j O R IG IN A L C O N T R IB U T IO N S f
D IA G N O S T IC C H A L L E N G E
A w h i t e le s io n o f t h e b u c c a l m u c o s a James Guggenheimer, DDS; Steven J. Barket, DMD; Elizabeth A. Bilodeau, DMD, MD, MSEd
THE CHALLENGE A 55-year-old woman visited an emergency clinic (Department of Diagnostic Sciences, School of Dental Medicine, University of Pitts burgh) with a five-day history of dental pain. Her medical history included hypertension that was controlled with a calcium channel blocker, type 2 dia betes that was controlled with glyburide and an allergy to penicillin. The patient reported that her mandibular left second molar had been restored several years earlier. Within the previous week, however, she had begun to experience increasingly intense, throbbing pain and pain when chewing with that tooth. In an effort to relieve the discomfort, the patient took 200-milligram ibuprofen tablets every few hours, which provided only minimal relief. Several days later, she sought treatment. The extraoral examination revealed no facial swelling.
A
Intraorally, the clinician (S.J.B.) observed an extensive, white, wrinkled lesion that involved the left buccal mu cosa, buccal sulcus and gingiva, with an area of mucosal erosion with focal sloughing (Figure 1). The involved area was soft and nontender. When the cheek was re tracted, the appearance of the lesion did not change. No abnormalities were evident elsewhere in the oral cavity. During the dental examination, the patient indicated that the mandibular left second molar was the source of her pain. This tooth had an occlusal amalgam restora tion, was painful to palpation and percussion, and did not respond to cold. A dental radiograph revealed an oc clusal restoration with an underlying base that appeared to encroach on the pulp chamber. Apically, there was loss of lamina dura with obliteration of the periodontal ligament space. A diffuse radiolucency was evident at the apex of the distal root (Figure 2). All of these findings were consistent with pulpal necrosis and acute (symp tomatic) apical periodontitis, with possible apical ab scess.1The patient requested that the tooth be extracted, which was accomplished without complications.
Figure 1. Appearance of the left buccal mucosa adjacent to the painful mandibular left second molar.
CAN YOU MAKE THE DIAGNOSIS? A. white sponge nevus (familial white folded dysplasia of mucous membrane) B. leukoedema
C. chemical burn of the buccal mucosa D. smokeless tobacco keratosis E. morsicatio buccarum (chronic cheek chewing)
JADA 145(9)
http ://ja d a .a d a .o rg
Septem ber 2014
961
| ORIGINAL CONTRIBUTIONS |
THE DIAGNOSIS
C. chemical bum of the buccal mucosa During the initial evaluation, the patient disclosed that when the ibuprofen did not provide adequate relief, she crushed the tablets and placed them in the buccal sulcus adjacent to the tooth every two hours in an effort to enhance their analgesic efficacy. The patient continued to do this for several days until she sought treatment at the emergency clinic. At the postoperative visit one week later, the buccal mucosa had healed completely. Chemical burns of the oral mucosa are not uncom mon and result most frequently from contact with a number of potentially caustic materials that are used in conjunction with various dental restorative pro cedures.2,3 Alcohol-containing mouthrinses and topical application of over-the-counter toothache remedies, such as eugenol-containing products, hydrogen perox ide3 and garlic cloves,4 also have caused mucosal burns. In 1965,5the dental literature began to cite aspirin or aspirin compounds as one of the more frequent causes of medication-induced burns of the oral mucosa.2,6,7 This occurred most often because patients placed the product adjacent to a painful tooth after systemic administration failed to achieve adequate relief. The newer nonsteroidal anti-inflammatory drugs (NSAIDs), however, have become patients’ preferred an algesics,8 in addition to acetaminophen products (such as Tylenol, McNeil Consumer Healthcare Division of McNEIL-PPC, Fort Washington, Pa.). In 2011, ibuprofen, in 600- to 800-mg doses, was ranked No. 18 among the 200 most prescribed drugs in the United States, with more than 21 million prescriptions written,8 in addition to countless 200-mg over-the-counter preparations. A review of medications taken by 891 patients who visited our emergency clinic between January and June 2010 with a chief complaint of dental pain revealed that 34 percent were taking an NSAID and 32 percent were us ing an acetaminophen product, but only 5.5 percent of patients were taking aspirin for the relief of pain (J.G., unpublished data, 2010). Our case report illustrates that the inappropriate topi cal application of an NSAID also can result in a chemical burn of the oral mucosa. Although not reported previ ously, it is a possible occurrence given the current prefer ence for NSAIDs for the relief of dental pain. The caustic effect of NSAIDs on the mucosa most likely is related to their chemical and physical properties. These agents are characterized as “relatively strong organic acids” with pKas that range from 3 to 5,9 which are similar to the pKa of aspirin (3.49).10 The acidic property of NSAIDs is necessary for them to inhibit cyclooxygenase effectively. Cyclooxygenase, in turn, is required for the synthesis of prostaglandins that mediate and promote the processes of inflammation and pain.9 DeRuiter9 suggested that the
