- Email: [email protected]
Amlodipine induced gingival enlargement: A case report
i n t e r n a t i o n a l j o u r n a l o f d e n t a l s c i e n c e a n d r e s e a r c h 1 ( 2 0 1 3 ) 6 4 e6 6
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ijdsr
Case Report
Amlodipine induced gingival enlargement: A case report Arti Saluja Sachdev c,*, R. Kamala b, Ankit Saha a, Sudhir Shukla a, Haider Iqbal a, Nitin Agarwal a a
Department of Oral Medicine and Radiology, Sardar Patel Post Graduate Institute of Dental & Medical Sciences, Lucknow, Uttar Pradesh, India b Narsinbhai Patel Dental College and Hospital, Visnagar, Gujarat, India c Career Dental College and Hospital, Lucknow, Uttar Pradesh, India
article info
abstract
Article history:
Gingival enlargement is seen due to a large number of local and systemic factors with
Received 8 May 2013
drugs being one of the common causative factors. Drug induced gingival hyperplasia has
Accepted 14 June 2013
posed a serious concern for both patients and the clinician. A large number of drugs are associated with gingival overgrowths, of which Amlodipine a frequently used antihyper-
Keywords:
tensive is a common offender. Amlodipine is being widely used because of its safety profile
Gingival hyperplasia
and duration of action. Hereby we present a case of 42-year-old hypertensive male patient
Amlodipine
who was taking Amlodipine (5 mg/day, single dose orally) from last three years and pre-
Calcium channel blocker
sented with a generalized diffuse gingival enlargement. This case rightly aims in showing that through altering the drug therapy and maintaining good oral hygiene we can achieve satisfactory clinical response. Copyright ª 2013, International Journal of Dental Science and Research Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
1.
Introduction
Gingival enlargement or Gingival overgrowth (GO) is one of the most important clinical features of gingival pathology.1 Its etiology is multifactorial and is associated with inflammatory changes in the gingiva. Other factors related to this condition are hereditary, malignancies and those resulting from adverse effects associated with systemic administration of certain drugs.2 Medication mainly implicated are the anticonvulsant such as phenytoin for treatment to control seizure disorders in epileptic patient, calcium channel blockers (CCB) such as nifedipine for treatment of hypertension or angina pectoris,
immunosuppressant such as cyclosporine for treatment to prevent rejection in patient receiving organ transplant.3 Amlodipine, a dihydropyridine derivative is a third generation calcium channel blocker, which has shown to have longer action and weaker side effect compared to the first generation such as nifedipine.4 The prevalence of GO in patients taking amlodipine was reported to be 3.3%, which is lower than the rate in patients taking nifedipine 47.8%.5The clinical features of GO usually present as enlarged interdental papillae resulting in a lobulated or nodular morphology.6 The effects are normally limited to the attached and marginal gingivae and more frequently observed anteriorly.7 In this case report, we treated severe GO in patient taking amlodipine for treatment of hypertension. The management
* Corresponding author. Tel.: þ91 9839485139 (mobile). E-mail address: [email protected] (A.S. Sachdev). 2213-9974/$ e see front matter Copyright ª 2013, International Journal of Dental Science and Research Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijdsr.2013.11.001
i n t e r n a t i o n a l j o u r n a l o f d e n t a l s c i e n c e a n d r e s e a r c h 1 ( 2 0 1 3 ) 6 4 e6 6
65
consisted of oral hygiene procedures and alteration in medication.
2.
