci of mineralised products, which consists of bone, cementum-like tissue, or a dystrophic calcification. The lesion is considered part of an ossifying fibroma, but that is usually considered to be a gnathic tumor. Because of its overwhelming incidence on the gingiva, the condition is associated with two other diseases, though not because they occur together. Instead, the three are associated with each other because they appear frequently on gingiva: pyogenic granuloma and peripheral giant cell granuloma. Some researchers believe peripheral ossifying fibromas to be related to pyogenic fibromas and, in some instances, are the result of a pyogenic granuloma which has undergone fibrosis and calcification.

The term "peripheral ossifying fibroma" has been criticized as this lesion is not related to the ossifying fibroma of bone and is not a fibroma. This term is used in America, however in Britain, this lesion would be termed a fibrous epulis containing bone.

The peripheral odontogenic fibroma is an uncommon gingival mass. It affects people across a large age range. It can be confused with the peripheral ossifying fibroma. In contrast to the peripheral ossifying fibroma, the peripheral odontogenic fibroma is a rare lesion.

No specific gender predilection while the ages of the patients ranged from 5 to 65 years.commonly seen in mandible than maxilla.

slow growing, solid, firmly attached gingival mass sometimes arising between teeth and sometimes displacing teeth.

consists of cellular fibrous connective tissue parenchyma with non neoplastic islands, strands of clouman or cuboidal odontogenic epithelium.

The standard treatment of COC is enucleation and curettage (E&C). Recurrence following E&C is rare.

Verruciform xanthoma is uncommon, with a female:male ratio of 1:1.1

The central odontogenic fibroma is a rare benign odontogenic tumor. It is more common in adults, with the average age being 40. It is twice as likely to affect women than men. It is usually found either in the anterior maxilla or the posterior mandible. Radiographically it presents with either radiolucency or mixed radiolucency/opaque. The simple type is characterized by delicate fibrillar stroma of collagen containing fibroblasts; the WHO type is characterized by more mature fibrillar stroma of collagen. Treatment is by surgical removal

Treatment usually involves surgical removal of the lesion down to the bone. If there are any adjacent teeth, they are cleaned thoroughly with scaling and root planing (SRP) to remove any possible source of irritation. Recurrence is around 10%.

Central giant-cell granuloma (CGCG) is a benign condition of the jaws. It is twice as likely to affect women and is more likely to occur in 20- to 40-year-old people. Central giant-cell granulomas are more common in the mandible and often cross the midline.

PCNA and Ki67 immunoreactivity happens in case of fibroma and peripheral granuloma.

This is a very rare phenomenon (50 years of age), and more commonly in women than men (5:1). There is an increased frequency in Okinawa, Japan, but this may be a reporting bias.

The tumor develops very specifically in the subscapular or infrascapular area, deep to the muscle, sometimes even attached to periosteum of ribs. It is usually between the shoulder blade and the lower neck, with rare tumors reported in the chest wall.

Giant-cell fibroma is a type of fibroma not associated with trauma or irritation. It can occur at any age and on a mucous membrane surface. The most common oral locations are on the gingiva of the mandible, tongue, and palate. It is a localized reactive proliferation of fibrous connective tissue.

Giant-cell fibroma (GCF) is a benign non-neoplastic lesion first described by Weathers and Callihan (1974). It occurs in the first three decades of life and predominates in females (Houston, 1982; Bakos, 1992). Clinically, the GCF presents as an asymptomatic, papillary and pedunculated lesion. The most predominant location is the mandibular gingiva (Houston, 1982; Bakos, 1992). Histologically, the GCF is distinctive, consisting of fibrous connective tissue without inflammation and covered with stratified squamous hyperplastic epithelium. The most characteristic histological feature is the presence of large spindle-shaped and stellate-shaped mononuclear cells and multinucleated cells. These cells occur in a variety of lesions, such as the fibrous papule of the nose, ungual fibroma, acral fibrokeratoma, acral angiofibroma and desmoplastic fibroblastoma (Swan, 1988; Pitt et al., 1993; Karabela-Bouropoulou et al., 1999; Jang et al., 1999).

Despite many studies, the nature of the stellated multinucleate and mononuclear cell is not clear (Weathers and Campbell, 1974; Regezi et al., 1987; Odell et al., 1994; Magnusson and Rasmusson, 1995).

Verruciform xanthoma is an uncommon benign lesion that has a verruciform (wart-like) appearance, but it may appear polypoid, papillomatous, or sessile. The verruciform was first described by Shafer in 1971 on the oral mucosa. Usually found on the oral mucosa of middle-aged persons, verruciform xanthomas have also been reported on the scrotum and penis of middle-aged to elderly Japanese males. While the most common site is the oral mucosa, lesions that occur elsewhere usually arise on the perineum or on the skin with some predisposing factor, such as lymphedema or an epidermal nevus.

The treatment for CGCG is thorough curettage. A referral is made to an oral surgeon. Recurrence ranges from 15%–20%. In aggressive tumors, three alternatives to surgery are undergoing investigation:

- corticosteroids;

- calcitonin (salmon calcitonin);

- interferon α-2a.

These therapeutic approaches provide positive possible alternatives for large lesions. The long term prognosis of giant-cell granulomas is good and metastases do not develop.

Pyogenic granuloma (also known as a "eruptive hemangioma", "granulation tissue-type hemangioma", "granuloma gravidarum", "lobular capillary hemangioma", "pregnancy tumor", and "tumor of pregnancy") is a vascular lesion that occurs on both mucosa and skin, and appears as an overgrowth of tissue due to irritation, physical trauma, or hormonal factors. It is often found to involve the gums, the skin and nasal septum, and has also been found far from the head such as in the thigh.

