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Doxycycline-induced staining of permanent adult dentition

C L I N I C A L R E P O R T
Australian Dental Journal 2005;50:(4):273-275 Doxycycline-induced staining of permanent adult dentition
E Ayaslioglu,* E Erkek,† AA Oba,‡ E Cebecio˘glu§ Abstract
scheme.2-4 Doxycycline is a semi-synthetic, lipophilic Background: Doxycycline is the most effective
and potent tetracycline congener.5-8 Owing to its antibiotic for managing brucellosis. Although it is superior pharmacokinetics, long half-life, better safety relatively free from side effects, complications profile, low resistance potential and lower cost, it is the involving the skin, nails and teeth may rarely be Although tetracyclines are relatively free from side Methods: Four patients with brucellosis developed
yellow-brown discolouration of teeth following a
effects,5,6 mucocutaneous complications may be 30-45 day course of doxycycline therapy during encountered, especially if given in high doses and/or during summer-time.7,9,10 Despite their well-known Results: All four patients were diagnosed as having
reputation in causing enamel hypoplasia and doxycycline-induced staining of the permanent irreversible staining of decidious teeth, staining of the dentition. In all cases, the staining completely permanent adult dentition is not well-known by resolved and the teeth recovered their original colourfollowing abrasive dental cleaning.
physicians.11-13 Herein, we present four cases of Conclusions: These observations indicate that the
doxycycline-induced staining of permanent teeth.
incidence of staining of the permanent dentition, asa complication of doxycycline, may be much higher than the literature indicates, especially if treatment is A 14 year old boy was referred to the Department of administered during summer months. Fortunately,this complication is reversible and does not require Infectious Diseases and Clinical Microbiology in June termination of doxycycline therapy. Complete 2003 with fever, malaise, sweating and severe back resolution following abrasive cleaning may suggest pain. He used to work on his father’s farm and had a that an extrinsic mechanism within the dental milieu history of contact with animals. A blood culture yielded may be involved in its pathogenesis. Strict avoidance B. melitensis and standard tube agglutination (STA) for of sunlight exposure during high-dose, long-term Brucella was positive with a titer of 1/1280. A doxycycline therapy might prevent the developmentof this complication.
combination treatment consisting of doxycycline2x100mg/day and rifampicin 600mg/day was initiated.
Key words: Tetracycline, doxycycline, teeth staining, teeth
Despite advice to avoid sunlight exposure, the patient continued working on the farm. At one-month follow- Abbreviation: STA = standard tube agglutination.
up, the boy complained of yellow discolouration of his (Accepted for publication 13 February 2005.) teeth. Oral examination revealed prominent yellow-brown staining, intensified at the gingival two-thirds ofanterior incisors (Fig 1). Treatment for brucellosis wasnot interrupted and doxycycline was continued for two INTRODUCTION
months along with warnings against sun exposure.
Since their introduction in 1947, tetracyclines have Abrasive cleaning resulted in complete resolution of been used in the treatment of various infections.1 They are the most effective antibiotics in Brucella infectionsand constitute the basic component of any therapeutic A 25 year old male presented in April 2003 with a three-month history of fever, chills, splenomegaly and *Assistant Professor in Infectious Diseases and Clinical arthralgia involving the knee joint. He was living in a Microbiology, Faculty of Medicine and Dentistry, Kirikkale village endemic for brucellosis and 25 citizens of that University, Kirikkale, Turkey.
†Associate Professor in Dermatology, Faculty of Medicine and village had been previously treated for Brucella Dentistry, Kirikkale University, Kirikkale, Turkey.
infection in our department. STA was positive (titer: ‡Assistant Professor in Department of Pedodontics, Faculty of 1/160) and a blood culture yielded Brucella spp. The Medicine and Dentistry, Kirikkale University, Kirikkale, Turkey.
§General Dentist in CE-SA Medical Center, Kirikkale, Turkey.
same combination protocol consisting of doxycycline Australian Dental Journal 2005;50:4.
Abrasive cleaning was effective in clearing toothstaining.