Case report
A 42-year-old male patient came to the Department of Oral Medicine and Radiology with the complaint of generalized swelling in the gums since 1 month. The patient noticed a nodular enlargement in the upper and lower front region of the gums which gradually progressed to involve whole of the gingiva to attain the present size. The enlargement was associated with discomfort in chewing and bleeding from gums. The patient was a known hypertensive since last 3 years and was taking tablets Amlodipine 5 mg/day. The personal history revealed that he cleaned his teeth once daily with brush and paste, which he discontinued since past 10 days due to enlarged and bleeding gums. Intraoral examination revealed there was generalized massive gingival enlargement, which was more prominent on the labial aspect of maxillary and mandibular teeth (Fig. 1). The interdental papillae were erythematous and lobulated with loss of stippling. On palpation the gingiva was firm and resilient. All the hematological parameters were found to be within normal limits. Orthopantomogram showed generalized bone loss with furcation involvement irt 46 47 (Fig. 2). A non-surgical treatment was planned for the patient. Prophylaxis and root planning was performed. Patient was referred to the physician for drug substitution. The drug was substituted with ACE inhibitor (Ramipril 5 mg, once daily). Patient reported after 1 month with regression in the size of gingival enlargement (Fig. 3).
Fig. 2 e OPG showing generalized bone loss.
“Gingival enlargement or gingival overgrowth” is the preferred term for all medication-related gingival lesions previously termed “gingival hyperplasia” or “gingival hypertrophy”.8 Several factors may lead to gingival enlargement. The factors are age, genetic predisposition, pharmacokinetic variables, and alteration in gingival connective tissue
homeostasis, histopathology, ultra structural factors, inflammatory changes and drug action on growth factors.7 Clinical manifestation of gingival enlargement frequently appears within 1e3 months after initiation of treatment with the associated medication.9 The increase in size is not because the epithelium or the cells within the connective tissue exhibit hyperplasia or hypertrophy but due to an increase in the amount of extracellular matrix, predominantly collagen. Cyclosporine, phenytoin and nifedipine are associated with calcium deregulation, which disrupts the normal collagen phagocytosis and remodeling process, which leads to impaired collagen degradation. There are two pathways suggested for this final outcome, they are inflammatory and noninflammatory pathways. The proposed non inflammatory mechanisms include defective collagenase activity due to decreased uptake of folic acid,10 blockages of aldosterone synthesis in adrenal cortex and consequent feedback increase in ACTH level,11 and upregulation of keratinocyte growth factor (KGF).12 Alternatively, inflammation may develop as a result of direct toxic effects of concentrated drug in crevicular gingival fluid (CGF) and/or bacterial plaques.13 This inflammation could lead to the upregulation of several cytokine factors such as TGF-ß1.14 The treatment is based on the offending medication being used and the clinical presentation. The most effective treatment of drug-induced gingival enlargement is withdrawal of the medication. The clinician should emphasize plaque
Fig. 1 e Intraoral photograph showing generalized gingival enlargement.
Fig. 3 e Intraoral photograph showing gingival regression 1 month after treatment.
3.
Discussion
66
i n t e r n a t i o n a l j o u r n a l o f d e n t a l s c i e n c e a n d r e s e a r c h 1 ( 2 0 1 3 ) 6 4 e6 6
control as part of the treatment strategy. Although the exact role played by plaque in drug-induced gingival enlargement is not proven, however it has been seen that elimination of local factors and maintaining good oral hygiene decrease the degree and severity of the gingival enlargement. Surgical periodontal treatment is commonly performed in severe cases that affect oral hygiene, functionality or for esthetic reasons. In this case patient showed significant reduction in gingival overgrowth after substitution in the medication and oral hygiene procedures (Fig. 3).
4.
Conclusion
This case report presents a clinical picture of a patient with gingival hyperplasia due to continuous use of Amlodipine for three years. Patient responded well to drug withdrawal and oral prophylaxis. As Amlodipine is a commonly prescribed antihypertensive drug every dental practitioner should be aware of this usually overlooked but potentially harmful side effect of generalized gingival enlargement.
Conflicts of interest All authors have none to declare.
references
1. Triveni MG, Rudrakshi C, Mehta DS. Amlodipine-induced gingival overgrowth. J Imdian Soc Periodontol. SepeDec 2009;13(3).
