Title Use of Topical Tetracycline-Class Antibiotics Can Reduce Pain and Formation of New Ulcers and Increase Speed of Recovery in Patients with Recurrent Aphthous Stomatitis
Clinical Question In an adult patient with recurrent aphthous stomatitis, does use of tetracycline-class drugs significantly reduce pain and increase speed of recovery when compared to placebo?
Clinical Bottom Line For patients with recurrent aphthous stomatitis, treatment with tetracycline is more effective than placebo in reducing pain and increasing speed of recovery. This is supported by three randomized controlled trials in which various doxycycline formulations showed significantly better healing, pain reduction, and prevention of ulcers versus placebo. Use of topical doxycycline is feasible in the setting of a dental practice, and patients are most likely able to comply, despite reports of a transient bitter sensation following application.
Best Evidence  
PubMed ID Author / Year Patient Group Study type
(level of evidence)
24035110Vijayabala/201350 patients with recurrent aphthous stomatitisRandomized Controlled Trial
Key resultsStarting at a baseline score of 6.4, the mean pain scores for the experimental group from day 1 to day 6, in order, were 3.7, 2.3, 0.9, 0.4, 0.1, and 0.1. Starting a baseline score of 5.9, the mean pain scores for the placebo group from day 1 to day 6, in order, were 5.3, 4.5, 3.1, 1.9, 0.9, and 0.2. This data indicates that doxycycline hyclate did significantly reduce pain by day 1 (P<0.001) and resulted in faster healing (P<0.001) of aphthous ulcers.
17391302Preshaw/200750 patients with a history of recurrent aphthous ulcerationRandomized Controlled Trial
Key resultsThere were fewer new ulcers per day in the subantimicrobial dose doxycycline (SDD) group, 0.17 vs. 0.36 (p = 0.07), fewer total ulcers over 90 days, 16 vs. 32.4 (p = 0308), more days with no new ulcers, 80.4 vs. 69.8 (p = 0.04), and more days without pain, 60.5 vs. 45.3 (p = 0.06) when compared to the placebo group.
18991147Skulason/200949 patients with recurrent aphthous stomatitis ulcersRandomized Controlled Trial
Key results68% of patients receiving the doxycycline gel reported complete healing of ulcers, defined as absence of awareness of the ulcer, within 3 days, compared to 24% in the placebo group (p <0.005). The initial pain scores of placebo and doxycycline groups were 5.3 and 5.1, respectively. Pain scores for day 2 and day 3 were 4.8 and 4.0 for the placebo group and 3.9 and 2.9 for the doxycycline group.
Evidence Search "Stomatitis, Aphthous"[Mesh] AND "Doxycycline"[Mesh]
Comments on
The Evidence
Each of the articles included was a randomized controlled trial. Groups were similar, with a random distribution of men and women over 18 years of age. The placebo groups and doxycycline groups were treated the same, and two of the three trials were double-blind. No issues regarding compliance were reported. However, competing interests may have had an influence, as Preshaw states the trial was supported by a grant from CollaGenex International Ltd and PubMed listed the Skulason trial as "Research Support/Non-US Gov't". Because patients were given diaries to record daily pain and ulcer healing, recall bias is unlikely.
Applicability The use of doxycycline in the treatment of recurrent aphthous stomatitis ulcers appears to be relatively quick and simple, with no remarks by the authors regarding non-compliance amongst patients. No patients reported serious side effects of the various treatments, although a transient bitter sensation was reported with the topical crushed doxycycline hyclate tablet. This, however, did not hinder completion of the trial. In a general practice, it would be more practical to use doxycycline on a single-application basis or for a short period of time, up to 1 week. The use of doxycycline as a preventative measure twice a day will most likely be too much of an expense for most patients.
Specialty (Oral Medicine/Pathology/Radiology) (General Dentistry)
Keywords Recurrent Aphthous Stomatitis, Tetracycline, Doxycycline
ID# 2830
Date of submission 03/30/2015
E-mail schantzm@livemail.uthscsa.edu
Author Michele Schantz
Co-author(s) e-mail
Faculty mentor Adriana V. Green, DDS, MPH
Faculty mentor e-mail greenav@uthscsa.edu
Basic Science Rationale
(Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?)
None available
Comments and Evidence-Based Updates on the CAT
None available