A comprehensive view of the etiology of ChRAS, taking into account potential risk factors
Literature review
DOI:
https://doi.org/10.11603/2311-9624.2023.4.14500Keywords:
oral mucosa, chronic recurrent aphthous stomatitis, risk factors, genetic predisposition, vitamin deficiencyAbstract
Summary. Chronic recurrent aphthous stomatitis (ChRAS) is currently one of the most common diseases affecting the oral mucosa, affecting 5 to 66 % of the population in different countries worldwide. The pathogenesis of ChRAS is unknown, and it is considered a multifactorial disease associated with local and systemic factors. Further research can be valuable for the prevention and treatment of ChRAS.
The aim of the study – to analyze data from scientific literature sources regarding potential risk factors, mechanisms of pathogenesis, including the immune response of mucous membranes and mechanisms of its modification to optimize the diagnosis and treatment of ChRAS.
Materials and Methods. The bibliosemantic method was applied to clarify the state of the problem, study the analysis of results of previous scientific research based on literature sources and electronic resources.
Results and Discussion. Clinical characteristics of ChRAS are well-defined, but its etiology and pathogenesis remain unresolved. The comprehensive investigation of the occurrence and recurrence of the disease is crucial for understanding the fundamental pathogenetic links, which would be valuable for the prevention and treatment of ChRAS. Potential risk factors for ChRAS, such as a family history, psychological stress, hormonal changes, food allergies, nutritional deficiencies, vitamins and minerals deficiencies, gastrointestinal disorders, certain viral and bacterial infections, medication use, and mechanical trauma to the oral mucosa, are reported. Genetic predisposition and genetic risk factors altering individual susceptibility to ChRAS play a significant role. Various DNA polymorphisms, widespread throughout the human genome, especially those associated with changes in interleukin metabolism, are involved. The unbalanced composition of the oral microbiota may play a key role, although no specific causative agents have been conclusively proven. Food markers related to vitamin and micro- and macroelement deficiencies are also reported, and these are more common in patients with ChRAS. These findings preliminarily explain the main mechanisms through which the oral mucosa is a potential high-risk site for ChRAS, providing evidence for future prevention and treatment strategies.
Conclusions. The results of the processed literature sources show that ChRAS is considered a multifactorial disease, but little is known about the mechanisms of pathogenesis and the possibilities of influencing its main links. Therefore, a comprehensive approach and the development and organization of complex rehabilitation plans are extremely important and decisive for assessing the condition of patients suffering from ChRAS.
References
Sánchez-Bernal, J., Conejero, C., & Conejero, R. (2020). Recurrent Aphthous Stomatitis. Actas Dermosifiliogr (Engl Ed), 111(6), 471-480. DOI: https://doi.org/10.1016/j.adengl.2019.09.006
DOI: 10.1016/j.ad.2019.09.004.
Staines, K., & Greenwood, M. (2015). Aphthous ulcers (recurrent). BMJ Clin. Evid., 26, 1303. PMID: 25720501.
Barrons, R.W. (2001). Treatment strategies for recurrent oral aphthous ulcers. Am. J. Health Syst. Pharm., 58(1), 41-50. PMID: 11194135. DOI: https://doi.org/10.1093/ajhp/58.1.41
Elias, M.L., Fatahzadeh, M., & Schwartz, R.A. (2022). Recurrent Aphthous Stomatitis: An Enigmatic Entity and Sign of Systemic Disease. Indian J. Dermatol., 67(6), 834. DOI: 10.4103/ijd.ijd_971_20.
Amador-Patarroyo, M.J., Rodriguez-Rodriguez, A., & Montoya-Ortiz, G. (2012). How does age at onset influence the outcome of autoimmune diseases? Autoimmune Dis., 251730. DOI: 10.1155/2012/251730. DOI: https://doi.org/10.1155/2012/251730
Wolach, B., Gavrieli, R., Roos, D., & Berger-Achituv, S. (2012). Lessons learned from phagocytic function studies in a large cohort of patients with recurrent infections. J. Clin. Immunol., 32(3), 454-466.
