There are several forms of gingival fibromatoses which are characterized by a generalized enlargement of the gingiva. Some are idiopathic, while some others are drug related, inflammatory or hereditary in nature.

Drug-Related Gingival Hyperplasia

Generalized gingival fibrous hyperplasia (GGFH) arising as a side effect of phenytoin therapy used in the control of epileptic convulsions and other neurologic disorders is a well known clinical reaction. Presently several other medications produce similar reactions, among the most frequent are nifedipin which is a calcium channel blocker (CCB) and cyclosporine, which is a immunosuppressant. A large number of CCB drugs used in controlling blood pressure are also responsible for producing gingival hyperplasia of various degrees i.e.: bleomycin, dilitiazem and felodipine, among others. When examining a patient with generalized fibrous gingival hyperplasia the use of any of these drugs should be investigated. Dental microbial plaque is central to the etiology of drug-related GGFH as well as individual patients' susceptibility. When oral hygiene is maintained at adequate level GGFH does not develop in those patients, or it is markedly improved. Around 50% of patients under phenytoin medication and almost 25% of patients taking cyclosporine develop GGFH. Control of dental hygiene in the later group of patients does not seem to have a significant effect on the clinical appearance of GGFH.

A diffused enlargement of the interdental papillae and marginal gingiva is seen. The tissue is painless, nodular, firm and pink with crevicular erythema, and may become lobulated and finely pebbled. It has little tendency to bleed. The severity of the condition is usually linked to the patient's oral hygiene and the duration of therapy. A daily dose relationship is harder to establish. The condition starts as a marginal gingivitis followed by the enlargement of individual papillae, which may grow to cover all but the occlusal surfaces of the teeth. Superimposed inflammation is responsible for marked erythema and edema as well as bleeding in extreme cases. Also, multiple individual nodular growths, especially on the interdental papillae, may develop associated to secondary inflammation. The various types of gingival fibromatosis and gingival hyperplasia associated with blood dyscrasias should be considered in the differential diagnosis. Wegener's granulomatosis also could be included in the differential diagnosis, especially in those cases of multiple nodular growths.

Biopsy reveals uniform, avascular proliferation of collagenic connective tissue, almost hyaline in appearance, with overlying epithelial hyperplasia. Secondary inflamed cases will show marked capillary proliferation as well as an inflammatory cellular infiltrate essentially composed of lymphocytes and plasma cells. Surgical excision is indicated for the more severe cases of GGFH. Prophylaxis by means of a careful oral hygiene program which may include rinses with chlorhexidine gluconate, is part of the treatment. Surgical removal is often followed by recurrence, especially when proper oral hygiene is not maintained. Hyperplasia is not the inevitable consequence for patients taking any of the drugs mentioned above, because patients with good oral hygiene can reduce the risk of the development of GGFH.

Figure 12. This 21 year-old woman was under phenytoin therapy (dilantin) to control epileptic convulsions. Note the marked drug induced gingival hyperplasia/hypertrophy. Also note areas of erythema as a consequence to superimposed inflammatory reaction. This patient had a poor oral hygiene.

Figure 13. This is the gingival appearance of another patient under phenytoin medication. There is marked generalized gingival hyperplasia accompanied by erythema and secondarily inflammatory response.

Hereditary gingival fibromatosis

There are several forms, as presented below of hereditary variants of gingival hyperplasias. All of them are extremely rare and share their oral appearance which is a diffused enlargement of the gingiva that generally coincides with the eruption of the primary incisors. This soft tissue proliferation is non-inflammatory and it appears normal in color and texture. This hypertrophic growth is progressive and eventually covers the crown of the tooth. Gingival fibromatosis with hypertrichosis. In addition to gingival fibromatosis this syndrome is characterized by epilepsy, mental retardation, and hypertrichosis. The mental retardation and epilepsy are inconsistent features. The syndrome is inherited as an autosomal dominant. The facies is characterized by protrusion of the lips, secondary to gingival enlargement, and hypertrichosis, especially of the eyebrows.

Gingival fibromatosis with ear, nose, bone and nail defects. This syndrome is characterized by gingival fibromatosis, dysplasia of nails, soft bulky cartilage in nose and ears, hepatosplenomegaly, and hypoplastic terminal phalanges. The syndrome is inherited as an autosomal dominant.

Gingival fibromatosis with multiple hyaline fibromas. This syndrome is characterized by hypertrophy of the gingiva, hypertrophy of the nail beds, and fibrotic tumors of the nose, chin, head, and palmar and digital surfaces of the hands. This syndrome is inherited as an autosomal recessive. Fibrotic hyaline tumors appear on the nose, chin and head usually after the age of 2. Multiple fibrous tumors resembling those on the face appear on the back, fingers, thighs, and legs, often producing flexion contractures at the knees, elbows, shoulders, and hips.

The differential diagnosis of these syndromes should include isolated gingival fibromatosis and generalized drug-related gingival hyperplasia. In the case of multiple hyaline fibromas, neurofibromatosis, Gardner syndrome and fibromatosis hyalinica multiplex juvenilis, should be considered. Surgical correction can be attempted but recurrences are bound to happen. In those cases in which teeth have been extracted, the gingiva resumes its normal position.

Figure 14. Note the diffuse enlargement of the gingiva in this patient with gingival fibromatosis associated with hypertrichosis.

Figure 15. Another patient with gingival fibromatosis and hypertrichosis. Note the marked generalized gingival enlargement which is almost covering the teeth's crowns. This condition is inherited as an autosomal dominant.

Leukemic hyperplasia

Leukemia is a disease characterized by the appearance of immature neoplastic white blood cells in the circulation. A viral cause is considered probable but is as yet not fully proven. The most frequent oral manifestation of leukemia is a generalized hyperplastic gingivitis with a cyanotic bluish-red discoloration. The lesions vary in degree and severity. In some patients there is diffuse enlargement of the gingiva. The oral tissues are friable and bleed easily. Frequently hyperplastic gingiva may completely cover the teeth. There is frequently hemorrhage into the tissues producing hematomas. In severe cases, purpuric lesions and necrotic ulceration of the oral mucous membranes are also seen. A noma-like complication may be associated with terminal cases of leukemia owing to lack of tissue defense against a minor irritant. Alveolar bone destruction and necrosis of the periodontal ligament may occasionally lead to loosening and exfoliation of teeth. Acute necrotizing ulcerative gingivitis may also be present.

The oral manifestations of leukemia result from both the basic systemic defect and local irritants. When the oral cavity is kept free of local irritants such as plaque, food debris, ill-fitting dentures, and the like, oral involvement may be minimal. The course and complications of the disease depend upon the basic systemic defect. The condition generally has a fatal outcome. Other blood dyscrasias, as well as advanced periodontitis, necrotizing ulcerative gingivostomatitis, hyperplastic gingivitis, and noma, should be considered in the differential diagnosis. A hemogram establishes the diagnosis. Gingival biopsy is only suggestive of the condition and must be corroborated by hematologic examination.

The treatment is systemic and mostly paliative encompassing a variety of means such as chemotherapy, radiation and bone marrow transplantation. The oral cavity should be free of local irritants and the patient must be instructed to maintain a high level of oral hygiene.

Figure 16. This 8 year-old boy had acute lymphocytic leukemia. Note the generalized gingival enlargement erythema and slight bleeding.