Drug-influenced gingival enlargement (DIGE) among hypertensive patients is commonly associated with antihypertensive drugs such as calcium channel blockers (CCBs). Immune response alteration is one of the proposed mechanisms for DIGE. Immunoglobulin A (IgA) in saliva which involves in defense mechanism was shown to be affected in patients with DIGE. Objective: This study aimed to determine the association of salivary IgA level with DIGE. Methods: This cross-sectional study comprised 47 hypertensive patients who had consumed antihypertensive drugs for at least 3 months. Twenty-one (44.7%) males and 26 (55.3%) females had participated in this study. Data was analyzed using SPSS version 26.0. The p-value of less than 0.05 at a 95% confidence interval is considered statistically significant. Results: Eighty-three percent and 17.0% of hypertensive patients were on CCBs and non- CCBs respectively. Amlodipine was found to be the most common (55.3%) antihypertensive drug consumed. Twenty- one (44.7%) patients presented with DIGE. The salivary IgA level was significantly decreased (p=0.03) among hypertensive patients with DIGE [Median 4.9 ng/mL (IQR 5.268)] compared to those without DIGE [median 15.03 ng/mL (IQR 32.246)]. Conclusion: This data indicates the level of salivary IgA was significantly affected in patients with DIGE which may compromise the defense mechanism of saliva.


  1. Safari-Faramani R, Rajati F, Tavakol K, et al. Prevalence, awareness, treatment, control, and the associated factors of diabetes in an Iranian Kurdish population. J Diabetes Res 2019;2019:5869206.
  2. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Executive summary: A report of the American College of Cardiology/ American Heart Association Task Force on clinical practice guidelines. Hypertension 2018;71:1269- 324.
  3. Brown RS, Arany PR. Mechanism of drug-induced gingival overgrowth revisited: A unifying hypothesis. Oral Dis 2015;21:e51-61.
  4. Madi M, Shetty SR, Babu SG, Achalli S. Amlodipine-induced gingival hyperplasia - A case report and review. West Indian Med J 2015;64:279-82.
  5. Könönen E, Gursoy M, Gursoy UK. Periodontitis: A multifaceted disease of tooth-supporting tissues. J Clin Med 2019;8.
  6. Abushama AA, Ramadan AM. Transforming growth factor-β profile in cyclosporine-A induced gingival enlargement in renal transplant patients. Saudi Dent J 2021;33:85-9.
  7. Lauritano D, Martinelli M, Baj A, et al. Drug-induced gingival hyperplasia: An in vitro study using amlodipine and human gingival fibroblasts. Int J Immunopathol Pharmacol 2019;33:2058738419827746.
  8. Tungare S, Paranjpe AG. Drug induced gingival overgrowth. In: StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC., 2022.
  9. Gopal S, Joseph R, Santhosh VC, Kumar VVH, Joseph S, Shete AR. Prevalence of gingival overgrowth induced by antihypertensive drugs: A hospital-based study. J Indian Society Periodontol. 2015;19:308.
  10. Aryal D, Shahi K, Shrestha SM. Amlodipine induced gingival overgrowth. J Nepalese Society Periodontol Oral Implantology. 2018;2:30-2.
  11. Ramírez-Rámiz A, Brunet-LLobet L, Lahor-Soler E, Miranda-Rius J. On the cellular and molecular mechanisms of drug-induced gingival overgrowth. The Open Dent J. 2017;11:420.
  12. Lauritano D, Moreo G, Vella FD, Palmieri A, Carinci F, Petruzzi M. Biology of drug-induced gingival hyperplasia: In vitro study of the fffect of nifedipine on human fibroblasts. Appl Sci. 2021;11:3287.
  13. Pooja S, Varghese S. Gingival crevicular fluid level of interleukin 1 in chronic periodontitis with diabetes mellitus. Drug Invention Today. 2019;12.
  14. Maity PC, Datta M, Nicolò A, Jumaa H. Isotype specific assembly of B cell antigen receptors and synergism with chemokine receptor CXCR4. Frontiers in Immunology. 2018:2988.
