JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL SCIENCES

G. Sree Vijayabala, Anupama N. Kalappanavar, Rajeshwari G Annigeri, Ramachandran

Sudarshan. Past and present concepts in the management of recurrent aphthous ulcers: a
review. Journal of pharmaceutical and biomedical sciences (J Pharm Biomed Sci.) 2013
May(Supplement 1); 30(30): S40-S49.

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ISSN NO- 2230 7885

CODEN JPBSCT
NLM Title: J Pharm Biomed Sci.

G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

Review article
Past and present concepts in the management of recurrent aphthous
ulcers: a review
*1G.

Sree Vijayabala,2Anupama N. Kalappanavar,3Rajeshwari G Annigeri,

4 Ramachandran Sudarshan

Affiliation:1Assistant

Professor in Dentistry, ESIC Medical

College and PGIMSR,KK Nagar, Ashok Pillar road,
Chennai, India.
2Professor,3Professor and Head, Department of Oral
Medicine and Radiology, College of Dental Sciences,
Davanagere, Karnataka, India.
4Senior Lecturer, Department of Oral Medicine and
Radiology, Best Dental Science College, Madurai,
Tamilnadu. India.
Authors contributions-All
equally to this paper.

authors

contributed

*Correspondence to:Dr. G Sree Vijayabala, M.D.S

Assistant Professor in dentistry,
ESIC Medical College and PGIMSR, KK Nagar, Ashok
Pillar road, Chennai, India.

Abstract:
Recurrent aphthous ulcers are painful ulcers of the
oral mucosa that affects individuals atleast once in
their lifetime. `An effective therapeutic strategy for
aphthous ulcer must address both pain reduction
as well as ulcer healing. Many therapies have been
advocated from the past for efficacious
management of these ulcers but no therapy
available to date has been validated as gold
standard for the management of aphthous ulcers.
This review elucidates in brief about the past and
current concepts in the management of aphthous
ulcers.

Key words: Recurrent aphthous stomatitis;

Ulcer; Management.

Article citation:G. Sree Vijayabala,Anupama N. Kalappanavar, Rajeshwari G Annigeri,Ramachandran Sudarshan.. Past and
present concepts in the management of recurrent aphthous ulcers: a review. Journal of pharmaceutical and
biomedical sciences (J Pharm Biomed Sci.) 2013 May (Supplement); 30(30):S40-S49.Available at
http://www.jpbms.info

Introduction

ecurrent aphthous stomatitis (RAS) is a pathologic condition

characterized by the onset of painful solitary or multiple
recurring ulcerations in nonkeratinized oral mucosa.
Aphthae appear rarely as a single episode. Patients affected by RAS
have relapsing ulcerative lesions that differ in number and
frequency for each episode1. The clinical features of RAS comprise
recurrent bouts of one or several rounded, shallow, painful oral
ulcers at intervals of a few months to a few days2.
As no single treatment have been found to be uniformly effective in
RAU, it may be necessary to explore a spectrum of therapies to
validate a definitive treatment strategy. Awareness about the
persistent nature of the disease and its association with
precipitating factors is critical. Treatment strategies can be
followed to give the patient maximum control with fewest adverse
effects. Periodic dental evaluation for the management of aphthous
ulcers is recommended3.

Management
1. Elimination of predisposing factors (if any)

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Stress,food etc
2. Topical therapy
Analgesics
Anti-inflammatory
agents
Non steroidal (NSAID)
Steroidal
Antimicrobials
3. Systemic Therapy
Immunomodulators
and
immunosupressants:
Prednisolone
Levamisole
Pentoxyphylline
Azelastine
Colchichine
Dapsone
Azathioprine
Thalidomide

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CODEN JPBSCT
NLM Title: J Pharm Biomed Sci.

