The multifactorial aetiology of gingival overgrowth: a case report illustrating diagnosis and management

Case report

A 28-year-old male patient was referred to the Restorative Dentistry department for management of his drug-influenced gingival overgrowth. His presenting complaint was of a 12-month history of red, tender, overgrown gingivae that bled on brushing. The gingival overgrowth had become progressively worse over the past year, despite there being no recent changes to his medication. This caused both aesthetic concerns and difficulty with toothbrushing. The patient had an irregular dental attendance history and his typical oral hygiene regimen comprised brushing once a day with a manual toothbrush. The patient was a non-smoker and admitted to having a diet deficient in both fruit and vegetables. The patient's medical history included end stage renal failure secondary to renal dysplasia, which had been successfully treated by a deceased donor transplant in 2007. Polypharmacy was noted and his immunosuppressive strategy comprised tacrolimus 2mg BD, prednisolone 5mg OD and mycophenolate mofetil 750mg BD, as well as amlodipine 10 mg OD for the management of his blood pressure.

Clinical examination revealed a generalized moderate to extensive gingival overgrowth (Figure 1). This was particularly pronounced in the lower right quadrant where the overgrowth extended onto the coronal two thirds of the teeth. The gingivae demonstrated a red, shiny appearance with profuse bleeding on probing. There were significant deposits of supra- and subgingival calculus and generalized 4–13 mm of periodontal pocketing. Six-point pocket charts were completed which revealed that 82% of sites had pocket probing depths ≥4 mm, 100% of sites had bleeding on probing and the pre-operative plaque score was 69%. Radiographic examination revealed generalized 10–20% horizontal bone loss with over 30% bone loss around the maxillary molars (Figure 2).

Additional investigations included a full blood count (FBC), haematinics, HbA1c and plasma vitamin C levels, which had been previously requested by Oral Medicine colleagues. The haematinics and HbA1c were normal. The FBC showed some abnormalities (Hb 116g/L (135-180), neutrophilia 11.28 x 10*9/L (2.00–7.50) and lymphopenia 0.79 x 10*9/L (1.00-4.50). There had been some variation in these parameters over time which were most likely due to the patient's renal condition and immunosuppression. His plasma vitamin C levels were ‹3 µmol/L (26.1–84.6).

The following diagnoses were made: generalized severe gingival overgrowth of a multifactorial aetiology (drug-influenced, poor oral hygiene and associated vitamin C deficiency), as well as generalized mild-moderate chronic periodontitis (which would now be diagnosed as generalized periodontitis; stage III, grade C; currently unstable). Management consisted of extensive oral hygiene instruction, the response to which was monitored throughout. Two courses of non-surgical periodontal therapy were provided comprising root surface debridement under local anaesthetic on a quadrant by quadrant basis over four appointments. Ascorbic acid supplementation was also requested by Oral Medicine colleagues.

Upon review, there had been a significant reduction in the gingival overgrowth and the gingivae were generally paler and firmer, with a generalized reduction in bleeding on probing and pocket probing depths (Figure 3). The 6-point pocket charts revealed that the proportions of sites with pockets ≥6 mm had reduced to 23%. The patient's level of oral hygiene had relapsed as the plaque score was 50%. Minor areas of mild gingival overgrowth remained in areas that the patient found challenging to maintain due to the malpositioning of particular teeth. Periodontal surgery was considered in localized sites to recontour the gingivae. However, this was declined by the patient on the basis that his functional and aesthetic concerns had been addressed.

The patient subsequently entered a maintenance phase of periodontal therapy which included the involvement of oral health educators to reinforce oral hygiene messages and a further course of root surface debridement within the secondary care setting. Debridement of residual pockets was provided on a half mouth basis over two appointments. This aimed to achieve further reduction in plaque scores and probing depths and allowed an assessment to be made regarding the stability of his gingival overgrowth. Long-term management will be undertaken by the patient's general dental practitioner (GDP) through ongoing reinforcement of oral hygiene advice and debridement of residual pockets.

Discussion and Conclusions

Gingival overgrowth can have a variety of underlying causes, including chronic inflammation, systemic medications, granulomatous diseases, vitamin deficiency, haematological diseases and genetic conditions.¹ Determining the aetiology of gingival overgrowth will therefore be aided by obtaining a thorough history comprising the relevant details from the patient's medical, social, family and dietary history (Table 2). In this case, the main contributing factors included the patient's systemic medications (amlodipine, tacrolimus and mycophenolate mofetil), poor oral hygiene maintenance and a vitamin C deficiency.

