Efficacy of Oral Colchicine and Intralesional Hyaluronidase with and without Ultrasound Therapy in the Management of Oral Submucous Fibrosis—A Comparative Study

ABSTRACT

Aim:

To determine the therapeutic effect and efficacy of oral colchicine tablet and intralesional injection of hyaluronidase with and without ultrasound therapy in the clinical course of oral submucous fibrosis.

Materials and Methods:

This comparative study involving 45 human participants was divided into three equal groups. The participants in group 1 received oral colchicine and intralesional hyaluronidase. The participants in group 2 received oral colchicine, intralesional hyaluronidase, and ultrasound therapy. The group 3 participants were treated with intralesional dexamethasone and hyaluronidase. Intergroup assessments were done using repeated measures of ANOVA test, where P value of <0.05 was considered as statistically significant difference.

Results:

Group 2 patients had maximum improvement with respect to all the parameters.

Conclusion:

Therapeutic ultrasound can be given effectively as an adjunct therapy along with conventional therapy in OSMF patients.

INTRODUCTION

Oral submucous fibrosis causes scarring of the oral cavity as a result of chronic inflammation.[1] The disease has a range of presentations, starting from hypersalivation or xerostomia, burning sensation, and mucosal blanching with marble-like appearance.[2] As the disease progresses, fibrosis of oral mucosa is noted. Consequently, trismus and inability to eat can be severely debilitating, increasing the chances of developing oral cancer.

The rate of transformation of OSMF into malignancy is 7.6%. Over the last 40 years, the prevalence rate of OSMF has increased drastically in India from 0.03% to 6.42%.[3,4]

Although a number of factors contribute to the etiology of OSMF, areca nut extracts are the primary culprit. The flavonoids and copper from areca nut cause activation of lysyl oxidase which increases the cross-linking of collagen.[5]

In the literature, a very limited number of papers are available regarding the significance of ultrasound therapy on OSMF, and it’s still a buried field looking forward to more exploration. A faster healing process, increased collagen fiber extensibility, and pain alleviation are the objectives.[6]

Therefore, this study aimed to evaluate the adjunct effects of therapeutic ultrasound with oral colchicine and intralesional hyaluronidase in OSMF patients. The complexity of the pathogenesis of the disease requires multimodal treatment.

MATERIALS AND METHODS

The Institutional Ethics Committee (Ref No. GDCH-IEC/PG/1901) of Government Dental College and Hospital, Hyderabad, examined and approved this study involving human subjects. Written informed permission was obtained from the participant.

Inclusion criteria

1. Patients of both sexes in the age group of 20–50 years.

2. OSMF stages 2 and 3 with clinical parameters:

   • Habits of chewing tobacco and having burning sensation on eating spicy food.

   • Restricted mouth opening and tongue movements and the presence of palpable fibrous bands.

Exclusion criteria

1. Patients with past or present systemic diseases.

2. Hypersensitivity to the study drug.

3. Pregnant and lactating women.

Sample size calculation

Sample size estimation was done using G power 3.1.9.4 using F test family and ANOVA for three groups keeping the effect size as 40%.

Case selection

In the proposed clinical comparative study, 45 systemically healthy OSMF patients were selected from the outpatient department of the institution. They were divided randomly into three groups by lottery method.

Treatment protocol

The staging of OSMF was given based on clinical and functional staging of More C et al., (2011).[7]

Pre-procedural evaluation was conducted for the following parameters in all the three groups at baseline, after 15 days, 1^st month, 2^nd month, 3^rd month, and 6^th month.

• Burning sensation – using visual analog scale.

• Mouth opening (interincisal distance IID)—using Vernier caliper.

• Tongue protrusion—using metal scale.

• Fibrous bands—digital palpation.

In Group 1: For 12 weeks, 15 patients received intralesional hyaluronidase 1500 IU (Hynidase) with 1 ml of lignocaine hydrochloride and 1 tablet of colchicine (Zycolchin) 0.5 mg twice a day.