962
JADA 145(9)
http://jada.ada.org
September 2014
adverse effects of NSAIDs on the gastric mucosa also may be related, in part, to their acidity. Other pharmaceutical agents, particularly if used inappropriately, also can cause injury to the oral mucous membranes. These include the phenothiazine antipsy chotic chlorpromazine.5 In addition, there have been sev eral reports of oral mucosal burns’ occurring as a conse quence of contact with the bisphosphonate alendronate (Fosamax, Merck Sharp & Dohme, Whitehouse Station, N.J.).11-14 There is an ongoing risk of these adverse oral reactions’ occurring if patients do not use medications as directed or do not adhere to package warning labels. Chemical burns of the oral mucosa are self-limiting and usually resolve within two weeks of discontinuation of the topical application of the irritant. If the lesion per sists, it should be biopsied to rule out other pathology, such as a premalignant condition. Most chemical burns are asymptomatic and require no treatment. Clinicians should advise patients to discontinue use of the caustic product immediately and to avoid alcohol-containing mouthrinses. If the burned area is extensive and symptomatic, it can be treated with topical analgesic mouthrinses, such as alcohol-free diphenhydramine hydrochloride3 or a 2 percent solution of lidocaine viscous.15,16 DIFFERENTIAL DIAGNOSIS
White sponge nevus (familial white folded dysplasia of mucous membrane). White sponge nevus is a rare hereditary condition manifesting as white, deeply folded, thickened, corrugated plaques that most often involve the buccal mucosa bilaterally.3’15 The tongue and other oral structures may be affected, but not the marginal gingiva. Lesions also can involve the mucosa of the anogenital regions. White sponge nevus may be present at birth or becomes evident during childhood but before puberty.3,17 Leukoedema. Leukoedema is a prevalent, innocuous anomaly of the buccal mucosa that appears as bilateral, filmy, grayish-white, slightly wrinkled mucosa, encoun tered predominantly in the African American popula tion.3,17 Its characteristic feature is that, when the cheek is stretched, the white lesion tends to fade or disappear. Although leukoedema demonstrates epithelial changes histologically, its widespread prevalence in the popula tion suggests that it is a natural variant of normal buccal mucosa.3,17 Smokeless tobacco keratosis. This lesion develops as a result of holding chewing tobacco against the posterior portion of the cheek. Although chewing tobacco primar ily is used by men, women occasionally may use chewing tobacco or snuff. People also may hold tobacco in the cheek to alleviate dental pain. Tobacco pouch keratosis is
j
ORIGINAL CONTRIBUTIONS |
a reactive response of the oral epithelium to the irritant properties of tobacco due to its natural constituents, as well as its alkaline pH .17 The oral mucosa that is in contact with tobacco has a white, wrinkled, fissured or granular appearance that may feel leathery to palpa tion .3,17 Tobacco staining and gingival recession may affect the adjacent teeth. Morsicatio buccarum (chronic cheek chewing). Chronic cheek chewing is a habit that can result in the development of a frictional keratosis that represents a protective response of the oral mucosa to continuous trauma from the teeth .17 Patients may rub the cheek or tongue against a tooth or teeth in an effort to alleviate dental pain. The traumatized area, which must be in proximity to the teeth, has a white, shredded or ragged appearance that may include reddened, eroded tissue.3 A lesion caused by chronic cheek chewing would not extend to the buccal sulcus or gingiva. CONCLUSION
In this report, we described a patient who developed a chemical burn of the buccal mucosa after placing crushed ibuprofen tablets adjacent to a painful tooth for several days. The NSAIDs appear to be preferred over aspirin for the relief of dental pain, but their acidic prop erty can have similar caustic effects on the oral mucosa. ■ doi:io.i42i9/jada.20i4.62 Dr. Guggenheimer is a professor, Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, 3501 Terrace St., Pittsburgh, Pa. 15261, e-mail [email protected]. Address correspondence to Dr. Guggenheimer. Dr. Barket was a resident, Oral and Maxillofacial Pathology, Depart ment of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, at the time the manuscript was written. He now is with the Dental Center, Bradford Regional Medical Center, Bradford, Pa. Dr. Bilodeau is an assistant professor, Department of Diagnostic Sci ences, School of Dental Medicine, University of Pittsburgh. Disclosure. None of the authors reported any disclosures.
