Clinical Review & Education
JAMA Clinical Challenge
Recurrent Gingival and Oral Mucosal Lesions Eric T. Stoopler, DMD, FDS RCSEd, FDS RCSEng; Thomas P. Sollecito, DMD, FDS RCSEd
Figure 1. Intraoral presentation of patient.
A 57-year-old woman presents for evaluation of gingival “peeling” associated with pain and bleeding and white patches on the oral mucosa for 7 years. She reports no new medications, foods, or oral hygiene products. She reports no involvement of other cutaneous or mucosal surQuiz at jama.com faces and no family history of oral lesions. The lesions cause pain and difficulty brushing her teeth. She has a history of hypertension, hypothyroidism, type 2 diabetes, gastroesophageal reflux disease, and seasonal allergies. Her medications are valsartanhydrochlorothiazide, levothyroxine sodium, metformin, insulin, and loratadine. Intraoral examination shows generalized erythema and sloughing of the maxillary and mandibular gingiva, without evidence of dental plaque, calculus, or both, and white striae (Wickham striae) affecting the gingiva and mucosa (Figure 1). Her physical examination is otherwise normal.
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WHAT WOULD YOU DO NEXT?
A. Prescribe valacyclovir (1000 mg 3 times daily) for the next 7 days B. Order a nutritional assay to evaluate for vitamin B 3 (niacin) deficiency C. Recommend increased use of an alcohol-based mouthwash to improve oral hygiene D. Biopsy the affected tissue
JAMA November 5, 2014 Volume 312, Number 17
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
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JAMA Clinical Challenge Clinical Review & Education
Diagnosis Lichen planus
What to Do Next D. Biopsy the affected tissue The desquamative appearance of the gingiva, presence of striae, absence of local irritants (dental plaque, calculus, or both), and chronic nature of the condition are consistent with lichen planus.
Discussion An etiology of herpes simplex virus is not supported by the clinical history and appearance of the gingiva and mucosa. Vitamin B3 deficiency is not associated with these oral findings. Increased use of an alcohol-based mouthwash is contraindicated due to the absence of local irritants and potential to exacerbate symptoms. Other mucocutaneous diseases, such as pemphigus vulgaris and mucous membrane pemphigoid, may present similarly, and biopsy of the affected tissue can establish the diagnosis. Oral lichen planus commonly affects women between the third and sixth decades, and prevalence is similar in white and African American persons.1,2 The prevalence of oral lichen planus ranges from 0.5% to 3% and is associated with cutaneous lichen planus in nearly 75% of patients.1-3 In comparison, the prevalence of cutaneous lichen planus is approximately 2%.1,2 The etiology of oral lichen planus is unclear. The pathophysiologic process involves a cellmediated immune response involving CD8+ T lymphocytes stimulating keratinocyte apoptosis and production of several inflammatory cytokines.4,5 Evidence suggests an association of hepatitis C and oral lichen planus.6 The most common presentation of oral lichen planus is the reticular form, which is often asymptomatic and observed as white lines (Wickham striae).3,7Variants of oral lichen planus include erythematous (atrophic), plaque-like, and erosive types. Clinical features of this case are consistent with erosive and reticular types of oral lichen planus. Oral lichen planus most commonly affects the buccal mucosa, tongue, and gingiva, with burning, stinging, textural changes, and/or alteration of taste associated with symptomatic lesions.2,5,7 Desquamative gingivitis, characterized by sloughing of the gingival epithelium, may be the initial and only presentation. Tissue biopsy is recommended to confirm the diagnosis, especially for atypical presentations, if other mucocutaneous diseases are considered or if dysplasia or malignancy is suspected.1,7,8 Routine staining of biop-
sied tissue classically demonstrates a band-like infiltrate of T lymphocytes, liquefactive degeneration of the basal cell layer, and sawtooth rete ridge formation (Figure 2).1,4,7 A biopsy of unaffected tissue for direct immunofluorescence analysis typically reveals linear fibrinogen deposition at the dermal-epidermal junction and differentiates oral lichenplanusfrompemphigusvulgaris and mucous membrane pemphigoid.4,5 Figure 2. Biopsy of the left buccal High-potency topical corti- mucosa reveals diffuse subepithelial infiltrate of chronic inflammatory costeroids represent first-line cells in the connective tissue therapy for symptom manage- subjacent to the basement ment and are often coadminis- membrane (basement membrane tered with a topical antifungal indicated by arrowheads) (hematoxylin-eosin, original agent to prevent oral candidi- magnification x20). asis.1,8,9Patients with severe or widespread disease may require systemic therapy, such as corticosteroids, steroid-sparing agents, or immunomodulators.1,8, Patients with oral lichen planus, especially erosive and erythematous types, are at increased risk for malignant transformation to squamous cell carcinoma, with an estimated lifetime incidence between 0.5% and 2.0%.1,10 The average time from initial diagnosis of oral lichen planus to malignant transformation is approximately 4 to 5 years, and the tongue is the most common site of malignant transformation.10 Oral lichen planus is a chronic condition and because of risk of malignant transformation, long-term follow-up monitoring is needed to identify new lesions, changes to chronic lesions, or lesions not responding to medications that may warrant biopsy or rebiopsy to rule out dysplasia.3
Patient Outcome The patient was prescribed topical clobetasol gel (0.05% twice daily) and nystatin rinse (100 000 units/mL, 5 mL 3 times daily) for her gingival and mucosal conditions. Because of the severe oral involvement and subsequent development of cutaneous lesions, the patient received systemic corticosteroid therapy. Her oral and cutaneous lesions have improved, and both conditions are managed with topical and systemic medications.