In Group 2: 15 patients received intralesional hyaluronidase 1500 IU (Hynidase) with 1 ml of lignocaine hydrochloride, once weekly for 12 weeks, and therapeutic ultrasound using a MEDGEARS Therapeutic Ultrasound Machine (MG-68) with a frequency of 3 MHz, pulsed mode 1:1, and an intensity of 1 to 2.5 W/cm² for 10 min for 15 days with a permissible one day off per week.

In Group 3: 15 patients were provided with intralesional dexamethasone 8 mg/2 ml (Dexona) and hyaluronidase 1500 IU (Hynidase) with lignocaine once a week for 12 weeks.

Statistical analysis

The statistical analysis was performed with IBM SPSS version 20.0. Throughout the study, a P value of <0.05 was considered as statistically significant difference.

RESULTS

At 2^nd-, 3^rd-, and 6^th-month follow-up, group 2 subjects had significantly maximum mouth opening, and tongue protrusion followed by group 1 and group 3 [Tables 1 and 2]. After a follow-up of 3^rd and 6^th months, burning sensation was not seen among group 2 subjects. There was no improvement in the fibrous bands at 1-month follow-up in all the groups. However, significantly all of the group 2 participants did not exhibit any fibrous bands at the 3- and 6-month follow-ups.

Table 1.

Mean comparison of mouth opening between three groups

Follow-up	n	Mean	SD	P
Baseline
Group 1	15	23.11	5.13	0.945
Group 2	15	23.41	3.96
Group 3	15	23.73	5.90
15 days
Group 1	15	24.81	4.94	0.335
Group 2	15	26.97	3.97
Group 3	15	24.45	5.83
1 month
Group 1	15	26.77	4.91	0.052
Group 2	15	29.95	4.24
Group 3	15	25.35	6.02
2 months
Group 1	15	29.71	4.81	0.009*
Group 2	15	32.38	4.00
Group 3	15	26.42	6.05
3 months
Group 1	15	32.94	4.59	0.001*
Group 2	15	35.09	4.04
Group 3	15	27.65	5.96
6 months
Group 1	15	32.84	4.59	0.000*
Group 2	15	34.78	4.02
Group 3	15	26.77	6.06

Table 2.

Mean comparison of tongue protrusion between three groups

	n	Mean	SD	P
Baseline
Group 1	15	16.10	2.97	0.766
Group 2	15	16.73	3.53
Group 3	15	15.87	3.56
15 days
Group 1	15	17.27	3.052	0.030*
Group 2	15	19.73	3.42
Group 3	15	16.50	3.56
1 month
Group 1	15	18.63	3.19	0.001*
Group 2	15	22.03	3.26
Group 3	15	17.03	3.69
2 months
Group 1	15	21.67	3.18	0.000*
Group 2	15	23.93	3.15
Group 3	15	17.83	3.77
3 months
Group 1	15	24.33	2.87	0.000*
Group 2	15	25.73	2.77
Group 3	15	18.67	3.86
6 months
Group 1	15	24.27	2.90	0.000*
Group 2	15	25.70	2.80
Group 3	15	18.53	3.72

DISCUSSION

There are several theories put forth to explain the etiopathogenesis of OSMF. There is increased collagen production and fibroblast proliferation as well as decreased activation of collagenase and the fibrin degradation system.[4]

It has been demonstrated that colchicines specifically impede collagen synthesis by preventing the secretion of procollagen and its conversion to collagen. It prevents microtubule elongation and microtubule polymerization.[5] It reduces the number of TNF-α receptors on the surface of macrophages and endothelial cells. Ultrasound has been used as a therapeutic modality in which energy is accumulated in tissues to produce a variety of biological effects.[6,7]

As there are various disadvantages of steroids; one of them is immunosuppression, it will be beneficial for the patient if similar or better results can be gained without using steroids. This is the first study on OSMF combining oral colchicine, intralesional hyaluronidase, and ultrasound therapy.

CONCLUSION

Therapeutic ultrasonography should be used as an additional treatment for OSMF patients. Colchicine and intralesional injection of hyaluronidase should be considered over intralesional injection of steroids in such patients who cannot attend constantly for 15 days for ultrasonography therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.