Drug-Induced Gingival Overgrowth (DIGO)

What Is Drug-Induced Gingival Overgrowth (DIGO)?

Previously known as drug-induced gingival hyperplasia, this condition is rather an impact or a known side-effect of certain drugs where the gingival tissue is affected as an accidental target when these drug therapies are meant to combat or be used for systemic conditions; hence the gingival enlargement induced would be a side effect of systemic drug therapies. Patients may frequently complain of a firm, painless nodules (because of the overgrowth, they appear as a cosmetic impediment to the patient's smile and expressions) that are persistent as a result of drug therapies. The gingival tissue in the affected region turns bluish red with altered contour and thus requires comprehensive treatment planning by the dentist.

What Is the Etiology of DIGO?

Drug-induced gingival overgrowth is most commonly seen in the group of male children or in adolescent population groups, with the prevalent location being gingival tissue in the anterior region of the jaw. Research suggests that the genotype of the individual may also lay a role in the development of DIGO, which gets aggravated or activated under local irritation or circumstance such as the extent or degree of gingival overgrowth in proportion to drug therapies. Commonly considered side effects from drugs such as Phenytoin, Cyclosporin, and Nifedipine are indicated in the literature as causative drugs for gingival overgrowth, with Phenytoin possessing the highest prevalence among the aforementioned drugs. Research statistics indicate patients on treatment, inclusive of up to 50 % of adults on Phenytoin therapy, experience some forms of gingival enlargement, while those on Cyclosporin report a 30 % incidence and 20 % incidence with Nifedipine.

What Are the Common Causes Of DIGO?

The offending drug classes are primary causatives in developing DIGO and hence can be classified into three major categories of anticonvulsants, immunosuppressants, and calcium channel blockers.

• Anticonvulsant drug examples include PHT, Phenobarbitone, Primidone, etc. These are responsible for localized outgrowths or the formation of gingival tissue overgrowths. In patients with multiple drug therapies, when anticonvulsants or immunosuppressive agents are given together, then the combined effect of drugs acts synergistically, aggravating the condition of DIGO.

• Immunosuppressants like Cyclosporin, Sirolimus, and Tacrolimus are some examples of immunosuppressants related to gingival enlargement. As Cyclosporine remains the most prescribed drug in organ transplant patients, research statistics reveal that the incidence of gingival overgrowth is directly linked to approximately 53 % after transplants.

• Calcium channel blockers are not only commonly indicated for treating hypertension but also in preventing angina pectoris and peripheral cardiovascular disease. Examples of calcium channel blockers are Nifedipine, Amlodipine, Verapamil, Diltiazem, etc. In addition, the incidence of DIGO in long-term use of calcium channel blockers is also linked in these patients.

• The mechanism of action at the cellular level for the mentioned three drug categories is mainly attributed to the inhibition of the cation influx mechanism, particularly the sodium and calcium ions causing an imbalanced oral atmosphere or breaching the immune defense.

• Gingival overgrowth has multifactorial origins, including the accumulation of bacterial plaque that appears to be a significant aggravator for the severity of gingival overgrowth.

• Case reports and evidence document that gingival overgrowth by drugs is proportional to the degree of plaque buildup and plaque-induced inflammatory mediators in the oral cavity, especially in immunocompromised patients or patients with poor oral hygiene.

• Decreased cation-dependent folic acid (FA) active transport within gingival fibroblasts causes reduced FA uptake by the cells, causing changes in the metabolism of matrix metalloproteinases and the inability to activate collagenase. This results in an accumulation of connective tissue and collagen due to a lack of collagenase. Inhibition of the activation of matrix metalloproteinase (MMPS) enzymes alongside inflammatory interleukin 1 or pro-inflammatory cytokines can also result in gingival inflammation and consequent accumulation of extracellular matrix and collagen and cause DIGO.

• The induction of drugs responsible for DIGO act as a trigger for the activation of gingival fibroblasts that proliferate and produce glycosaminoglycans (GAGs) in the connective tissues.

• The concentration of drugs within the crevicular gingival fluid or even the accumulation of bacterial plaque in patients with poor oral hygiene as in epileptics exerts toxic effects on the gingival tissues that pose a clinical challenge to the dentist.

How to Manage DIGO?

• Plaque control is always the first step in the treatment of DIGO as advised by the dental surgeon. For effective plaque control, proper oral hygiene and plaque removal, including surface cleaning or deep scaling followed by regular periodic scaling in the clinic by the dentist is mandatory for reducing physiologic gingival inflammation.

• For control of chronic drug-related inflammation, non-steroidal anti-inflammatory (NSAIDs) agents or antibiotic therapy can be used to control DIGO. If needed, topical antifungal medication like Nystatin can be applied to reduce the risk of infection from gingival inflammation.

• Folate supplementation has also been used in traditional research to curb gingival overgrowth.

• The dentist may also recommend biopsy in moderate to severe cases of drug-induced gingival overgrowth to rule out a differential diagnosis for scurvy, and pseudo enlarged gingival or false enlargement, systemic diseases like gingival enlargement associated with leukemia, hematologic disorders, tuberculosis, sarcoidosis, etc.

• The surgical strategies for DIGO in severe cases, even after no improvement post six months of non-surgical therapy, are gingivectomy and periodontal flap surgical procedure.

• Electrocautery is particularly useful in challenging cases like children and young adults where the gingiva is fragile and has a high bleeding tendency. CO2 laser with the wavelength of 10600 nm is also a laser therapy effective in soft tissue surgery to reduce high water content in gingival overgrowth conditions.

Conclusion:

To conclude, gingival enlargement can persist in patients on drug therapies despite drug substitution and effective plaque control. In such cases, surgical management is needed to restore gingival form and function. The important treatment aspect of DIGO is Regular follow-ups with the dental surgeon with frequent professional cleaning of the teeth coupled with measures of mechanical and chemical plaque control and oral hygiene measures. Correct methods advised by dentists in the clinic like brushing, flossing, interdental aids, and mouth washing can prevent or decrease the rate and the degree to which the condition can recede and also impact the recurrence rate of drug-induced gingival lesions.