DISCUSSION
Due to their deposition in actively calcifying teeth and bones, tetracyclines are contraindicated inpregnant females and in children less than eight years ofage.4,5,6,14 Their use during development of dentine andenamel may cause permanent yellow-browndiscolouration of teeth and hypoplasia of enamel.4-6,15-17The discolouration varies with the specific tetracyclinecongener, the duration of therapy, the dosage ofoffending agent, the number of separate treatmentcourses, the concurrent activity of calcification and the Fig 1. Prominent yellowish-brown staining of anterior incisors in a
proximity of the deposits to dentino-enamel 14 year old boy receiving doxycycline therapy for brucellosis.
Tetracycline-induced discolouration in developing decidious teeth results from the formation of insolubletetracycline-calcium orthophosphate complexes whichare deposited in dentine and enamel and darken uponexposure to light.13,17-20 Calcification of permanent teethbegins around 4-6 months of life and is largelycomplete by 5-6 years. The risk of dental staining isconsidered negligible after the age of five years,especially if treatment duration is less than a few weeksand multiple courses are avoided.5,6 The relative lack of free calcium protects the erupted permanent adult dentition against tetracyclinehydrochloride-induced tooth discolouration. However,green-grey or blue-grey staining of previously normal- Fig 2. Band-like yellow-brown staining of maxillary teeth in a 25
coloured and fully mineralized permanent adult teeth year old man receiving doxycycline therapy for brucellosis.
as a complication of long-term minocycline ordoxycycline therapy has been documented.15,21 Thediscolouration may develop as early as one month after and rifampicin was initiated. A prominent band-like initiation of therapy and affects 3-6 per cent of patients yellow-brown discolouration of maxillary teeth was receiving minocycline at doses greater than noted at one-month follow-up (Fig 2). Dental hygiene 100mg/day.15,18,19,21 However, this complication is not measures and regular brushing were effective in absolutely dose-dependent and requires an inherent predisposition.15 Clinically, the staining is pronouncedat the incisal and middle third of crown and may fail to resolve after discontinuation of treatment.3,13,18,19,21 The A 28 year old woman was admitted in July 2003 mechanism of minocycline-induced discolouration in with a week-history of fever, profound sweating and permanent teeth remains controversial. The intrinsic right shoulder pain. STA test was positive (titer: 1/640).
theory proposes that minocycline is directly deposited Brucella spp. were isolated from blood culture. The in teeth by binding to plasma proteins and diffusing same combination protocol of doxycycline and into collagen-rich tissues like dental pulp and slowly rifampicin was initiated. At 45-day follow-up, she was being oxidized upon exposure to light.18 Dentinogenesis completely symptom-free but had mild brown staining continues life-long, albeit at a greatly reduced rate after of anterior incisors. Abrasive cleaning resulted in the eruption of permanent teeth. Although theoretically complete resolution of teeth discolouration.
possible, intrinsic minocycline deposition is not likelyto have a profound influence on the apparent colour of permanent dentition.15 Doxycycline binds less calcium A 12 year old boy presented in July 2003 with a five- than other tetracyclines and theoretically it is less likely month history of fever, chills, night-sweats and orchitis.
to produce intrinsic discolouration of teeth.5,6,20 STA was positive with a titer of 1/640. A combination According to extrinsic theory, the attachment of protocol consisting of doxycycline 2x100mg/day and minocycline to acquired pellicle’s glycoproteins etches streptomycin 1gr/day was initiated. At one-month the enamel and oxidation upon air exposure or as a follow-up, oral examination revealed a slight brown result of bacterial activity transforms the complex into discolouration of the right anterior incisor tooth.
insoluble black quinone.11,15,18 The concentration of Australian Dental Journal 2005;50:4.
