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 Table of Contents  
Year : 2021  |  Volume : 33  |  Issue : 3  |  Page : 236-241

Colchicine as a therapeutic drug in the management of oral submucous fibrosis - A randomized clinical study

1 Department of Oral Medicine and Radiology, Narayana Dental College and Hospital, Nellore, Andhra Pradesh, India
2 Department of Pediatric and Preventive Dentistry, SVS Institute of Dental Sciences, Mahabubnagar, Telangana, India

Date of Submission24-Apr-2021
Date of Decision13-May-2021
Date of Acceptance28-Jun-2021
Date of Web Publication28-Sep-2021

Correspondence Address:
Dr. Somisetty V M. Mounika
Post-Graduate Student, Department of Oral Medicine and Radiology, Narayana Dental College and Hospital, Nellore, Andhra Pradesh - 524 003
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaomr.jiaomr_108_21

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Aim: The present study was planned to clinically determine the effectiveness of colchicine as a monotherapy in oral submucous fibrosis (OSMF) patients. Materials and Methods: Thirty OSMF patients were enrolled in the study and randomly divided into two groups by permuted-block randomization. Group A: Patients were treated with 0.5 mg colchicine (Goutnil) tablets twice daily for 3 months. Whereas, in Group B, intralesional injection of dexamethasone 2 mL, hyaluronidase 1,500 IU with 2 mL lignocaine HCl biweekly for 4–6 weeks were given. For all the individuals, baseline parameters like mouth opening, buccal mucosal flexibility, burning sensation, and tongue protrusion were recorded and reassessment was done at 1, 3, and 6 months followed by statistical analysis. Results: A significant decrease in the Visual Analogue Scale (VAS) score for severity of burning sensation was observed in Group A whereas mouth opening and tongue protrusion were higher in Group B patients. Statistically significant differences in the buccal mucosal flexibility were appreciable in the intragroup comparisons of both the groups from baseline to 6-month follow-up. Conclusion : Colchicine can be suggested as an adjuvant drug for reducing the burning sensation for the OSMF patients in whom steroids are contraindicated.

Keywords: Colchicine, dexamethasone, hyaluronidase, intralesional injections, oral submucous fibrosis

How to cite this article:
M. Mounika SV, Manne RK, Kannan N, Beeraka SS, Sarath PV, Saikiran KV. Colchicine as a therapeutic drug in the management of oral submucous fibrosis - A randomized clinical study. J Indian Acad Oral Med Radiol 2021;33:236-41

How to cite this URL:
M. Mounika SV, Manne RK, Kannan N, Beeraka SS, Sarath PV, Saikiran KV. Colchicine as a therapeutic drug in the management of oral submucous fibrosis - A randomized clinical study. J Indian Acad Oral Med Radiol [serial online] 2021 [cited 2022 Dec 7];33:236-41. Available from: http://www.jiaomr.in/text.asp?2021/33/3/236/326890

   Introduction Top

Human beings are more prone to physical and mental stress in recent years due to urbanization and industrialization. Some humans respond to this stress by indulging in habits like smoking, alcohol consumption, areca nut, tobacco chewing, and pan chewing. Apart from being addictive, these habits may also cause many detrimental effects on the human body. Medical practitioners and dental surgeons often encounter a wide variety of oral mucosal lesions in routine clinical practice. One such oral potentially malignant disorder is oral submucous fibrosis (OSMF).[1]

OSMF is a chronic, insidious mucosal disease caused mainly by the usage of areca nut and other factors like excessive chilly consumption, nutritional deficiencies, autoimmunity, genetic, and environmental factors.[2] In the early stages, it is characterized by a burning sensation, increased or decreased salivation, and mucosal blanching with a marble-like appearance. Later, the mucosa becomes leathery with palpable fibrous bands resulting in the progressive reduction of mouth opening and tongue protrusion. Eventually, it leads to difficulty in swallowing, speech and hearing defects and defective gustatory sensation.[3] Untreated and neglected cases can end up as squamous cell carcinoma. The malignant transformation rate is about 7–12%.[4],[5]

Currently, almost 10–20% of the world's population consumes areca nut in a wide variety of formulations. Various studies have been attempted to treat OSMF, including intralesional steroids, antioxidants, surgical therapy, and physiotherapy.[6],[7],[8] But none have been able to show the complete regression of the condition. Hence, the search for an effective treatment modality continues.

