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Short Communication

A Novel Treatment Modality for Recurrent Aphthous

Stomatitis – Single Application of Doxycycline Hyclate
R Thriveni, Gulnaaz Anjum, D N S V Ramesh, Amit Byatnal, Mahalakshmi Wale, K Pragati
Department of Oral Medicine and Radiology, AME’S Dental College and Hospital, Raichur, Karnataka, India

Abstract
Background and Objectives: Recurrent aphthous ulcers are common painful mucosal conditions affecting the oral cavity. Despite of so many
treatment modalities, there is no specific and definitive treatment. Hence a study was carried out to evaluate the clinical effects Single Application
of Doxycycline Hyclate 100 mg for Recurrent apthous Stomatitis (RAS). Materials and Methods: Forty study subjects were included in the
study. Patients were randomly assigned into two groups. There were 20 patients in each group; Group A patients received Doxycycline Hyclate
100 mg in the first visit, Group B patients received placebo. The results were analyzed with unpaired ‘t’ test. Results: The data indicated a
significant reduction in pain in group A (i.e., faster reduction in pain) compared with group B. Interpretation and Conclusion: A single
application of doxycycline hyclate decreased pain and speeded recovery.

Keywords: Doxycycline hyclate, recurrent apthous stomatitis, pain

Introduction glycolate, talc, and magnesium stearate) prepared by AME’s

Recurrent aphthous stomatitis  (RAS) is the most common
oral mucosal disease known to human beings; it carries no
mortality but a high morbidity.[1] The prevalence of RAS in
general population is of the order of 5%–25%.[2]
Materials and Methods
Forty study subjects were included in the study. Twenty
patients in Group A received 100 mg of doxycycline hyclate
in their first visit, whereas 20 patients in Group B received
placebo.
Patients with history of recurrence ulcers in the oral cavity
with at least two episodes per year and with no signs of any
systemic disease were selected.
Then all study subjects underwent a clinical examination to
assess the size of the ulcer with calibrated periodontal probe
and pain using Visual Analog Scale  (VAS) from 1 to 10
(10 being most severe).
Drugs used for the study included doxycycline hyclate100 mg
tablets  (Doxy 1) manufactured by USV Private Limited
and placebo 100  mg tablets  (starch, lactose, sodium starch
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DOI:
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College of Pharmacy, Raichur. Twenty patients in Group A
received powdered doxycycline hyclate tablet topically,
whereas 20 patients in Group B received powdered placebo
tablet topically.
Doxycycline hyclate or the placebo tablet was ground to fine
powder using a glass mortar and pestle. A pinch of denture
adhesive was added so that the medicament is retained on the
ulcer, with few drops of saline. About 50% of the medicament
or placebo was used for ulcers  <5  cm and 100% of the
medicament was used for ulcers >5 cm. A few drops of saline
solution were added to this mixture. Afterward, the final freshly
prepared medicament was placed over the ulcer using a plastic
instrument. After the application of medicament, patients were
informed not to eat or drink for a period of 3 h. The results
were analyzed with unpaired t‑test.
Address for correspondence: Dr. Amit Byatnal,
AME’s Dental College and Hospital, Bijengera Road, Raichur - 584 102,
Karnataka, India.
E‑mail: amitbyatnal@gmail.com
This is an open access journal, and articles are distributed under the terms of the
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
appropriate credit is given and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
How to cite this article: Thriveni R, Anjum G, V Ramesh DN, Byatnal A,
Wale M, Pragati K. A novel treatment modality for recurrent aphthous
stomatitis – Single application of doxycycline hyclate. J Indian Acad Oral
Med Radiol 2018;30:96-8.
Received: 16-12-2017   Accepted: 16-03-2018   Published: 23-04-2018

96 © 2018 Journal of Indian Academy of Oral Medicine & Radiology | Published by Wolters Kluwer - Medknow
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Thriveni, et al.: A novel treatment modality for recurrent apthous stomatitis – Single

