ArticlePDF AvailableLiterature Review

Serum level of vitamin D in patients with recurrent aphthous stomatitis: A systematic review and meta‐analysis of case control studies

Wiley
Clinical and Experimental Dental Research
Authors:

Abstract

Objectives Recurrent aphthous stomatitis (RAS) is an ulcerative condition with unknown etiology. The effect of vitamin D in the etiology of RAS is still a matter of controversy. In this study, we aimed at review the available evidence on the role of vitamin D deficiency in RAS etiology. Material and Methods PubMed, Cochrane Library for Systematic Reviews, ISI Web of Science, Scopus, and EmBase were systematically searched for evidence on RAS and vitamin D up to January 2020. Retrieved records were screened and assessed by two of the authors independently. Newcastle−Ottawa scale was used to assess the quality of individual studies. AMSTAR tool was used for assessing the quality of the study. Results Eight studies including 383 healthy control and 352 patients with RAS were eligible for the meta‐analysis. Serum vitamin D levels were significantly lower in RAS patients. The weighted mean difference was −7.90 (95% CI: −11.96 to −3.85). Conclusions The results highlighted the importance of vitamin D deficiency in the etiology of RAS. However, more studies are needed to reach a robust decision. The observed association between vitamin D and RAS is probably due to the effect of vitamin D on the immune system.
Received: 14 April 2023
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Revised: 16 September 2023
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Accepted: 20 September 2023
DOI: 10.1002/cre2.794
REVIEW ARTICLE
Serum level of vitamin D in patients with recurrent aphthous
stomatitis: A systematic review and metaanalysis
of case control studies
Roya SafariFaramani
1
|Mohsen Salehi
2
|Saman Ghambari Haji Shore
2
|
Neda Omidpanah
3
1
Research Center for Environmental
Determinants of Health, School of Public
Health, Kermanshah University of Medical
Sciences, Kermanshah, Iran
2
Students Research Committee, Kermanshah
University of Medical Sciences,
Kermanshah, Iran
3
Department of Oral and Maxillofacial
Medicine, School of Dentistry, Kermanshah
University of Medical Sciences,
Kermanshah, Iran
Correspondence
Neda Omidpanah, Department of Oral and
Maxillofacial Medicine, School of Dentistry,
Kermanshah University of Medical Sciences,
Dental School, Shariati Ave, Kermanshah, Iran.
Email: n.omidpanah20000@gmail.com
Funding information
Research Committee of Kermanshah
University of Medical Sciences
Abstract
Objectives: Recurrent aphthous stomatitis (RAS) is an ulcerative condition with
unknown etiology. The effect of vitamin D in the etiology of RAS is still a matter of
controversy. In this study, we aimed at review the available evidence on the role of
vitamin D deficiency in RAS etiology.
Material and Methods: PubMed, Cochrane Library for Systematic Reviews, ISI Web of
Science, Scopus, and EmBase were systematically searched for evidence on RAS and
vitamin D up to January 2020. Retrieved records were screened and assessed by two
of the authors independently. NewcastleOttawa scale was used to assess the quality
of individual studies. AMSTAR tool was used for assessing the quality of the study.
Results: Eight studies including 383 healthy control and 352 patients with RAS were
eligible for the metaanalysis. Serum vitamin D levels were significantly lower in RAS
patients. The weighted mean difference was 7.90 (95% CI: 11.96 to 3.85).
Conclusions: The results highlighted the importance of vitamin D deficiency in the
etiology of RAS. However, more studies are needed to reach a robust decision. The
observed association between vitamin D and RAS is probably due to the effect of
vitamin D on the immune system.
KEYWORDS
recurrent aphthous stomatitis, vitamin D
1|BACKGROUND
Recurrent aphthous stomatitis (RAS) is the most common lesion
of the oral mucosa, with a prevalence of from 5% to 66% in the
general population (Akintoye & Greenberg, 2005; Scully, 2006). RAS
is diagnosed by ruling out other possible causes of stomatitis
(Krisdapong et al., 2012; Tabolli et al., 2009). RAS is morphologically
divided into three categories: minor, major, and herpetiform, the most
common form of which is minor and accounts for 85% of RAS lesions
and it does not leave scars. The major type is more widespread and
its size is larger than 10 mm, and its recovery is accompanied by the
creation of scars. The herpetic type is a form of multiple deep
wounds with irregular edges (Feng et al., 2015).