DOI: 10.1007/s10875-011-9633-4. DOI: https://doi.org/10.1007/s10875-011-9633-4
Rivera, C. (2019). Essentials of recurrent aphthous stomatitis. Biomed. Rep., 11(2), 47-50.
DOI: 10.3892/br.2019.1221. DOI: https://doi.org/10.3892/br.2019.1221
Ślebioda, Z., Szponar, E., & Kowalska, A. (2014). Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. Arch. Immunol. Ther. Exp. (Warsz.), 62(3), 205-215.
DOI: 10.1007/s00005-013-0261-y. DOI: https://doi.org/10.1007/s00005-013-0261-y
Porter, S.R., Scully, C., & Pedersen, A. (1998). Recurrent Aphthous Stomatitis. Critical Reviews in Oral Biology & Medicine, 9(3), 306-321.
DOI: 10.1177/10454411980090030401. DOI: https://doi.org/10.1177/10454411980090030401
Zunt, S.L. (2003). Recurrent aphthous stomatitis. Dermatol. Clin., 21(1), 33-39. DOI: 10.1016/s0733-8635(02)00075-x. DOI: https://doi.org/10.1016/S0733-8635(02)00075-X
Edgar, N.R., Saleh, D., & Miller, R.A. (2017). Recurrent Aphthous Stomatitis: A Review. J. Clin. Aesthet. Dermatol., 10(3), 26-36. PMID: 28360966; PMCID: PMC5367879.
Bratel, J., & Hakeberg, M. (2014). Anamnestic findings from patients with recurrent aphthous stomatitis. Swed. Dent. J., 38(3), 143-149. PMID: 25796808.
McCullough, M.J., Abdel-Hafeth, S., & Scully, C. (2007). Recurrent aphthous stomatitis revisited; clinical features, associations, and new association with infant feeding practices? J. Oral. Pathol. Med., 36(10), 615-620. DOI: 10.1111/j.1600-0714.2007.00589.x. DOI: https://doi.org/10.1111/j.1600-0714.2007.00589.x
Al-Johani, K. (2019). Prevalence of Recurrent Aphthous Stomatitis among Dental Students: A Cross Sectional Study. J. Contemp. Dent. Pract., 20(8), 893-895. PMID: 31797843. DOI: https://doi.org/10.5005/jp-journals-10024-2630
Queiroz, S.I.M.L., Silva, M.V.A.D., Medeiros, A.M.C., Oliveira, P.T., Gurgel, B.C.V., & Silveira, É.J.D.D. (2018). Recurrent aphthous ulceration: an epidemiological study of etiological factors, treatment and differential diagnosis. An. Bras. Dermatol., 93(3), 341-346.
DOI: 10.1590/abd1806-4841.20186228. DOI: https://doi.org/10.1590/abd1806-4841.20186228
Manoj, M.A., Jain, A., Madtha, S.A., & Cherian, T.M. (2023). Prevalence and risk factors of recurrent aphthous stomatitis among college students at Mangalore, India. Peer J., 11, e14998. DOI: 10.7717/peerj.14998. DOI: https://doi.org/10.7717/peerj.14998
Verma, S., Srikrishna, K., Srishti, Shalini, K., Sinha, G., & Srivastava, P. (2023). Recurrent Oral Ulcers and Its Association With Stress Among Dental Students in the Northeast Indian Population: A Cross-Sectional Questionnaire-Based Survey. Cureus, 15(2), e34947.
DOI: 10.7759/cureus.34947. DOI: https://doi.org/10.7759/cureus.34947
Ajmal, M., Ibrahim, L., Mohammed, N., & Al-Qarni, H. (2018). Prevalence and psychological stress in recurrent aphthous stomatitis among female dental students in Saudi Arabia. Clujul Med., 91(2), 216-221.
DOI: 10.15386/cjmed-840. DOI: https://doi.org/10.15386/cjmed-840
Dhopte, A., Naidu, G., Singh-Makkad, R., Nagi, R., Bagde, H., & Jain, S. (2018). Psychometric analysis of stress, anxiety and depression in patients with recurrent aphthous Stomatitis-A cross-sectional survey based study. J. Clin. Exp. Dent., 10(11), e1109-e1114.