The appearance of pyogenic granuloma is usually a color ranging from red/pink to purple, and can be smooth or lobulated. Younger lesions are more likely to be red because of the high number of blood vessels. Older lesions begin to change into a pink color. Size commonly ranges from a few millimeters to centimeters, though smaller or larger lesions may occur. A pyogenic granuloma can be painful, especially if located in an area of the body where it is constantly disturbed. Pyogenic granulomas can grow rapidly and will often bleed profusely with little or no trauma. They may exude an oil like substance, causing the surface to be damp. This is especially true if the granuloma is located on the scalp.

Pyogenic granulomas may be seen at any age, and are more common in females than males. In pregnant women, lesions may occur in the first trimester with an increasing incidence up until the seventh month, and are often seen on the gums. Epulis granulomatosum is a variant of pyogenic granuloma that forms only on gingiva, and is often seen forming in a recent extraction socket. Pyogenic granulomas appear on the gingiva in 75% of cases, more often in the maxillary than mandibular jaw. Anterior areas are more often affected than posterior areas. It can also be found on the lips, tongue, and inner cheek. Poor oral hygiene or trauma are usually precipitating factors.

One study has suggested a correlation between pyogenic granulomas and Bartonella seropositivity. However, this association has been questioned by others. The microscopic appearance of a pyogenic granuloma consists of highly vascular granulation tissue. Inflammation is present. The lesion may have a fibrous character if it is older, and the surface may have ulcerations. Pyogenic granulomas rarely occur in the conjunctiva, cornea or connective tissue of the eye following minor local trauma. Grossly these mass lesions resemble those occurring at more common sites. The relationship of these lesion to lobular capillary hemangiomas of skin and oropharyngeal mucosa commonly referred to as pyogenic granuloma is uncertain.

Benign fibrous histiocytomas (also known as dermal dendrocytoma, dermatofibroma, fibrous dermatofibroma, fibrous histiocytoma, fibroma simplex, nodular subepidermal fibrosis, and sclerosing hemangioma) are benign skin growths.

Dermatofibromas are hard solitary slow-growing papules (rounded bumps) that may appear in a variety of colours, usually brownish to tan; they are often elevated or pedunculated. A dermatofibroma is associated with the dimple sign; by applying lateral pressure, there is a central depression of the dermatofibroma. Although typical dermatofibromas cause little or no discomfort, itching and tenderness can occur. Dermatofibromas can be found anywhere on the body, but most often they are found on the legs and arms. They occur most often in women; the male to female ratio is about 1:4. The age group in which they most commonly occur is 20 to 45 years.

Some physicians and researchers believe dermatofibromas form as a reaction to previous injuries such as insect bites or thorn pricks. They are composed of disordered collagen laid down by fibroblasts. Dermatofibromas are classed as benign skin lesions, meaning they are completely harmless, though they may be confused with a variety of subcutaneous tumours. Deep penetrating dermatofibromas may be difficult to distinguish, even histologically, from rare malignant fibrohistocytic tumours like dermatofibrosarcoma protuberans.

Dermatofibromas typically have a positive "buttonhole sign", or central dimpling in the center.

Peripheral giant-cell granuloma (PGCG) is an oral pathologic condition that appears in the mouth as an overgrowth of tissue due to irritation or trauma. Because of its overwhelming incidence on the gingiva, the condition is associated with two other diseases, though not because they occur together. Instead, the three are associated with each other because they appear frequently on gingiva: pyogenic granuloma and peripheral ossifying fibroma. Because of its similar microscopic appearance to the bony lesions called central giant-cell granulomas, peripheral giant-cell granulomas are considered by some researchers to be a soft tissue equivalent.

The appearance of peripheral giant-cell granulomas is similar to pyogenic granulomas. The color ranges from red to bluish-purple, but is usually more blue in comparison to pyogenic granulomas. It can be sessile or pedunculated with the size usually being less than 2 cm.

There is a gender difference with 60% of the disease occurring in females. The prevalence of peripheral giant-cell granulomas is highest around 50 - 60 years of age. It appears only on the gingiva or on an edentulous (without teeth) alveolar ridge. It is more often found in the mandible rather than the maxilla but can be found in either anterior or posterior areas. The underlying alveolar bone can be destroyed, leaving a unique appearance referred to as "cupping resorption" or "saucerization".

Some researchers suggest that HGF is transmitted as a Mendelian trait since both autosomal dominant and autosomal recessive transmission has been reported since the early 1970s. (SOURCE 1) In more recent scientific literature, there is evidence in which pedigree analyses confirm autosomal dominant, autosomal recessive or even as X-linked inherited cases of the HGF trait.

In 2002, researchers described the SOS1 gene and proved for the first time that a single-nucleotide–insertion mutation of the SOS1 gene on codon 1083 is the preliminary cause of HGF1 in humans. (Source 1) Later on in 2010, there was a case study done on a 16-year-old male with severe gingival overgrowth, almost covering all teeth. Researchers approached this issue with periodontics - a partial gingivectomy and flap surgery. This case study concluded that surgery followed by regular follow-ups is a good way to treat HGF despite the fact that the risks of re-occurrence of the condition remain high.

Even more recently, a study was done in 2013 on a family that showed history of autosomal recessive inheritance of HGF. The study did not dismiss the return of HGF after treatment but did claim that general surgical intervention after scaling and root planning of teeth supplemented with good oral hygiene is good enough to prevent the re-occurrence of HGF. This case study also acknowledged how HGF can be part of a multi-system syndrome associated with disorders such as Zimmermann Laband syndrome (ear, nose, bone, and nail defects with hepatosplenomegaly), Rutherford syndrome (microphthalmia, mental retardation, athetosis, and hypopigmentation), Murray-Puretic Drescher syndrome and Ramon syndrome.