Diagnostic Challenge is published in collaboration with the American Academy of Oral and Maxillofacial Pathology and the American Acad emy of Oral Medicine. 1. McClannahan SB, Balsden MK, Bowles WR. Endodontic diagnostic terminology update. Northwest Dent, www.dentistry.umn.edu/prod/ groups/sod/@pub/@sod/documents/content/sod_content_45io29.pdf. Accessed June 10,2014. 2. Gilvetti C, Porter SR, Fedele S. Traumatic chemical oral ulceration: a case report and review of the literature. Br Dent J 20i0;208(7):297-300. 3. Neville B, Damm DD, Allen CM, Bouquot J, eds. Oral and Maxillofa cial Pathology. 3rd ed. St. Louis: Saunders Elsevier; 2009. 4. Bagga S, Thomas BS, Bhat M. Garlic burn as self-inflicted mucosal injury: a case report and review of the literature. Quintessence Int 2008;39(6):49i-494.
5. Buck IF, Zeff S, Kalnins L, Heiser RA, Bentham WL, Pollack B. The treatment of intraoral chemical burns. J Oral Ther Pharmacol i965;2(2):ioi-io6. 6. Glick GL, Chaffee RB Jr, Salkin LM, Vandersall DC. Oral mucosal chemical lesions associated with acetyl salicylic acid: two case reports. N Y State Dent J 1974;4o(8):475-478. 7. Kawashima Z, Flagg RH, Cox DE. Aspirin-induced oral lesion: report of case. JADA I975;9i(i):i30-i3i. 8. Bartholow M. Pharmacy Times. Top 200 drugs of 2011. www. pharmacytimes.com/publicati0ns/issue/2012/July2012/T0p-200-Drugsof-2011. Accessed June 10, 2014. 9. DeRuiter J. Non-steroidal anti-inflammatory drugs (NSAIDS). Principles of Drug Action 2. Fall 2002. www.auburn.edu/~deruija/ nsaids_2002.pdf. Accessed July 31, 2014. 10. DrugBank. Acetylsalicylic acid. www.drugbank.ca/drugs/DB00945. Accessed July 31, 2014. 11. Gonzalez-Moles MA, Bagan-Sebastian JV. Alendronate-related oral mucosa ulcerations. J Oral Pathol Med 200o;29(io):5i4-5i8. 12. Krasagakis K, Kriiger-Krasagakis S, Ioannidou D, Tosca A. Chronic erosive and ulcerative oral lesions caused by incorrect administration of alendronate. J Am Acad Dermatol 2004;5o(4):65i-652. 13. Rubegni P, Fimiani M. Bisphosphonate-associated contact stomati tis. N Engl J Med 20o6;355(22):e25. 14. Madoka I, Nana A, Nakamura S, Okumura K, Takeoka T, Tagawa T. Chemical burn of the tongue resulting from improper use of oral bisphosphonate. Asian J Oral Maxillofac Surg 20ii;23(4):204-208. 15. Gibbs RC. Xylocaine (lidocaine) viscous: a topical anesthetic agent of value for the relief of pain associated with oral mucous membrane lesions. Arch Dermatol i96o;8i(4):6o9-6io. 16. Crossley HL, Wynn RL, Meiller TF. Drug Information Handbook for Dentistry. 19th ed. Hudson, Ohio: Lexi-Comp; 2013:818-820. 17. Regezi JA, Sciubba J. Oral pathology: Clinical-Pathologic Correla tions. 2nd ed. Philadelphia: Saunders; 1993.