Although the underlying causes of RAS are unclear, some
research has shown that systemic factors, including genetics,
immunological, and hematological abnormalities, as well as other
Clin Exp Dent Res. 2023;17. wileyonlinelibrary.com/journal/cre2
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© 2023 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.
factors such as trauma, smoking, stress, nutritional deficiencies, and
allergies, are among the potential causes (RiveraHidalgo et al., 2004;
Slebioda et al., 2014). These initiating factors cause the secretion of
preinflammatory cytokines by infiltration of leukocytes against a
specific area of the oral mucosa depending on the extent and severity
of the disease (RiveraHidalgo et al., 2004; Slebioda et al., 2014;
Tabolli et al., 2009).
Hydroxyvitamin D (25OHD), also known as vitamin D, is a type
of fatsoluble vitamin. It is produced in the skin through exposure to
sunlight and can also be obtained from certain foods and supple-
ments. Vitamin D deficiency can occur due to insufficient sunlight
exposure, reduced availability, or certain medications such as
glucocorticoids, antiretroviral drugs, or anticonvulsants (Straube
et al., 2015). Vitamin D receptors (VDR) are present in many tissues
throughout the body, and a lack of 25OHD has been associated with
various health conditions, including musculoskeletal disorders,
metabolic and autoimmune diseases, respiratory and cardiovascular
issues, cancer, psychiatric disorders, chronic pain, and hypo-
thyroidism (Adorini, 2005; Taheriniya et al., 2021).
Recently, the role of vitamin D in the etiopathogenesis of RAS
has been highlighted, (Ali, 2019; Bahramian et al., 2018).
1,25 Dihydroxyvitamin D, a bioactive form of vitamin D3, a
steroid hormone, has a crucial role in calcium and bone metabolism
(Adorini, 2005). Vitamin D endocrine system has the property of
regulating immune and inflammatory responses. The cells of the
innate and adaptive immune system, such as macrophages, T cell,
B cell, express the dendritic cells that receive vitamin D (VDR) and are
involved in the production and response to vitamin D. The net effect
of vitamin D on the immune system is to increase intrinsic immunity
with multiple adaptive immune systems (Adorini et al., 2004).
The role of vitamin D in the development of RAS has been a
subject of debate in recent studies. Several investigations have
examined the potential connection between low levels of vitamin D
and the occurrence of RAS, yielding conflicting findings. While certain
studies have indicated a correlation between vitamin D deficiency
and the onset of RAS, (Ali, 2019; Bahramian et al., 2018; Khabbazi
et al., 2015; Öztekin & Öztekin, 2018) others have not definitively
established the role of vitamin D deficiency in RAS lesions (Krawiecka
et al., 2017; Suhail et al., 2019). The objective of the current study
was to conduct a systematic review of the available evidence
concerning the influence of vitamin D deficiency on the pathogenesis
of RAS.
2|METHODS
2.1 |Protocol and registration
The Preferred Reporting Items for Systematic Review and Meta
Analyses (PRISMA) guideline followed to report the results of this
systematic review (Liberati, 2009) and was registered on the
International prospective register of systematic reviews, PROSPERO
(CRD42019138725).
2.2 |Focused question (based on PICO criteria)
The study was designed to answer if the level of serum vitamin D is
different between patients with RAS and healthy controls. The study
question was clarified based on the PICO categories (i.e., population,
intervention [exposure in this study], comparison group, and
outcomes).
2.3 |Search strategy
A systematic search was conducted in electronic databases (Scopus,
Web of Science, PubMed, Embase, and Cochrane Library) up to January
2020, without language restrictions. The search terms used Aphthous
or Oral ulceror Sutton's diseaseor recurrent aphthous were
Stomatitisand 25hydroxy vitamin Dor vitamin D.