G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

4. Others
Topical:

Amlexanox,

Silver nitrate,

KNO3,

Prostaglandins,

Hyaluronic acid,

Sucralfate,

Azathioprine,

Cyclosporine,

Bioadhesive patches.
Systemic:

Clofazimine,

Ascorbic acid,

Cromoglycic acid,

Zinc sulphate,

Longovital,

Honey,

Licorice,

Hybenex.
5. Physical therapies

Lasers

Ultrasound

Ozone

Cryotherapy
6. Newer therapy

Probiotics
Elimination of predisposing factors:
If an underlying disorder is present, effective treatment of the
condition may result in the remission or amelioration of the ulcers4.
Patients with RAS, which is possibly secondary to systemic disease,
require referral to an appropriate specialist for detailed evaluation
and suitable therapy. Individuals with RAS possibly related to
foodstuffs may occasionally benefit from dietary alterations, while
hematinic replacement can be of value in patients with hematinic
deficiency of unknown cause2.
Prevention of RAU involves meticulous oral hygiene and avoidance
of foods known to precipitate ulcers such as citrus fruits, tomatoes
and walnuts. The patient with onset of RAU linked to tobacco
cessation may require nicotine supplements3.

Topical therapy:
Analgesics:
Lidocaine is an amide-type local anaesthetic. It decreases
permeability to sodium ions in neuronal membranes, inhibits
depolarization and blocks transmission of nerve impulses. 5 ml of
2% viscous solution is swished for 5 min and expectorated thrice a
day5.
Benzocaine is a para-aminobenzoic acid (PABA) derivative and
ester-type local anaesthetic. It inhibits neuronal membrane
depolarization by blocking nerve impulses. 10-20% gel is applied to
affected areas four times daily5.

S41

Diclonine HCl, 0.5% or 1% and

diphenhydramine HCl elixir 12.5
mg/5ml have also been used as
potent analgesic agents for
symptomatic relief6.

Anti-inflammatory agents:
Non steroidal:
Fariba I conducted a study in 44
patients to evaluate the effects of
3%
diclofenac
in
2.5%
hyaluronan base versus 2.5% gel
base alone on the pain duration
and healing time of the minor
aphthous ulcers. Results showed
that the mean of time for lesions
to become pain free was 5.51.5
days and 4.091.3 days, for
controls and cases patients
respectively and this difference
was significant. The difference in
healing time was not significant
statistically. It was concluded that
diclofenac gel was effective in
reducing pain duration of the
minor RAS although it was not
effective in healing of them7.
Steroidal agents:
Topical steroids are the standard
regimen
used
to
evade
immunologic and inflammatorymediated attacks resulting in
ulceration5. Topical therapy could
be administered in the form of
creams, ointment, elixirs and
injections6.
Glucocorticoid
Creams/ointments:
Triamcinolone acetonide - 0.1
or 0.5% in orabase
Fluocinonide - 0.05% gel or
ointment
Betamethasone valerate 0.1%
Clobetasol propionate - 0.05%
cream or ointment.
Glucocorticoid elixir:
Dexamethasone
elixir
0.5mg/5ml
Glucocorticoid injection:
Triamcinolone diacetate - 25
mg/ml

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G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

Betamethasone sodium phosphate - 6 mg/ml3.

Muzio LL evaluated the clinical use of a corticosteroid in three
preparations (topical clobetasol propionate ointment, clobetasol
propionate in an oral analgesic base, and clobetasol propionate in
an adhesive denture paste) for the treatment of 30 patients with
recurrent aphthous ulcers. Each subject scored the symptoms daily
from most severe (7) to none (0) by verbal assessments using a
categorical scale. Result showed that corticosteroid was effective in
producing remission of symptoms and clobetasol and adhesive
denture paste correlated with an early remission of pain in
aphthous lesions8.
Pimlott SJ and Walker DM conducted a cross over trial for 6 weeks
in 22 patients with RAS to evaluate the efficacy of 0.05%
fluocinonide in orabase, applied up to five times daily for treatment
of RAS. After a period of no therapy for 2 weeks, only orabase was
prescribed for another 6 weeks. 22 patients completed the trial and
18 preferred the active preparation. There was a significant
reduction in the duration of ulcers and increase in number of ulcer
free days9.
Miles DA et al. conducted a placebo controlled study to compare the
efficacy of triamcinolone acetonide (0.025%) and chlorhexidine
digluconate (0.12%) in a cyanoacrylate barrier in thirty patients
with recurrent aphthous stomatitis for 12 weeks. Patients kept a
diary to record their pain level on a 10 cm visual analog scale until
the lesion healed. A highly significant reduction in pain was found
in both the groups on comparing with the placebo. No significant
difference was found between the triamcinolone acetonide and
chlorhexidine gluconate group10.

