Oral & Maxillofacial Surgery

Original Article

ORAL SUBMUCOUS FIBROSIS: COMPARISON OF DIFFERENT

TREATMENT MODALITIES
OMAR ARSHAD
KHALID MAHMOOD SIDDIQI
3
ZAHOOR AHMAD RANA
1

ABSTRACT

Oral submucous fibrosis (OSMF) is a chronic, insidious, fibrotic disease that predominantly
affects people of South-East Asian origin. The majority of patients present with an intolerance to spicy
food, rigidity of lip, tongue and palate leading to varying degrees of limitation of mouth opening and
tongue movement. The use of areca nut has been strongly implicated as the principal etiological factor
in the pathogenesis of OSMF which involves cytokine mediated collagen synthesis and deposition and
reduced collagen degradation. Various modalities have been proposed for the management of OSMF.
Aimed primarily at increasing oral opening, surgical treatments have been hampered by relapse and
medical agents have yielded limited success. In this prospective comparative study we tested a hypothesis
that a combination of intralesional steroid and oral antioxidant would prove to be of maximal efficacy
than either of the two agents used alone. Forty five patients with a clinical and histologic diagnosis of
OSMF were randomly divided into three treatment groups of fifteen patients each. Patients in group
A received monthly intralesional injections of methylprednisolone acetate, those in group B were put
on daily lycopene supplements while the ones in group C received monthly intralesional injections of
methylprednisolone acetate and concurrently were put on daily lycopene supplements as well. Mouth
opening values for patients showed an average increase of 3.46 mm, 2.46 mm and 7 mm for groups
A, B and C respectively. The difference in mouth openings at the end of treatment was found to be
statistically insignificant between groups A and B (p > 0.05), significant between groups A and C (p <
0.05) while it was very significant between groups B and C (p 0.01). We therefore conclude that the
most favorable response in terms of clinical efficacy was derived from the combination of intralesional
steroid and oral antioxidant therapy in patients abstaining from areca nut habit and indulging in
rigorous physiotherapy. We further suggest that this modality may be used as a frontline therapy for
the pharmacologic and physiotheraputic management of oral submucous fibrosis.
Key Words: Mouth Opening, Areca Nut, Fibrous Bands, Oral Submucous Fibrosis.
INTRODUCTION

Oral Submucous Fibrosis (OSMF) is a debilitating
but preventable oral disease.1 A condition similar to
OSMF was described as early as 600 BC by Sushruta,
who named it Vidari which presented as progressive
narrowing of the mouth, depigmentation of the oral
For correspondence: 1Dr Omar Arshad, BDS, MDS, Assistant
Professor and Head, Department of Dental and Maxillofacial
Surgery, Pakistan Atomic Energy Commission (PAEC) General
Hospital, Islamabad
Email: [email protected]
Cell: 0321-9549466
2
Dr Khalid Mahmood Siddiqi, BDS, MDS, Assistant Professor and
Head Department of Oral and Maxillofacial Surgery, Islamabad
Medical and Dental College, Bahria University, Islamabad
Email: [email protected]
Cell: 0321-5032203
3
Dr Zahoor Ahmed Rana, BDS, MDS, Professor and Chairman,
Department of Oral and Maxillofacial Surgery, Pakistan Institute
of Medical Sciences, Islamabad
Email: [email protected]
Cell: 051-9261170
Received for Publication:
July 28, 2015
Revised:
August 24, 2015
Approved:
September 10, 2015

mucosa and pain during eating. The first documentation of this disease during recent times came from
Schwartz in 1952, who described a similar entity in five
Indian females from Kenya and he designated the term
AtropicaI diopathica Mucosae Oris to this condition.
In 1953, Joshi described this condition as Submucous
fibrosis.2

Oral Submucous Fibrosis (OSMF) is a chronic disease of insidious onset affecting the oral mucosa with
progressive involvement of the pharynx and esophagus.3 Patients frequently present with a history of oral
pain, intolerance to spicy food and gradual reduction
of oral opening.4 Areca nut usage has strongly been
implicated in the development of this condition. Review
of literature on OSMF reveals a condition where main
burden of disease lies in developing countries of Asia
and the Indian Subcontinent.5 Other causes of reduced
mouth opening including odontogenic infections, TMJ

