Article_6_4_3-Obradovic
ORAL MEDICINE
SMOKING AND RECURRENT APHTHOUS STOMATITIS
Original Articles
Radmila Radisa Obradović1a* , Marija LJ Igic2a, Aleksandar D Mitic3a , Ana S Pejcic1a , Kosta M Todorovic4b ,
Zana Popovic5c
1
Department of Periodontology and Oral Medicine, Faculty of Medicine, Niš University, Serbia
2
Department of Children and Preventive Dentistry, Faculty of Medicine, Niš University, Serbia
3
Department of Dental Pathology and Endodontics, Faculty of Medicine, Niš University, Serbia
4
Department of Oral Surgery, Faculty of Medicine, Niš University, Serbia
5
Department of Dentistry, Faculty of Medical Sciences, Kragujevac University, Serbia
a
DDS, PhD, Professor
b
DDS, Assistant
c
DDS, Postdoctoral Student
ABSTRACT DOI: https://doi.org/10.25241/stomaeduj.2019.6(4).art.3 OPEN ACCESS This is an Open Access
article under the CC BY-NC 4.0 license.
Introduction: Recurrent aphthous stomatitis (RAS) is one of the most usual
inflammatory diseases of the oral mucosa. The clinical characteristics of RAS are Peer-Reviewed Article
well defined, but the exact etiology and pathogenesis of the disease are not. Citation: Obradović RR, Igic M, Mitic A, Pejcic A,
Todorovic K, Popovic Z. Smoking and recurrent
Several investigations have noticed cigarette smoking to have a protective effect aphthous stomatitis. Stoma Edu J. 2019;6(4):237-240
on RAS. The aim of the study is to investigate the association between cigarette Received: July 08, 2019
smoking and RAS in order to improve the current knowledge on this issue. Revised: October 25, 2019
Accepted: October 28, 2019
Methodology: 68 patients with RAS participated in the study. A full mouth Published: December 16, 2019
clinical examination was performed and an anamnesis was taken for each patient. *Corresponding author:
The statistical analysis was performed using Student t-test. Professor Radmila Radisa Obradović, DDS, PhD
Department of Periodontology and Oral Medicine,
Results: While 6 (8.9%) of patients with RAS were smokers, a significantly higher Faculty of Medicine, Niš University 81, Dr Zoran Djindjic
percentage (24.9%) among the subjects with RAS were not smokers (group II) (χ2 Blvd, 18000 Niš, Serbia
Tel: +381-64-235-9595,
=70.4; d.f. = 2, P < 0.001). Fax: +381-18-42-38-770,
e-mail: dr.rada@yahoo.com
Conclusion: The negative association between smoking and RAS indicated by
Copyright: © 2019
this investigation is not meant to encourage people to smoke nor to spare them the Editorial Council for the Stomatology Edu Journal.
from the intention to quit their habit. These conclusions should be used to clear
up the cause and pathogenesis of the RAS and to identify better prevention and
treatment.
Keywords: Oral medicine; Aphthae; Mouth; Smoking; Oral health,
Recurrent Aphthous Stomatitis, Smoking.
1. Introduction are produced [3]. Inheritance of HLA-B51 antigen,
Recurrent aphthous stomatitis (RAS) is a very common vitamin B12 deficiency, recurrent herpes labialis,
disease of the oral mucosa. It is called minor aphthous Helicobacter pylori, hepatitis C and hypersensitivity
ulcers, herpetiform ulcers, aphthosis and many other to nickel are involved in the development of
names. Aphthous ulcers can occur alone or as part of RAS [4,5]. It is necessary to better understand
a syndrome [1]. RAS occurs only in non-keratinized the pathogenesis and primary cause of RAS [2].
