Efficacy of Curcumin and Topical Steroids in the Treatment for Oral Submucous Fibrosis: A Comparative study.

CONTEXT: Oral submucous fibrosis (OSMF) is a chronic debilitating disease of the oral cavity, characterized by inflammation and progressive fibrosis of the submucosal tissues. The main agent involved in the pathogenesis of OSMF is areca nut. A wide range of treatment, including drug management, surgical therapy, and physiotherapy, has been attempted till date, with varying degrees of benefit. AIMS: The objective of this study was to assess efficacy of curcumin for the treatment of OSMF; to asses efficacy of topical steroids for the treatment of OSMF; and to compare the efficacy of curcumin and topical steroid for the treatment of OSMF. SETTING AND
DESIGN: Participants were assessed based subjective and objective feature of OSMF, i.e., burning sensation of the oral cavity and interincisal distance, respectively.
METHODOLOGY: Thirty participants were categorized into two groups: Group A was administered curcumin and Group B was administered topical steroids for a period of 3 months and followed up after 6 months. The assessment was based on maximal incisal opening and burning sensation for spicy food on Visual Analog Scale score. ANALYSIS: Independent t test was applied for comparison within the group, ANOVA Bonferroni post hoc test was applied for multiple comparison of mean and Mann-Whitney U test was applied to compare the groups.
RESULTS: The statistical analysis revealed curcumin to be more efficient than topical steroid.
CONCLUSION: The present study demonstrates the efficiency of curcumin and topical steroid to alleviate the clinical findings of OSMF. However, curcumin is comparatively more efficient than steroids for the treatment of OSMF. Copyright:

INTRODUCTION

Oral submucous fibrosis (OSMF) is an insidious, chronic, progressive potentially malignant condition disease affecting any part of the oral cavity characterized by juxta epithelial inflammatory reaction and progressive fibrosis of the submucosal tissues. The symptoms of OSMF include burning pain in the oral cavity, difficulty in mouth opening, loss of gustatory sensation, the presence of blanched fibrous bands, and stiffening of the oral mucosa and oropharynx. The prevalence rate of OSMF in India, Burma, and Africa ranges from 0% to 1.2% in India.[123]

The use of areca nut mainly results in disruption of homeostatic equilibrium between synthesis and degradation of extracellular matrix and affects the lamina propria of the oral mucosa and progresses to involve the submucosa of deeper tissue and muscles of oral cavity with resulting loss of fibro elasticity.[45]

Turmeric (Curcumin longa) is a medicinal plant extensively used in Ayurveda. Curcumin is a yellow colour phenolic pigment obtained from C. Longa Linn and has been demonstrated to have a wide spectrum of therapeutic effects.[6] Curcumin reduces the neutrophil infiltration in inflammatory conditions and inhibit platelet aggregation. It maybe hence hypothesized that anti inflammatory, antioxidant, and antifibrotic properties of curcumin acting simultaneously, may interfere with progression of OSMF at multiple stages in the pathogenesis of complex disease.[7]

Corticosteroids such as hydrocortisone, tri amcinolone, dexamethasone, and betamethasone have been used in the treatment of OSMF. Steroids suppress inflammatory reactions, thereby preventing fibrosis by decreasing fibroblastic proliferation and deposition of collagen.[2]

Hence, this study is an attempt to evaluate the efficacy of curcumin and topical corticosteroids in the treatment for oral submucous fibrosis.

METHODOLOGY

This study was conducted on a total of 30 participants of clinically diagnosed OSMF reporting to the Outpatient Department of Oral Medicine and Radiology, V. S. Dental College and Hospital, Bangalore, India.

It included subject in the age group of 20–60 years, clinically diagnosed with OSMF with features of inability to open mouth, blanching, burning sensation on intake of hot and spicy food, and palpable fibrous bands.

The sample design selected was purposive sampling with a duration of 1½ years.

Materials used in clinical examination

Conventional dental chair with illumination, A pair of disposable sterile gloves and mouth mask, 1 plain of mouth mirror (No. 5), straight probe, metal scale, gauze and cotton roll, tumbler with water, pair of tweezers and kidney tray [Figure 1].

Figure 1

Armamentarium for clinical examination

Methodology

A brief case history was recorded and if the clinical findings matched with inclusion criteria, the patients were informed about the procedures to be performed during the study. The patient was asked to sign the consent form, if they agreed to be a part of the study.