2.4 |Eligibility criteria and study selection process
Inclusion criteria were observational studies that reported levels
vitamin D in saliva or serum, between the RAS patients and healthy
controls. Exclusion criteria included commentaries, letters to the
editor, editorials, case reports, reviews/systematic reviews, confer-
ence abstracts, book chapters, and studies with irrelevant data.
Based on the inclusion criteria, the eligibility of each article was
evaluated by reviewing their titles and abstracts. Two reviewers
independently evaluated the titles and abstracts for this purpose.
Disagreements were resolved following discussion with a third
reviewer. Next, the fulltexts of the suggested potential eligible
articles were retrieved and screened. The reasons for exclusion of
articles were documented.
2.5 |Data extraction
Two reviewers independently extracted the data from the fulltexts
of articles based on a predetermined form and a third reviewer
checked the extracted data. The following details were extracted:
authors, publication year, sample size in each group, mean age of the
participants, male percent, laboratory method, and serum or saliva
level of vitamin D in each group.
2.6 |Risk of bias assessment
NewcastleOttawa quality assessment scale for case control
studies was used to assess the risk of bias in the individual studies
(Wells et al., 2014).
The NewcastleOttawa scale is based on three main domains
including selection, comparability, and exposure. This tool also served
to classify the quality of each study as either high (7 or above), fair
(between 4 and 7), or low (less than 4). One of the authors performed
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SAFARIFARAMANI ET AL.
this quality assessment. The quality assessment was conducted by
one author. To assess the quality of the present systematic review,
AMSTAR 2 (Assessing the Methodological Quality of Systematic
Reviews) tool was used (Shea et al., 2017).
2.7 |Statistical methods
The standard mean difference and its 95% confidence interval (CI)
were calculated for each study using Review Manager 5.3 (RevMan
5.3; Cochrane Collaboration). These values were used to assess the
difference in salivary and serum vitamin D levels between patients
with RAS and healthy controls. A pvalue less than .05 was
considered statistically significant. To evaluate the heterogeneity
among the studies, the I
2
statistic was used. A pvalue less than .1
(I
2
> 50%) indicated significant heterogeneity, leading to the use of a
randomeffects model for the analysis.
Funnel plot analysis was performed using the Comprehensive
MetaAnalysis version 2.0 (CMA 2.0) software. Both Egger's and
Begg's tests were used to assess publication bias, with a pvalue less
than .05 (twotailed) indicating significant publication bias.
The unit of measurement for salivary and serum vitamin D levels
in this metaanalysis was ng/mL.
The study protocol was funded and registered in the Research
Committee of Kermanshah University of Medical Sciences.
3|RESULTS
3.1 |Study selection
After removing the duplicates literature search yielded 120 records.
After excluding the irrelevant title and abstracts, 17 studies were
chosen to be potentially eligible for the review. Of which, three did
not report vitamin D levels; one did not have a control group and in
the other five, RAS was the manifestation of the other disease.
Finally, eight studies were included for the final review. Details of the
study selection are depicted in Figure 1.
FIGURE 1 Flow diagram of literature search.
SAFARIFARAMANI ET AL.
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3.2 |Study characteristics
The characteristics of the included casecontrol studies are presented
in Table 1.
Eight studies including 383 healthy control and 352 patients with
RAS were eligible for the metaanalysis. The mean age of the
participants ranged from 8.7 to 36.4 in RAS patients and 7.6 to 40.8
in healthy controls.
Out of eight studies included in the metaanalysis, two studies
were from Iran (Bahramian et al., 2018; Khabbazi et al., 2015),
three from Turkey (Nalbantoğlu & Nalbantoğlu, 2019; Öztekin &
Öztekin, 2018; Tamer & Avcı,2019), one from Poland (Krawiecka
et al., 2017), one from United Arab Emirates (Suhail et al., 2019), and
one from Iraq (Ali, 2019).
One study (Bahramian et al., 2018) reported vitamin D levels on
saliva and serum and the rest of studies on serum. Five studies assessed
the association between serum levels of vitamin D and RAS variables
such as duration, severity, and frequency (Ali, 2019; Khabbazi
et al., 2015; Krawiecka et al., 2017; Liberati, 2009; Suhail et al., 2019).