mucosa as painful, shallow round ulcers with an Previously, it is thought that approximately 0.89%
erythematous halo covered by a membranous layer. of the adults over 17 years of age have at least one
The clinical ulcerative period for minor aphthous aphthous lesion and that males (1.13%) have almost
ulcers may last for 2 weeks and lesions usually heal twice the RAS than females (0.67%). It is noticed
without a scar [2]. The clinical characteristics of RAS that reported prevalence of RAS varies according
are well known, but the exact etiology and patho- to patient selection, presence of lesions at the time
genesis of the disease are not complete. The etiology of investigation or during a specified period and
of RAS includes stress, microorganisms, food hyper- newer literature data show that the RAS prevalence
sensitivity, immune dysregulation, hormonal fac- is between 5 and 60%, depending on the population
tors and a genetic predisposition, usage of the group studied [2].
toothpaste with SLS [1,2]. Current investigations It is estimated that tobacco use is the major cause of
have focused on a possible immunopathogenesis of more than 5 million deaths every year [6]. Smoking
RAS [2,3]. The epithelial cell death and the creation is a common risk factor in a number of chronic
of ulceration probably results from the activation of diseases like lung diseases, cancer, cardiovascular
a cell-mediated immune response in which Tumor diseases; and a major risk factor in the prevalence of
Necrosis Factor Alpha (TNFα) and other cytokines periodontal diseases [6-10]. Cigarette smoke contains
Stomatology Edu Journal 237
SMOKING AND RECURRENT APHTHOUS STOMATITIS
Table 1. Relationship between RAS and smoking.
Original Articles
RAS (no RAS or RAS history) Total
Smoking (group I) 6 (8.9%) 68 (91.9%) 74
Nonsmoking (group II) 62 (24.9%) 202 (76.5%) 264
Total 68 (20.1%) 270 (79.9%) 338
approximately 4800 chemicals, with over 60 of them patients constituted group II (264 patients).
known to have 3 damaging effects on human cells
[11]. Cigarette smoking could camouflage signs of 4. Results
periodontal disease like gingival bleeding or redness, There were 68 participants with RAS, out of which 31
by suppressing the immune response which could (46.92%) were men and 37 (53.1%) were women. The
cause a problem in the diagnosis of the disease. average age was 29.7± 8.8 years. 66 (97.1%) had the
Several studies have noticed cigarette smoking to minor type of the disease, 2 (2.9%) had both minor
have a protective effect on RAS [12-15]. It is not clear and major RAS.
how cigarette smoking can reduce RAS prevalence The relationship between RAS and smoking is
but it is thought that immunological mechanisms shown in Table 1. While 6 (8.9%) of patients with RAS
are involved and that the cytokine (TNF) plays an were active smokers (group I), a significantly higher
important role in the pathogenesis. Nicotine has percentage (24.9%) among the subjects with RAS
been shown to influence the immune response in were not smokers (group II) (χ2 =70.4; d. f. = 2, P <
inflammatory conditions [16,17]. It acts through the 0.001).
central nervous system inducing the production
of glucocorticoids and activating the autonomic 5. Discussion
nervous system and consequently reducing the level Smoking is a known risk factor in a number of chronic
of inflammation [16]. diseases and major risk factor of periodontal disease
Nicotine can activate the nicotinic acetylcholine [2-6]. Cigarette smoking suppresses the immune
receptors on macrophages and reduce the host response, masks early signs of periodontal
production of TNF1and interleukins [17]. disease and has as reported by some authors a
beneficial protective effect on RAS. It has also been
2. The aim of the study noticed that the incidence of RAS is higher among
The aim of the study is to investigate the association young individuals and that adults younger than 40
between cigarette smoking and RAS in order to years of age have more than twice higher RAS rate
increase current knowledge on this issue. than those older than 40 years [12-15]. We noticed
similar results in our study where the average age
3. Methodology of the patients with RAS was 29.7±8.8 years. It
The study was conducted on 338 patients who could be suspected that stress could be an aphthae
came at the Department of Oral Medicine and provoking factor. Previously, lifestyle could induce
Periodontology of the Dental Clinic of Faculty of stress and social conditions and self-management
Medicine, Niš University, for one year. The Ethics are important determinants of health. The effects
Committee of the Faculty of Medicine Niš approved of living exposed to many stress factors may cause
the study protocol (evidential number 01-2800-7). poorer health and more frequent occurrence of RAS
After the medical history was taken, the patients [18,19]. Literature data reveal a significant reduction
who had undergone antibiotic and corticosteroid of RAS in individuals who smoke. The prevalence
therapy in the last three months, were not included and odds ratios for number of cigarettes smoked is
in the study. A full mouth clinical examination was significant and suggest a dose response effect [14,15].