Results There are many previous reports in which tetracyclines and

minocyclines have been used in management of RAS[5];
The comparison of ulcer size and maximum pain was made
between first‑day values  (baseline value) and third‑day
values. The mean pain score of the study group was 8.05 and Table 1: Comparison of pain in terms of visual analog
in control group 7.70 at the baseline level. On the third day, scale (Mean [SD]) among cases and controls at different
pain score was 3.80 in the study group and 5.65 in the control time intervals using unpaired t‑test
group [Table 1] with P value of 0.014 which was found to be Group n Mean Std. t P
significant and it was found highly significant on the fifth day deviation
with a P value of  <0.001 using unpaired t‑test. These data Pretreatment Cases 20 8.05 0.7 1.418 0.164
[Figures 1 and 2] indicate a significant reduction in pain in Controls 20 7.70 0.8
Group A (i.e., faster reduction in pain) compared with Group B Day 1 Cases 20 7.85 0.8 1.309 0.198
(P < 0.014 using unpaired t‑test) [Figure 3]. Controls 20 7.45 1.0
Day 2 Cases 20 6.65 0.6 0.202 0.841
Intergroup comparison of days taken for ulcer healing
Controls 20 6.60 0.8
Figure  4 shows that the mean time required for ulcer
Day 3 Cases 20 3.80 0.7 1.807 0.079
healing was significantly less in Group A (1.85 ± 0.5, range Controls 20 5.65 0.9
2–7 days) than that of Group B (3.32 ± 1.1, range 3–7 days; Day 4 Cases 20 3.02 0.8 2.570 0.014*
P < 0.001). Controls 20 4.50 0.8
Day 5 Cases 20 1.85 1.2 3.658 <0.001**
Discussion Controls 20 3.20 1.1
Day 6 Cases 20 0.75 1.0 4.196 <0.001**
Tetracyclines have been shown to inhibit prostaglandin
Controls 20 2.15 1.0
production, suppress leukocyte activities, and inhibit
Day 7 Cases 20 0.15 0.3 3.753 <0.001**
collagenase and gelatinase activities as well as oxidative
Controls 20 1.10 1.0
activation of their latent forms. As there is no specific
Day 8 Cases 20 0.00 0.0 2.179 0.036
management for RAS, this study was undertaken to Controls 20 0.20 0.4
examine pain reduction in RAS following topical Day 9 Cases 20 0.00 0.0 NA NA
application of doxycycline hyclate  (single application), Controls 20 0.00 0.0
an inhibitor of matrix metalloproteinases  (MMPs). [3] Day 10 Cases 20 0.00 0.0 NA NA
Tetracyclines, in addition to their antimicrobial effect, have Controls 20 0.00 0.0
been shown to reduce collagen breakdown by collagenase *P<0.05 ‑ Significant, **P<0.001 ‑ Highly significant. NA: Not applicable
activity.[4]

Figure 1: Group A with doxycycline hyclate application Figure 2: Group B with placebo

Figure 3: Pain incidence in VAS before and after treatment Figure 4: Decrease in intensity of pain in Group A (cases) and Group B (controls)

Journal of Indian Academy of Oral Medicine & Radiology  ¦  Volume 30 ¦ Issue 1 ¦ January‑March 2018 97
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Thriveni, et al.: A novel treatment modality for recurrent apthous stomatitis – Single

however, our study was in accordance to Vijayabala et al. J Oral Maxillofac Pathol 2011;15:252‑6.
who proved that a single application of doxycycline hyclate 2. Ship JA. Recurrent aphthous stomatitis: An update. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 1996;81:141‑7.
decreased pain and speeded recovery.
3. Vijayabala G, Kalappanavar AN, Annigeri RG, Sudarshan R, Shettar SS.
Financial support and sponsorship Single application of topical doxycycline hyclate in the management of
Nil. recurrent aphthous stomatitis. Oral Med Oral Pathol Oral Radiol Endod
2013;116:440‑6.
Conflicts of interest 4. Gorsky  M, Epstein  JB, Rabenstein  S, Elishoov  H, Yarom  N. Topical
There are no conflicts of interest. minocycline and tetracycline rinses in treatment of recurrent aphthous
stomatitis: A  randomized cross‑over study. Dermatol Online J
2007;13:1.
References 5. Graykowski  EA, Kingman. A. Double‑blind trial of tetracycline in
1. Preeti  L, Magesh  KT, Rajkumar  K. Recurrent aphthous stomatitis. recurrent aphthous ulceration. J Oral Pathol Med 1978;7:376‑82.

98 Journal of Indian Academy of Oral Medicine & Radiology  ¦  Volume 30  ¦  Issue 1  ¦  January‑March 2018