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia.
1. Al-Hashimi I, Schifter M, Lockhart PB, et al. Oral lichen planus and oral lichenoid lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103 (suppl):e1-e12.
Corresponding Author: Eric T. Stoopler, DMD, FDS RCSEd, FDS RCSEng, University of Pennsylvania School of Dental Medicine, 240 S 40th St, Philadelphia, PA 19104 ([email protected]). Section Editor: Mary McGrae McDermott, MD, Senior Editor. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Additional Contributions: We thank the patient for providing permission to share her information.
2. Parashar P. Oral lichen planus. Otolaryngol Clin North Am. 2011;44(1):89-107. 3. Le Cleach L, Chosidow O. Clinical practice: lichen planus. N Engl J Med. 2012;366(8):723-732. 4. Crincoli V, Di Bisceglie MB, Scivetti M, Lucchese A, Tecco S, Festa F. Oral lichen planus: update on etiopathogenesis, diagnosis and treatment. Immunopharmacol Immunotoxicol. 2011;33(1):11-20. 5. Au J, Patel D, Campbell JH. Oral lichen planus. Oral Maxillofac Surg Clin North Am. 2013;25(1):93100.
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6. Lodi G, Giuliani M, Majorana A, et al. Lichen planus and hepatitis C virus. Br J Dermatol. 2004; 151(6):1172-1181. 7. DeRossi SS, Ciarrocca KN. Lichen planus, lichenoid drug reactions, and lichenoid mucositis. Dent Clin North Am. 2005;49(1):77-89. 8. Lodi G, Carrozzo M, Furness S, Thongprasom K. Interventions for treating oral lichen planus. Br J Dermatol. 2012;166(5):938-947. 9. Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions for treating oral lichen planus. Cochrane Database Syst Rev. 2011;7(7):CD001168. 10. Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions. J Am Dent Assoc. 2014;145(1): 45-56.
JAMA November 5, 2014 Volume 312, Number 17
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
1795
JAMA Clinical Challenge
Recurrent Gingival and Oral Mucosal Lesions Eric T. Stoopler, DMD, FDS RCSEd, FDS RCSEng; Thomas P. Sollecito, DMD, FDS RCSEd
Figure 1. Intraoral presentation of patient.
A 57-year-old woman presents for evaluation of gingival “peeling” associated with pain and bleeding and white patches on the oral mucosa for 7 years. She reports no new medications, foods, or oral hygiene products. She reports no involvement of other cutaneous or mucosal surQuiz at jama.com faces and no family history of oral lesions. The lesions cause pain and difficulty brushing her teeth. She has a history of hypertension, hypothyroidism, type 2 diabetes, gastroesophageal reflux disease, and seasonal allergies. Her medications are valsartanhydrochlorothiazide, levothyroxine sodium, metformin, insulin, and loratadine. Intraoral examination shows generalized erythema and sloughing of the maxillary and mandibular gingiva, without evidence of dental plaque, calculus, or both, and white striae (Wickham striae) affecting the gingiva and mucosa (Figure 1). Her physical examination is otherwise normal.
1794
WHAT WOULD YOU DO NEXT?
A. Prescribe valacyclovir (1000 mg 3 times daily) for the next 7 days B. Order a nutritional assay to evaluate for vitamin B 3 (niacin) deficiency C. Recommend increased use of an alcohol-based mouthwash to improve oral hygiene D. Biopsy the affected tissue
JAMA November 5, 2014 Volume 312, Number 17
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
jama.com
JAMA Clinical Challenge Clinical Review & Education
Diagnosis Lichen planus
What to Do Next D. Biopsy the affected tissue The desquamative appearance of the gingiva, presence of striae, absence of local irritants (dental plaque, calculus, or both), and chronic nature of the condition are consistent with lichen planus.