The measurement method of serum levels of vitamin d in three
(Ali, 2019; Khabbazi et al., 2015;Nalbantoğlu & Nalbantoğlu, 2019)
studies was ELISA (enzymelinked immunosorbent assay) and four
(Bahramian et al., 2018; Krawiecka et al., 2017; Öztekin & Öztekin, 2018;
Suhail et al., 2019) studies was ECLAI (electrochemiluminescencbinding
assay) and one study did not report (Tamer & Avcı,2019).
Mean age, male percent, rest of the data are shown in Table 1.
3.3 |Risk of bias assessment
Results of the risk of bias assessment for individual studies are presented
in Table 2. The total score for all the included studies was more than 5.
3.4 |Metaanalysis reports
Figure 2shows serum levels of vitamin D in RAS and healthy controls.
Out of the eight included studies, two studies didn't find significant
differences between serum vitamin D levels in patients with RAS and
healthy controls (Bahramian et al., 2018; Krawiecka et al., 2017). One
study demonstrated a significant association between serum levels of
vitamin D and number ulcer in patients with RAS (Bahramian et al., 2018).
In general, serum vitamin D levels were significantly lower in RAS
patients. The weighted mean difference was 7.90 (95% CI: 11.96 to
3.85) which was significantly differ from zero, (z= 3.82, p<.0001).
Heterogeneity χ
2
was 45.7 (degree of freedom = 7, p< .0001) (Figure 2).
3.5 |Publication bias
The symmetrical funnel plot using the Begg's and Egger's tests
showed low risk of publication bias (the pvalues for the Begg' and
Egger's tests were .536 and .851, respectively).
TABLE 1 Characteristics of studies included in the systematic review on comparing the level of vitamin D levels in RAS patients and the healthy controls.
Author Year of publication, country
Mean age, male percent (%)
Method RAS type
Sample size
Mean ± SD of serum vitamin D
(ng/mL)
RAS patients Healthy controls RAS patients Healthy controls RAS patients Healthy controls
Funda Tamer 2018, Turkey 3425 33.930 NR Minor 20 20 13.6 ± 6.5 20.9 ± 10
AlAmad Suhail 2019, United Arab Emirates 3466 3166 ECLIA Idiopathic minor 52 52 53.6 ± 24.6 51.1 ± 26.9
Ayla Bahramian 2018, Iran 38.861.5 40.865.4 ECLIA Idiopathic minor 26 26 33.07 ± 12.41 50.89 ± 9.3
Alireza Khabbazi 2014, Iran 33.460.8 34.161.2 ELISA Idiopathic minor 46 49 12.1 ± 7.7 27.4 ± 9.7
Ewa Krawiecka1 2017, Poland 34.1536.4 32.0524.2 ECLIA Minor, major, herpetiform 66 66 16.81 ± 8.45 19.22 ± 10.44
Aynure Öztekin 2018, Turkey 31.237.5 27.445.7 ECLIA Idiopathic minor 40 70 11 ± 7.03 16.4 ± 10.19
Nalbantoğlu, A. 2019, Turkey 8.746.1 7.651.4 ELISA Idiopathic minor 72 70 16.4 ± 8.6 23.1 ± 11.5
Ali, N. S. M. 2019, Iraq 36.40 33.640 ELISA Idiopathic minor 30 30 13.9 ± 12.72 22.08 ± 17.779
Abbreviations: ELISA, enzymelinked immunosorbent assay; RAS, recurrent aphthous stomatitis.
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SAFARIFARAMANI ET AL.
3.6 |Sensitivity analysis
Sensitivity analysis was performed by omitting one study in turn, with
the pooled weighted mean difference varied between 9.04 (95% CI:
10.72 to 7.37) and 5.97 (95% CI: 7.62 to 4.34), supporting the
stability of the results.
3.7 |The quality of the systematic review
The quality of evidence was evaluated using the second version of
AMSTAR tool. A score of 15 out of 16 was obtained.
