Oral Pathologic Alterations of Gingiva and Periodontium*


Oral Pathologic Alterations of Gingiva and Periodontium*

As they traverse their clinical course, plaque-induced inflammatory gingival and periodontal diseases may be enhanced or co-initiated by hormonal disturbances and the side effects of systemic medications. Additional oral pathologic alterations accompanying systemic diseases are frequently observed on the gingiva and in the periodontium. In this milieu, clinical differentiation between gingivitis and periodontitis on the one hand and diseases of the oral mucosa on the other may become blurred.

It is impossible in this book to depict and describe each and every oral pathologic alteration that also manifests on the gingiva or in the periodontium. A comprehensive review of all such oral lesions can be found in the Color Atlas of Oral Pathology (Reichart & Philipsen 1999).

In the pages that follow, several of the relatively frequently occurring diseases or alterations will be described:

Primarily Gingival Alterations

  • Hormonal complications (p.91)

  • Hyperplasia caused by medicaments

  • Gingival overgrowth, tumors

  • Autoimmune diseases, desquamative and bullous gingival alterations, anomalies of keratinization, dermatologic diseases

  • Specific infections

  • Allergies

  • Toxic manifestations

  • Injuries, chemical injuries

Gingival and Periodontal Disorders

  • Metabolic disturbances

  • Nutritional deficiencies

  • Genetically-related systemic syndromes

  • Blood cell disorders

  • Immune deficiency, AIDS

* In the new AAP Classification (Armitage 1999, see Appendix pp. 327–330), a portion of the oral pathologic alterations on the gingiva are classified under Type I A and B, and in the periodontium under Type IV, “periodontitis as a manifestation of systemic diseases.”

Primarily Gingival Alterations (Type I B)

In the following pages, the disorders shown below with a black dot are described and depicted.

Hormonal Complications

  • Pregnancy gingivitis (p. 92)

  • ˆ Gingivitis due to the “pill”

  • Puberty gingivitis (p. 92)

  • ˆ Gingivitis menstrualis and intermenstrualis

  • ˆ Gingivitis climacterica

Medicament-Elicited Hyperplasia

  • Phenytoin gingival overgrowth (p. 121)

  • Dihydropyridine-induced gingival overgrowth (p. 122)

  • Cyclosporine-induced gingival overgrowth (p. 123)

  • Medicament combinations (cyclosporine/nifidepine, p. 124)

Gingival Overgrowth, Tumors

  • Epulis (p. 125)

  • Idiopathic and hereditary fibrosis (p. 126)

  • Neoplasms

    • benign tumors (p. 126)

    • malignant tumors (p. 127)

Autoimmune Diseases, Desquamative and Bullous Gingival Alterations, Anomalies of Keratinization, Dermatologic Diseases

  • Gingivosis (p. 128)

  • Pemphigoid (p. 128)

  • Pemphigus vulgaris (p. 128)

  • ˆ Epidermolysis bullosa

  • ˆ Exudative erythema multiforme

  • Lichen (p. 129)

  • Leukoplakia–precancerous lesions (p. 130)

  • Oral granulomatosis (p. 130)

  • ˆ Dermatomyositis, scleroderma, psoriasis etc.

Specific Infections

  • Herpes (p. 131)

  • Aphthae ? (p. 131)

  • ˆ Toxoplasmosis

  • ˆ Actinomycosis, candidiasis

  • ˆ Gonorrhea, syphilis etc.


  • To medicaments

  • To metals, mercury

Toxic Reactions

These may occur locally in the oral cavity through release of metal ions possessing high toxic potential, from dental materials (nickel, cadmium, bismuth, beryllium, vanadium etc; Wirz et al. 1997 a, b):

  • Dental materials of varying composition

  • Lead and other metals

Injuries, Chemical Injuries

Gingival and Periodontal Alterations (Type IV A/B)

Metabolic Disturbances

  • Diabetes (p. 132)

  • Acatalasemia (Takahara’s Disease)

  • Eosinophilic granuloma

  • Pre-leukemic syndrome

Nutritional Deficiency

Nutritional deficiency as a cause or co-factor in gingivitis or periodontitis is practically no longer observed in the western/northern hemispheres. In extreme conditions (e.g., in the Third World) one may observe:

  • Ascorbic acid deficiency (scurvy)

  • Kwashiorkor (protein deficiency) etc.

Genetically-Elicited Systemic Syndromes

It is not uncommon that rare, partially inherited systemic syndromes are characterized by severe periodontitis:

  • Down syndrome (p. 134)

  • Papillon-Lefèvre syndrome (p. 136)

  • Chediak-Higashi Syndrome

  • Hypophosphatasia (Rathbun Syndrome)

  • Pelger-Huet nucleus anomaly

  • Ehlers-Danlos syndrome etc.

Blood Cell Diseases

Every blood cell disorder reduces the immune response and, therewith, local defense reactions.

  • Leukemia

  • Panmyelopathy—Fanconi anemia

  • Cyclic neutropenia

  • Agranulocytosis

  • Erythroblastic anemia etc.

Immune Deficiencies

Any weakening of the immune system may elicit or enhance periodontitis. Perhaps most important today is infection by the human immunodeficiency virus HIV.