2. Bhatia V, Mittal A, Parida AK, et al. Amlodipine-induced gingival hyperplasia: a rare entity. Int J Cardiol. 2007;122:23e24. 3. Seymour RA, Thomason JM, Ellis JS. The pathogenesis of drug-induced gingival overgrowth. J Clin Periodontol. 1996;23:165e175. 4. Ellis JS, Seymour RA, Thomason JM, Monkman SC, Idle JR. Gingival sequestration of amlodipine and amlodipineinduced gingival overgrowth. Lancet. 1993;341:1102e1103. 5. Nery EB, Edson RG, Lee KK, Pruthi VK, Watson J. Prevalence of nifedipine-induced gingival hyperplasia. J Periodontol. 1995;66:572e578. 6. Hallmon WM, Rossmann JA. The role of drugs in the pathogenesis of gingival overgrowth. A collective review of current concept. Periodontol 2000. 1999;21:176e196. 7. Taib H, Ali TBT, Kamin S. Amlodipine-induced gingival overgrowth: a case report. Arch Orofacial Sci. 2007;2:61e64. 8. Grover Vishaka, Kapoor Anoop, Marya CM. Amlodipine induced gingival hyperplasia. J Oral Health Comm Dent. 2007;1(1):19e22. 9. Meraw SJ, Sheridan PJ. Medically induced gingival hyperlasia. Mayo Clin Proc. 1996;73:1196e1199. 10. Brown RS, Sein P, Corio R, Bottomley WK. Nitrendipineinduced gingival hyperplasia. Oral Surg Oral Med Oral Pathol. 1990;70:593e596. 11. Nyska A, Shemesh M, Tal H, Dayan D. Gingival hyperplasia induced by calcium-channel blockers: mode of action. Med Hypotheses. 1994;43:115e118. 12. Das SJ, Olsen I. Keratinocyte growth factor is upregulated by hyperplasia-inducing drug nifedipine. Cytokine. 2000;12:1566e1569. 13. van der Vleuten CJ, Trijbels-Smeulders MA, van de Kerkhof PC. Telangiectasia and gingival hyperplasia as sideeffects of amlodipine (Norvasc) in a 3-year-old girl. Acta Derm Venereol. 1999;79:323e324. 14. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286e1292.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ijdsr
Case Report
Amlodipine induced gingival enlargement: A case report Arti Saluja Sachdev c,*, R. Kamala b, Ankit Saha a, Sudhir Shukla a, Haider Iqbal a, Nitin Agarwal a a
Department of Oral Medicine and Radiology, Sardar Patel Post Graduate Institute of Dental & Medical Sciences, Lucknow, Uttar Pradesh, India b Narsinbhai Patel Dental College and Hospital, Visnagar, Gujarat, India c Career Dental College and Hospital, Lucknow, Uttar Pradesh, India
article info
abstract
Article history:
Gingival enlargement is seen due to a large number of local and systemic factors with
Received 8 May 2013
drugs being one of the common causative factors. Drug induced gingival hyperplasia has
Accepted 14 June 2013
posed a serious concern for both patients and the clinician. A large number of drugs are associated with gingival overgrowths, of which Amlodipine a frequently used antihyper-
Keywords:
tensive is a common offender. Amlodipine is being widely used because of its safety profile
Gingival hyperplasia
and duration of action. Hereby we present a case of 42-year-old hypertensive male patient
Amlodipine
who was taking Amlodipine (5 mg/day, single dose orally) from last three years and pre-
Calcium channel blocker
sented with a generalized diffuse gingival enlargement. This case rightly aims in showing that through altering the drug therapy and maintaining good oral hygiene we can achieve satisfactory clinical response. Copyright ª 2013, International Journal of Dental Science and Research Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
1.