Mouth opening was determined by measuring the inter incisal distance, i.e., distance from mesioincisal angle of upper central incisor to mesioincisal angle of lower incisor with the help of a metal scale [Figure 2].

Figure 2

Method of measurement of mouth opening

Based on interincisor distance, the participants were divided into three functional stage according to Haider et al:[3]

Stage 1: mouth opening >20 mm

Stage 2: mouth opening 11–19 mm

Stage 3: mouth opening <10 mm.

Based on clinical examination, the participants were classified into three clinical stage according to Haider et al:[3]

Stage 1: Faucial bands only

Stage 2: Faucial and buccal bands only

Stage 3: Faucial, buccal, and labial bands.

Following this, a subjective examination was performed wherein the subject was asked to rate his/her burning sensation on intake of hot/spicy food using a Visual Analog Scale (VAS).[12345678910] [Figure 3].

Figure 3

Visual Analog Scale

The participants were recalled every 15 days for 3 months for the treatment, i.e., tablet curcubest 500 mg B. D for Group A [Figure 4] and topical steroid 0.01% thrice daily for Group B [Figure 5] and then after 6 months for follow-up.

Figure 4

Tablet curcubest

Figure 5

Triamcinolone acetonamide 0.1% (kenocortointment)

Statistical analysis

Independent Student's t-test: For comparison within the group.

ANOVA Bonferroni's post hoc test: For multiple comparison of mean.

Mann–Whitney U-test: For comparison between the groups.

RESULTS

The comparison of mean percentage increase in mouth opening between two groups at different time intervals using the Mann–Whitney U-test is shown in Table 1 and Graph 1.

Table 1

Comparison of mean percentage increase in mouth opening between two groups at different time intervals using Mann-Whitney U-test

Time	Group	n	Mean	SD	Mean Diff	Z	P
1 Month	Curcumin	15	10.65	17.33	4.28	-0.108	0.91
	Top Steroids	15	6.37	7.65
2 Months	Curcumin	15	19.75	17.12	0.76	-0.914	0.36
Top Steroids	15	18.99	25.22
3 Months	Curcumin	15	23.48	17.89	-1.10	-0.249	0.80
	Top Steroids	15	24.58	24.67
6 Months	Curcumin	15	25.65	18.25	8.85	-0.934	0.35
	Top Steroids	15	16.79	23.73

Graph 1

Comparison of mean percentage increase in mouth opening between two groups at different time intervals using the Mann–Whitney U-test

Test results demonstrated that curcumin group showed relatively higher mean mouth opening as compared to topical steroid group at different time intervals ranging from 1 to 6 months. The mean increase in mouth opening between curcumin group and topical steroid group in 6th mouth opening showed no difference (P = 0.35).

The comparison of mean percentage decrease in burning sensation between two groups at different time intervals using the Mann–Whitney U-test is shown in Table 2 and Graph 2.

Table 2

Comparison of mean percentage decrease in burning sensation between two groups at different time intervals using Mann Whitney U test

Time	Group	n	Mean	SD	Mean Diff	Z	P
1 Month	Curcumin	15	22.53	18.69	6.41	-1.08	0.28
	Top Steroids	15	16.12	18.71
2 Months	Curcumin	15	31.56	14.48	-4.99	-0.957	0.34
	Top Steroids	15	36.55	20.93
3 Months	Curcumin	15	43.75	20.19	-14.06	-1.834	0.07
	Top Steroids	15	57.81	18.04
6 Months	Curcumin	15	69.22	14.38	-4.76	-1.044	0.30
	Top Steroids	15	73.98	12.37

Graph 2

Multiple comparison of mean difference in mouth opening (in cm) between different time intervals in topical steroid group

Test results demonstrated that curcumin group showed relative decrease in burning sensation as compared to topical steroid group at different time intervals ranging from 1 to 6 months. The mean decrease in burning sensation between curcumin group and topical steroid group in the 6th month showed no difference (P = 0.30).

Multiple comparison of mean difference in burning sensation between different time intervals in curcumin group using Bonferroni post hoc test is shown in Table 3 and Graph 3.