4|DISCUSSION
In the present study published evidence on the role of vitamin D
deficiency in the occurrence of RAS has been systematically
reviewedandtheresultshavebeensummedupviameta
analysis. Based on the results, the serum level of vitamin D was
significantly lower in patients suffering RAS compared to the
healthy controls. However, we did not find an association between
a vitamin D deficiency and frequency of ulcers in RAS patients.
Previous research has often associated multivitamin deficiency in
RAS patients with hematinic deficiencies such as vitamin B12, folic
acid, and iron (Chen et al., 2015). However, our systematic review
indicates that vitamin D levels appear to be lower in RAS patients
compared to controls.
RAS is a painful condition that negatively impacts eating, speech,
and oral hygiene. The frequent and severe relapses can significantly
reduce the quality of life. The exact cause of RAS is not completely
understood (LopezJornet et al., 2014; Saikaly et al., 2018). The
results of the current study consistent with many previous studies
that demonstrated Low levels of vitamin D in autoimmune diseases
such as rheumatoid arthritis, systemic lupus erythematosus, MS, type
1 diabetes, inflammatory bowel disease, and psoriasis (BerglerCzop
& BrzezińskaWcisło, 2016; Cutolo et al., 2006; Hyppönen
et al., 2001; Teichmann et al., 1999).
How vitamin D affects RAS is not yet well understood. Given
that the immunological context for RAS has been determined. The
VDR and the vitamin D activating enzyme (1αhydroxylase)
TABLE 2 Risk of bias assessment of primary studies based on
NewcastleOttawa scale for case control studies.
Author Selection Comparability Exposure
Total
score
Funda Tamer 2 1 2 5
AlAmad Suhail 3 1 2 6
Ayla Bahramian 3 1 2 6
Alireza Khabbazi 3 1 2 6
Ewa Krawiecka1 3 1 2 6
Aynure Öztekin 3 1 2 6
Nalbantoğlu, A. 3 1 3 7
Ali, N. S. M. 2 1 2 5
FIGURE 2 Weighted mean difference (WMD) of vitamin D levels between RAS patients and the healthy controls. Random effects model
was applied. RAS, recurrent aphthous stomatitis.
SAFARIFARAMANI ET AL.
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are expressed in various immune cells found, including T cells,
macrophages, and dendritic cells and in the epithelial tissue of the
oral mucosa. Low levels of vitamin D in RAS patients were associated
with the VDR, proinflammatory cytokines, strong immunomodulatory
effects, and T helper cells. T helper cells induce proinflammatory
cytokines, leading to epithelial damage or ulcers (Adorini, 2002; Chen
et al., 2015).
Vitamin D deficiency in RASrelated diseases such as Behcet's
syndrome and PFAPA (priodic fever, aphthous stomatitis, pharangits,
and cervical adenitis) that one of the main symptoms of which is RAS,
has been proven (Aslan et al., 2017; Faydhi et al., 2022). According to
Ainure Oztekin study, patients with RAS could benefit from taking
vitamin D as a supportive treatment (Öztekin & Öztekin, 2018).
Therefore, reducing vitamin D levels might play a role in the
development of RAS, for the reasons mentioned above.
Limitations: (1) Studies did not have a similar method for
measuring vitamin D levels. (2) Patients with different types of RAS
were included in the studies. (3) varying maletofemale ratios.
(4) The geographical location of the studies, which were seven
conducted in Asia. These factors contributed to high heterogeneity
between the studies.
Strengths: (1) we had no publication bias across studies. (2) One
study being of high quality and seven studies being of moderate
quality according to the NOS tool. (3) Most studies were matched
by sex and age. (4) Sensitivity analysis supported the stability
of the results.
5|CONCLUSION
There was a relationship between low vitamin D in serum and RAS.
Therefore, it may be worthwhile to check vitamin D levels in patients
with RAS.
AUTHOR CONTRIBUTIONS
Roya SafariFaramani, Mohsen Salehi, and Saman Ghambari Haji
Shore conceived and designed the study, formulated the research
question, helped in the design of the study, including the screening of
the retrieved records, interpretation of the results as well as the draft
of this paper. Neda Omidpanah, Mohsen Salehi, and Saman Ghambari
Haji Shore screened the retrieved records, extracted the data for this
study, and performed the statistical analysis and interpretation of the
results as well as the draft of this paper. All three authors have given
final approval for this study to be published.