Introduction
Gingival enlargement or Gingival overgrowth (GO) is one of the most important clinical features of gingival pathology.1 Its etiology is multifactorial and is associated with inflammatory changes in the gingiva. Other factors related to this condition are hereditary, malignancies and those resulting from adverse effects associated with systemic administration of certain drugs.2 Medication mainly implicated are the anticonvulsant such as phenytoin for treatment to control seizure disorders in epileptic patient, calcium channel blockers (CCB) such as nifedipine for treatment of hypertension or angina pectoris,
immunosuppressant such as cyclosporine for treatment to prevent rejection in patient receiving organ transplant.3 Amlodipine, a dihydropyridine derivative is a third generation calcium channel blocker, which has shown to have longer action and weaker side effect compared to the first generation such as nifedipine.4 The prevalence of GO in patients taking amlodipine was reported to be 3.3%, which is lower than the rate in patients taking nifedipine 47.8%.5The clinical features of GO usually present as enlarged interdental papillae resulting in a lobulated or nodular morphology.6 The effects are normally limited to the attached and marginal gingivae and more frequently observed anteriorly.7 In this case report, we treated severe GO in patient taking amlodipine for treatment of hypertension. The management
* Corresponding author. Tel.: þ91 9839485139 (mobile). E-mail address: [email protected] (A.S. Sachdev). 2213-9974/$ e see front matter Copyright ª 2013, International Journal of Dental Science and Research Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijdsr.2013.11.001
i n t e r n a t i o n a l j o u r n a l o f d e n t a l s c i e n c e a n d r e s e a r c h 1 ( 2 0 1 3 ) 6 4 e6 6
65
consisted of oral hygiene procedures and alteration in medication.
2.
Case report
A 42-year-old male patient came to the Department of Oral Medicine and Radiology with the complaint of generalized swelling in the gums since 1 month. The patient noticed a nodular enlargement in the upper and lower front region of the gums which gradually progressed to involve whole of the gingiva to attain the present size. The enlargement was associated with discomfort in chewing and bleeding from gums. The patient was a known hypertensive since last 3 years and was taking tablets Amlodipine 5 mg/day. The personal history revealed that he cleaned his teeth once daily with brush and paste, which he discontinued since past 10 days due to enlarged and bleeding gums. Intraoral examination revealed there was generalized massive gingival enlargement, which was more prominent on the labial aspect of maxillary and mandibular teeth (Fig. 1). The interdental papillae were erythematous and lobulated with loss of stippling. On palpation the gingiva was firm and resilient. All the hematological parameters were found to be within normal limits. Orthopantomogram showed generalized bone loss with furcation involvement irt 46 47 (Fig. 2). A non-surgical treatment was planned for the patient. Prophylaxis and root planning was performed. Patient was referred to the physician for drug substitution. The drug was substituted with ACE inhibitor (Ramipril 5 mg, once daily). Patient reported after 1 month with regression in the size of gingival enlargement (Fig. 3).
Fig. 2 e OPG showing generalized bone loss.
“Gingival enlargement or gingival overgrowth” is the preferred term for all medication-related gingival lesions previously termed “gingival hyperplasia” or “gingival hypertrophy”.8 Several factors may lead to gingival enlargement. The factors are age, genetic predisposition, pharmacokinetic variables, and alteration in gingival connective tissue
homeostasis, histopathology, ultra structural factors, inflammatory changes and drug action on growth factors.7 Clinical manifestation of gingival enlargement frequently appears within 1e3 months after initiation of treatment with the associated medication.9 The increase in size is not because the epithelium or the cells within the connective tissue exhibit hyperplasia or hypertrophy but due to an increase in the amount of extracellular matrix, predominantly collagen. Cyclosporine, phenytoin and nifedipine are associated with calcium deregulation, which disrupts the normal collagen phagocytosis and remodeling process, which leads to impaired collagen degradation. There are two pathways suggested for this final outcome, they are inflammatory and noninflammatory pathways. The proposed non inflammatory mechanisms include defective collagenase activity due to decreased uptake of folic acid,10 blockages of aldosterone synthesis in adrenal cortex and consequent feedback increase in ACTH level,11 and upregulation of keratinocyte growth factor (KGF).12 Alternatively, inflammation may develop as a result of direct toxic effects of concentrated drug in crevicular gingival fluid (CGF) and/or bacterial plaques.13 This inflammation could lead to the upregulation of several cytokine factors such as TGF-ß1.14 The treatment is based on the offending medication being used and the clinical presentation. The most effective treatment of drug-induced gingival enlargement is withdrawal of the medication. The clinician should emphasize plaque
Fig. 1 e Intraoral photograph showing generalized gingival enlargement.