Antimicrobials:
Meiller TF et al. conducted a study to compare an antimicrobial
mouthrinse Listerine Antiseptic [LA] and a hydroalcoholic control
to evaluate the effects of vigorous twice-daily rinsing on the
incidence, duration, and severity of 96 RAU persons. LA rinse and
the hydroalcoholic rinse resulted in a statistically significant
reduction in the incidence of RAU occurrences from baseline. The
duration of lesions and the severity of pain in subjects with ulcers
during the treatment period were also significantly reduced in the
LA rinse group of patients when compared with baseline. The
hydroalcoholic rinse had no significant effect compared to baseline
for either severity or duration of the lesions. LA rinse could reduce
the occurrence of RAU and decrease the duration and severity of
RAU11.
Gorsky M et al. conducted a crossover trial to assess the efficacy of
0.2 % minocycline and 0.25 % tetracycline oral rinses in 17
patients with frequent episodes of RAS. The minimum interval
between the cross-over was 30 days. The intensity of pain was
noted every day using a visual analogue scale. Minocycline
mouthwashes had significant improvement in alleviating the pain,
by decreasing the severity and duration of pain as compared to
tetracycline mouthwashes12.
Denman AM and Schiff AA conducted a study on 20 patients with
recurrent oral ulceration to determine the efficacy of Mysteclin

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syrup (tetracycline hydrochloride

and
amphotericin)
as
a
mouthwash given 5 ml three
times a day for 16 weeks. It was
concluded that Mysteclin syrup is
efficacious
in
significantly
reducing the pain and frequency
of RAS13.
Henricsson V et al. conducted a
cross-over trial to test the
therapeutic
effects
of
chlortetracycline (Aureomycin)
and
the
enzyme-containing
dentifrice Zendium on recurrent
aphthous ulcers. Aureomycin was
found to decrease the pain and
number of ulcers as compared
with the placebo. No statistically
significant difference could be
found among patients treated
with Zendium and placebo
dentifrices14.
Ylikontiola L conducted a placebo
controlled study to investigate
the efficacy of singularly applied
topical doxymycine in an isobutyl
cyanoacrylate vehicle in the pain
relief treatment of 31 patients
with
recurrent
aphthous
stomatitis. Patients recorded
their pain level on a visual analog
scale for 10 days during healing.
A statistically significant pain
reduction was found from the
second to the seventh day after
application of doxymycine. It was
concluded that in recurrent
aphthous
ulcers,
single
application
of
topical
doxymycine-cyanoacrylate
relieved the pain intensity
remarkably for 6 days after a 1
day latency period15.
Zhou Y conducted a clinical study
on 258 subjects with aphthous to
explore the effectiveness and
safety of topical application of 50
mg penicillin G potassium troches
in the treatment of minor
recurrent aphthous ulcerations.
Troches
were
consecutively
applied 4 times per day for 4
days.
The
dimension
and
intensity of pain due to ulcers
were measured and recorded on

ISSN NO- 2230 7885

CODEN JPBSCT
NLM Title: J Pharm Biomed Sci.

G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

days 0, 3, 4, 5, and 6. Penicillin G potassium significantly reduced

ulcer size and alleviated ulcer pain. No severe adverse reactions
were observed. Only 4 subjects had mild adverse reaction. It was
concluded that Penicillin G potassium troches were effective in
reducing ulcer size and alleviating ulcer pain of the patients in the
treatment of a single episode of RAU16.