ACKNOWLEDGMENTS
This study is a part of dissertation for Doctoral degree in dentistry
approved in Kermanshah University of Medical Sciences by Mohsen
Salehi. The work was supported by the research deputy of
Kermanshah University of Medical Sciences. This study is a part of
Mohsen Salehi's thesis and has been approve and funded by the
Research Committee of Kermanshah University of Medical Sciences.
The grant number was 980874.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
DATA AVAILABILITY STATEMENT
The data will be avaible upon the request.
ETHICS STATEMENT
This article does not contain any studies with human participants or
animals performed by any of the authors.
ORCID
Neda Omidpanah http://orcid.org/0000-0003-4300-8785
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How to cite this article: SafariFaramani, R., Salehi, M.,
Ghambari Haji Shore, S., & Omidpanah, N. (2023). Serum level
of vitamin D in patients with recurrent aphthous stomatitis: A
systematic review and metaanalysis of case control studies.
Clinical and Experimental Dental Research,17.
https://doi.org/10.1002/cre2.794
SAFARIFARAMANI ET AL.
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Background The contribution of vitamin D to thyroid disorders has received paramount attention; however, results are mixed. Hence, we designed a systematic review and meta-analysis to obtain a definitive conclusion. Methods The search included PubMed, ISI Web of Science, Scopus, and Google Scholar databases up to March 2021 to collect available papers reporting the relationship between serum levels of vitamin D and thyroid disorders. The pooled effect was reported as weighted mean difference (WMD) and 95% confidence interval (CI). Results Out of 6123 datasets, 42 were eligible to get into this systematic review and meta-analysis. Serum vitamin D was markedly lower in autoimmune thyroid diseases (AITD) (WMD − 3.1 ng/dl; 95% CI, − 5.57 to − 0.66; P = 0.013; I ² = 99.9%), Hashimoto’s thyroiditis (HT) (WMD − 6.05 ng/dl; 95% CI, − 8.35 to − 3.75; P < 0.001; I ² = 91.0%) and hypothyroidism patients (WMD − 13.43 ng/dl; 95% CI, − 26.04 to − 0.81; P = 0.03; I ² = 99.5%), but not in subjects with Graves’ disease (GD) (WMD − 4.14 ng/dl; 95% CI, − 8.46 to 0.17; P = 0.06; I ² = 97.5%). Conclusions Our findings suggested lower vitamin D levels in patients with hypothyroidism, AITD, and HT compared to healthy subjects. However, the link between serum vitamin D and GD was only significant among subjects ≥40 years old.
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Background Recurrent aphthous stomatitis is one of the most prevalent oral mucosa diseases and the etiology is unclear. As a potent anti-inflammatory and immunomodulating agent, vitamin D can significantly affect oral cavity homeostasis. However, to the best of our knowledge, no study has been conducted in pediatric population on the potential role of vitamin D in recurrent aphthous stomatitis to date. The aim of the present study is to determine the vitamin D status in recurrent aphthous stomatitis in children. Methods This study is conducted retrospectively. Seventy-two patients with minor recurrent aphthous stomatitis and 70 age-matched healthy controls included in the study. 25-Hydroxyvitamin D levels were measured in all patients using enzyme immunoassay. Results Serum vitamin D levels were 16.4 (8.6) ng/mL in patient group and 23.1 (11.5) ng/mL in healthy controls. There was a statistically significant difference between the groups in terms of serum vitamin D levels ( P = .002). There was no significant correlation between serum vitamin D levels and the severity of the recurrent aphthous stomatitis ( r = 0.54, P = .76). Conclusions Our study showed a significant difference in vitamin D levels between patients with recurrent aphthous stomatitis and the healthy control group. We also found no correlation between vitamin D status and the severity of the disease.