Table 3

Multiple comparison of mean difference in burning sensation between different time intervals in curcumin group using Bonferroni post hoc test

(I) TIME	(J) TIME	Mean Diff (I-J)	95% CI for the Diff Lower Upper	P
1st Visit	1 Month	1.40	0.44 2.36	0.003*
	2 Months	2.07	1.31 2.83	<0.001*
	3 Months	3.00	1.92 4.08	<0.001*
	6 Months	4.73	3.63 5.83	<0.001*
1 Month	2 Months	0.67	0.05 1.29	0.03*
	3 Months	1.60	0.35 2.85	0.008*
	6 Months	3.33	1.89 4.77	<0.001*
2 Months	3 Months	0.93	-0.07 1.93	0.08
	6 Months	2.67	1.47 3.87	<0.001*
3 Months	6 Months	1.73	0.85 2.62	<0.001*

Graph 3

Comparison of mean percentage decrease in burning sensation between two groups at different time intervals using Mann–Whitney U-test

The multiple mean comparison by ANOVA and Bonferroni correction showed that there was a statistical significant difference between the baseline and the subsequent visit (P < 0.05).

The mean difference between the 1st month visit with other subsequent visit was statistically significant (P < 0.05).

The mean difference between the 2nd month follow-up with the subsequent follow-up showed statistically significant difference except for the 3rd month follow-up (P > 0.05).

Multiple comparison of mean difference in mouth opening (in cm) between different time intervals in curcumin group using Bonferroni s post hoc test is shown in Table 4 and Graph 4.

Table 4

Multiple comparison of mean difference in mouth opening (in cms) between different time intervals in curcumin group using Bonferroni’s Post hoc Test

(I) TIME	(J) TIME	Mean Diff (I-J)	95% CI for the Diff Lower Upper	P
1st Visit	1 Month	-0.21	-0.47 0.04-0.65-0.13-0.75-0.20-0.77-0.25	0.15
	2 Months	- 0.39		0.002*
	3 Months	- 0.47		0.001*
	6 Months	- 0.51		<0.001*
1 Month	2 Months	-0.18	-0.34-0.02-0.47-0.05-0.49-0.11	0.02*
	3 Months	- 0.26		0.009*
	6 Months	- 0.30		0.001*
2 Months	3 Months	-0.08	-0.16 0.00-0.20-0.04	0.04*
	6 Months	- 0.12		0.002*
3 Months	6 Months	-0.04	-0.09-0.09	0.28

Graph 4

Multiple comparison of mean difference in mouth opening (in cm) between different time intervals in curcumin group using Bonferroni post hoc test

The multiple mean comparison by ANOVA and Bonferroni correction showed that there was a statistical significant difference between the baseline and the subsequent visit (P < 0.05).

The mean difference between the 1st month visit with other subsequent visit was statistically significant (P < 0.05).

The mean difference between the 2nd month follow-up with the subsequent follow-up showed statistically significant difference except for the 3rd month follow-up (P > 0.05).

The mean difference between the 3rd month follow-up with the subsequent follow-up showed no statistical significance (P < 0.05).

Multiple comparison of mean difference in mouth opening (in cm) between different time intervals in topical steroid group is shown in Table 5 and Graph 5.

Table 5

Multiple comparison of mean difference in mouth opening (cm) between different time intervals in topical steroid group

(I) TIME	(J) TIME	Mean Diff (I-J)	95% CI for the Diff Lower Upper	P
1st Visit	1 Month	-0.13	-0.24-0.02-0.82 0.04-0.90-0.11-0.72 0.03	0.02*
	2 Months	- 0.39		0.10
	3 Months	- 0.51		0.008*
	6 Months	- 0.35		0.08
1 Month	2 Months	-0.26	-0.71 0.19-0.80 0.04-0.35-0.11	0.74
	3 Months	- 0.38		0.09
	6 Months	- 0.22		0.46
2 Months	3 Months	-0.12	-0.21-0.03-0.67 0.75	0.004*
	6 Months	0.04		1.00
3 Months	6 Months	0.16	-0.52 0.84	1.00

Graph 5

Multiple comparison of mean difference in burning sensation between different time intervals in topical steroid group

The multiple mean comparison by ANOVA and Bonferroni correction showed that there was a statistical significant difference between the baseline and the subsequent visit (P < 0.05) except for the 2nd month and 6th month visit (P > 0.05).

The mean difference between the 1st month visit with other subsequent visit was not statistically significant (P > 0.05).

The mean difference between the 2nd month visit was statistically significant (P < 0.05) except for the 6th month visit (P > 0.05).

The mean difference between the 3rd month visit was not statistically significant (P > 0.05).

Multiple comparison of mean difference in burning sensation between different time intervals in topical steroid group is shown in Table 6 and Graph 6.