DOI: 10.4317/jced.55012. DOI: https://doi.org/10.4317/jced.55012
Sánchez-Bernal, J., Conejero, C., & Conejero, R. (2020). Aftosis oral recidivante. Actas Dermo-Sifiliográficas, 111(6), 471-480. DOI: 10.1016/j.ad.2019.09.004. DOI: https://doi.org/10.1016/j.ad.2019.09.004
Wardhana, Datau E.A. (2010). Recurrent aphthous stomatitis caused by food allergy. Acta Med. Indones., 42(4), 236-240. PMID: 21063045.
Dudding, T., Haworth, S., Lind, P.A., Sathirapongsa-suti, J.F., Tung, J.Y., Mitchell, R., … & Timpson, N.J. (2019). Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci. Nat. Commun., 10(1), 1052. DOI: 10.1038/s41467-019-08923-6. DOI: https://doi.org/10.1038/s41467-019-08923-6
Kalkan, G., Yigit, S., Karakus, N., Baş, Y., & Seçkin, H.Y. (2013). Association between interleukin 4 gene intron 3 VNTR polymorphism and recurrent aphthous stomatitis in a cohort of Turkish patients. Gene, 527(1), 207-210. DOI: 10.1016/j.gene.2013.05.053. PMID: 23756192. DOI: https://doi.org/10.1016/j.gene.2013.05.053
Pekiner, F.N., Aytugar, E., Demirel, G.Y., & Bora-han, M.O. (2012). Interleukin-2, interleukin-6 and T regulatory cells in peripheral blood of patients with Behçet's disease and recurrent aphthous ulcerations. J. Oral. Pathol. Med., 41(1), 73-79.
DOI: 10.1111/j.1600-0714.2011.01061.x. DOI: https://doi.org/10.1111/j.1600-0714.2011.01061.x
Surboyo, M.D.C., Boedi, R.M., Hariyani, N., Santosh, A.B.R., Manuaba, I. B. P. P., Cecilia, P.H., … & Ernawati, D. S. (2022). The expression of TNF-α in recurrent aphthous stomatitis: A systematic review and meta-analysis. Cytokine, 157, 155946. DOI: 10.1016/j.cyto.2022.155946. DOI: https://doi.org/10.1016/j.cyto.2022.155946
Xiao, X., Deng, Y., Long, Y., Liu, W., & Shi, H. (2023). Evaluation of cytokines as diagnostic and therapeutic indicators for recurrent aphthous stomatitis: A statistical study. J. Dent. Sci., 18(2), 883-888.
DOI: 10.1016/j.jds.2022.10.013. DOI: https://doi.org/10.1016/j.jds.2022.10.013
Shen, C., Ye, W., Gong, L., Lv, K., Gao, B., & Yao, H. (2021). Serum interleukin-6, interleukin-17A, and tumor necrosis factor-alpha in patients with recurrent aphthous stomatitis. J. Oral. Pathol. Med., 50(4), 418-423. DOI: 10.1111/jop.13158. DOI: https://doi.org/10.1111/jop.13158
Poulter, L.W., & Lehner, T. (1989). Immunohistology of oral lesions from patients with recurrent oral ulcers and Behçet's syndrome. Clin. Exp. Immunol., 78(2), 189-195. PMID: 12412747; PMCID: PMC1534655.
Li, X., Liu, Y., Yang, X., Li, C., & Song, Z. (2022). The Oral Microbiota: Community Composition, Influencing Factors, Pathogenesis, and Interventions. Front. Microbiol., 13, 895537. DOI:10.3389/fmicb.2022.895537. DOI: https://doi.org/10.3389/fmicb.2022.895537
Gasmi Benahmed, A., Noor, S., Menzel, A., & Gasmi, A. (2021). Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment. Arch. Razi Inst., 76(5), 1155-1163. DOI: 10.22092/ari.2021.356055.1767.
Lamont, R.J., Koo, H., & Hajishengallis, G. (2018). The oral microbiota: dynamic communities and host interactions. Nat. Rev Microbiol., 16(12), 745-759.