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Statement of the problem: Recurrent aphthous stomatitis (RAS) is the most prevalent ulcerative condition of the oral mucosa. Many studies have emphasized on immunologic factors as the reason of inducing RAS; however, the exact etiologic cause of RAS has not been identified yet. Vitamin D has an endocrine function and regulatory effects on the immune system. It has potential therapeutic effects on autoimmune diseases, psoriasis, and neoplasms. Vitamin D deficiency has been detected in some autoimmune diseases such as rheumatoid arteritis. Purpose: The aim of the present study was to compare the serum and salivary levels of vitamin D in patients with RAS and healthy individuals. Materials and method: In this cross sectional study, patients with RAS, referring to the Department of Oral Medicine, Tabriz Faculty of Dentistry, were evaluated after taking medical history, clinical examinations, and completing an informed consent form. The serum and salivary vitamin D levels were compared between case (n=26) and control (n=26) groups. Results: The mean serum vitamin D levels in the case and control groups were 33.0.7±12.41 and 50.89±9.30 (ng/dL), respectively, with a statistically significant difference (p<0.001). On the other hand, the mean salivary vitamin D levels in the case and control groups were 17.36± 8.01 and 20.79±6.31 (ng/dL), respectively, with no statistically significant difference (p= 0.09). In addition, the correlation between the serum and salivary levels of vitamin D was 56%, being statistically significant (p< 0.001). Conclusion: The serum levels of vitamin D in patients with RAS were significantly less than that in healthy individuals; however, there were no significant differences in salivary vitamin D levels between patients with RAS and healthy individuals. In addition, there was a significant and positive correlation between serum and salivary levels of vitamin D in all patients.
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Background Lower serum vitamin D levels, a major public health problem worldwide, has been found to be associated with various infectious diseases, cancers, autoimmune and dermatological diseases. The serum levels of vitamin D in patients with recurrent aphthous stomatitis are not clear. We investigated the vitamin D levels in patients with recurrent aphthous stomatitis. Methods Forty patients with recurrent aphthous stomatitis (Group I) and 70 healthy controls (Group II) included in the study. The characteristics of aphthous lesions (duration of disease and remission, frequency, diameter and number of the lesions) and demographics of the participants were recorded. Serum 25-hydroxycholecalciferol levels were measured using electrochemiluminescence binding method. Results There was no statistically significant difference between the groups in terms of age (p = 0.06) and sex (p = 0.4). Other baseline characteristics were not significantly different between the groups (p > 0.05 for all). The mean diameter of aphthous lesions was 0.5 (0.4–0.6) cm and the mean number of lesions was 2.2 ± 1.5. Serum vitamin D levels were 11 ± 7.04 ng/ml in Group I and 16.4 ± 10.19 ng/ml in Group II. Serum vitamin D levels were significantly lower in patients with recurrent aphthous stomatitis (p = 0.004). Conclusions The present study showed lower vitamin D levels in patients with recurrent aphthous stomatitis compared to healthy controls.
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Introduction: Recurrent aphthous stomatitis (RAS) is a common chronic inflammatory oral mucosa disease with an unknown cause. However, dysregulation of the immune response seems to play an important role in this disease. Aim : To evaluate the vitamin D status in RAS patients and its effects on RAS severity, given the likely immunomodulatory function of vitamin D in the human organism. Material and methods : Sixty-six patients with RAS and 66 controls were examined. Immunomodulatory or immunosuppressive treatment and other ulcerative oral diseases were used as exclusion criteria. The severity of RAS was assessed according to the clinical classification of the disease, the number of lesions per flare-up and the length of intervals between the attacks. The serum vitamin D level was established in each participant. Results : The mean serum vitamin D (25(OH)D) levels were found to be 16.81 ng/ml in the study group and 19.22 ng/ml in the control group, with no statistically significant difference between the two groups. In the study group, 5 (7.6%) participants were diagnosed with the “normal” vitamin D levels, while 16 (24.2%) had “insufficient” levels and 45 (68.2%) had “deficient” levels. The corresponding distribution in the control group was 8 (12.1%), 18 (27.3%) and 40 (60.6%), respectively. There was no statistical significance in the difference of vitamin D deficits between the study and the control groups. No correlation was detected between the severity of RAS and the serum vitamin D level. Conclusions : Vitamin D does not seem to be a trigger factor for RAS occurrence and does not appear to influence the severity of the disease in the studied group.