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364

Oral submucous fibrosis

ankylosis and myositis ossificans traumatica must be

set apart from OSMF.6,7

The clinical criteria used for diagnosing OSMF is
the presence of palpable fibrous bands which give a
leathery texture, leading to a blanching and yellowish-white discoloration of the oral mucosa.8 Mouth
opening is limited, which can be categorized on the
basis of its clinical and functional severity.9 Although
provisional diagnosis is made by clinical examination,
the disorder is confirmed and graded histopathologically
with quantification of the collagen fibers and presence
of hyalinization in the lamina propria.10

No known treatment for OSMF is curative, although
some conservative and surgical interventions may result in improvement of oral function.11,12 Steroids are
said to inhibit fibroblast proliferation at high doses.13
Lycopene, a naturally occurring carotenoid responsible
for tomatos bright red color has shown to have potent
anti-carcinogenic and antioxidant properties and inhibition of human fibroblast activity in vitro. It has been
used in the treatment of OSMF in some studies and
found efficacious.14,15

Improved oral opening is an important objective of
OSMF treatment and whichever modality of management is used; the core concept relies on the cessation of
the quid habit and vigorous physiotherapy to exploit the
accelerated tissue remodeling potential of the disease
to advantage.16
Although there have been several reports on the
institution of diverse treatment protocols in the management of OSMF, especially in Indian and Sri Lankan
populations, no clinical reports are available for Pakistani patients. This study was done after the approval
of ethical committee which presents the experience of
randomized uncontrolled trial at the Department of
Oral and Maxillofacial Surgery, Pakistan Institute of
Medical Sciences, Islamabad, Pakistan, with intralesional methyl prednisolone or oral lycopene alone and
in combination along with conservative measures like
discontinuation of quid habit and rigorous jaw stretching exercises to improve mouth opening in OSMF
patients.
METHODOLOGY

Forty five patients with a diagnosis of oral submucous fibrosis presenting to the Department of Oral &
Maxillofacial Surgery, Pakistan Institute of Medical
Sciences were selected as the study sample. After informed consent participants were randomly distributed
into one of the three treatment groups (15 patients each)
using computer lottery system at Random Sequence
Generator at www.random.org. Patients not willing

to participate in study or not ready to quit the use of

quid were excluded from study. Patients having clinical
or histological evidence of malignant change, extension
of the disease either onto the pharynx or floor of mouth
were also excluded. Patients having history of recent
myocardial infarction, uncontrolled hypertension, diabetes, peptic ulcer, tuberculosis, cirrhotic liver disease
and current pregnancy were all excluded as steroids
can potentially worsen the aforementioned conditions.
After a clinical diagnosis, the case was discussed
with patients in detail and risk-benefit ratio explained.
Those who wished to participate in the study were
designated a numeric identification in sequence. A
specially designed proforma containing demographics
and clinical findings was filled for every patient. A
vernier caliper was used to measure the maximum
unaided inter incisal opening in millimeters. Oral hygiene improvement measures were employed and they
were instructed and strongly counseled to discontinue
the quid habit. An incisional biopsy was carried out in
all participants under local anesthesia (LA) to confirm
clinical diagnosis.

After confirmation of diagnosis histopathologically, patients falling in group A were administered
intralesional methyl prednisolone, group B were
prescribed oral lycopene and group C were given a
combination of both intralesional methyl prednisolone
and oral lycopene. Methyl prednisolone (Depo-Medrol;
Pharmacia & Upjohn Company, Puurs, Belgium) 20
mg/0.5 ml preparation was injected every month, at
a single site on the buccal mucosa, bilaterally (40 mg
in total) to patients in groups A and C for a total
duration of six months.

Lycopene 10 mg soft gels (Lycopene; General Nutrition Corporation, Pittsburgh, PA, USA) were advised to
all the patients of groups B and C as a single daily
dose for six months. Patients were assessed monthly
for six months and after that, bi-monthly for a total of
one year and interincisal opening assessed. During this
one year period, an aggressive physiotherapy regimen
consisting of rigorous jaw stretching (wooden spatula)
exercises was instituted.
All the data collected was entered in SPSS and
analyzed accordingly. The qualitative variables in the
demographic data (e.g. gender, predictor and outcome
variable) are presented as percentages and proportions
and quantitative data presented as means and standard
deviations. All the groups were compared with each
other using student t-test and intra-group pre and
post-treatment interincisal opening was compared
using paired sample t-test. A p-value of less than
0.05 is considered significant with a confidence interval
of 95%.

