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Oral mucosal white lesions associated with excessive use of Listerine mouthwash
Oral mucosalwhite lesions associatedwith excessiveuse of Listerine mouthwash Report of two cases Mark L. Bernstein, D.D.S., Louisville,
Ky.
SCHOOL OF DENTISTRY, UNIVERSITY OF LOUISVILLE HEALTH SCIENCES CENTER Two patients were observed to have asymptomatic, diffuse, filmy white lesions involving large portions of the oral mucosa. Both patients admitted to the topical use of Listerine mouthwash in excessof recommendeddoses.Other considerationsin the differential diagnosis were eliminated by history. The lesions showedcomplete regressionin 2 weeks following discontinuanceof the lavage.
C linical oral white lesions can represent a multitude of specific diseasesas well as nonspecific irritations. They are of considerable concern to the dentist because many squamous-cellcarcinomasbegin as nondescriptwhite patches.Fortunately, the number of white lesions that are benign far exceedsthe number that are malignant,‘, ’ but it is this very fact which allows the early cancer to remain camouflaged without provoking concern. It therefore becomes desirable to characterize and separate white lesions more precisely with refined clinical and historical data. This article reports two casesin which Listerine * mouthwashappearsto have induced white, diffuse lesions in patients who had experiencedprolonged surfacecontact with the drug. CASEREPORTS Case 1
A 68-year-oldwhiteman came to thedentalschoolrequestingroutinedentalcare.Pastmedical historyrevealedpulmonaryemphysema andseveresystemichypertensiontreatedwith Aldometand Diuril. Oral examination disclosed extensive filmy, translucent, white lesions affecting most of the
labial, buccal,andlaterallingual mucosaaswell asinvolvementof thefloor of the mouth, sulci, and edentulous ridges (Fig. 1). When stretched,a fissured pattern becameapparent, showing nonulcerated, linear, pink, parallel fissures interrupting the confluent white patches (Fig. 2). The relaxed *Warner-Lambert Company, Morris Plains, N.J 0030.4220/78/I20781+05$00.50/0
0
1978 The C. V. Mosby Co.
781
782
Oral Surg. Dcccmbcr. I978
Bernstein
Figs. I and 2. mucosa obscured this tissured texture, giving the impression that the white portions represented the most exposed mucosa subjected to a contacting surface irritant. The lesions could not be removed by scraping. Other conditions considered in the differential diagnosis of extensive and bilateral white Icsions were ruled out by history and/or clinical appearance. The patient was interrogated with regard to habits, denture-related and other mcdicaments. toothpaste, and mouthwash, Hc admitted to the occasional use of cough drops and the cxccssive use of Listcrine mouthwash as a rinse. He denied the use of alcohol or tobacco. The patient was asked to maintain the normal regimen of all drugs and mcdicaments except for the Listerinc. Two weeks later, examination of the patient revealed the complete disappearance of all white lesions (Figs. 3 and 4). Cose 2 A M-year-old Indian man came to the dental clinic for a routine checkup. Initial examination revealed diffuse. filmy. fissured. or corrugated white lesions of the lloor of the mouth and lower labial mucosa. They could not bc scraped off. Past medical history was noncontributory. and spccilic conditions which were the initial differential diagnosis were eliminated. Comprehensive interrogation revealed that the patient used betel chew or indulged in highly seasoned foods only mrely. and he denied consumption of tobacco or alcohol. He also stated that he used Listerinc mouthwash daily. habitually holding it in his mouth for IS minutes while he shaved. He was asked to discontinue the mouthwash but to maintain all other habits and activities at the usual schedule. Two weeks later there were no detectable lesions. DISCUSSION
cally
The clinical finding to hyperkeratosis.
certain
organisms
of whiteness acanthosis.
