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British Journal of Oral and Maxillofacial Surgery 52 (2014) 382–383
Short communication
Tetracycline: a cure all? Robert Kennedy 1 , Mustansir Alibhai, Kaveh Shakib ∗ Barnet & Chase Farm Hospital, Department of Oral & Maxillofacial Surgery, The Ridgeway, Enfield Middlesex, EN2 8JL, United Kingdom Accepted 31 January 2014 Available online 5 March 2014
Abstract Tetracyclines are used to treat a range of oral conditions. Their efficacy in the treatment of periodontitis is well established, and they are authoritatively recommended in the management of avulsed teeth. There is a growing evidence base to support the use of tetracycline to treat recurrent aphthous stomatitis, but its use in white spongy naevus is limited to a handful of case reports. The mechanism of action in these conditions is either unknown or indicated to be through the inhibition of matrix metalloproteinases (MMP). The use of a single agent to treat diverse oral conditions has important implications for oral medicine. © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Keywords: Dental trauma; Periodontitis; Recurrent aphthous stomatitis; Tetracycline; Vesiculobullous; White spongy naevus
Introduction In recent decades tetracyclines have emerged as effective inhibitors of collagenases (a subgroup of matrix metalloproteinases or MMP) with important applications in oral medicine and dentistry.1 They are therefore enjoying a renaissance despite growing bacterial resistance, which limits their use as antibiotics.
Recurrent aphthous stomatitis The aetiology of recurrent aphthous stomatitis is multifactorial and incompletely understood, and treatments are largely empirical. Use of topical tetracycline as an oral rinse, or applied locally covered by a mucoadhesive gel, reduces the pain associated with the condition.2,3 ∗ Corresponding author at: Oral and Maxillofacial surgery, chase farm Hospital. The Ridgeway, Enfield, Middlesex EN2 8JL, United kingdom. Tel.: +02083751764; fax: +44 020 8375 1764. E-mail addresses: [email protected] (R. Kennedy), [email protected] (M. Alibhai), [email protected], [email protected] (K. Shakib). 1 Tel.: +44 0781 550 1088.
A Cochrane review of systemic interventions included 2 randomised controlled trials that examined the efficacy of tetracycline.4 Subantimicrobial doses of doxycycline (20 mg twice daily) reduced the number of new ulcers and increased the number of pain-free days. However, there was no significant difference in the mean pain score or in the number of ulcers present at the end of the 90-day trial. Tetracycline (250 mg) used as an oral rinse and then swallowed, reduced the pain and size of ulcers, but did not affect their incidence. The authors concluded that there was no enough evidence to support the use of any medicament in clinical practice, but that among other interventions, subantimicrobial doses of doxycycline warranted further investigation. As increased MMP concentrations are detected by the immunostaining of recurrent lesions,5 it may be suggested that inhibition of MMP relieves the condition. Alternatively, it may be that the prevention of secondary bacterial infection is involved.
Dental trauma Systemic tetracycline is recommended as the antibiotic of choice after replacement of avulsed teeth.6 Topical
0266-4356/$ – see front matter © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bjoms.2014.01.020
R. Kennedy et al. / British Journal of Oral and Maxillofacial Surgery 52 (2014) 382–383
application of minocycline or doxycycline can also be considered in immature teeth.6 These recommendations are based on animal studies which showed reduced root resorption and increased pulpal revascularisation when tetracycline antibiotics were applied topically to the avulsed tooth. Again, the mechanism of action may involve inhibition of MMP, although prevention of bacterial infection may also contribute.
White spongy naevus White spongy naevus, which is a rare condition inherited in an autosomal dominant manner, presents as bilateral white spongy plaques on the buccal mucosa. Several case reports document remission with the use of tetracycline oral rinse,7 and the authors have also seen similar results. It may be hypothesised that the architecture of these lesions encourages bacterial colonisation, and this has a function in the expression of the condition despite its genetic aetiology. The mechanism of tetracycline action may therefore be antibacterial.
Periodontitis and peri-implantitis MMP concentrations are increased in periodontitis and in association with loss of clinical attachment.1 A subantimicrobial dose of doxycycline (20 mg twice daily) inhibits the activity of MMP, and in combination with conventional scaling, leads to improved levels of clinical attachment. A number of randomised placebo controlled trials support this,1 and in the UK doxycycline is licensed as an adjunct to scaling for the treatment of periodontitis. Local delivery of doxycycline as an adjunct to manual debridement leads to improved levels of clinical attachment in peri-implantitis.8
Vesiculobullous diseases Herpes labialis treated with a gel combining low dose doxycycline with monocaprin shortened healing time and reduced pain.9 The authors suggested a mechanism based on the inhibition of MMP.