performed and the patients with active aphthous A reduction in RAS prevalence with higher blood
lesions and who per medical history had suffered levels of nicotine is found to be significant [20].
from oral ulcers at least once within a period of 5 Our study noticed a similar situation. where 8.9%
months were considered to suffer from RAS. The of patients with RAS were active smokers and a
patients with other oral diseases who came at the significantly higher percentage (24.9%) among
Dental Clinic of the Medical Faculty Niš for other the subjects with RAS were not smokers (group II)
medical reasons were also included in this study. (χ2 =70.4; d. f. = 2, P < 0.001). Kalpana [13] noticed
Out of all the examined patients, 68 patients had that significant differences exist in the prevalence
RAS and 270 had no RAS or RAS history. Patients of RAS among cigarette smokers, which could be
who smoked over 10 cigarettes per day (per medical related to the number of cigarettes smoked per day
history) were considered to be “smokers” and they and duration of the habit. The “protective effect” on
constituted group I (74 patients). The nonsmoking RAS was noticed only when the persons were heavy
238 Stoma Edu J. 2019;6(4): 237-240 www.stomaeduj.com
SMOKING AND RECURRENT APHTHOUS STOMATITIS
smokers or had smoked for longer periods of time. by a bias of selection of the sample. Other researchers
Original Articles
Cigarette non-smokers have far greater odds of RAS have found a lower incidence of RAS in smokers on
than individuals who smoked >1 pack per day. It the basis of the disease history but not by direct
could was concluded that the associations of RAS detection of present lesions by a practitioner [12-14].
with cigarette smoking and with cotinine levels A similar negative correlation between smoking and
were significant. Our study noticed similar results, RAS was noticed in our study. The treatment and,
namely that a higher number of individuals with many times, the diagnosis of RAS are a challenge
RAS were nonsmokers (24.9%). RAS is characterized in the daily life of the clinician. Dental professionals
by recurrences of short-lived lesions. The lesions and otorhinolaryngologists are usually responsible
are not always noticed at the time of examination for the first contact with the patients who have RAS.
and the diagnosis is often based on the patient’s These professionals should be alert to the clinical
clinical history. The statistical evaluation of RAS is aspects of this condition since each patient will
hampered because lesions cannot be evaluated by be treated in an individualized manner, because
the investigator at any time and is usually based on treatment is usually palliative and not curative.
a self-reported history of RAS. Such a diagnosis is
less reliable that one based upon the observation of 6. Conclusion
present lesions by a practitioner. It is to be noticed On the basis of the aim of the study, its applied
that many of the studies which found a negative methodology and the results obtained it can be
correlation between RAS and smoking were based concluded that the incidence of RAS is higher
on a self-reported history of RAS [21]. Information among young individuals and among subjects who
should be carefully interpreted, especially where do not smoke. The negative association between
there is some basis to suspect response bias. The smoking and RAS in our study is not indeed meant to
findings in this study were based on anamnesis encourage people to smoke nor to sway them in the
and clinical examination conducted by an decision to quit their habit. Smoking cessation is the
experienced practitioner and provide data on the main option to remove the harmful tobacco effects
general prevalence of RAS in smokers. There is a on oral tissues and to improve the quality of life.
small number of studies in which patients were
diagnosed by direct detection of present lesions Author Contributions
by a practitioner. Queiroz et al [22] evaluated 4895 All authors (RO, MI, AM, AP, KT, and ZP) contributed in
cases of recurrent aphthous ulcerations with a focus data collection and analysis, and manuscript writing.
on treatment, diagnosis and etiology. Data such All authors agree to be accountable for the content
as sex, age, race, location, smoking habits, types of the work.