JADA 145(9)
http ://ja d a .a d a .o rg
Septem ber 2014
963
Copyright of Journal of the American Dental Association (JADA) is the property of American Dental Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
D IA G N O S T IC C H A L L E N G E
A w h i t e le s io n o f t h e b u c c a l m u c o s a James Guggenheimer, DDS; Steven J. Barket, DMD; Elizabeth A. Bilodeau, DMD, MD, MSEd
THE CHALLENGE A 55-year-old woman visited an emergency clinic (Department of Diagnostic Sciences, School of Dental Medicine, University of Pitts burgh) with a five-day history of dental pain. Her medical history included hypertension that was controlled with a calcium channel blocker, type 2 dia betes that was controlled with glyburide and an allergy to penicillin. The patient reported that her mandibular left second molar had been restored several years earlier. Within the previous week, however, she had begun to experience increasingly intense, throbbing pain and pain when chewing with that tooth. In an effort to relieve the discomfort, the patient took 200-milligram ibuprofen tablets every few hours, which provided only minimal relief. Several days later, she sought treatment. The extraoral examination revealed no facial swelling.
A
Intraorally, the clinician (S.J.B.) observed an extensive, white, wrinkled lesion that involved the left buccal mu cosa, buccal sulcus and gingiva, with an area of mucosal erosion with focal sloughing (Figure 1). The involved area was soft and nontender. When the cheek was re tracted, the appearance of the lesion did not change. No abnormalities were evident elsewhere in the oral cavity. During the dental examination, the patient indicated that the mandibular left second molar was the source of her pain. This tooth had an occlusal amalgam restora tion, was painful to palpation and percussion, and did not respond to cold. A dental radiograph revealed an oc clusal restoration with an underlying base that appeared to encroach on the pulp chamber. Apically, there was loss of lamina dura with obliteration of the periodontal ligament space. A diffuse radiolucency was evident at the apex of the distal root (Figure 2). All of these findings were consistent with pulpal necrosis and acute (symp tomatic) apical periodontitis, with possible apical ab scess.1The patient requested that the tooth be extracted, which was accomplished without complications.
Figure 1. Appearance of the left buccal mucosa adjacent to the painful mandibular left second molar.
CAN YOU MAKE THE DIAGNOSIS? A. white sponge nevus (familial white folded dysplasia of mucous membrane) B. leukoedema
C. chemical burn of the buccal mucosa D. smokeless tobacco keratosis E. morsicatio buccarum (chronic cheek chewing)
JADA 145(9)
http ://ja d a .a d a .o rg
Septem ber 2014
961
| ORIGINAL CONTRIBUTIONS |
THE DIAGNOSIS
C. chemical bum of the buccal mucosa During the initial evaluation, the patient disclosed that when the ibuprofen did not provide adequate relief, she crushed the tablets and placed them in the buccal sulcus adjacent to the tooth every two hours in an effort to enhance their analgesic efficacy. The patient continued to do this for several days until she sought treatment at the emergency clinic. At the postoperative visit one week later, the buccal mucosa had healed completely. Chemical burns of the oral mucosa are not uncom mon and result most frequently from contact with a number of potentially caustic materials that are used in conjunction with various dental restorative pro cedures.2,3 Alcohol-containing mouthrinses and topical application of over-the-counter toothache remedies, such as eugenol-containing products, hydrogen perox ide3 and garlic cloves,4 also have caused mucosal burns. In 1965,5the dental literature began to cite aspirin or aspirin compounds as one of the more frequent causes of medication-induced burns of the oral mucosa.2,6,7 This occurred most often because patients placed the product adjacent to a painful tooth after systemic administration failed to achieve adequate relief. The newer nonsteroidal anti-inflammatory drugs (NSAIDs), however, have become patients’ preferred an algesics,8 in addition to acetaminophen products (such as Tylenol, McNeil Consumer Healthcare Division of McNEIL-PPC, Fort Washington, Pa.). In 2011, ibuprofen, in 600- to 800-mg doses, was ranked No. 18 among the 200 most prescribed drugs in the United States, with more than 21 million prescriptions written,8 in addition to countless 200-mg over-the-counter preparations. A review of medications taken by 891 patients who visited our emergency clinic between January and June 2010 with a chief complaint of dental pain revealed that 34 percent were taking an NSAID and 32 percent were us ing an acetaminophen product, but only 5.5 percent of patients were taking aspirin for the relief of pain (J.G., unpublished data, 2010). Our case report illustrates that the inappropriate topi cal application of an NSAID also can result in a chemical burn of the oral mucosa. Although not reported previ ously, it is a possible occurrence given the current prefer ence for NSAIDs for the relief of dental pain. The caustic effect of NSAIDs on the mucosa most likely is related to their chemical and physical properties. These agents are characterized as “relatively strong organic acids” with pKas that range from 3 to 5,9 which are similar to the pKa of aspirin (3.49).10 The acidic property of NSAIDs is necessary for them to inhibit cyclooxygenase effectively. Cyclooxygenase, in turn, is required for the synthesis of prostaglandins that mediate and promote the processes of inflammation and pain.9 DeRuiter9 suggested that the