Bacterial infections affecting the oropharyngeal region Despite the emergence of bacterial resistance, tetracyclines remain the antibiotic of choice for the treatment of infections
383
caused by Chlamydia trachomatis. Tetracyclines, as prescribed in the British National Formulary, also continue to be used in the management of infections caused by Mycoplasma hominis.
Conclusion Tetracyclines have a role in the treatment of diverse conditions that affect the soft and hard tissues of the oral cavity. The implication that MMP has a function in the aetiology of such a range of conditions may allow other drugs to be developed for use in oral medicine.
Conflict of interest None.
Ethics statement/confirmation of patient permission No patient identifying information is included. No human or animal studies were performed.
References 1. Gu Y, Walker C, Ryan ME, Payne JB, Golub LM. Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine. J Oral Microbiol 2012;4:19227. 2. Henricsson V, Axéll T. Treatment of recurrent aphthous ulcers with aureomycin mouth rinse or zendium dentifrice. Acta Odontol Scand 1985;43:47–52. 3. Ylikontiola L, Sorsa T, Häyrinen-Immonen R, Salo T. Doxymycine–cyanoacrylate treatment of recurrent aphthous ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:329–33. 4. Brocklehurst P, Tickle M, Glenny AM, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev 2012;9:CD005411. 5. Häyrinen-Immonen R, Sorsa T, Nordström D, Malmström M, Konttinen YT. Collagenase and stromelysin in recurrent aphthous ulcers (RAU). Int J Oral Maxillofac Surg 1993;22:46–9. 6. Andersson L, Andreasen JO, Day P, et al. International Association of Dental Traumatology guidelines for the management of traumatic dental injuries. 2. Avulsion of permanent teeth. Dent Traumatol 2012;28:88–96. 7. McDonagh AJ, Gawkrodger DJ, Walker AE. White sponge naevus successfully treated with topical tetracycline. Clin Exp Dermatol 1990;15:152–3. 8. Büchter A, Meyer U, Kruse-Lösler B, Joos U, Kleinheinz J. Sustained release of doxycycline for the treatment of peri-implantitis: randomised controlled trial. Br J Oral Maxillofac Surg 2004;42:439–44. 9. Skulason S, Holbrook WP, Thormar H, Gunnarsson GB, Kristmundsdottir T. A study of the clinical activity of a gel combining monocaprin and doxycycline: a novel treatment for herpes labialis. J Oral Pathol Med 2012;41:61–7.
British Journal of Oral and Maxillofacial Surgery 52 (2014) 382–383
Short communication
Tetracycline: a cure all? Robert Kennedy 1 , Mustansir Alibhai, Kaveh Shakib ∗ Barnet & Chase Farm Hospital, Department of Oral & Maxillofacial Surgery, The Ridgeway, Enfield Middlesex, EN2 8JL, United Kingdom Accepted 31 January 2014 Available online 5 March 2014
Abstract Tetracyclines are used to treat a range of oral conditions. Their efficacy in the treatment of periodontitis is well established, and they are authoritatively recommended in the management of avulsed teeth. There is a growing evidence base to support the use of tetracycline to treat recurrent aphthous stomatitis, but its use in white spongy naevus is limited to a handful of case reports. The mechanism of action in these conditions is either unknown or indicated to be through the inhibition of matrix metalloproteinases (MMP). The use of a single agent to treat diverse oral conditions has important implications for oral medicine. © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Keywords: Dental trauma; Periodontitis; Recurrent aphthous stomatitis; Tetracycline; Vesiculobullous; White spongy naevus
Introduction In recent decades tetracyclines have emerged as effective inhibitors of collagenases (a subgroup of matrix metalloproteinases or MMP) with important applications in oral medicine and dentistry.1 They are therefore enjoying a renaissance despite growing bacterial resistance, which limits their use as antibiotics.
Recurrent aphthous stomatitis The aetiology of recurrent aphthous stomatitis is multifactorial and incompletely understood, and treatments are largely empirical. Use of topical tetracycline as an oral rinse, or applied locally covered by a mucoadhesive gel, reduces the pain associated with the condition.2,3 ∗ Corresponding author at: Oral and Maxillofacial surgery, chase farm Hospital. The Ridgeway, Enfield, Middlesex EN2 8JL, United kingdom. Tel.: +02083751764; fax: +44 020 8375 1764. E-mail addresses: [email protected] (R. Kennedy), [email protected] (M. Alibhai), [email protected], [email protected] (K. Shakib). 1 Tel.: +44 0781 550 1088.