Colchicine is an alkaloid found in the crocus-like plant, Colchicum Autumnale, chemically known as colchicum-N-(5, 5, 7, 9-tetrahydro-1, 2, 3, 10-tetramethoxy 9 oxo benzo[alpha] heptalen-7-yl) acetamide. It has anti-fibrotic and anti-inflammatory properties. It has been reported that colchicine-inhibited procollagen secretion and its conversion to collagen, and thus, specifically inhibited collagen synthesis. Colchicine is toxic in doses greater than 0.1 mg/kg. The most common toxic side effect of long-standing colchicine therapy may cause nausea, vomiting, diarrhea, and abdominal pain due to its action on the rapidly proliferating gastrointestinal tract epithelial cells. These symptoms are especially frequent at dosage levels 2–3 mg/day although they are completely reversible by appropriate symptomatic management.[9] The side effects are very minimal at doses less than or equal to 1 mg/day.

It has shown promising results in treating gout, recurrent aphthous stomatitis, and oral lichen planus and reducing fibrosis in liver and kidney diseases.[10],[11],[12],[13],[14] Very few studies have reported the use of colchicine in the management of OSMF. Daga D et al.[15] and Krishnamoorthy B et al.[16] stated that patients receiving colchicine along with an intralesional injection of hyaluronidase had better response in the management of OSMF in terms of increase in mouth opening and improvement in burning sensation without notable side effects. Buccal mucosal flexibility and tongue protrusion were not assessed in these studies. This is the first study to be carried out to clinically determine the effectiveness of colchicine as a monotherapy in the management of OSMF in terms of clinical status such as burning sensation, buccal mucosal flexibility, interincisal distance, and tongue protrusion.

   Materials and Methods Top

The present study was a therapeutic trial with a parallel study design and an allocation ratio of 1:1. The study has been carried out in the Department of Oral Medicine and Radiology in a dental College, India. Ethical clearance was obtained from the Institutional Ethical Committee (NDC/IECC/OMR/DISS/12-18/02) under the guidelines provided by the World Medical Association Declaration of Helsinki on ethical principles for medical research involving humans for studies. The study period was from January 2019 to January 2020. Before commencing the study, CTRI registration was done with vide letter no. (CTRI/2020/10/028680). A total of 30 participants were employed in the current study based on the previous study by Daga D et al.[15]

Sample size analysis

The sample size determination was done using the following formula:

n(sample size) = [z2s2]/d2

= (1.96)2 (1.75)2/1

= 3.8416×3.06/1

= 11.7649/1

= 11.7649

n= sample size, z=1.96 (95% confidence interval), s= 1.75 (mean value), d= 1 (Precision).

Hence 12 patients could be included.

Inclusion criteria

Patients clinically diagnosed as having OSMF of stages I, II, III were informed about the study protocol and recruited based on their willingness to take part in the study and readiness to accept regular follow-up protocol.

Exclusion criteria

The exclusion criteria included patients already receiving other treatment for OSMF, stage IV patients in whom oral carcinoma is present along with OSMF, pregnant patients, patients receiving immunosuppressant drugs, patients with difficulty in mouth opening due to reasons other than OSMF, and patients having fibrotic lesions other than OSMF.

Written informed consent was obtained from all the patients after explaining the study and treatment protocols. Detailed case history was recorded with particular emphasis on type, frequency per day, and duration of adverse habits (areca nut, gutka, or a combination of both). Based on the clinical findings, the final diagnosis of OSMF is given based on the criteria given by Babu S et al.[17] and was staged according to the criteria given by More CB et al. (2011).[18]

A table of random numbers was used to generate the random allocation sequence. Patients were assigned in two groups [Figure 1] using block randomization (permuted block randomization), with random block sizes of 4 and 6. A centralized assignment was used as an allocation concealment mechanism to prevent selection bias.
Figure 1: CONSORT flow diagram

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Group A: Treatment with 0.5 mg colchicine (Goutnil) tablets twice daily for 3 months. Group B: Treatment with intralesional injection of 2 mL dexamethasone, hyaluronidase 1,500 IU with 2 mL lignocaine biweekly for 4–6 weeks.