Systemic therapy:
Prednisolone:
Femiano F et al. conducted a study to test the efficacy of systemic
prednisone and systemic Montelukast for 60 patients with
recurrent oral aphthae nonresponsive to local corticosteroid
therapy. Patients were randomly assigned to 3 groups (20 in each
group). Patients of group A were orally adminstered 25 mg
prednisone and tapered for every 15 days to 12.5 mg, 6.25 mg and
finally to 6.25 mg on every alternate day. Patients of group B and
group C took 10 mg montelukast and 100 mg cellulose (placebo)
respectively every evening for one month and then on alternate
days in the second month. Results showed that both prednisone
and montelukast were effective in reducing the number of lesions
and improving pain relief and ulcer healing when compared with
placebo. Prednisone was better than montelukast in pain cessation
and in accelerating ulcer healing. These data suggested that the
effectiveness of systemic montelukast was similar to that of
systemic prednisone in patients with RAS1.
Levamisole:
Meyer DJ conducted a study to assess the effectiveness of
levamisole in 124 patients with recurrent aphthous stomatitis
(RAS). In study 1 and the first half of study 2, both of which were
doubleblind, levamisole 150 mg/day (or placebo) was given on
three consecutive days in every fifteen days. In the second two
months of study 2 and in the open trial (study 3) three-day courses
were given only when an episode of RAS occurred. Statistically
significant improvement in signs and symptoms of RAS were
present in levamisole treated patients but not in those on placebo,
and intergroup differences were also significantly in favour of the
active drug. Improvement occurred earlier in study 3 compared
with other two studies. It was hence concluded that levamisole
might prevent new episodes of RAS17.
Pentoxyphylline:
Thornhill MH carried out a 60 days trial to evaluate the efficacy of
400mg pentoxifylline (PTX) 3 times daily for the treatment of 49
recurrent aphthous stomatitis patients with a 60-day no treatment
follow-up. Results depicted that patients taking pentoxifylline had
less pain and reported smaller and fewer ulcers compared with
baseline. Patients taking pentoxifylline also reported more ulcerfree days than those taking placebo. However, the differences were
negligent to be statistically significant. It was concluded that
although PTX had some benefit in the treatment of recurrent
aphthous stomatitis, the benefit was limited. It might have a role in
the treatment of patients unresponsive to other treatments, but
could not be recommended as a first-line treatment18.

S43

Azelastine:
Ueta E et al. conducted a study to
determine
the
efficacy
of
Azelastine in 43 patients with
recurrent aphthous ulcers and its
in vitro influence on leukocytes
were examined. Post- treatment
follow up for 6 months after drug
treatment showed no oral ulcers
in
7
patients,
and
an
improvement
of
the
oral
condition was exhibited in all
except 4 of the remaining
patients. The parameters like
frequency of occurrence of RAU,
ulcer duration and oral irritation
were significantly reduced. These
clinical and experimental results
had lead to the conclusion that
improvement
of
RAU
by
Azelastine depended on the
protection of cell membranes and
the suppression of leukocytefunction,
including
reactive
oxygen generation19.
Colchicine:
Katz J et al. performed a study to
evaluate the prophylactic effect of
colchicine in the treatment of 20
patients with RAS. During the
first 2 months of the study no
medications were given and in
the last 2 months colchicine, 1.5
mg/day was prescribed. The
mean number of aphthae per
week and the subjective daily
pain scores were reduced by 71%
and 77%, respectively, during
colchicine treatment as compared
with the previous period. These
findings suggested a role for
continuous colchicine therapy in
the prevention of RAS20.
Dapsone:
Lynde
CB
conducted
a
retrospective study to investigate
the effectiveness of colchicine and
dapsone in the treatment of 55
patients with complex aphthosis
(recurrent oral and genital
aphthous ulcers or severe,
persistent, multiple oral aphthae
in the absence of Behet