(Cnndidn
of the oral mucosa generally corresponds histologifibrosis, fibrin, coagulated protein, overgrowth of alhicans).“~” or combinations of these patterns occasionally
Volume Number
46 6
Oral lesions associated
with overuse of tnouthwnsh
783
Figs. 3 and 4.
combined with dysplasia or carcinoma. In the absence of histologic confirmation in these two cases, it is desirable to speculate about the histopathologic findings as a predictor of their biologic behavior. Frequently. hyperkeratosis or acanthosis reflects an adaptive change or, teleologically speaking, a protective response to a low-grade chronic irritant.** ” The removal of the irritant usually encourages remission of the lesion. Denaturation of epithelial proteins as seen with caustic agents also creates a white lesion* which will heal after removal of the irritant. Fibrosis is a more permanent change, and the lesions of candidosis can be scraped off. Fibrin pseudomembranes are associated with ulcers. Thus, one would predict that hyperkeratosis, acanthosis, and coagulation are the most plausible microscopic findings in a nonscrapable, nonulcerated, reversible white lesion. Several reports concerning the adverse effects of mouthwashes appear in the literature.“. r The most common side effect is that of a primary irritant or hypersensitivity stomatitis’ manifested by erythema, ulceration, or epithelial sloughing.6 Essential oils, astringents, and antiseptics are usually implicated in the etiology of these reactions.‘They occur as isolated cases in persons with idiosyncrdcies to the preparations and are manifested by acute, symptomatic responses that are not necessarily correlated with abuse of the product. The pathogenesis of this type of reaction appears to be different from the two reported cases in which prolonged contact of a chemical was associated with an asymptomatic, nonallergic white lesion. Few articles documenting white lesions associated with mouthwash or their ingredients have been published. Although sloughing white patches following the use of chlorhexidine mouthwash was reported by Flotra and colleagues,x a subsequent study failed to reveal increased thickness of the stratum corneum in biopsy specimens taken from human subjects rinsing with chlorhexidine.” These results are not pertinent to this report, as both the lesions and the ingredients are dissimilar. Bacr and Archard”’ observed the development of white lesions of the gingiva and
784
Bernstein
Oral Surg. December, 1978
alveolar mucosa following the chronic and excessive topical application of isopropyl alcohol. Histologic sections revealed coagulative hyperparakeratosis and acanthosis. Discontinuation of the alcohol resulted in remission of the lesion. Listerine mouthwash contains 25 to 26.9 percent alcohol, thymol, eucalyptol, methyl salicylate, menthol, benzoic acid, and boric acid and has a pH of 4.4.” Any one or a combination of these ingredients, as well as the acid pH or tonicity, must be considered in the etiology of the white lesions described. Alcohol is a likely suspect in view of the previous report by Baer and Archard. lo Listerine leads most other popular brands of mouthwashes in alcoholic content. Some of the other ingredients (menthol, thymol, methyl salicylate) have been implicated in irritant stomatitis7 and must also be included as candidates. Finally, Listerine as well as other acid mouthwashes has been shown to cause transient lowering of pH of the oral mucosa of monkeys.” The relationship of this finding to the production of lesions is unknown. SUMMARY AND CONCLUSION The excessive topical application of Listerine mouthwash was found to be associated with asymptomatic, diffuse oral white lesions in two patients. The lesions, which were nonulcerated and did not scrape off, disappeared 2 weeks after Listerine lavage was discontinued. Although histologic material from these lesions was not sampled, the most plausible microscopic changes accounting for such lesions would be hyperkeratosis, acanthosis, and/or coagulation of epithelial proteins. Features of an allergic response were not present, and it is hypothesized that the change represents either cellular damage or an adaptive cellular response secondary to minor irritation from one or more of the consituents of the mouthwash. The