Drug-Induced Gingival Hyperplasia

About

Drug-induced gingival hyperplasia, also referred to as drug-induced gingival overgrowth or enlargement, is a frequent side effect associated with certain medications that impact the gums, leading to abnormal enlargement. This condition arises from adverse reactions to drugs, resulting in hypertrophy or swelling of the gingiva (gums), which can hinder proper oral hygiene, cause discomfort, and create both functional and aesthetic issues. While not the intended outcome of these medications, gingival hyperplasia can become serious if not addressed, as it may disrupt chewing, speaking, and dental care(1^✔ ✔Trusted Source
Drug-Induced Gingival Overgrowth

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Drugs Associated with Gingival Hyperplasia

Drug-induced gingival hyperplasia usually arises from the use of certain medications. The main drug classes involved in this condition are anticonvulsants, immunosuppressants, and calcium channel blockers.

Anticonvulsants: Phenytoin is the most frequently associated medication in this category. Other drugs such as sodium valproate, phenobarbitone, vigabatrin, primidone, mephenytoin, and ethosuximide are also linked to gingival overgrowth. These medications, particularly phenytoin, can lead to abnormal proliferation of gingival fibroblasts, resulting in excessive collagen production in the gums. The precise mechanism involves a complex interaction between the drug's metabolic byproducts and gingival tissue, which triggers cell proliferation and inflammation.

Immunosuppressants: Medications like cyclosporine, tacrolimus, and sirolimus, often used after organ transplants, are well recognized for causing gingival hyperplasia. Cyclosporine, in particular, has been associated with gingival overgrowth in as many as 53% of renal transplant patients. The underlying process involves the drug's interference with collagen metabolism and its impact on gingival fibroblasts, leading to collagen accumulation and tissue enlargement.

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Calcium Channel Blockers (CCBs): These medications are primarily prescribed for hypertension and angina. Nifedipine, amlodipine, verapamil, and diltiazem are commonly linked to gingival hyperplasia. CCBs promote gingival overgrowth by affecting calcium influx into gingival cells, which results in fibroblast proliferation and excessive collagen production.

Other drugs that may cause gingival hyperplasia include topiramate, lamotrigine, ethosuximide, primidone, and phenobarbitone.

Pathophysiology of Drug-Induced Gingival Hyperplasia

The development of gingival hyperplasia involves several important biological processes:(3^✔ ✔Trusted Source
Medically Induced Gingival Hyperplasia

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Fibroblast Proliferation: Medications such as phenytoin, cyclosporine, and calcium channel blockers encourage the growth of gingival fibroblasts. These cells are crucial for producing collagen, the primary structural protein found in the gums. When collagen is overproduced, it leads to swelling and enlargement of the tissue.

Collagen Accumulation: These drugs disrupt the normal turnover of collagen in the gingival tissue, causing an excess buildup that results in gingival hypertrophy.

Inflammatory Response: Inflammation can arise as a secondary effect due to plaque buildup, inadequate oral hygiene, or bacterial infections. This inflammation can worsen the extent of gingival overgrowth.

Genetic Predisposition: Genetic factors significantly influence an individual's likelihood of developing gingival hyperplasia. Those with a family history of the condition may be at a higher risk.

Impaired Immune Response: Immunosuppressant medications like cyclosporine can modify immune function, leading to an exaggerated inflammatory response in the gums, which further encourages tissue overgrowth.

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Symptoms of Drug-Induced Gingival Hyperplasia

The main symptoms include:

• Painless Gingival Enlargement: In the early stages, the gums typically become firm and painless, often starting at the interdental papilla and extending to the facial and lingual gingival margins.
• Redness and Inflammation: If secondary inflammation occurs, the gums may look red, swollen, and feel tender.
• Bleeding: The gums can bleed easily, particularly during brushing or flossing.
• Plaque Accumulation: Gingival overgrowth can hinder proper oral hygiene, resulting in plaque and bacteria buildup.
• Difficulty Chewing: Significant gingival enlargement can lead to functional issues, such as trouble chewing and discomfort while eating.
• Cosmetic Concerns: The appearance of the gums may be affected, causing the patient to feel self-conscious or embarrassed.