  • HIV infection, AIDS (p. 139)

Phenytoin-induced Gingival Overgrowth

Phenytoin (hydantoin) prevents or reduces the incidence or severity of seizures associated with most types of epilepsy (grand mal), with the exception of petit mal. Phenytoin is also often prescribed following neurosurgical operations or cranial trauma. The anticonvulsive effect is probably due to the inhibition of the spread of nerve potentials in the brain cortex (Hassell 1981).

Systemic side effects of phenytoin are relatively minor. Some bone pathology may be observed after long-term therapy. The patient’s mental capacity and reaction time may be negatively influenced (thus, no driver’s license!).

The most important oral side effect is an often pronounced and secondarily inflamed gingival overgrowth.

Therapy: Motivation, repeated oral hygiene instructions, professional plaque and calculus removal. Once inflammation subsides, fibrous tissue can be excised. Lesions frequently recur.

In collaboration with the patient’s physician, in some cases it may be possible to change to a different medication, e.g., valproic acid, benzodiazepine, barbituric acid derivatives, etc.

248 Mild Phenytoin-induced Gingival Overgrowth Fibrous form of phenytoin induced overgrowth in a 19-year-old female with epilepsy. Following initial periodontal therapy, a gingivoplasty was performed. The oral hygiene of this patient was relatively good, and this made it possible to eliminate secondary inflammation for the most part.
249 Phenytoin—Structural and Chemical Formula The medicament phenytoin (diphenylhydantoin) is a 5,5-diphenyl-2,4-imidazolodine-dione. The overgrowth occurs in only approximately 50% of patients, usually young individuals (pharmacogenetic factor; Hassell 1981). Participating in the etiology are probably macrophages and fibroblasts that stimulate catabolic mediators, growth factors and collagen (Type IV; Sinha Morton & Dongari-Bagtzoglon 1999).
250 Severe Phenytoin Overgrowth-Severe Secondary Inflammation This 44-year-old female had taken phenytoin on a chronic regimen for six years, since a neurosurgical procedure. She was mildly debilitated and therefore unable to perform adequate oral hygiene. Following initial periodontal therapy, gingivoplasty was performed. Left: There is radiographic evidence of bone resorption at the interdental septa.

Dihydropyridine-induced Gingival Overgrowth

The substituted dihydropyridines (nifedipine, nitrendipine etc.) are calcium antagonists that reduce the influx of calcium ions into heart muscle and thereby reduce the strength of contraction as well as the vascular resistance. This reduces oxygen consumption by the heart while simultaneously increasing cardiac circulation. Thus, dihydropyridines exert both anti-anginal and anti-hypertensive effects. Some general side effects as well as interactions with other drugs are observed. In contrast to phenytoin, dihydropyridines are taken by primarily by older cardiac patients, who often have a pre-existing periodontitis.

The most important oral side effect is an often pronounced, secondarily inflamed gingival overgrowth. The pathogenesis of the overgrowth is suspected to be similar to that observed in phenytoin-treated individuals (connective tissue accumulation), but an increase in acid mucopolysaccharides (ground substance) also appears to occur (Lucas et al. 1985, Barak et al. 1987).

Therapy: Following patient motivation, repeated oral hygiene instruction and initial periodontal therapy, severe lesions may be eliminated surgically (gingivoplasty).

251 Mild to Moderate Nifedipine-induced Gingival Overgrowth This 55-year-old male exhibited lesions of varying severity, with evidence of secondary inflammation. He had been taking “Adalat” (nifedipine) for two years because of his high blood pressure. The physician changed his medication to a different drug. Right: The radiograph clearly shows that the gingival alterations were superimposed upon an existing periodontitis; the latter is not due to the drug.
252 Nifedipine—Structure and Chemical Formula This drug is a 1,4-dihydro-2,6-di-methyl-4-(2-nitrophenyl)-3,5-pyridine-dicarbonic acid dimethyl ester.
253 Severe Nifedipine-induced Gingival Overgrowth This 58-year-old Black female presented with severe, secondarily highly inflamed gingival overgrowth. The patient had taken “Procardia” (nifedipine) for four years. Note also the mild gingival pigmentation.

Cyclosporine-induced Gingival Overgrowth

The immunosuppressive effect of cyclosporine-A (“Sandimmune,” Novartis Co.) derives from the suppression of antibody formation against T cell-dependent antigens, the suppression of cell-mediated immunity, and interference with the production of cytokines (IL-2 etc).

Systemic side effects occur frequently: increased blood pressure, increase in body hair (hirsutism), formation of lymphoma, as well as nephro– and hepatotoxicity.

The oral manifestation of cyclosporine is the side effect of gingival overgrowth, which is usually secondarily inflamed. The incidence and severity of the gingival lesions are strictly dose-dependent and correlated to blood levels of the drug. New medicines (e.g., Prograf, Cellcept etc.) are reported to have fewer side effects.

Therapy: Good oral hygiene coupled with initial periodontal therapy can reduce both the inflammation and the overgrowth. If instituted early, such measures may actually prevent development. In severe cases, surgical gingivoplasty may be indicated. Organ transplant patients should receive comprehensive dental care before organ transplant (Rateitschak-Plüss et al. 1983a, b).