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G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

syndrome). All the patients were treated according to a therapeutic

hierarchy, starting with colchicine and supplementing dapsone to
treatment of patients who did not have a substantial response
(>75% improvement) to colchicine or who discontinued colchicine
use because of adverse effects. Most patients had a substantial
response to therapy and had no serious adverse effects. It was
concluded that Colchicine and dapsone were effective, safe
therapies for the treatment of complex aphthosis21.
Azathioprine:
Brown RS et al. treated a refractory case with 3 months history of
RAS in a 32 year old woman using a combination therapy with 50
mg azathioprine and topical steroids. The lesion resolved within 90
days without side effects22.
Thalidomide:
M Youle carried out a study to determine the efficacy of
thalidomide in 7 patients positive for HIV antibody. Thalidomide
100 mg was given at night for two weeks, and thereafter a
maintenance regimen of 100 mg every fifth day was followed.
Treatment was stopped after six weeks in cases 1, 4 and 5 but was
given continuously for three to six months in cases 2, 3, 6 and 7.
The ulcers healed rapidly in all seven patients. It was concluded
that thalidomide seemed to have a place in the treatment of
resistant aphthous ulceration in patients positive for HIV
antibody23.

Others:
Amlexanox:
Liu J et al. conducted a study to clinically determine the topical
efficacy and safety of amlexanox oral adhesive tablets in the
treatment of recurrent minor aphthous ulcerations. The tablets
were applied by subjects themselves 4 times a day for 5 days. Four
parameters (pain scale, size change, degree of erythema and
exudation, and efficacy index) were noted both before (baseline)
and during the trial (on the morning of days 4 and 6). Results
showed that the reduction in degree of erythema and exudation at
day 4 and day 6 were statistically significant and no systemic side
effects were reported24.
Rodrguez M conducted a study to compare the effectiveness of 5%
amlexanox and 0.05% clobetasol propionate in 96 patients with
RAS. Ulcer size and pain were measured on treatment days 0, 2 and
5. Both treatment medications significantly reduced pain
magnitude and the ulcers size on days 2 and 5 compared with day
0 without adverse reactions. No statistical differences between
groups of the study medications were found. It was hence
concluded that the two treatments applied had similar
effectiveness as they both relieved pain and reduced the size of
recurrent aphthous ulcers25.
Silver nitrate:
Alidaee MR conducted a study in 97 patients to evaluate the effect
of chemical cautery with silver nitrate in aphthous ulceration. The
severity of pain was rated on a three-category scale (severe, mild,

S44

none) and was recorded each day

until the seventh day after the
procedure. In the treatment
group, the ulcer was gently
painted with a silver nitrate stick
until it changed white in colour.
The ulcer was gently painted with
a placebo stick in the placebo
group. Results showed there was
a statistically significant pain
reduction in the silver nitrate
group. It was concluded that one
application of silver nitrate could
decrease the severity of pain in
aphthous ulceration without any
side-effects26.
Potassium nitrate:
Concentrated potassium nitrate
has been used to lessen the pain
caused by aphthous stomatitis.
When dimethyl isosorbide (DMI)
is added to potassium nitrate in
an
aqueous
hydroxyethyl
cellulose gel, it augments the
ability of potassium nitrate to
more completely permeate these
tissues and predictably promote
rapid pain control and aphthae
healing27.
Hodosh M et al. conducted a trial
to determine the efficacy of KNO3
in the treatment of 54 RAS
patients. They were divided into
three groups, 18 in each group.
1st group received gel 1 (35%
KNO3 aqueous hydroxyethyl
cellulose and 25 drops of DMI per
ounce of gel), 2nd group received
gel 2 (35% KNO3 and aqueous
hydroxyethyl cellulose) and 3rd
group
received
gel
3
(hydroxyethyl cellulose). The
results depicted that all 18
patients
receiving
gel
1
experienced pronounced relief
from their pain within 3-5
minutes of the gel application and
were completely relieved from
pain by the end of day four. Gel 1
outperformed the other 2 agents
and
the
differences
were
statistically significant. It was
found that DMI significantly

ISSN NO- 2230 7885

CODEN JPBSCT
NLM Title: J Pharm Biomed Sci.