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Oral submucous fibrosis

RESULTS

Patients of OSMF were between 13-75 years of age
with a mean of 36.4911.82 years and majority (38%)
in (31-40) year age bracket followed by 25% in (21-30)
years. Females predominated over males. There were

Female
62%

Fig 1: Gender distribution in total sample

10
Group (A)

Group (C)

22%
20% 20%

6
13% 13%
11%
4

0
Male

Female

Fig 2: Gender distribution in different groups

11-15 Years
42%

The median inter-incisal opening (MIIO) opening was recorded at the start (MIIO1) of treatment
and there on, every month for a period of six months
(MIIO2-6). Form the seventh month onwards the MIIO
was recorded at two month intervals till the completion
of study duration at twelve months (MIIO7-9).

The mean MIIO at the start of study (MIIO1) of all
45 patients was 16.875.33 mm while it was 21.186.27
mm at the end of study (MIIO9). In group A MIIO1
was 15.676.46 mm while MIIO9 was 19.136.79 mm.
In group B MIIO1 was 17.07+4.2 mm while MIIO9 was
19.534.54 mm. In group C MIIO1 was 17.875.23 mm
while MIIO9 was 24.87+5.9 mm as shown in Table 1.

Male
38%

Group (B)

62.2% (n-28) female and 37.8% (n-17) male patients

as shown in figure1 and Fig 2. Duration of their quid
chewing habit is shown in Fig 3.

1-5 Years
31%

6-10 Years
27%

Fig 3: Duration of quid chewing habit

The difference between MIIO at the start (MIIO1)
and completion (MIIO9) of study was statistically highly significant in all the study groups (p < 0.001). The
difference in mouth openings at the end of study was
found to be statistically insignificant between groups A
and B (p > 0.05), significant between groups A and
C (p < 0.05) while it was highly significant between
groups B and C (p 0.01).
DISCUSSION
OSMF is a chronic, debilitating and a well-recognized potentially malignant condition associated with
areca nut chewing, an ingredient of betel quid and is
prevalent in South Asian population. Pathogenesis is
not yet established but is believed to be multifactorial;
hence the treatment of OSMF presents a major challenge for oral and maxillofacial surgeons. Patients
age in present study ranges from 13 to 75 years with a
mean of 36.4911.82 years. Majority are in 4th decade
followed by the 3rd. It is very interesting to note that
only two patients (4%) presented in second decade. This
might be considered indicative of the time dependent
and insidious pathogenesis of the disorder. Other researchers also found a comparable mean age in their
studies.1,2,3,4

There was a distinct preponderance of females in
our study, with a female to male ratio of 1.6:1. Maher
et al in their two different studies conducted in Karachi
found the female to male ratio to be 1.6:1 and 2:1.5.18,19
Isaac et al in a study reported a contrasting predominance of men.20 Male preponderance was also observed
in studies by other researchers.10,5,6 Rana et al however,
in an earlier study to evaluate the risk factors for the
development of oral precancers in patients presenting
to the oral and maxillofacial surgery department of
PIMS, Islamabad, found the female to male ratio to
be 1.4:1.7 If one closely observes the demographic data
regarding oral submucous fibrosis in Pakistan, distinct

Pakistan Oral & Dental Journal Vol 35, No. 3 (September 2015)

366

Group A

Group B

Pakistan Oral & Dental Journal Vol 35, No. 3 (September 2015)