254 Mild to Moderate Cyclosporine-induced Gingival Overgrowth This 45-year-old female began taking cyclosporine-A two years previously, following kidney transplantation. The gingival overgrowth is pronounced only in the maxilla; secondary inflammation is in evidence. In order to avoid excessive doses of cyclosporine-A, this medicament is often combined today with azathioprine and/or cortisone.
255 Cyclosporine-A—Structure and Chemical Formula The drug is a cyclic peptide (undecapeptide) consisting of eleven amino acids. It is used to prevent rejection reactions following solid organ and bone marrow trans-plantation. Left: Tolypocladium inflatum is the fungus from which cyclosporine was originally isolated during research on antibiotics. SEM courtesy R. Guggenheim
256 Severe Cyclosporine A-induced Gingival Overgrowth: Overdose Dramatic enlargements such as in this 51-year-old female are infrequently observed today. This patient had received approximately three times the dosage of cyclosporine-A that is common to-day. In addition, the patient exhibited poor oral hygiene. Left: PMN granulocytes and plasma cells are observed histologically in the infiltrated subepithelial connective tissue.

Gingival Hyperplasia Following Combined Drug Therapies

Dihydropyridine and Cyclosporine

When systemic medications are prescribed, every effort should be made to reduce adverse side effects by setting the dose as low as possible. In certain cases, the use of a combination of medications can also serve to reduce the dosage. For example, today, following organ transplantation (kidney, heart etc.), cyclosporine is often combined with azathioprine and prednisone.

On the other hand, the necessary combination of two medications that may both possess the same side effect (e.g., gingival overgrowth) may massively increase the adverse effect.

Therapy: In the case presented here, a 30-year-old male (kidney transplant), cyclosporine was prescribed. This medicament can increase blood pressure, so she was also treated with the calcium-antagonist nifedipine (p. 122). Very severe gingival overgrowth was the consequence of this co-medication. In such cases, alternative antihypertensive medications should be employed.

257 Severe Gingival Overgrowth Simultaneous use of Sandimmune (cyclosporine-A) and Adalat (nifedipine), in conjunction with inadequate oral hygiene, led to severe and secondarily inflamed gingival overgrowth (with formation of pseudopockets) throughout the entire dentition.
258 Following Gingivoplasty in the Maxilla The “contouring” gingivectomy shown here in the maxillary anterior and canine regions was subsequently performed throughout the entire dentition. Unfortunately, no particular efforts were expended to improve the patient’s oral hygiene.
259 Recurrence in the Maxilla Eight months after the surgery, a recurrence of the tissue overgrowth was obvious in the maxilla. This occurred despite changing the patient’s antihypertensive medication to a different class of drugs (beta blocker). The patient’s oral hygiene remains less than optimum. Patients who have undergone a serious medical procedure such as organ transplantation have more important “problems” to deal with than the achievement of “maximal” oral hygiene!

Benign Tumors—Epulis

Gingival epulis represents a family of benign tumors. The classification includes:

  • Granulomatous epulis, pyogenic granuloma

  • Giant cell epulis

  • Fibrous epulis

Giant cell epulis and granulomatous epulis may develop relatively quickly; fibrous epulis grows slowly. The etiology of such tumors is not completely understood, but marginal irritation is one likely cause. Some pathologists contend that giant cell epulis is the only true epulis. It is a fact that no histologic differences exist between fibrous epulis and fibromas in other areas of the oral cavity.

Therapy: Pyogenic granuloma and fibrous epulis can be removed by simple excision.

The giant cell epulis has a tendency to recur; following excision of such tumors, a gingival flap should be reflected, the tooth (and root) surfaces thoroughly cleaned and planed, and the bone filed.

260 Pyogenic Granuloma, Granulomatous Epulis Localized, tumor-like bright red, soft mass on the labial gingival margin in a 34-year-old female. Epulis is usually seen in the papillary region, and less frequently, as in the present case, on the gingival margin. When probed or injured, the lesion exudes a copiousmixture of blood and pus. Left: The histologic view exhibits a loose granulation tissue that is highly vascularized (HE, ×40).
261 Giant Cell Epulis–“True” Epulis Clinically resembling the granulomatous epulis, the giant cell epulis can only be differentiated and diagnosed histologically. Such lesions can become very large and, as in this 50-year-old female, can cause displacement of adjacent teeth. Left: The histologic section reveals an inflammatory infiltrate including multinucleated giant cells in the subepithelial connective tissue (HE, ×400).
262 Fibrous Epulis This 45-year-old female exhibited a localized, fibrous, firm mass upon the gingiva between the central and lateral incisors. The etiology of such lesions can only seldom be ascertained. Left: Histologically one observes an accumulation of fibrous connective tissue. If the mass becomes secondarily inflamed, a typical inflammatory infiltrate can be expected. Courtesy B. Maeglin
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Jul 2, 2020 | Posted by in Dental Hygiene | Comments Off on Oral Pathologic Alterations of Gingiva and Periodontium*
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