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The number of published systematic reviews of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions. Systematic reviews are subject to a range of biases and increasingly include non-randomised studies of interventions. It is important that users can distinguish high quality reviews. Many instruments have been designed to evaluate different aspects of reviews, but there are few comprehensive critical appraisal instruments. AMSTAR was developed to evaluate systematic reviews of randomised trials. In this paper, we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic reviews, including those based on non-randomised studies of healthcare interventions.
Article
Periodic Fever, Aphthous Ulcers, Pharyngitis and Adenitis (PFAPA) Syndrome’s etiology is not well understood. The objective of this study is to explore the association between vitamin D level and PFAPA syndrome. A systematic review of all publications addressing the association between vitamin D level and PFAPA syndrome prior to May 2019 was conducted. Data were collected from online medical databases namely, PubMed, Ovid Medline, Embase, Cochrane Library, Google Scholar, and Scopus. The review adhered to the PRISMA statement and was performed in 3 main phases; an initial screening review of abstracts was performed, followed by a detailed review of full articles based on inclusion and exclusion criteria, and lastly a final review to extract data from selected articles. 3 prospective review-based and one case report articles were included with a total of 281 patients, 98 of whom were cases of PFAPA, while 183 were controls. Vitamin D levels were deficient in 27% of PFAPA group as compared with the control. Vitamin D supplementation was given as an initial treatment in 25/98 of the patients. Only 1 patient received it as a second treatment. After vitamin D supplementation, a marked reduction of the number of febrile episodes and modification of the mean duration were recognized. There may be an association between Vitamin D deficiency and a higher frequency of PFAPA episodes. Vitamin D supplementation in children with PFAPA may reduce the frequency of episodes and help manage the condition.
Article
Background: Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosa diseases characterized by recurrent, shallow, round or oval painful oral ulcers surrounded by inflammatory erythematous halos, the condition is chronic and self-limiting in immunocompetent patients. Aim of the study: to investigate the serum vitamin D levels in Iraqi female patients with RAS and the relationship between vitamin D levels and the severity of RAS. In this cross sectional study 30 female patients with idiopathic RAS, and 30 age and sex matched healthy controls were included, the severity of RAS is assessed by the number of oral aphthous ulcers in each attack and the frequency of attacks. Serum 25(OH) D levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method in both RAS patients and control groups. The mean serum vitamin D (25(OH)D) levels were found to be below the normal range (< 30 ng/ml) in both the RAS patients (13.9±12.72 ng/ml) and the control (22.08 ±17.779 ng/ml) groups, with statistically significant difference between the groups (p =0.045). There was a significant correlation between the serum levels of 25(OH) D and the number of oral aphthous ulcers in each attack (r =0.435; p= 0.016). © 2019, Indian Journal of Public Health Research and Development. All rights reserved.
Article
Purpose of Article: This review examines studies published between May 2012 and May 2017 with a specific interest in potential recurrent aphthous ulceration (RAU) etiologies and treatment modalities/efficacy, including topical treatments, systemic regimens, vitamin repletion, and laser therapy, among others. Materials and Methods: PubMed MEDLINE and Cochrane Database of Systematic Reviews were searched using various combinations of: ‘aphthous’, ‘ulcer’, and ‘treatment’. The titles and abstracts from the initial literature search were appraised to identify articles for full review, and reference sections from each article were searched manually for relevant publications. Both randomized controlled trials and observational reports were included in this review, as some treatment types have not been formally examined in randomized trials. Relevant studies were reviewed, compared, and summarized. Results: RAU can result from systemic disease and trauma, but recent studies have shown a variety of potential etiologies, ranging from vitamin deficiencies, oral microbiota derangements, hematological considerations, stress, genetic polymorphisms to oxidant-antioxidant imbalances, among others. Many modalities of therapy are available and have proven efficacious. Conclusions: As the exact etiology of RAU is still unknown, therapy is based on symptomatic relief.