What are the risk factors for chlorhexidine staining of the teeth? Are certain products/concentrations, frequency, or duration of use associated with this complication?

Comment by InpharmD Researcher

As the proposed mechanism of chlorhexidine teeth staining is closely linked with its mechanism of action as an antiseptic, all concentrations of chlorhexidine are associated with teeth staining. Studies suggest chlorhexidine use for greater than four weeks is associated with teeth staining. Risk factors that may accelerate tooth staining with chlorhexidine use include dietary factors (e.g., tea, coffee, wine intake), poor oral hygiene, and smoking.

Background

Chlorhexidine mouthwash is used as an antiseptic to reduce gum disease, prevent plaque buildup, and to slow the development of tartar (chalky deposits). Chlorhexidine is a positively charged molecule that can bind to negatively charged microbial cell walls to interfere with the microorganism’s equilibrium. At lower concentrations, chlorhexidine is bacteriostatic by way of causing leakage of low molecular weight substances from the microbial cell and inhibiting reproduction. At higher concentrations, chlorhexidine is bactericidal by precipitating the cytoplasmic contents of the microbial cell through adsorption to the negatively charged cell wall. [1], [2]

While its use is associated with tooth staining, the exact mechanism of this side effect is not completely understood. Current hypotheses suggest the staining is due to anionic dietary chemogens (e.g., from tea, coffee, tannins from wine) that adsorb to chlorhexidine cations. Because this is closely linked with chlorhexidine’s mechanism of action, lack of staining is likely to indicate a lack of efficacy and teeth staining can be expected with very low concentration rinses. [1], [2]

A 2017 Cochrane review and meta-analysis studied the use of chlorhexidine mouthwash and the incidence of teeth staining. While chlorhexidine can reduce plaque build-up for the first weeks or months of use, it can lead to tooth staining or tartar buildup when used for longer than four weeks. A review of 51 randomized controlled trials included people brushing their teeth, either with or without using floss, and professional tooth cleaning during chlorhexidine use. Results found a large increase in extrinsic tooth staining after 3-6 weeks of chlorhexidine use. This effect continued to increase in participants using chlorhexidine mouthwash after 7-12 weeks and after 6 months. Chlorhexidine concentrations studied in the papers discussing tooth staining ranged from 0.06% to 0.2%. The authors conclude that chlorhexidine mouthwash causes tooth staining, which requires polishing carried out by a dental professional, after four weeks or longer of use. [2]

A 2019 systematic review and meta-analysis evaluated whether chlorhexidine mouthwash with an anti-discoloration system is effective in preventing extrinsic tooth surface discoloration without sacrificing efficacy. Thirteen randomized studies were identified for this meta-analysis. For non-brushing studies, there was a significant difference in staining scores between chlorhexidine mouthwash with anti-discoloration systems and normal chlorhexidine. However, when studies involved toothbrushing, there was no difference in staining between the two formulations of chlorhexidine. Studies between the two formulations found no differences in efficacy in terms of plaque scores and gingival inflammation. [3]

An in vitro study assessing the role of saliva in chlorhexidine-induced tooth staining used tea as the staining agent and hydroxyapatite as mimicking teeth. Various combinations of tea, chlorhexidine and parotide saliva were used to investigate different substances binding to hydroxyapatite by performing sodium dodecyl sulfate–polyacrylamide gel electrophoresis with Coomassie Brilliant Blue (R250). While tea interacted with several salivary proteins including proline-rich proteins and histamines, chlorhexidine did not bind to salivary proteins. Additionally, the combination of tea and chlorhexidine increased binding of both agents to hydroxyapatite. The authors suggested that a possible mechanism of stain promotion by chlorhexidine could be through accelerating formation of acquired pellicle and the accumulation of tea and chlorhexidine onto tooth surfaces. [4]

References:

[1] Addy M, Moran J. Mechanisms of stain formation on teeth, in particular associated with metal ions and antiseptics. Adv Dent Res. 1995;9(4):450-456. doi:10.1177/08959374950090041601
[2] James P, Worthington HV, Parnell C, et al. Chlorhexidine mouthrinse as an adjunctive treatment for gingival health. Cochrane Database Syst Rev. 2017;3(3):CD008676. Published 2017 Mar 31. doi:10.1002/14651858.CD008676.pub2
[3] Van Swaaij BWM, van der Weijden GAF, Bakker EWP, Graziani F, Slot DE. Does chlorhexidine mouthwash, with an anti-discoloration system, reduce tooth surface discoloration without losing its efficacy? A systematic review and meta-analysis. Int J Dent Hyg. 2020;18(1):27-43. doi:10.1111/idh.12402
[4] Carpenter GH, Pramanik R, Proctor GB. An in vitro model of chlorhexidine-induced tooth staining. J Periodontal Res. 2005;40(3):225-230. doi:10.1111/j.1600-0765.2005.00791.x

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What are the risk factors for chlorhexidine staining of the teeth? Are certain products/concentrations, frequency, or duration of use associated with this complication?

Please see Table 1 for your response.


 

Staining and calculus formation after 0.12% chlorhexidine rinses in plaque-free and plaque covered surfaces: a randomized trial

Design

Single-blind, randomized, split-mouth, experimental gingivitis clinical trial

N= 20

Objective

To compare the side effects of 0.12% chlorhexidine gluconate (CHX) on previously plaque-free (control group) and plaque-covered surfaces (test group).

Study Groups

Test site (n= 20)

Control surfaces (n= 20)

Inclusion Criteria

Age 18 to 35 years, male (to avoid hormonal influences), no medical conditions that can interfere with periodontal health

Exclusion Criteria

Probing pocket depth > 3 mm and/or clinical attachment loss > 2 mm at any site, antibiotic and/or anti-inflammatory therapy within 3 months prior to baseline examination, oral mucosal lesions, smokers, need for antibiotic premedication, history of hypersensitivity to chlorhexidine gluconate (CHX), any condition device that could act as plaque retentive factor

Methods

Included patients completed a 14-day pretrial period where they received professional scaling and polishing, leading up to day zero of the study where the presence of calculus and stain index were recorded (0 to 3 for the intensity of stain. If intensity was scored 2 to 3, then the area of stain was recorded from 1 to 3). Patients were, then, discontinued on all plaque control measurements aside from chlorhexidine. On day 4, a single upper and lower quadrant was assigned as the Test site while the other quadrants were assigned as the Control surface. The presence of calculus and stains were examined on days 11, 18, and 25.

The product was chlorhexidine 0.12% rinsed twice daily with 15 mL.

Duration

25 days

Outcome Measures

Stain intensity

Baseline Characteristics

Not available

Results

Endpoint

Test site (N= 20)

Control surfaces (N= 20)

Higher degrees of staining discoloration occurred significantly on Test site at days 11, 18, and 25 (p<0.05) versus the Control surface

Stain area index at day 25

 

1.62 ± 0.09

1.59 ± 0.13

Stain area index score frequency on day 25

Score 1

Score 2

Score 3

 

8.66%

10.22%

0.71%

 

3.03%

3.88%

0.17%

Study Author Conclusions

The presence of plaque increased 0.12% CHX side effects. These results strengthen the necessity of biofilm disruption prior to the start of CHX mouth rinses in order to reduce side effects.

InpharmD Researcher Critique

Though baseline characteristics were not described, patients underwent a 2-week regimen of professional cleaning to establish similar baselines and were compared between themselves as control and experimental group for chlorhexidine staining. The results are only applicable to the 0.12% concentration as up to 2% concentration have also been observed for plaque control.



References:

Zanatta FB, Antoniazzi RP, Rösing CK. Staining and calculus formation after 0.12% chlorhexidine rinses in plaque-free and plaque covered surfaces: a randomized trial. J Appl Oral Sci. 2010;18(5):515-521. doi:10.1590/s1678-77572010000500015