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Treatment and Management of Drug-Induced Gingival Hyperplasia

The treatment for drug-induced gingival hyperplasia focuses on relieving symptoms, restoring oral function, and enhancing the aesthetic appearance of the gums. Management includes both medical and surgical methods.

Medical Management:

• Plaque Control: The initial approach to managing gingival hyperplasia involves enhancing oral hygiene practices. Consistent brushing and flossing can help eliminate plaque, which in turn reduces inflammation and helps prevent further tissue growth.
• Discontinuing or Substituting the Offending Drug: If feasible, stopping the medication responsible for the condition is crucial. However, if discontinuation isn't an option due to the drug's importance in treating the patient's condition, the physician may suggest an alternative medication that poses a lower risk of causing gingival enlargement. For instance, tacrolimus can be used instead of cyclosporine, as it has a reduced likelihood of leading to gingival overgrowth(2^✔ ✔Trusted Source
  Pathogenesis of drug-induced gingival overgrowth. A review of studies in the rat model
  
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• Azithromycin: Azithromycin has demonstrated effectiveness in decreasing gingival overgrowth caused by cyclosporine, without impacting cyclosporine levels or kidney function. It works by inhibiting the proliferation of fibroblasts and the production of collagen in the gums.
• Anti-Inflammatory Treatment: Non-steroidal anti-inflammatory drugs (NSAIDs) may be recommended to alleviate inflammation and discomfort. Additionally, topical corticosteroids can be applied to address localized inflammation.

Surgical Management:

Gingivectomy: In cases where medical management is ineffective, surgical intervention may be required. Gingivectomy entails the removal of excess gingival tissue. This procedure is generally conducted under local anesthesia.

Periodontal Flap Surgery: This method involves lifting the gum tissue to facilitate deeper cleaning of the tooth roots and the removal of inflamed tissues.

Laser Surgery: Utilizing lasers, particularly carbon dioxide (CO2) lasers, offers a minimally invasive approach to eliminating gingival overgrowth. Lasers provide benefits such as less bleeding, faster healing, and a lower risk of infection.

Electrosurgery: For situations where the gingiva is delicate or in younger patients, electrosurgery might be the preferred option. This technique employs electric current to eliminate the excess tissue.

Follow-up and Recurrence:

Recurrence of gingival overgrowth is common if the causative medication is not modified. Recurrence is frequent, necessitating long-term monitoring. Surgical interventions may need to be repeated periodically, typically every 6 to 12 months, based on the severity of the condition.

Prevention of Drug-Induced Gingival Hyperplasia

To reduce the risk of gingival hyperplasia, patients should:

• Keep up with excellent oral hygiene.
• Schedule regular dental visits for professional cleanings and check-ups.
• Discuss any medications that may cause oral side effects with their healthcare providers.

Differential Diagnosis of Drug-Induced Gingival Hyperplasia

It's important to distinguish drug-induced gingival enlargement from other conditions that can lead to similar symptoms, such as:

• Pseudo-enlargement: This occurs due to underlying bony tissue enlargement rather than true gingival overgrowth.
• Inflammation: Conditions like chronic gingivitis or periodontitis can present similar symptoms, typically involving red, bleeding, and painful gums.
• Hereditary Gingival Hyperplasia: A rare genetic condition that results in diffuse gingival overgrowth.
• Systemic Conditions: Diseases such as leukemia, sarcoidosis, or vitamin deficiencies (like scurvy) can also lead to gingival enlargement.

While drug-induced gingival hyperplasia is a manageable issue, it requires prompt identification and intervention. By stopping the offending medication, managing plaque, and considering surgical options for severe cases, most patients can see significant improvement. Dental professionals are vital in diagnosing, managing, and preventing the recurrence of this condition. Open communication among patients, dentists, and healthcare providers is essential for addressing the underlying cause of DIGO while ensuring the patient's overall health and comfort.