  15. Dewi SRP, Lutfi AB, Veronita V, et al. Perbandingan efektivitas berbagai obat kumur terhadap kadar Imunoglobulin A pada saliva penderita karies Comparison of mouthwashes effectiveness to the level of salivary immunoglobulin A in caries patients. Jurnal Kedokteran Gigi Universitas Padjadjaran. 2018;30:138-45.
  16. Lauritano D, Moreo G, Limongelli L, Tregambi E, Palmieri A, Carinci F. Drug-induced gingival overgrowth: a pilot study on the effect of diphenylhydantoin and gabapentin on human gingival fibroblasts. Int J Environ Res Public Health. 2020;17:8229.
  17. Nayyar AS, Khan M, Subhas G, Nataraju B, KR V, BM R. Gingival enlargement in epileptic patients on phenytoin therapy-An evidence based approach. J Neurol Neurophysiol. 2012;3:1000127.
  18. Nayyar A. Phenytoin and gingival enlargement: A brief overview of etiopathogenesis. Int J Health Sci Res. 2012;2:127-34.
  19. Ya z d a n i R , A z i z i G , A b o l h a s s a n i H , Aghamohammadi A. Selective IgA deficiency: Epidemiology, pathogenesis, clinical phenotype, d ia g no si s , p r og no si s a nd m a n a ge me nt . Scandinavian J Immunol. 2017;85:3-12.
  20. Lin K, Guilhoto LM, Yacubian EMT. Drug-induced gingival enlargement-Part II. Antiepileptic drugs: not only phenytoin is involved. J Epilepsy Clinical Neurophysiol. 2007;13:83-8.
  21. Tonsekar P, Tonsekar V. Calcium-channel-blocker-influenced gingival enlargement: A Conundrum Demystified. Oral 2021;1:236-49.
  22. Ebersole JL, Hamzeh R, Nguyen L, Al-Sabbagh M, Dawson III D. Variations in IgG antibody subclass responses to oral bacteria: Effects of periodontal disease and modifying factors. J Periodontal Res. 2021;56:863-76.
  23. Taib H, Mohd Radzwan MH, Sabaruddin MA, Wan Mohamad WM, Mohamad N. Prevalence and risk factors of drug-induced gingival overgrowth in hypertensive patients. J Dent Indones. 2021;28:8- 14.
  24. Vidal F, de Souza RC, Ferreira DdC, Fischer RG, Gonçalves LS. Influence of 3 calcium channel blockers on gingival overgrowth in a population of severe refractory hypertensive patients. J Periodontal Res. 2018;53:721-6.
  25. Sabarudin MA, Taib H. Drug-influenced gingival enlargement: Overview of the clinical features and assessment methods. J Dent. 2019;7:1-7.
  26. Brandtzaeg P. Secretory immunity with special reference to the oral cavity. J Oral Microbiol. 2013;5:20401.
  27. Genco RJ, Mashimo PA, Krygier G, Ellison SA. Antibody-mediated effects on the periodontium. J Periodontol. 974;45:330-37.
  28. Setterstrom JA, Gross A, D›Alessandro SM, Godat RF. Concentrations of immunoglobulins in dilantin-induced and idiopathic gingival hyperplastic tissues. J Periodontol. 1980;51:25-9.
  29. Vezzani A, Fujinami RS, White HS, et al. Infections, inf lammation and epilepsy. Acta Neuropathologica 2016;131:211-34.
  30. Li Y, Jin L, Chen T. The effects of secretory IgA in the mucosal immune system. BioMed Res Int. 2020;2020.
  31. Asano T, Kaneko H, Terada T, et al. Molecular analysis of B-cell differentiation in selective or partial IgA deficiency. Clin Exp Immunol. 2004;136:284-90.
  32. Trackman P, Kantarci A. Connective tissue metabolism and gingival overgrowth. Crit Rev Oral Biol Med. 2004;15:165-75.
  33. Fu M, Peng D, Lan T, Wei Y, Wei X. Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases. Acta Pharmaceutica Sinica B 2022.



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