962
JADA 145(9)
http://jada.ada.org
September 2014
adverse effects of NSAIDs on the gastric mucosa also may be related, in part, to their acidity. Other pharmaceutical agents, particularly if used inappropriately, also can cause injury to the oral mucous membranes. These include the phenothiazine antipsy chotic chlorpromazine.5 In addition, there have been sev eral reports of oral mucosal burns’ occurring as a conse quence of contact with the bisphosphonate alendronate (Fosamax, Merck Sharp & Dohme, Whitehouse Station, N.J.).11-14 There is an ongoing risk of these adverse oral reactions’ occurring if patients do not use medications as directed or do not adhere to package warning labels. Chemical burns of the oral mucosa are self-limiting and usually resolve within two weeks of discontinuation of the topical application of the irritant. If the lesion per sists, it should be biopsied to rule out other pathology, such as a premalignant condition. Most chemical burns are asymptomatic and require no treatment. Clinicians should advise patients to discontinue use of the caustic product immediately and to avoid alcohol-containing mouthrinses. If the burned area is extensive and symptomatic, it can be treated with topical analgesic mouthrinses, such as alcohol-free diphenhydramine hydrochloride3 or a 2 percent solution of lidocaine viscous.15,16 DIFFERENTIAL DIAGNOSIS
White sponge nevus (familial white folded dysplasia of mucous membrane). White sponge nevus is a rare hereditary condition manifesting as white, deeply folded, thickened, corrugated plaques that most often involve the buccal mucosa bilaterally.3’15 The tongue and other oral structures may be affected, but not the marginal gingiva. Lesions also can involve the mucosa of the anogenital regions. White sponge nevus may be present at birth or becomes evident during childhood but before puberty.3,17 Leukoedema. Leukoedema is a prevalent, innocuous anomaly of the buccal mucosa that appears as bilateral, filmy, grayish-white, slightly wrinkled mucosa, encoun tered predominantly in the African American popula tion.3,17 Its characteristic feature is that, when the cheek is stretched, the white lesion tends to fade or disappear. Although leukoedema demonstrates epithelial changes histologically, its widespread prevalence in the popula tion suggests that it is a natural variant of normal buccal mucosa.3,17 Smokeless tobacco keratosis. This lesion develops as a result of holding chewing tobacco against the posterior portion of the cheek. Although chewing tobacco primar ily is used by men, women occasionally may use chewing tobacco or snuff. People also may hold tobacco in the cheek to alleviate dental pain. Tobacco pouch keratosis is
j
ORIGINAL CONTRIBUTIONS |
a reactive response of the oral epithelium to the irritant properties of tobacco due to its natural constituents, as well as its alkaline pH .17 The oral mucosa that is in contact with tobacco has a white, wrinkled, fissured or granular appearance that may feel leathery to palpa tion .3,17 Tobacco staining and gingival recession may affect the adjacent teeth. Morsicatio buccarum (chronic cheek chewing). Chronic cheek chewing is a habit that can result in the development of a frictional keratosis that represents a protective response of the oral mucosa to continuous trauma from the teeth .17 Patients may rub the cheek or tongue against a tooth or teeth in an effort to alleviate dental pain. The traumatized area, which must be in proximity to the teeth, has a white, shredded or ragged appearance that may include reddened, eroded tissue.3 A lesion caused by chronic cheek chewing would not extend to the buccal sulcus or gingiva. CONCLUSION
In this report, we described a patient who developed a chemical burn of the buccal mucosa after placing crushed ibuprofen tablets adjacent to a painful tooth for several days. The NSAIDs appear to be preferred over aspirin for the relief of dental pain, but their acidic prop erty can have similar caustic effects on the oral mucosa. ■ doi:io.i42i9/jada.20i4.62 Dr. Guggenheimer is a professor, Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, 3501 Terrace St., Pittsburgh, Pa. 15261, e-mail [email protected]. Address correspondence to Dr. Guggenheimer. Dr. Barket was a resident, Oral and Maxillofacial Pathology, Depart ment of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, at the time the manuscript was written. He now is with the Dental Center, Bradford Regional Medical Center, Bradford, Pa. Dr. Bilodeau is an assistant professor, Department of Diagnostic Sci ences, School of Dental Medicine, University of Pittsburgh. Disclosure. None of the authors reported any disclosures.