minocycline in the gingival fluid is five times that of 5. Shetty AK. Tetracyclines in pediatrics revisited. Clin Pediatr serum and the drug has the ability to form insoluble salts by chelating with divalent metal ions like iron in 6. Committee on Infectious Diseases and Immunization of the Canadian Pediatric Society (CPS). Tetracycline use in children saliva or gingival fluid.15,18 Another theory depicts that update. URL: ‘http://www.cpc.ca/english/statements/ID/id94- haemosiderin, the breakdown product of minocycline, may chelate with iron and form an insoluble complex.18 7. Layton AM, Cunliffe WJ. Phototoxic eruptions due to Thus, extrinsic deposition of minocycline or doxycycline – a dose-related phenomenon. Clin Exp Dermatol doxycycline on the surface of teeth seems the most plausible mechanism for discolouration of permanent 8. Bonnetblanc JM. Doxycycline. Ann Dermatol Venereol 9. Bjellerup M, Ljunggren B. Differences in phototoxic potency should be considered when tetracyclines are prescribed during CONCLUSION
summer-time. A study on doxycycline and lymecycline in human Poor oral hygiene and intense sunlight exposure may volunteers, using an objective method for recording erythema. BrJ Dermatol 1994;130:356-360.
be exacerbating factors in prominent staining ofpermanent dentition by doxycycline.13 All patients 10. Bryant SG, Fisher S, Kluge RM. Increased frequency of doxycycline side effects. Pharmacotherapy 1987;7:125-129. presented herein had poor oral hygiene and all were 11. de Wit ME, Stricker BH, Porsius AJ. Discoloration of teeth by treated during summer and had more prominent drugs. Ned Tijdschr Tandheelkd 1996;103:3-5.
staining of UV-exposed upper incisors. Advising oral 12. Ayaslioglu E, Erkek E, Beygo B, Cebecioˇglu E. Cutaneous hygiene measures and strict avoidance of sunlight, complications of doxcycyline therapy. Infect Med 2004;21:24. particularly in countries with a sunny climate, may 13. Patel K, Cheshire D, Vance A. Oral and systemic effects of prevent staining of permanent dentition in patients prolonged minocycline therapy. Br Dental J 1998;185:560-562.
receiving high-dose, long-term doxycycline therapy. For 14. Chan-Tompkins NH. Toxic effects and drug interactions of minocycline, reduction of dose to less than 100mg/day antimycobacterial therapy. Clin Dermatol 1995;13:223-233.
and use of vitamin C have been reported as alternative 15. Siller GM, Tod MA, Savage NW. Minocycline-induced oral pigmentation. J Am Acad Dermatol 1994;30:350-354.
Vital bleaching with H O and composite/porcelain 16. Lochary ME, Lockhart PB, Williams WT Jr. Doxycycline and staining of permanent teeth. Pediatr Infect Dis J 1998;17:429- veneers/crowns remain as the best possible therapeutic approaches for staining of permanent dentition by 17. Kashyap AS, Sharma HS. Discolouration of permanent teeth and tetracycline analogues.13,18 In our patients, the staining enamel hypoplasia due to tetracycline. Postgrad Med J was reversible, responded to abrasive dental cleaning along with proper mouth hygiene measures and did not 18. Good ML, Hussey DL. Minocycline: stain devil? Br J Dermatol require cessation of doxycycline therapy. This may implicate extrinsic staining in the pathogenesis of 19. Rosen T, Hoffmann TJ. Minocycline-induced discoloration of the permanent teeth. J Am Acad Dermatol 1989;21:569.
doxycycline-induced discolouration of permanent 20. Benavides S, Nahata MC. Anthrax: safe treatment for children.
21. Ayangco L, Sheridan PJ. Minocycline-induced staining of torus REFERENCES
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1. Standiford HC. Tetracyclines and chloramphenicol. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of InfectiousDiseases. 5th edn. New York: Churchill Livingstone, 2000:336,348.
Address for correspondence/reprints: 2. Ariza J, Gudiol F, Pallares R, Viladrich PF, Rufi G, Corredoira J, Miravitlles MR. Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study. Ann Intern Med 1992;117:25- 3. Morrow GL, Abbott RL. Minocycline-induced scleral, dental, and dermal pigmentation. Am J Ophtalmol 1998;125:396-397.
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Australian Dental Journal 2005;50:4.

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