DOI: 10.1038/s41579-018-0089-x. DOI: https://doi.org/10.1038/s41579-018-0089-x
Yamashita, Y., & Takeshita, T. (2017). The oral microbiome and human health. J. Oral. Sci., 59(2), 201-206. DOI: 10.2334/josnusd.16-0856. PMID: 28637979. DOI: https://doi.org/10.2334/josnusd.16-0856
Zhu, Z., He, Z., Xie, G., Fan, Y., & Shao, T. (2021). Altered oral microbiota composition associated with recurrent aphthous stomatitis in young females. Medicine (Baltimore), 100(10), e24742.
DOI: 10.1097/MD.0000000000024742. DOI: https://doi.org/10.1097/MD.0000000000024742
Min, Z., Yang, L., Hu, Y., & Huang, R. (2023). Oral microbiota dysbiosis accelerates the development and onset of mucositis and oral ulcers. Front. Microbiol., 14, 1061032. DOI: 10.3389/fmicb.2023.1061032. DOI: https://doi.org/10.3389/fmicb.2023.1061032
Kim, Y.J., Choi, Y.S., Baek, K.J., Yoon, S.H., Park, H.K., & Choi, Y. (2016). Mucosal and salivary microbiota associated with recurrent aphthous stomatitis. BMC Microbiol., 16(1), 57. DOI: 10.1186/s12866-016-0673-z. DOI: https://doi.org/10.1186/s12866-016-0673-z
Hijazi, K., Lowe, T., Meharg, C., Berry, S.H., Foley, J., & Hold, G.L. (2015). Mucosal microbiome in patients with recurrent aphthous stomatitis. J. Dent. Res., 94(3), 87S-94S. DOI: 10.1177/0022034514565458. DOI: https://doi.org/10.1177/0022034514565458
Xu, K., Zhou, C., Huang, F., Duan, N., Wang, Y., Zheng, L., Wang, X., & Wang, W. (2021). Relationship between dietary factors and recurrent aphthous stomatitis in China: a cross-sectional study. J. Int. Med. Res., 49(5). DOI: 10.1177/03000605211017724. DOI: https://doi.org/10.1177/03000605211017724
Porter, S.R., Scully, C., & Flint, S. (1988). Hematologic status in recurrent aphthous stomatitis compared with other oral disease. Oral. Surg. Oral. Med. Oral. Pathol., 66(1), 41-44. DOI: 10.1016/0030-4220(88)90064-3. DOI: https://doi.org/10.1016/0030-4220(88)90064-3
Chen, H., Sui, Q., Chen, Y., Ge, L., & Lin, M. (2015). Impact of haematologic deficiencies on recurrent aphthous ulceration: a meta-analysis. Br. Dent. J., 218(4), E8. DOI: 10.1038/sj.bdj.2015.100. DOI: https://doi.org/10.1038/sj.bdj.2015.100
Nolan, A., McIntosh, W.B., Allam, B.F., & Lamey, P.J. (1991). Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy. J. Oral. Pathol. Med., 20(8), 389-391.
DOI: 10.1111/j.1600-0714.1991.tb00950.x. DOI: https://doi.org/10.1111/j.1600-0714.1991.tb00950.x
Al-Amad, S.H., & Hasan, H. (2020). Vitamin D and hematinic deficiencies in patients with recurrent aphthous stomatitis. Clin. Oral. Investig., 24(7), 2427-2432. DOI: 10.1007/s00784-019-03102-9. DOI: https://doi.org/10.1007/s00784-019-03102-9
Hernández-Olivos, R., Muñoz, M., Núñez, E., Camargo-Ayala, P.A., Garcia-Huidobro, J., Pereira, A., …, & Rivera, C. (2021). Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria. Sci. Rep., 11(1), 15646. DOI: 10.1038/s41598-021-95228-8. DOI: https://doi.org/10.1038/s41598-021-95228-8
Al-Maweri, S.A., Halboub, E., Al-Sufyani, G., Alqutaibi, A.Y., Shamala, A., & Alsalhani, A. (2020). Is vitamin D deficiency a risk factor for recurrent aphthous stomatitis? A systematic review and meta-analysis. Oral. Dis., 26(6), 1116-1123. DOI: 10.1111/odi.13189. DOI: https://doi.org/10.1111/odi.13189
Zakeri, M., Parsian, H., Bijani, A., Shirzad, A., & Neamati, N. (2021). Serum levels of vitamin D in patients with recurrent aphthous stomatitis. Dent. Med. Probl., 58(1), 27-30. DOI: 10.17219/dmp/126360. PMID: 33754499. DOI: https://doi.org/10.17219/dmp/126360
Nalbantoğlu, B., & Nalbantoğlu, A. (2020). Vitamin D Levels in Children With Recurrent Aphthous Stomatitis. Ear Nose Throat J., 99(7), 460-463.