Diagnostic Challenge is published in collaboration with the American Academy of Oral and Maxillofacial Pathology and the American Acad emy of Oral Medicine. 1. McClannahan SB, Balsden MK, Bowles WR. Endodontic diagnostic terminology update. Northwest Dent, www.dentistry.umn.edu/prod/ groups/sod/@pub/@sod/documents/content/sod_content_45io29.pdf. Accessed June 10,2014. 2. Gilvetti C, Porter SR, Fedele S. Traumatic chemical oral ulceration: a case report and review of the literature. Br Dent J 20i0;208(7):297-300. 3. Neville B, Damm DD, Allen CM, Bouquot J, eds. Oral and Maxillofa cial Pathology. 3rd ed. St. Louis: Saunders Elsevier; 2009. 4. Bagga S, Thomas BS, Bhat M. Garlic burn as self-inflicted mucosal injury: a case report and review of the literature. Quintessence Int 2008;39(6):49i-494.
5. Buck IF, Zeff S, Kalnins L, Heiser RA, Bentham WL, Pollack B. The treatment of intraoral chemical burns. J Oral Ther Pharmacol i965;2(2):ioi-io6. 6. Glick GL, Chaffee RB Jr, Salkin LM, Vandersall DC. Oral mucosal chemical lesions associated with acetyl salicylic acid: two case reports. N Y State Dent J 1974;4o(8):475-478. 7. Kawashima Z, Flagg RH, Cox DE. Aspirin-induced oral lesion: report of case. JADA I975;9i(i):i30-i3i. 8. Bartholow M. Pharmacy Times. Top 200 drugs of 2011. www. pharmacytimes.com/publicati0ns/issue/2012/July2012/T0p-200-Drugsof-2011. Accessed June 10, 2014. 9. DeRuiter J. Non-steroidal anti-inflammatory drugs (NSAIDS). Principles of Drug Action 2. Fall 2002. www.auburn.edu/~deruija/ nsaids_2002.pdf. Accessed July 31, 2014. 10. DrugBank. Acetylsalicylic acid. www.drugbank.ca/drugs/DB00945. Accessed July 31, 2014. 11. Gonzalez-Moles MA, Bagan-Sebastian JV. Alendronate-related oral mucosa ulcerations. J Oral Pathol Med 200o;29(io):5i4-5i8. 12. Krasagakis K, Kriiger-Krasagakis S, Ioannidou D, Tosca A. Chronic erosive and ulcerative oral lesions caused by incorrect administration of alendronate. J Am Acad Dermatol 2004;5o(4):65i-652. 13. Rubegni P, Fimiani M. Bisphosphonate-associated contact stomati tis. N Engl J Med 20o6;355(22):e25. 14. Madoka I, Nana A, Nakamura S, Okumura K, Takeoka T, Tagawa T. Chemical burn of the tongue resulting from improper use of oral bisphosphonate. Asian J Oral Maxillofac Surg 20ii;23(4):204-208. 15. Gibbs RC. Xylocaine (lidocaine) viscous: a topical anesthetic agent of value for the relief of pain associated with oral mucous membrane lesions. Arch Dermatol i96o;8i(4):6o9-6io. 16. Crossley HL, Wynn RL, Meiller TF. Drug Information Handbook for Dentistry. 19th ed. Hudson, Ohio: Lexi-Comp; 2013:818-820. 17. Regezi JA, Sciubba J. Oral pathology: Clinical-Pathologic Correla tions. 2nd ed. Philadelphia: Saunders; 1993.
JADA 145(9)
http ://ja d a .a d a .o rg
Septem ber 2014
963
Copyright of Journal of the American Dental Association (JADA) is the property of American Dental Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