importance of this observation is twofold. First, identification of factors which induce white lesions permits the diagnosis, treatment, and categorization of these lesions so that they might be separated from those idiopathic white lesions in which cancers hide. Second and more compelling is the fact that the prevalence, natural history, or histology of this lesion is unknown and yet the existence of a synergistic relationship between alcohol and tobacco in the incidence of oral cancer is widely accepted. If the cocarcinogenic effect of alcohol is topical rather than systemic, alcohol-containing mouthwashes could pose potential dangers.‘” REFERENCES I. Abrama, A. M.: The Significance of Oral Leukoplakia, Ariz. Dent. .I. 17: t7-20, 1971. 2. Shafer, W. G., Hine, M. K., and Levy, B. M.: A Textbook of Oral Pathology, ed. 3, Philadelphia, 1974, W. B. Saunders Company, p. 92. 3. Mitchel, D. F., Standish, S. M., and Fast, T. B.: Oral Diagnosis/Oral Medicine, ed. 3. Philadelphia, 1978, Lea & Febiger, pp. X69-371 4. Wood, N. K., and Goaz, P. W.: Differential Diagnosis of Oral Lesions, St. Louis. 1975. The C. V. Mosby Company, p. 83. 5. Lynch, M. A.: Burket’s Oral Medicine, ed. 7, Philadelphia, 1977. .I. B. Lippincott Company, p. 66. 6. Kowitz, G. M., Lucatorto. F. M., and Cherrick, H. M.: Effects of Mouthwashes on the Oral Soft Tissues, J. Oral Med. 31: 47-50. 1976. 7. Fisher. A. A.: Contact Stomatitis, Glossitis, and Cheilitis, Otol. Clin. North Am. 7: X27-843, 1974. 8. Flotra, L., Gjermo, P., Rolla, G., and Waerhaug. J.: Side Effects of Chlorhexidine Mouthwashes, Stand. .I. Dent. Res. 79: 119.125, 1971. 9. Mackenzie, 1. C., Nuki, K.. Loe, H., and Schiott, C. R.: Two Years of Oral Use ofCh]orhexidine in Man: V. Effects on Stratum Corneum of Oral Mucosa, J. Periodont. Res. 11: 165-171, 1976.
Volume 46 Number 6
Oral lesions associated with overuse of mouthwash 785
10. Baer, P. N., and .&hard, H. 0.: Factitial Diseaseof the Gingiva and Buccal Mucosa: Report of a Case, N. Y. State Dent. J. 40: 33-36, 1974. I I. Esposito, E. J., and Gray, W. A.: Effect of Water and Mouthwashes on pH of Oral Monkey Mucosa, PharmacolTher. Dent. 2: 33-41, 1975. 12. Epstein, S., and Goldberg, M.: Letters to the Editor: Follow Directions, J. Am. Dent. Assoc. 91: 720, 1975.
Reprint
requests to:
Dr. Mark L. Bernstein Department of Oral Pathology/Pathology School of Dentistry University of Kentucky Health SciencesCenter Louisville, Ky. 40232
Ky.
SCHOOL OF DENTISTRY, UNIVERSITY OF LOUISVILLE HEALTH SCIENCES CENTER Two patients were observed to have asymptomatic, diffuse, filmy white lesions involving large portions of the oral mucosa. Both patients admitted to the topical use of Listerine mouthwash in excessof recommendeddoses.Other considerationsin the differential diagnosis were eliminated by history. The lesions showedcomplete regressionin 2 weeks following discontinuanceof the lavage.
C linical oral white lesions can represent a multitude of specific diseasesas well as nonspecific irritations. They are of considerable concern to the dentist because many squamous-cellcarcinomasbegin as nondescriptwhite patches.Fortunately, the number of white lesions that are benign far exceedsthe number that are malignant,‘, ’ but it is this very fact which allows the early cancer to remain camouflaged without provoking concern. It therefore becomes desirable to characterize and separate white lesions more precisely with refined clinical and historical data. This article reports two casesin which Listerine * mouthwashappearsto have induced white, diffuse lesions in patients who had experiencedprolonged surfacecontact with the drug. CASEREPORTS Case 1
A 68-year-oldwhiteman came to thedentalschoolrequestingroutinedentalcare.Pastmedical historyrevealedpulmonaryemphysema andseveresystemichypertensiontreatedwith Aldometand Diuril. Oral examination disclosed extensive filmy, translucent, white lesions affecting most of the
labial, buccal,andlaterallingual mucosaaswell asinvolvementof thefloor of the mouth, sulci, and edentulous ridges (Fig. 1). When stretched,a fissured pattern becameapparent, showing nonulcerated, linear, pink, parallel fissures interrupting the confluent white patches (Fig. 2). The relaxed *Warner-Lambert Company, Morris Plains, N.J 0030.4220/78/I20781+05$00.50/0