G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

potentiated the ability of KNO3 to eliminate the pain associated

with aphthous lesions27.
Prostaglandin:
Taylor LJ conducted a clinical trial in 35 patients suffering from
RAU. The topical prostaglandin E2 (PGE2) was applied as a gel at a
dose of 0.3 mg twice daily for 10 days. The vehicle alone acted as
control. Patients were examined on days 1, 3, 5, 7 and 10 and also
maintained daily diary cards. Patients using the active PGE 2 gel
experienced significantly fewer new lesions than those on placebo.
There were no significant differences between the PGE2 and
placebo gels in terms of speed of healing or pain relief of
established aphthous ulcers. Prostaglandin E2 may therefore had a
useful prophylactic activity in RAU28.
Hyaluronic acid:
Nolan A conducted a study to evaluate the efficacy of a topical
hyaluronic acid (HA) preparation (0.2%) in 120 patients with RAU.
Patients completed a log diary recording soreness from the ulcers,
incidence of new ulcers and ulcer duration. Results showed that
both topical HA and placebo resulted in a significant reduction in
ulcer soreness following immediate application. Throughout the
rest of the investigation period, there were no significant
differences between the treatments for decresing soreness.
Patients treated with topical HA recorded few ulcers on day 5 of the
investigation than those treated with placebo which was
statistically significant. Likewise, the occurrence of new ulcers was
significantly lower in the HA treated group on day 4 when
compared with placebo. It was concluded that Topical HA might be
of benefit in the management of RAU29.
Sucralfate:
Delavarianto et al. determined the efficacy of oral sucralfate
suspension (1gm/10ml) in the treatment of 55 patients with
recurrent aphthous stomatitis (RAS). In the first part of the study,
all subjects were advised to rinse with a 10% suspension of
sucralfate or placebo, 4 times a day for 2 weeks. Clinical
examination was performed two times a week. The second part
consisted of topical use of sucralfate or placebo 2 times a day for 4
weeks, followed by biweekly inspections for 6 months. Results
showed that on the fourth day of the study, pain relief was
encountered in 59% and 14% of the case and control patients,
respectively. During the first 7 days of treatment, the number of
ulcers reduced in both the groups, which was significantly larger in
the case group. It was concluded that a 10% suspension of
sucralfate accelerated pain relief in aphthous patients and its use
was recommended as an adjunct for the treatment of RAS30.
Cyclosporine:
Eisen D conducted a study to assess the efficacy of topical
cyclosporine in the treatment of RAU. 4 of 8 patients with
persistent aphthous stomatitis remained virtually free of ulcers
during 8 weeks of topical cyclosporine therapy. These results
proved that topical cyclosporine is beneficial as a therapy for oral
aphthous ulcers31.

S45

Azathioprine:
Eggleston et al. conducted a study
to evaluate the efficacy of topical
azathioprine in RAS. 14 women
and 12 men with RAS were
enrolled in the study. They
received 2 mg of Azathioprine
daily for 2 weeks. But it was
proved to be of no value in the
treatment of RAS32.
Bioadhesives:
Ludlow JB et al. investigated the
efficacy of 2-octyl cyanoacrylate
(OC) tissue adhesives along with
a digital intraoral camera on ulcer
size and healing of minor
aphthous ulcers in 42 subjects.
Daily images were made until
ulcers were healed. A mean
difference of 0.15 mm2 was seen
between baseline and next-day
measurements. The cumulative
ulcer area was meaningfully
reduced in one OC group
compared with the sham group.
Time to healing was reduced by
1.9 days in the same group
compared with the sham group. It
was concluded
that
2-OC
adhesives hold promise as
devices to promote healing of
recurrent aphthous ulcers33.
Clofazimine:
Morgado de Abreu MAM et al.
conducted a study to investigate
the safety and efficacy of
clofazimine for the treatment of
recurrent aphthous stomatitis for
a duration of 6 months. In this
study, 23 patients received
clofazimine 100 mg daily for 30
days and then 100 mg every other
day.
23 patients received
colchicine 0.5 mg 3 times daily.
20 patients received 1 placebo
pill 2 times daily. Results showed
that a greater percentage of
individuals in the clofazimine
group had no further aphthous
episodes (17%-44% compared
with 6% in the other groups). A
significantly larger percentage of
treatment interruption occurred

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CODEN JPBSCT
NLM Title: J Pharm Biomed Sci.

G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

in the colchicine group because of gastrointestinal effects.