A Cochrane review of systemic interventions included 2 randomised controlled trials that examined the efficacy of tetracycline.4 Subantimicrobial doses of doxycycline (20 mg twice daily) reduced the number of new ulcers and increased the number of pain-free days. However, there was no significant difference in the mean pain score or in the number of ulcers present at the end of the 90-day trial. Tetracycline (250 mg) used as an oral rinse and then swallowed, reduced the pain and size of ulcers, but did not affect their incidence. The authors concluded that there was no enough evidence to support the use of any medicament in clinical practice, but that among other interventions, subantimicrobial doses of doxycycline warranted further investigation. As increased MMP concentrations are detected by the immunostaining of recurrent lesions,5 it may be suggested that inhibition of MMP relieves the condition. Alternatively, it may be that the prevention of secondary bacterial infection is involved.
Dental trauma Systemic tetracycline is recommended as the antibiotic of choice after replacement of avulsed teeth.6 Topical
0266-4356/$ – see front matter © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bjoms.2014.01.020
R. Kennedy et al. / British Journal of Oral and Maxillofacial Surgery 52 (2014) 382–383
application of minocycline or doxycycline can also be considered in immature teeth.6 These recommendations are based on animal studies which showed reduced root resorption and increased pulpal revascularisation when tetracycline antibiotics were applied topically to the avulsed tooth. Again, the mechanism of action may involve inhibition of MMP, although prevention of bacterial infection may also contribute.
White spongy naevus White spongy naevus, which is a rare condition inherited in an autosomal dominant manner, presents as bilateral white spongy plaques on the buccal mucosa. Several case reports document remission with the use of tetracycline oral rinse,7 and the authors have also seen similar results. It may be hypothesised that the architecture of these lesions encourages bacterial colonisation, and this has a function in the expression of the condition despite its genetic aetiology. The mechanism of tetracycline action may therefore be antibacterial.
Periodontitis and peri-implantitis MMP concentrations are increased in periodontitis and in association with loss of clinical attachment.1 A subantimicrobial dose of doxycycline (20 mg twice daily) inhibits the activity of MMP, and in combination with conventional scaling, leads to improved levels of clinical attachment. A number of randomised placebo controlled trials support this,1 and in the UK doxycycline is licensed as an adjunct to scaling for the treatment of periodontitis. Local delivery of doxycycline as an adjunct to manual debridement leads to improved levels of clinical attachment in peri-implantitis.8
Vesiculobullous diseases Herpes labialis treated with a gel combining low dose doxycycline with monocaprin shortened healing time and reduced pain.9 The authors suggested a mechanism based on the inhibition of MMP.
Bacterial infections affecting the oropharyngeal region Despite the emergence of bacterial resistance, tetracyclines remain the antibiotic of choice for the treatment of infections
383
caused by Chlamydia trachomatis. Tetracyclines, as prescribed in the British National Formulary, also continue to be used in the management of infections caused by Mycoplasma hominis.
Conclusion Tetracyclines have a role in the treatment of diverse conditions that affect the soft and hard tissues of the oral cavity. The implication that MMP has a function in the aetiology of such a range of conditions may allow other drugs to be developed for use in oral medicine.
Conflict of interest None.
Ethics statement/confirmation of patient permission No patient identifying information is included. No human or animal studies were performed.
References 1. Gu Y, Walker C, Ryan ME, Payne JB, Golub LM. Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine. J Oral Microbiol 2012;4:19227. 2. Henricsson V, Axéll T. Treatment of recurrent aphthous ulcers with aureomycin mouth rinse or zendium dentifrice. Acta Odontol Scand 1985;43:47–52. 3. Ylikontiola L, Sorsa T, Häyrinen-Immonen R, Salo T. Doxymycine–cyanoacrylate treatment of recurrent aphthous ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:329–33. 4. Brocklehurst P, Tickle M, Glenny AM, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev 2012;9:CD005411. 5. Häyrinen-Immonen R, Sorsa T, Nordström D, Malmström M, Konttinen YT. Collagenase and stromelysin in recurrent aphthous ulcers (RAU). Int J Oral Maxillofac Surg 1993;22:46–9. 6. Andersson L, Andreasen JO, Day P, et al. International Association of Dental Traumatology guidelines for the management of traumatic dental injuries. 2. Avulsion of permanent teeth. Dent Traumatol 2012;28:88–96. 7. McDonagh AJ, Gawkrodger DJ, Walker AE. White sponge naevus successfully treated with topical tetracycline. Clin Exp Dermatol 1990;15:152–3. 8. Büchter A, Meyer U, Kruse-Lösler B, Joos U, Kleinheinz J. Sustained release of doxycycline for the treatment of peri-implantitis: randomised controlled trial. Br J Oral Maxillofac Surg 2004;42:439–44. 9. Skulason S, Holbrook WP, Thormar H, Gunnarsson GB, Kristmundsdottir T. A study of the clinical activity of a gel combining monocaprin and doxycycline: a novel treatment for herpes labialis. J Oral Pathol Med 2012;41:61–7.