Fig. 3 e Intraoral photograph showing gingival regression 1 month after treatment.
3.
Discussion
66
i n t e r n a t i o n a l j o u r n a l o f d e n t a l s c i e n c e a n d r e s e a r c h 1 ( 2 0 1 3 ) 6 4 e6 6
control as part of the treatment strategy. Although the exact role played by plaque in drug-induced gingival enlargement is not proven, however it has been seen that elimination of local factors and maintaining good oral hygiene decrease the degree and severity of the gingival enlargement. Surgical periodontal treatment is commonly performed in severe cases that affect oral hygiene, functionality or for esthetic reasons. In this case patient showed significant reduction in gingival overgrowth after substitution in the medication and oral hygiene procedures (Fig. 3).
4.
Conclusion
This case report presents a clinical picture of a patient with gingival hyperplasia due to continuous use of Amlodipine for three years. Patient responded well to drug withdrawal and oral prophylaxis. As Amlodipine is a commonly prescribed antihypertensive drug every dental practitioner should be aware of this usually overlooked but potentially harmful side effect of generalized gingival enlargement.
Conflicts of interest All authors have none to declare.
references
1. Triveni MG, Rudrakshi C, Mehta DS. Amlodipine-induced gingival overgrowth. J Imdian Soc Periodontol. SepeDec 2009;13(3).
2. Bhatia V, Mittal A, Parida AK, et al. Amlodipine-induced gingival hyperplasia: a rare entity. Int J Cardiol. 2007;122:23e24. 3. Seymour RA, Thomason JM, Ellis JS. The pathogenesis of drug-induced gingival overgrowth. J Clin Periodontol. 1996;23:165e175. 4. Ellis JS, Seymour RA, Thomason JM, Monkman SC, Idle JR. Gingival sequestration of amlodipine and amlodipineinduced gingival overgrowth. Lancet. 1993;341:1102e1103. 5. Nery EB, Edson RG, Lee KK, Pruthi VK, Watson J. Prevalence of nifedipine-induced gingival hyperplasia. J Periodontol. 1995;66:572e578. 6. Hallmon WM, Rossmann JA. The role of drugs in the pathogenesis of gingival overgrowth. A collective review of current concept. Periodontol 2000. 1999;21:176e196. 7. Taib H, Ali TBT, Kamin S. Amlodipine-induced gingival overgrowth: a case report. Arch Orofacial Sci. 2007;2:61e64. 8. Grover Vishaka, Kapoor Anoop, Marya CM. Amlodipine induced gingival hyperplasia. J Oral Health Comm Dent. 2007;1(1):19e22. 9. Meraw SJ, Sheridan PJ. Medically induced gingival hyperlasia. Mayo Clin Proc. 1996;73:1196e1199. 10. Brown RS, Sein P, Corio R, Bottomley WK. Nitrendipineinduced gingival hyperplasia. Oral Surg Oral Med Oral Pathol. 1990;70:593e596. 11. Nyska A, Shemesh M, Tal H, Dayan D. Gingival hyperplasia induced by calcium-channel blockers: mode of action. Med Hypotheses. 1994;43:115e118. 12. Das SJ, Olsen I. Keratinocyte growth factor is upregulated by hyperplasia-inducing drug nifedipine. Cytokine. 2000;12:1566e1569. 13. van der Vleuten CJ, Trijbels-Smeulders MA, van de Kerkhof PC. Telangiectasia and gingival hyperplasia as sideeffects of amlodipine (Norvasc) in a 3-year-old girl. Acta Derm Venereol. 1999;79:323e324. 14. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286e1292.