Individuals in the clofazimine group who continued to suffer from
aphthous stomatitis presented with better results for the evaluated
variables. It was concluded that Clofazimine should be considered
for the treatment of recurrent aphthous stomatitis34.
Ascorbic acid:
Yasui K performed a study to evaluate the potential of ascorbate
(vitamin C) to reduce the frequency of RAS and severity of pain in
16 RAS patients who were assigned to take an oral dosage of 2000
mg m2 day ascorbate. The data indicated a statistically
significant 50% reduction in oral ulcer outbreaks and a decline of
pain level35.
Cromoglycic acid:
Dolby AE conducted a crossover trial on 24 patients with recurrent
aphthous ulcers (RAU). Cromoglycic acid tablets significantly
reduced the pain experienced when compared with placebo but did
not reduce the number of days with oral ulceration. It was
concluded that the cromoglycate compounds might have a valuable
part to play in the symptomatic relief of RAU36.
Zinc sulphate:
Bor NM conducted a study to determine the efficacy of zinc and
copper in 67 patients with recurrent aphthous stomatitis. Before
the treatment, serum zinc and copper deficiencies were observed in
54 cases of the entire series. Of these 40 patients were deficient in
serum Zn only, 2 cases in serum Cu only and the remaining 12 were
deficient in both trace metals. The remaining 15 patients revealed
normal values for these two trace metals at the first evaluation.
Following three months of treatment serum Zn and Cu levels of the
patients rose parallel to the improvement in clinical findings. Of the
67 patients on systemic zinc sulfate and copper sulfate treatment,
40 patients had complete remission of ulceration, and twenty-two
showed definite improvement after 3 months of treatment. In the
remaining 5, recurrences were observed but the lesions were of
shorter duration, painless, and smaller in size37.
Longo vital:
LongoVital (LV) is an herbal-based tablet enriched with the
recommended daily doses of vitamins. Kolseth I conducted a
clinical study to investigate possible prevention of recurrent
aphthous ulceration (RAU) in 60 patients during 4 months daily
intake of the Norwegian LV. The patients were randomly divided
into three groups and given LV, the herbs of LV only, or placebo.
Three test tablets were taken every day together with breakfast for
4 months and the patients followed up for another 4 months. All
three groups, however, showed a significant increase in ulcer free
days during the first 2 months of treatment Period. It was
concluded that neither the Norwegian LV nor the herbal
component alone was superior to placebo in the prevention of
RAU38.
Honey:

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Mohamed SS assessed the effect

of honey on healing of 50 patients
with recurrent aphthous ulcers.
They were treated by either
kenalog in orabase or the
application of honey dressing.
Results
showed
that
the
ulcerations
have
almost
completely disappeared after 3
days
treatment
by
honey
dressing. It was concluded that
Honey had an obvious influence
on the rate of healing process of
the oral ulcers39.
Licorice:
Moghadamnia AA evaluated the
efficacy of licorice bioadhesive
hydrogel patches in recurrent
aphthous ulcer. This study was
carried out in three episodes of
ulcers: in the first episode of
ulcer, all 15 patients were asked
to record their baseline individual
pain level by a visual analog scale.
In the second and third episodes,
comparative evaluation of the
bioadhesive were done. A
significant reduction in VAS was
recorded following application of
the licorice patches on days 2, 3, 4
and 5 compared with the notreatment group. Licorice patches
caused a significant reduction in
the diameter of the inflammatory
halo
and
necrotic
center
compared with the placebo
group. According to the results of
this study, licorice bioadhesive
could be effective in the reduction
of pain and of the inflammatory
halo and necrotic center of
aphthous ulcers40.
HybenX:
SR Porter carried out a
prospective study to determine
the
efficacy
of
HybenX
(concentrated aqueous mixture of
free sulphate and sulphonated
aromatics,
specifically
hydroxybenzene sulphonic acid,
hydroxymethoxybenzene
suphonic acid and suphuric acid)
vs Salicept (control device) for

ISSN NO- 2230 7885

CODEN JPBSCT
NLM Title: J Pharm Biomed Sci.