DOI: 10.1177/0145561319882783. DOI: https://doi.org/10.1177/0145561319882783
Başarslan, F., & Kaba, İ. (2022). Evaluation of Vitamin D Levels in Pediatric Patients With Recurrent Aphthous Stomatitis. Cureus, 14(11), e32064.
DOI: 10.7759/cureus.32064. DOI: https://doi.org/10.7759/cureus.32064
Öztekin, A., & Öztekin, C. (2018). Vitamin D levels in patients with recurrent aphthous stomatitis. BMC Oral. Health, 18(1), 186. DOI: 10.1186/s12903-018-0653-9. DOI: https://doi.org/10.1186/s12903-018-0653-9
Ślebioda, Z., Szponar, E., & Kowalska, A. (2013). Recurrent aphthous stomatitis: genetic aspects of etiology. Adv. Dermatol. Allergol., 30(2), 96-102.
DOI: 10.5114/pdia.2013.34158. DOI: https://doi.org/10.5114/pdia.2013.34158
Kvam, E., Gjerdet, N.R., & Bondevik, O. (1987). Traumatic ulcers and pain during orthodontic treatment. Community Dent. Oral. Epidemiol., 15(2), 104-107. DOI: 10.1111/j.1600-0528.1987.tb00493.x. DOI: https://doi.org/10.1111/j.1600-0528.1987.tb00493.x
Wray, D., Graykowski, E.A., & Notkins, A.L. (1981). Role of mucosal injury in initiating recurrent aphthous stomatitis. Br. Med. J. (Clin. Res. Ed.), 283(6306), 1569-1570. DOI: 10.1136/bmj.283.6306.1569. DOI: https://doi.org/10.1136/bmj.283.6306.1569
Baricevic, M., Mravak-Stipetic, M., Majstorovic, M., Baranovic, M., Baricevic, D., & Loncar, B. (2011). Oral mucosal lesions during orthodontic treatment. Int. J. Paediatr. Dent., 21(2), 96-102.
DOI: 10.1111/j.1365-263X.2010.01078.x. DOI: https://doi.org/10.1111/j.1365-263X.2010.01078.x
AlDahash, F., AlShamali, D., AlBander, W., Bakhsh, R., AlMadhi, W., & AlSenani, S. (2020). Oral mucosal ulceration during orthodontic treatment: The perception of patients and knowledge and attitude of the orthodontic practitioners. J. Family Med. Prim. Care, 9(11), 5537-5541. DOI: 10.4103/jfmpc.jfmpc_1197_20. DOI: https://doi.org/10.4103/jfmpc.jfmpc_1197_20
Staines, K., & Greenwood, M. (2015). Aphthous ulcers (recurrent). BMJ Clin. Evid., 26, 1303. PMID: 25720501; PMCID: PMC4356175.
Al-Maweri, S.A., Al-Qadhi, G., Halboub, E., Alaizari, N., Almeslet, A., Ali, K., & Osman, S.A.A. (2023). Vitamin D deficiency and risk of recurrent aphthous stomatitis: updated meta-analysis with trial sequential analysis. Front. Nutr., 10, 1132191.
DOI: 10.3389/fnut.2023.1132191. DOI: https://doi.org/10.3389/fnut.2023.1132191
Ziaei, S., Raeisi Shahraki, H., & Dadvand Dehkordi, S. (2022). The association of recurrent aphthous stomatitis with general health and oral health related quality of life among dental students. Int. J. Physiol. Pathophysiol. Pharmacol., 14(4), 254-261. PMID: 36161262;
PMCID: PMC9490208.
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