Discussion An etiology of herpes simplex virus is not supported by the clinical history and appearance of the gingiva and mucosa. Vitamin B3 deficiency is not associated with these oral findings. Increased use of an alcohol-based mouthwash is contraindicated due to the absence of local irritants and potential to exacerbate symptoms. Other mucocutaneous diseases, such as pemphigus vulgaris and mucous membrane pemphigoid, may present similarly, and biopsy of the affected tissue can establish the diagnosis. Oral lichen planus commonly affects women between the third and sixth decades, and prevalence is similar in white and African American persons.1,2 The prevalence of oral lichen planus ranges from 0.5% to 3% and is associated with cutaneous lichen planus in nearly 75% of patients.1-3 In comparison, the prevalence of cutaneous lichen planus is approximately 2%.1,2 The etiology of oral lichen planus is unclear. The pathophysiologic process involves a cellmediated immune response involving CD8+ T lymphocytes stimulating keratinocyte apoptosis and production of several inflammatory cytokines.4,5 Evidence suggests an association of hepatitis C and oral lichen planus.6 The most common presentation of oral lichen planus is the reticular form, which is often asymptomatic and observed as white lines (Wickham striae).3,7Variants of oral lichen planus include erythematous (atrophic), plaque-like, and erosive types. Clinical features of this case are consistent with erosive and reticular types of oral lichen planus. Oral lichen planus most commonly affects the buccal mucosa, tongue, and gingiva, with burning, stinging, textural changes, and/or alteration of taste associated with symptomatic lesions.2,5,7 Desquamative gingivitis, characterized by sloughing of the gingival epithelium, may be the initial and only presentation. Tissue biopsy is recommended to confirm the diagnosis, especially for atypical presentations, if other mucocutaneous diseases are considered or if dysplasia or malignancy is suspected.1,7,8 Routine staining of biop-
sied tissue classically demonstrates a band-like infiltrate of T lymphocytes, liquefactive degeneration of the basal cell layer, and sawtooth rete ridge formation (Figure 2).1,4,7 A biopsy of unaffected tissue for direct immunofluorescence analysis typically reveals linear fibrinogen deposition at the dermal-epidermal junction and differentiates oral lichenplanusfrompemphigusvulgaris and mucous membrane pemphigoid.4,5 Figure 2. Biopsy of the left buccal High-potency topical corti- mucosa reveals diffuse subepithelial infiltrate of chronic inflammatory costeroids represent first-line cells in the connective tissue therapy for symptom manage- subjacent to the basement ment and are often coadminis- membrane (basement membrane tered with a topical antifungal indicated by arrowheads) (hematoxylin-eosin, original agent to prevent oral candidi- magnification x20). asis.1,8,9Patients with severe or widespread disease may require systemic therapy, such as corticosteroids, steroid-sparing agents, or immunomodulators.1,8, Patients with oral lichen planus, especially erosive and erythematous types, are at increased risk for malignant transformation to squamous cell carcinoma, with an estimated lifetime incidence between 0.5% and 2.0%.1,10 The average time from initial diagnosis of oral lichen planus to malignant transformation is approximately 4 to 5 years, and the tongue is the most common site of malignant transformation.10 Oral lichen planus is a chronic condition and because of risk of malignant transformation, long-term follow-up monitoring is needed to identify new lesions, changes to chronic lesions, or lesions not responding to medications that may warrant biopsy or rebiopsy to rule out dysplasia.3
Patient Outcome The patient was prescribed topical clobetasol gel (0.05% twice daily) and nystatin rinse (100 000 units/mL, 5 mL 3 times daily) for her gingival and mucosal conditions. Because of the severe oral involvement and subsequent development of cutaneous lesions, the patient received systemic corticosteroid therapy. Her oral and cutaneous lesions have improved, and both conditions are managed with topical and systemic medications.
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia.
1. Al-Hashimi I, Schifter M, Lockhart PB, et al. Oral lichen planus and oral lichenoid lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103 (suppl):e1-e12.
Corresponding Author: Eric T. Stoopler, DMD, FDS RCSEd, FDS RCSEng, University of Pennsylvania School of Dental Medicine, 240 S 40th St, Philadelphia, PA 19104 ([email protected]). Section Editor: Mary McGrae McDermott, MD, Senior Editor. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Additional Contributions: We thank the patient for providing permission to share her information.
2. Parashar P. Oral lichen planus. Otolaryngol Clin North Am. 2011;44(1):89-107. 3. Le Cleach L, Chosidow O. Clinical practice: lichen planus. N Engl J Med. 2012;366(8):723-732. 4. Crincoli V, Di Bisceglie MB, Scivetti M, Lucchese A, Tecco S, Festa F. Oral lichen planus: update on etiopathogenesis, diagnosis and treatment. Immunopharmacol Immunotoxicol. 2011;33(1):11-20. 5. Au J, Patel D, Campbell JH. Oral lichen planus. Oral Maxillofac Surg Clin North Am. 2013;25(1):93100.
jama.com
6. Lodi G, Giuliani M, Majorana A, et al. Lichen planus and hepatitis C virus. Br J Dermatol. 2004; 151(6):1172-1181. 7. DeRossi SS, Ciarrocca KN. Lichen planus, lichenoid drug reactions, and lichenoid mucositis. Dent Clin North Am. 2005;49(1):77-89. 8. Lodi G, Carrozzo M, Furness S, Thongprasom K. Interventions for treating oral lichen planus. Br J Dermatol. 2012;166(5):938-947. 9. Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions for treating oral lichen planus. Cochrane Database Syst Rev. 2011;7(7):CD001168. 10. Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions. J Am Dent Assoc. 2014;145(1): 45-56.
JAMA November 5, 2014 Volume 312, Number 17
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
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