Group A

6
28

Minimum

Maximum

5.235

Std. Deviation
22

18.00

Median

Range

17.87

Mean

Missing

15

24

Maximum

N Valid

Minimum

4.200

Std. Deviation
16

17.00

Median

Range

17.07

Mean

Missing

15

26

Maximum

N Valid

Minimum

6.466

Std. Deviation
20

13.00

Median

Range

15.67

15

Mean

Missing

N Valid

Post-Operative
Interincisal
Opening
at one
Month

29

23

5.447

19.00

18.67

15

24

16

4.200

17.00

17.07

15

26

20

6.549

14.00

15.80

15

Post-Operative
Interincisal
Opening at 2
months

31

24

5.574

19.00

19.73

15

24

16

4.256

17.00

17.40

15

27

20

6.770

14.00

16.47

15

Post-Operative
Interincisal
Opening at 3
Months

34

26

6.034

20.00

21.47

15

25

17

4.480

18.00

17.93

15

27

20

6.899

16.00

17.20

15

Post-Operative
Interincisal
Opening at 4
months

35

27

6.137

22.00

22.67

15

25

17

4.518

19.00

18.47

15

28

20

6.782

17.00

18.00

15

Post-Operative
Interincisal
Opening at 5
months

36

27

6.158

23.00

24.07

15

26

17

4.486

20.00

19.13

15

28

20

6.808

18.00

18.73

15

Post-Operative
Interincisal
Opening at 6
months

37

28

6.300

25.00

24.87

15

26

10

16

4.373

20.00

19.47

15

29

21

6.887

18.00

19.00

15

Post-Operative
Interincisal
Opening at 8
months

TABLE 1: MEDIAN INTER-INCISAL OPENING (MIIO1-9) - TREATMENT GROUPS

37

10

27

6.017

25.00

24.93

15

26

10

16

4.549

20.00

19.53

15

29

21

6.871

19.00

19.27

15

Post-Operative
Interincisal
Opening
at 10
months

36

10

26

5.902

25.00

24.87

15

26

10

16

4.549

20.00

19.53

15

29

21

6.791

19.00

19.13

15

Post-Operative
Interincisal
Opening
at 12
months

Oral submucous fibrosis

367

Oral submucous fibrosis

female predilection in this region will be found.18,19 This

might be due to the practice that women locally tend
to sit at home and have more time on hands to indulge
in habits like areca nut chewing; also areca chewing is
considered a more socially acceptable habit than (for
example) smoking, especially in women.

Mouth opening is an objectively verifiable criterion
by which the severity of oral submucous fibrosis can be
assessed. The involvement of submucosal tissues in the
oral cavity by severe fibrosis tends to significantly decrease the elasticity of oral tissues, thereby disallowing
stretch on them while the jaw is opened. It is logical to
believe therefore, that severer disease activity would
mean a more debilitating effect on mouth opening.
Inter-incisal distance may successfully be used as an
outcome measure of response to intervention and it is
less likely to be affected by observer bias than other
criteria used for physically examining a patient with
OSMF. In the present study, inter-incisal opening was
assessed using a graduated vernier caliper at start and
throughout the study. Patients in all three groups, who
received Lycopene or methyl prednisolone alone or in
combination showed a statistically significant (p < 0.001)
improvement in their mouth opening. Comparatively
speaking, the group which received a combination therapy consisting of both agents had the most significant
increase in their mouth opening. Ariyawardana et
al8 concluded that 86% of patients showed significant
improvement in mouth opening after six months with
intralesional methylprednisolone. In another study, Lai
et al8 reported improvement in 83% of patients receiving
submucosal injections of steroid with hyaluronidase.
Kumar et al9 carried out a study to demonstrate the
efficacy of lycopene, alone and in combination with
intralesional steroids for the management of OSMF.
They reported statistically significant mouth opening
values in patients, an average increase of 3.4 mm (Lycopene) and 4.6 mm (Lycopene + Steroid).

All the patients had reportedly discontinued areca
chewing habit and indulged in physiotherapy, which are
believed to be the core requisites for any treatment to be
efficacious in the management of OSMF. A particularly
remarkable finding, when comparing our results with
these studies8,17,25,10 was that none of the other authors,
except Lai et al24 included physiotherapy as part of their
treatment regimen, which is believed to be a fundamental requirement in the quest for a successful, stable,
long-term results. Cox and Zoellner,16 in probably the
only study of its kind, quite astonishingly demonstrated
physiotherapy to be efficacious as the primary/only
treatment option for OSMF. However, there is plenty
of anecdotal evidence from fellow maxillofacial surgery
colleagues about the lack of efficacy of mouth opening
exercises alone in the management of OSMF. There is

a need of longer follow up and larger sample size study

to be conducted in different settings.
CONCLUSION
This study was able to address the fundamental
pathogenic mechanisms of OSMF and devise a therapy
that targeted the basic disease process leading to limited mouth opening, in patients who were not subjected
further to noxious stimulation by areca nut constituents
due to cessation of the habit and participated in their
own recovery through mouth opening exercises. The
authors were thus able to achieve results that were
statistically significant, encouraging and point towards
a definitive role of this multi-modality approach towards
alleviation of this debilitating condition.
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CONTRIBUTION BY AUTHORS
1 Omar Arshad & Khalid Mahmood Siddiqi: Made substantial contributions to conception and
design of the manuscript as well as data acquisition.
2 Khalid Mahmood Siddiqi:
Were involved in drafting and revising the manuscript.
3 Zahoor Ahmad Rana:
Also made the statistical analysis.

Pakistan Oral & Dental Journal Vol 35, No. 3 (September 2015)

369