In the OSMF patients, the following parameters were measured:

  1. The intensity of the burning sensation using a Numerical Rating 10-point Visual Analogue Scale (VAS).
  2. The interincisal mouth opening between the mesioincisal edge of the upper-right central incisor to the mesioincisal edge of the lower right central incisor with the help of a scale [Figure 2].
  3. Buccal mucosal flexibility [Figure 3] according to Bailoor and Nagesh[6] V2 = Marked at 1/3rd the distance from the angle of the mouth on a line joining tragus and the angle of the mouth; V1 = patient was asked to blow his/her cheeks entirely, and the distance was measured between two points marked on the cheek. Buccal mucosal flexibility = V2 − V1.
  4. Tongue protrusion [Figure 4] with the scale from the normal mesioincisal angle of the upper central incisor to the tip of the tongue when maximally extended with mouth wide open.
Figure 2: Measurement of interincisal distance.

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Figure 3: Measurement of cheek flexibility.

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Figure 4: Measurement of tongue protrusion.

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All the clinical examinations were performed by a single trained and calibrated examiner. The selection of the areas of injection was based on clinical judgment. The baseline intensity of the burning sensation, interincisal mouth opening, buccal mucosal flexibility, and tongue protrusion values were recorded. This was followed by full-mouth scaling and therapeutic intervention was provided to the participant according to the group assigned. Reassessment of all the participants was done after 3 and 6 months. All the data obtained were subjected to statistical analysis at the end of the study.

The data were entered the Microsoft Excel spreadsheet 2013. The statistical analysis was performed by using the SPSS 17.0 version for Windows (Chicago, IL, USA). The normality of the data was tested using the Shapiro–Wilk test. To test the association between the groups, the Chi-square test was used. To test the mean difference between two groups, a Student's t-test (paired sample t-test and independent sample t-test) was used. All the P values less than 0.05 were considered statistically significant.

   Results Top

A total of 30 participants, 15 in each group with 11 males, 4 females in group A and 10 males, 5 females in group B, and mean age of 42.65 ± 11.51 were recruited into the study.

Intragroup comparisons:

The mean values of burning sensation, mouth opening, cheek flexibility, and tongue protrusion in group A and group B before the treatment were 6.33 ± 1.56, 29.00 ± 1.76, 10.42 ± 3.90, 30.93 ± 3.00 and 6.57 ± 1.70, 29.93 ± 2.50, 10.36 ± 4.19, 31.58 ± 4.74 respectively [Table 1]. Intragroup comparisons of the patients receiving colchicine showed significant improvement in burning sensation and mouth opening at all the follow-up intervals (P < 0.05). The buccal mucosal flexibility and tongue protrusion values were not significant at 1 month to 3 months follow-up.
Table 1: Intragroup comparisons of study parameters at different intervals of follow-up

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Whereas in group B, significant improvement was found in mouth opening and tongue protrusion at all intervals of follow-up. The values of burning sensation and buccal mucosal flexibility were not significantly altered at 3 months to 6 months follow-up.

Intergroup comparisons:

On observing the intergroup comparisons [Table 2], significant P values were found between both the groups at baseline to 1 month and 3 months to 6 months follow-up visits, whereas, from baseline to 6 months, no statistical difference was observed between the two groups in burning sensation. Similarly, statistical significance between both the groups for mouth opening was appreciated at baseline to 1 month only. Finally, there was no statistically significant difference seen in the buccal mucosal flexibility and tongue protrusion at all the time intervals between both the groups.
Table 2: Intergroup comparisons of study parameters at different intervals of follow-up

