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§
scheme.2-4 Doxycycline is a semi-synthetic, lipophilic
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
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
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
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
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.
Tetracycline, doxycycline, teeth staining, teeth
Despite advice to avoid sunlight exposure, the patient
continued working on the farm. At one-month follow-
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
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
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.
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
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-
. 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).
proposes that minocycline is directly deposited
. 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
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
palatinus and alveolar bone. J Periodontol 2003;74:669-671.
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.
4. Solera J, Martinez-Alfaro E, Espinosa A. Recognition and
optimum treatment of brucellosis. Drugs 1997;53:245-256.
Australian Dental Journal 2005;50:4.
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