0
1978 The C. V. Mosby Co.
781
782
Oral Surg. Dcccmbcr. I978
Bernstein
Figs. I and 2. mucosa obscured this tissured texture, giving the impression that the white portions represented the most exposed mucosa subjected to a contacting surface irritant. The lesions could not be removed by scraping. Other conditions considered in the differential diagnosis of extensive and bilateral white Icsions were ruled out by history and/or clinical appearance. The patient was interrogated with regard to habits, denture-related and other mcdicaments. toothpaste, and mouthwash, Hc admitted to the occasional use of cough drops and the cxccssive use of Listcrine mouthwash as a rinse. He denied the use of alcohol or tobacco. The patient was asked to maintain the normal regimen of all drugs and mcdicaments except for the Listerinc. Two weeks later, examination of the patient revealed the complete disappearance of all white lesions (Figs. 3 and 4). Cose 2 A M-year-old Indian man came to the dental clinic for a routine checkup. Initial examination revealed diffuse. filmy. fissured. or corrugated white lesions of the lloor of the mouth and lower labial mucosa. They could not bc scraped off. Past medical history was noncontributory. and spccilic conditions which were the initial differential diagnosis were eliminated. Comprehensive interrogation revealed that the patient used betel chew or indulged in highly seasoned foods only mrely. and he denied consumption of tobacco or alcohol. He also stated that he used Listerinc mouthwash daily. habitually holding it in his mouth for IS minutes while he shaved. He was asked to discontinue the mouthwash but to maintain all other habits and activities at the usual schedule. Two weeks later there were no detectable lesions. DISCUSSION
cally
The clinical finding to hyperkeratosis.
certain
organisms
of whiteness acanthosis.
(Cnndidn
of the oral mucosa generally corresponds histologifibrosis, fibrin, coagulated protein, overgrowth of alhicans).“~” or combinations of these patterns occasionally
Volume Number
46 6
Oral lesions associated
with overuse of tnouthwnsh
783
Figs. 3 and 4.
combined with dysplasia or carcinoma. In the absence of histologic confirmation in these two cases, it is desirable to speculate about the histopathologic findings as a predictor of their biologic behavior. Frequently. hyperkeratosis or acanthosis reflects an adaptive change or, teleologically speaking, a protective response to a low-grade chronic irritant.** ” The removal of the irritant usually encourages remission of the lesion. Denaturation of epithelial proteins as seen with caustic agents also creates a white lesion* which will heal after removal of the irritant. Fibrosis is a more permanent change, and the lesions of candidosis can be scraped off. Fibrin pseudomembranes are associated with ulcers. Thus, one would predict that hyperkeratosis, acanthosis, and coagulation are the most plausible microscopic findings in a nonscrapable, nonulcerated, reversible white lesion. Several reports concerning the adverse effects of mouthwashes appear in the literature.“. r The most common side effect is that of a primary irritant or hypersensitivity stomatitis’ manifested by erythema, ulceration, or epithelial sloughing.6 Essential oils, astringents, and antiseptics are usually implicated in the etiology of these reactions.‘They occur as isolated cases in persons with idiosyncrdcies to the preparations and are manifested by acute, symptomatic responses that are not necessarily correlated with abuse of the product. The pathogenesis of this type of reaction appears to be different from the two reported cases in which prolonged contact of a chemical was associated with an asymptomatic, nonallergic white lesion. Few articles documenting white lesions associated with mouthwash or their ingredients have been published. Although sloughing white patches following the use of chlorhexidine mouthwash was reported by Flotra and colleagues,x a subsequent study failed to reveal increased thickness of the stratum corneum in biopsy specimens taken from human subjects rinsing with chlorhexidine.” These results are not pertinent to this report, as both the lesions and the ingredients are dissimilar. Bacr and Archard”’ observed the development of white lesions of the gingiva and