Drug-influenced gingival overgrowth (DIGO) can occur as a recognized side-effect of calcineurin inhibitors (eg cyclosporin and tacrolimus), immunosuppressants (eg azathioprine and mycophenolate mofetil), anti-convulsants (eg phenytoin) and calcium channel blocking agents (eg amlodipine and nifedipine).⁹ Immunosuppressive drug regimens for renal transplant patients often consist of multiple therapeutic agents to reduce the risk of rejection, as well as calcium channel blocking agents to control hypertension.⁷

There is a wide variation in the reporting of the prevalence of DIGO with different medications and with renal transplant patients.^7,18 Not all patients develop DIGO and it appears that there is a minimal threshold plasma level below which it is unlikely to occur.⁶ The reported prevalence of DIGO is around 50% with phenytoin, 30% with cyclosporin, 5–85% with nifedipine and <5% with amlodipine, although these values should be interpreted with caution due to variation in study designs and the populations evaluated.^{6, 18} Approximately 30% (range 20–80%) of dentate adult transplant patients develop DIGO,⁷ although this may reduce with increasing prescription of alternative immunosuppressants (eg tacrolimus).^1,6 It has been suggested that the extent of DIGO may be related to factors such as the drug dose, duration, level of oral hygiene,¹⁹ existing periodontal disease and genetic susceptibility.⁷ Additionally, the combination of different drugs prescribed may have a positive or negative effect on DIGO severity, eg increased dosage of prednisolone may be associated with reduced DIGO severity in adult patients taking cyclosporin.⁷ Determining the exact relationship between plaque and DIGO has been problematic as there is a bidirectional relationship whereby bacterial deposits will influence gingival inflammation and the presence of DIGO will impair oral hygiene.⁷

Scurvy is a multi-system disease caused by prolonged vitamin C (or ascorbic acid) deficiency. Vitamin C is typically found in fruit, vegetables and organ meats. A nutritional intake of 40 mg has been recommended for adults (approximately half an orange), although lower doses may still prevent scurvy.^20,21 Vitamin C deficiency can lead to capillary haemorrhages, defective growth of fibroblasts, osteoblasts and odontoblasts, and impaired collagen, osteoid and dentine synthesis.²¹ The main criteria for diagnosing scurvy are outlined in Table 3.²¹

It is generally thought that scurvy is an uncommon disease, however, a number of case reports and studies suggest that vitamin C deficiency is still present in developed nations. Populations at-risk include older adults, chronic alcoholics and patients with restrictive diets, cancer, malabsorption or those undergoing renal dialysis.²² There may also be an increased prevalence in low income households,²³ and with the homeless.²⁴ Early symptoms of latent scurvy include lassitude, weakness, irritability, vague muscular or joint aches, and weight loss.²¹ Oral involvement in scurvy is characterized by haemorrhagic gingivitis, especially at the interdental papillae,²¹ with gingival overgrowth described as a rarer manifestation.¹⁶ Vitamin C deficiencies may be overlooked due to the presumed uncommon nature of the disease and misdiagnosed due to non-specific systemic symptoms which may mimic other conditions, eg vasculitis, rheumatic disorders or reduced lung function.^25,26 Gingival overgrowth or other oral signs may therefore be the presenting feature which leads to a diagnosis of vitamin C deficiency.^15,16 Dental practitioners should be aware of this as a potential aetiological factor in at-risk groups.

The effective management of gingival overgrowth will depend upon the correct diagnosis of underlying aetiological factors.²⁷ The initial cause-related therapy will vary on an individual basis and may require involvement from different medical and dental professionals. The role of GDPs will involve motivating patients to change lifestyle, dietary and oral hygiene habits, as well as the provision of non-surgical periodontal therapy. Medical professionals will aid the correction of any underlying vitamin C deficiency and they may also offer advice regarding the possibility of altering a patient's drug regimen. In the longer term, periodontal surgery may be considered to resect or recontour the gingivae. However, in this case, the initial cause-related therapy achieved a satisfactory resolution of the gingival overgrowth and resolved the patient's functional and aesthetic concerns. The patient entered a maintenance phase of periodontal therapy comprising further debridement of residual pockets on a three-monthly basis and a focus on maintaining life-long lifestyle changes.

In conclusion, this case serves as a useful reminder of the importance of a detailed history and examination to enable all the underlying aetiological factors to be correctly identified. The patient was prescribed multiple therapeutic agents which could impact on the development of DIGO, as well as having poor oral hygiene and a diet deficient in vitamin C. Despite the severity of his gingival overgrowth, relatively straightforward cause-related therapy comprising oral hygiene instruction, non-surgical periodontal therapy, and correction of the underlying vitamin C deficiency was sufficient to achieve satisfactory resolution of the patient's aesthetic and functional concerns and offer a substantial benefit to the patient's quality of life.