of treatment, relapsing episodes, laboratory test
results and clinical characteristics were collected. Acknowledgment
Regarding smoking habits, in the majority of This research was supported by a grant from the
patients, 59 (77.6%) smoking was not recorded. The Internal project number 11, Medical Faculty,
investigators did not consider the percentages of University of Niš, Niš, Serbia.
smoking notifications because they are influenced
References
1. Cui RZ, Bruce AJ, Rogers RS. Recurrent aphthous stomatitis. Clin 7. Holde GE, Baker SR, Jőnson B. Periodontitis and quality of life:
Dermatol. 2016;34(4):475-481. What is the role of socioeconomic status, sense of coherence,
2. Edgar NR, Saleh D, Miller RA. Recurrent aphthous stomatitis: a dental service use and oral health practices? An exploratory theory-
review. J Clin Aesthetic Dermatol. 2017;10(3):26-36. guided analysis on a Norweigan population. J Clin Periodontol.
Scopus 2018;45(7):768-779.
3. Manthiram K, Lapidus S, Edwards K. Unraveling the pathogenesis [CrossRef] Google Scholar
of periodic fever, aphthous stomatitis, pharyngitis, and cervical 8. Waziry R, Jawad M, Ballout RA, AlAkel M, Akl EA. The effects
adenitis through genetic, immunologic, and microbiologic of waterpipe tobacco smoking on health outcomes: an updated
discoveries: an update. Curr Opinion Rheumatol. 2017;29(5):493- systematic review and meta-analysis. Int J Epidemiol. 2017;46(1):
499. 32-43.
[Full text links] [CrossRef] [PubMed] Google Scholar Scopus [Full text links] [CrossRef] [PubMed] Google Scholar Scopus
4. Najafi S, Mohammadzadeh M, Zare Bidoki A, et al. HLA-DRB and 9. Chaffee BW, Couch ET, Ryder MI. The tobacco-using periodontal
HLA-DQB allele and haplotype frequencies in Iranian patients with patient: role of the dental practitioner in tobacco cessation and
recurrent aphthous stomatitis. Iran J Allergy Asthma Immunol. periodontal disease management. Periodontol 2000. 2016;71(1):
15(4):289-295. 52-64.
[Full text links] [PubMed] Google Scholar Scopus [Full text links] [Free PMC Article] [CrossRef] [PubMed] Google
5. Kuo YS, Chang JYF, Wang YP, et al. Significantly higher frequencies Scholar Scopus
of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of 10. Mahmud SZ, Amin MS. Association between tobacco
hyperhomocysteinemia in patients with Behcet’s disease. J Formos consumption and periodontal diseases among type 2 diabetes
Med Assoc. 2018;117(10):932-938. mellitus patients. Saudi J Oral Sci. 2016;3:90-96.
[Full text links] [CrossRef] [PubMed] Google Scholar Scopus [CrossRef] Google Scholar
6. Britton J. Death, disease and tobacco. Lancet 2017;389(10082): 11. Jeong M, Noar SM, Zhang D, et al. Public understanding of
1861-1862. cigarette smoke chemicals: Longitudional study of US adults and
[Full text links] [CrossRef] [PubMed] Google Scholar adolescents. Nicotine Tob Res. 2019;pii:ntz035
[Full text links] [CrossRef] [PubMed] Google Scholar
Stomatology Edu Journal 239
SMOKING AND RECURRENT APHTHOUS STOMATITIS
12. Peruzzo DC, Gimenes JH, Taiete T, et al. Impact of smoking on 17. Hosseinzadeh A, Thompson PR, Segal BH, Urban CF. Nicotine
Original Articles experimental gingivitis. A clinical, microbiological and immunological induces neutrophil extracellular traps. JLB 2016;100(5):1105-1112.
prospective study. J Periodontal Res. 2016;51(6):800-811. [Full text links] [CrossRef] [PubMed] Google Scholar Scopus
[Full text links] [CrossRef] [PubMed] Google Scholar Scopus 18. Chaudry A, Wimer C. Poverty is not just an indicator: The rela-
13. Kalpana R. Relation between smoking and recurrent aphthous tionship between income, poverty, and child well-being. Acad
stomatitis. Oral Maxillofac Pathol J. 2016;7(2):761-762. Pediatr. 2016;16(3):23-29.