784
Bernstein
Oral Surg. December, 1978
alveolar mucosa following the chronic and excessive topical application of isopropyl alcohol. Histologic sections revealed coagulative hyperparakeratosis and acanthosis. Discontinuation of the alcohol resulted in remission of the lesion. Listerine mouthwash contains 25 to 26.9 percent alcohol, thymol, eucalyptol, methyl salicylate, menthol, benzoic acid, and boric acid and has a pH of 4.4.” Any one or a combination of these ingredients, as well as the acid pH or tonicity, must be considered in the etiology of the white lesions described. Alcohol is a likely suspect in view of the previous report by Baer and Archard. lo Listerine leads most other popular brands of mouthwashes in alcoholic content. Some of the other ingredients (menthol, thymol, methyl salicylate) have been implicated in irritant stomatitis7 and must also be included as candidates. Finally, Listerine as well as other acid mouthwashes has been shown to cause transient lowering of pH of the oral mucosa of monkeys.” The relationship of this finding to the production of lesions is unknown. SUMMARY AND CONCLUSION The excessive topical application of Listerine mouthwash was found to be associated with asymptomatic, diffuse oral white lesions in two patients. The lesions, which were nonulcerated and did not scrape off, disappeared 2 weeks after Listerine lavage was discontinued. Although histologic material from these lesions was not sampled, the most plausible microscopic changes accounting for such lesions would be hyperkeratosis, acanthosis, and/or coagulation of epithelial proteins. Features of an allergic response were not present, and it is hypothesized that the change represents either cellular damage or an adaptive cellular response secondary to minor irritation from one or more of the consituents of the mouthwash. The importance of this observation is twofold. First, identification of factors which induce white lesions permits the diagnosis, treatment, and categorization of these lesions so that they might be separated from those idiopathic white lesions in which cancers hide. Second and more compelling is the fact that the prevalence, natural history, or histology of this lesion is unknown and yet the existence of a synergistic relationship between alcohol and tobacco in the incidence of oral cancer is widely accepted. If the cocarcinogenic effect of alcohol is topical rather than systemic, alcohol-containing mouthwashes could pose potential dangers.‘” REFERENCES I. Abrama, A. M.: The Significance of Oral Leukoplakia, Ariz. Dent. .I. 17: t7-20, 1971. 2. Shafer, W. G., Hine, M. K., and Levy, B. M.: A Textbook of Oral Pathology, ed. 3, Philadelphia, 1974, W. B. Saunders Company, p. 92. 3. Mitchel, D. F., Standish, S. M., and Fast, T. B.: Oral Diagnosis/Oral Medicine, ed. 3. Philadelphia, 1978, Lea & Febiger, pp. X69-371 4. Wood, N. K., and Goaz, P. W.: Differential Diagnosis of Oral Lesions, St. Louis. 1975. The C. V. Mosby Company, p. 83. 5. Lynch, M. A.: Burket’s Oral Medicine, ed. 7, Philadelphia, 1977. .I. B. Lippincott Company, p. 66. 6. Kowitz, G. M., Lucatorto. F. M., and Cherrick, H. M.: Effects of Mouthwashes on the Oral Soft Tissues, J. Oral Med. 31: 47-50. 1976. 7. Fisher. A. A.: Contact Stomatitis, Glossitis, and Cheilitis, Otol. Clin. North Am. 7: X27-843, 1974. 8. Flotra, L., Gjermo, P., Rolla, G., and Waerhaug. J.: Side Effects of Chlorhexidine Mouthwashes, Stand. .I. Dent. Res. 79: 119.125, 1971. 9. Mackenzie, 1. C., Nuki, K.. Loe, H., and Schiott, C. R.: Two Years of Oral Use ofCh]orhexidine in Man: V. Effects on Stratum Corneum of Oral Mucosa, J. Periodont. Res. 11: 165-171, 1976.
Volume 46 Number 6
Oral lesions associated with overuse of mouthwash 785
10. Baer, P. N., and .&hard, H. 0.: Factitial Diseaseof the Gingiva and Buccal Mucosa: Report of a Case, N. Y. State Dent. J. 40: 33-36, 1974. I I. Esposito, E. J., and Gray, W. A.: Effect of Water and Mouthwashes on pH of Oral Monkey Mucosa, PharmacolTher. Dent. 2: 33-41, 1975. 12. Epstein, S., and Goldberg, M.: Letters to the Editor: Follow Directions, J. Am. Dent. Assoc. 91: 720, 1975.
Reprint
requests to:
Dr. Mark L. Bernstein Department of Oral Pathology/Pathology School of Dentistry University of Kentucky Health SciencesCenter Louisville, Ky. 40232