G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

the treatment of RAS in 63 individuals. Results showed that painful

symptoms over a 5-day posttreatment period were reduced by
both agents although HybenX was statistically more effective at day
2 than Salicept, and HybenX treated patients had greater pain
reduction than Salicept over this 5-day period. It was concluded
that HybenX safely and effectively reduces the painful symptoms of
RAS41.

Physical therapies:
Laser:
Colvard M and Kuo P conducted a study in 18 patients with 25
aphthous ulcers using a 10 watt CO2 laser. Each sore was radiated
with 4W of CO2 generated photon energy through a 2 mm focal spot
for photon pulse duration of 10 milliseconds. All ulcers healed
within 7 10 days. 13 patients had not experienced recurrence for
a period of 6 12 months42.
Ultrasound:
Brice SL and Colo D conducted a study to assess the efficacy of lowintensity ultrasound in 50 patients with recurrent aphthous
stomatitis. The ultrasound was self-administered by twice daily use
of an ultrasonic toothbrush. An ultrasonic or placebo toothbrush
over a 6 month period to assess ulcer activity. Patients were then
observed for a 2 to 4 month period while using the alternate
toothbrush. Results indicated that during the initial study period,
the level of aphthous ulcer activity was lower for patients in the
ultrasonic toothbrush group than for those in the placebo group,
but this difference was statistically insignificant. When the patients
who used the placebo switched to the ultrasonic toothbrush, there
was a reduction of aphthous ulcer activity by 46%. Those patients
who started with the ultrasonic toothbrush worsened slightly after
switching to the placebo. It was concluded that routine use of low
intensity ultrasound appeared to have a modest beneficial effect on
recurrent aphthous stomatitis43.
Ozone:
Logan R demonstrated the beneficial use of topical application of
ozone using the Healozone appliance (Kavo) in a 56 year old female
patient with long standing aphthous ulceration involving the lateral
border of the tongue. The ozone was applied twice for a period of
sixty seconds in an interval of two days. On review, one week later,
the patient reported a slight improvement in symptoms, however,
clinically the tongue ulcer was still present. On reviewing after one
month the ulcer had completely healed. The topical application of
ozone provided an effective means of producing resolution of
clinical symptoms related to aphthous ulceration for this patient44.
Cryotherapy:
Arikan OK et al. conducted a study to determine whether the
application of cryotherapy could reduce the pain of 20 adult
patients, who had 2 discrete aphthous stomatitis in the labial
mucosa at the same time, were included in this study. One of the
two aphthous stomatitis was treated with cryotherapy, the other
serving as a control. Results showed that at any interval, no
statistical difference was found in the value of pain severity or the

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size of the ulcers. However, a

trend towards less pain in the
aphthous stomatitis receiving
cryotherapy
was
noted,
suggesting that application of
cryotherapy on minor form of
recurrent
oral
aphthous
stomatitis had no beneficial
analgesic effect compared to
placebo45.

Newer therapy:
Probiotics:
Trinchieri V et al. evaluated the
efficacy and rapidity of response
of
a
lozenge
containing
Lactobacillus brevis CD2 in
aphthous ulccers. 30 patients
were randomized to take 4
lozenges a day of active product
or placebo for 7 days. Signs and
symptoms as well as laboratory
parameters in the saliva were
assessed at the start of the study
and after 7 days of treatment. The
study
demonstrated
the
effectiveness of the Lactobacillus
brevis CD2 lozenges in resolving
the clinical signs and symptoms
of aphthous stomatitis, with a
significant
improvement
of
pain46.

Conclusion
Although many topical and
systemic modes of therapy have
been tried for treating aphthous
ulcers, search for a standard
treatment protocol still continues.
Many researches are being
carried out day to day to
effectively combat these painful
ulcers of the crimson mucosa.
Treatment must be tailor made
for individual patients in order to
render efficacious cure and
improve their quality of lives.

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G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan

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46.Trinchieri V, Di Carlo S, Bossu M,

Polimeni A. Use of Lozenges Containing
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Copyright 2013 G. Sree Vijayabala,Anupama N. Kalappanavar,Rajeshwari G Annigeri,Ramachandran Sudarshan .

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