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   Discussion Top

OSMF is predominantly seen in South Asian countries like India, Sri Lanka, Pakistan, China, and Bangladesh, apart from its recorded presence in people of Indian origin in South Africa and a few parts of America. Consumption of excessive red chilies, chewing of areca nut, nutritional deficiencies, genetic susceptibility, autoimmunity, and collagen disorders are involved in the pathogenesis of OSMF. Teenagers and young adults are getting attracted to consuming commercially available areca nut products like gutka and pan masala due to marketing, publicity, and easy availability of such products.[19] The mean age of the OSMF patients in this study is like the mean age of OSMF patients stated by Sadaksharam J et al. and Yadav M et al.[20],[21] In our study, gutka chewers were more significant than betel quid chewers and other forms of smokeless tobacco. Similar findings were seen in the studies by Ali et al.[22] and Reichart et al.[23] about gutka and other areca nut products. This indicates that people having the areca nut as gutka are more likely to have the occurrence of OSMF. The abrasive nature of the areca nut causes continuous local trauma and irritation to the oral mucosa, leading to morphological changes.[24]

Though the contributory factors in the pathogenesis of OSMF are well-known, the treatment of this condition is still not curative. Many surgical treatments have been tried to cure OSMF, but no definitive or widely accepted treatment is currently available to date. Discontinuation of the habit is an essential foremost step before starting any treatment.[25] Intralesional injections with steroids have been used widely to treat OSMF. The mechanism of action of the steroids is by opposing the action of soluble factors generated by sensitized lymphocytes after activation by specific antigens. Steroids also act as immunosuppressive agents and suppress inflammatory reactions. This prevents fibrosis by decreasing fibroblastic proliferation and collagen deposition.[26],[27],[28] Many studies reported the beneficial effects of colchicine in treating disorders like gout in animals and human beings. A few authors have proposed colchicine as an effective agent to treat Behcet's syndrome, recurrent aphthous stomatitis, and oral lichen planus with positive results.[10],[11],[12] Daga D et al.[15] stated that intralesional injection of hyaluronidase along with oral colchicine gave better results in the management of OSMF without notable side effects.

A history of burning sensation was reported by all the patients at the start of the study. The decrease in the severity of burning sensation was more rapid in group A than group B suggestive of the usefulness of colchicine in the management of OSMF. This might be probably due to the anti-inflammatory effect of colchicine by its destabilizing action on the microtubules.

Group B patients had significant improvement only during the administration of intralesional injections. Group A patients showed a sustained increase in the mouth opening even after cessation of the treatment. However, the overall improvement in the mouth opening was higher in the group B patients. The improvement in the mouth opening in group A can be attributed to colchicine's anti-fibrotic effect as it inhibits procollagen secretion, reduces collagen synthesis, and downregulates fibroblast proliferation. It also prevents the extrusion of collagen fibers from the fibroblast and increases collagenolytic activity. One participant in group A did not show any clinical improvement during the study.

Buccal mucosal flexibility or cheek flexibility refers to suppleness and elasticity of the buccal mucosa. Cheek flexibility in our study was calculated based on the method given by Bailoor and Nagesh.[6] In the present study, a substantial difference in the comparison of cheek flexibility in both group A and group B with 5.95 and 9.94%, respectively was found, indicating the positive role of colchicine and the combination of dexamethasone + hyaluronidase. The increase in cheek flexibility might be due to decreased fibrinogenesis in both groups. The present study results were in accordance with a study done by Yadav M et al.[21] in the patients receiving a weekly intralesional injection of 4 mg dexamethasone and 1,500 IU hyaluronidase. In the present study, interventional drugs were well-tolerated by patients in both groups. Both the therapeutic interventions used in the present study help in reducing the symptoms of OSMF.

Limitations and Future Prospects

The limitation of the study was the relatively small sample size owing to time and resource constraints. Multicentric studies involving a larger sample size with more extended periods of follow-up would help to confirm the true efficacy of colchicine along with enhancing generalizability of the findings.

   Conclusion Top

The management of OSMF with colchicine can be one of the adjuvant treatment modalities in patients in whom steroids are contraindicated due to medical conditions as a steroid-sparing agent. Though there was no statistically significant difference between both the groups in alleviating the signs and symptoms, clinically there was rapid improvement in reducing burning sensation, improvement in buccal mucosal flexibility, and tongue protrusion in patients receiving colchicine. Because of the easy availability of colchicine, cost-effectiveness and good patient compliance, colchicine can be used as an adjuvant treatment modality in the management of OSMF.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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