Google Scholar [CrossRef] Google Scholar Scopus
14. Oliveira MJ, Coimbra F, Mesquita P, Carvalho J, Pereira-Lopes O. 19. Ismayilova L, Karimli L, Sanson J, et al. Improving mental
Characterization of recurrent aphthous stomatitis in a young population. health among ultra-poor children: Two-year outcomes of a cluster-
Rev Port Estomatol Med Dent Cir Maxilofac. 2018;59(1):10-17. randomized trial in Burkina Faso. Soc Sci Med. 2018; 208:180-189.
Scopus [Full text links] [CrossRef] [PubMed] Google Scholar Scopus
15. Souza PRM, Doquia RP, Breunig JA, Almeida JRHL. Recurrent 20. Zakaria M, El-Meshad A. Clinical efficacy of nicotine replacement
aphthous stomatitis in 18-year-old adolescents - Prevalence and therapy in the treatment of minor recurrent aphthous stomatitis.
associated factors: a population-based study. An Bras Dermatol. J Arab Society Medical Res. 2018;13(2):106-112.
2017;92(5):626-629. [CrossRef] Google Scholar
[Full text links] [Free PMC Article] [CrossRef] [PubMed] Google 21. Namrata M, Abilasha R. Recurrent aphthous stomatitis. Int J
Scholar Scopus Orofacial Biol. 2017;1(2):43-47.
16. Rothbard JB, Rothbard JJ, Soares L, Fathman G, steinman L. 22. Queiroz SIML, Silva MVA, Medeiros AMC, et al. Reccurrent
Identification of a common immune regulatory pathaway induced aphthous ulceration: an epidemiological study of etiological
by small heat shock proteins, amyloid fibrils, and nicotine. PNAS factors, treatment and differential diagnosis. An Bras Dermatol.
2018;115(27):7081-7086. 2018;93(3):341-346.
[Full text links] [Free PMC Article] [CrossRef] [PubMed] Google [Full text links] [Free PMC Article] [CrossRef] [PubMed] Google
Scholar Scholar
Radmila Radisa OBRADOVIĆ
DDS, PhD, Professor
Department of Oral Medicine and Periodontology
Dental Clinic
Faculty of Medicine
Niš University
Niš, Serbia
CV
Doctor Radmila Radisa Obradović is a Professor at the Department of Oral Medicine and Periodontology, Dental Clinic,
Faculty of Medicine, Niš University and at the Department of Oral Medicine and Periodontology, Faculty of Medical
Sciences, Kragujevac, Serbia. She is also a member of the Niš Dental Clinic’s Ethical Committee, Serbian Medical Society,
Serbian Anthropological Society and Serbian Oral Laser Society (SOLAS).
She participates in national projects, and delivers many dental courses and conferences as a lecturer.
She has many scientific publications in international and Serbian medical and dental journals.
Questions
1. Recurrent aphthous stomatitis (RAS) is very common disease of the oral mucosa. It is
called:
qa. Minor aphthous ulcers;
qb. Herpetiform ulcers;
qc. Simple aphthosis;
qd. All of the above answers are correct
2. Cigarette smoking could influence signs of periodontal disease like:
qa. Provoking bleeding;
qb. Provoking gingival redness;
qc. Camouflage gingival bleeding or redness;
qd. Provoking gingival swelling.
3. The etiology of RAS includes:
qa. Stress and immune dysregulation;
qb. Microorganisms and food hypersensitivity;
qc. Hormonal factors and a genetic predisposition;
qd. All of the above answers are correct.
4. The patients were divided into:
qa. Two groups: smokers and nonsmoking patients;
qb. Three groups: smokers, nonsmoking patients and patients with RAS;
qc. Two groups: smokers and patients with RAS;
qd. Two groups: nonsmoking patients and patients with RAS.
240 Stoma Edu J. 2019;6(4): 237-240 www.stomaeduj.com