Table 6

Multiple comparison of mean difference in burning sensation between different time intervals in topical steroid group

(I) TIME	(J) TIME	Mean Diff (I-J)	95% CI for the Diff Lower Upper	P
1st Visit	1 Month	1.13	0.07 2.18	0.03*
	2 Months	2.59	1.27 3.92	<0.001*
	3 Months	4.06	2.83 5.30	<0.001*
	6 Months	5.20	4.22 6.18	<0.001*
1 Month	2 Months	1.47	0.26 2.68	0.01*
	3 Months	2.93	1.43 4.44	<0.001*
	6 Months	4.07	2.85 5.30	<0.001*
2 Months	3 Months	1.47	0.30 2.63	0.009*
	6 Months	2.61	1.71 3.50	<0.001*
3 Months	6 Months	1.14	0.35 1.93	0.003*

Graph 6

Multiple comparison of mean difference in burning sensation between different time intervals in curcumin group using Bonferroni post hoc test

The multiple mean comparison by ANOVA and Bonferroni correction showed that there was a statistical significant difference between the baseline and the subsequent visit (P < 0.05).

The mean difference between the 1st month visit with other subsequent visit was statistically significant (P < 0.05).

The mean difference between the 2nd month follow-up with the subsequent follow-up showed statistically significant (P < 0.05).

The mean difference between the 3rd month follow-up with the subsequent follow-up showed statistically significant (P < 0.05).

Statistical analysis with unpaired t-test shows significant relation with P < 0.05.

DISCUSSION

In Oral submucous fibrosis is a chronic debilitating disease and a well recognized potentially malignant condition of oral cavity associated with betel nut chewing. OSMF is characterized by a generalized submucosal fibrosis of the oral soft tissue, resulting in marked rigidity and progressive inability to open the mouth.

The disease was first termed as Atrophia Idiopathica Mucosae Oris and was reported by Schwartz. The definition, which is most widely accepted, was stated by Pindborg J.J. and Sirsat S.M. The disease is characterized by blanching and stiffness of oral mucosa, trismus, burning sensation, loss of mobility of tongue and loss of gustatory sensation. Majority of these cases are seen in Indian population. The prevalence varies from 0.20-0.5% in India with a higher percentage being found in the Southern parts of the country.[8]

In the present study the 30 subjects were in age range of 20-60 years with a mean of age of 40.0% who were divided in groups of 2. Group A was administered curcumin and group B were administered with topical steroids for a period of 3 months and were clinically and functionally assessed after 6 months.

Out of 30 subjects, 22 were males and 8 were females. A literature survey shows shows a wide variation in age and sex distribution of OS. A male predominance in OSF cases was shown by Sinor et al in India.[9] We also observed a male predominance similar to observation by Kiran Kumar et al.[10]

A study conducted by Hazarey et al (2014) to compare curcumin with clobetasol propionate in treatment of OSMF was done for a period of 3 months. The P value for test of the difference in the pre and postop interincisal opening between the test (curcumin) and control (topical steroid) group was found to be 0.0002, which is statistically significant. The P value for the difference between the VAS score of the test (curcumin) and control group was found to be 0.0047, which is statistically significant.[7]

Another study 30 subjects diagnosed with OSMF were included for the study. The patients were administered 4% curcumin orabase topically three times a day; efficacy of the therapy was evaluated considering the mouth opening and burning sensation of the subjects as parameters. The evaluation was done on a timely basis for a period of three months, and the data was then evaluated. The results showed a improvement in mouth opening and the decrease in burning sensation which were statistically significant (p<0.0001). It was thus concluded that 4% Curcumin orabase can also be considered as a best alternative treatment in OSMF.[11]

CONCLUSION

Based on the observation of our study, the following conclusion can be drawn:

A definite correlation exists between OSMF and reduction in mouth opening and increase in burning sensation on intake of normal and spicy food

Exclusion of contributory factors such as trismus, temporomandibular joint disorders, and pericoronitis is mandatory to clinically diagnose OSMF

The sample size in the present study consists of 30 participants which is relatively small as compared to other studies undertaken for similar objective with varying result. Therefore, multicentric studies with definitely larger sample size are required

The efficacy of curcumin for the treatment of OSMF for a period of 3 months proved to be statistically significant

The efficacy of topical steroids for the treatment of OSMF for a period of 3 months proved to be statistically significant

Comparison of increase in mouth opening between curcumin and steroids at the end of 6 months shows curcumin to be more efficient than steroids

Comparison of decrease in burning sensation between curcumin and steroids at the end of 6 months also shows curcumin to be more efficient than steroids.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.