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Home , Aphthous stomatitis, Dental trauma, Erythroplakia, Hairy leukoplakia, Leukoplakia, Pemphigus

William D. Anderson, III, MD, DABFM, FAAFP; Oral health: you can’t Nathaniel S. Treister, DMD, DMSc; E.J. Mayeaux, Jr., MD, afford to miss DABFM, FAAFP; Romesh P. Nalliah, DMD University of South Carolina School of Medicine, Being able to promptly recognize and diagnose oral Columbia (Drs. Anderson and Mayeaux); Brigham lesions is critical to heading off several potentially and Women’s Hospital, Boston (Dr. Treister); serious conditions. This article and photo guide can help. Harvard Medical School, Boston (Dr. Nalliah)

william.anderson@ uscmed.sc.edu amily physicians can play an essential role in managing Practice The authors reported no their patients’ oral health by promptly recognizing and potential conflict of interest recommendations diagnosing conditions that demand further medical at- relevant to this article. F › Perform a and tention, including non-odontogenic and odontogenic infec- carefully monitor all tions, primary oral mucosal diseases, oral manifestations of potentially malignant oral , and malignancy. Many conditions are ame- lesions, including leuko­plakia nable to treatment by the family physician, while others will and . A require referral to a specialist. › Consider evaluation for hu- This article and accompanying photo guide describe the man types of lesions you may encounter during examinations of the for any patient who oral cavity, and the corresponding diagnoses. has acute necrotizing - ative /acute necro- tizing ulcerative periodontitis, recurrent , or Be vigilant for non-odontogenic conditions oral hairy . A that may require urgent treatment There are several uncommon, acute non-odontogenic condi- › Include in the tions that affect the oral cavity that, when severe, can require of oral pigmented lesions that have urgent medical attention and possible hospitalization. any features of cutaneous z Primary virus 1 (HSV-1) infection is melanoma (eg, asymmetry, generally subclinical, but some patients develop significant irregular borders, or variable oral disease—called primary herpetic gingivostomatitis— or changing color). A that’s characterized by painful diffuse, irregular, crop-like ul- cerations throughout the oral cavity and lips1 (FIGURE 1). The Strength of recommendation (SOR) gingiva is nearly universally affected, which distinguishes this A Good-quality patient-oriented evidence condition from multiforme and aphthous , B Inconsistent or limited-quality which are described below. The incidence is highest in chil- patient-oriented evidence dren, followed by adolescents and young adults.2 C Consensus, usual practice, z . This mucocutaneous hypersen- opinion, disease-oriented evidence, case series sitivity reaction can be limited to the oral cavity and , with- out accompanying lesions. Flu-like symptoms, including and chills, are followed by acute onset of diffuse oral ulcerations that are generally limited to non-keratinized mu- cosa, and spare the gingiva (FIGURE 2).3 Ulceration and crusting of the lips is common. z . Recurrent aphthous stomati-

392 The Journal of Family Practice | JULY 2015 | Vol 64, No 7 tis (RAS) is a common immune-mediated gross caries, fracture, heavy calculus depos- inflammatory condition characterized by its, or marked periodontal attachment loss. “canker sores,” or small round/ovoid ul- Oral examination may reveal a parulis (focal cers with a well-defined erythematous halo erythematous swelling of the adjacent gingi- (FIGURE 3). Lesions almost exclusively affect va with a central draining sinus tract) (FIGURE non-keratinized mucosa (and never the 6) and percussion of the affected is gen- vermillion) and heal within 7 to 10 days, al- erally painful. though “major” (>0.5 cm) lesions may per- z is infection and swelling sist much longer (FIGURE 4). A herpetiform of the gingival tissues that surround a tooth, pattern with multiple coalescing typically in association with a partially erupt- closely mimics HSV. ed third molar. include Small subsets of patients develop “com- pain, discomfort with eating and swallowing, plex” RAS, which is characterized by con- and limited opening. Examination tinuous and often multiple ulcerations that demonstrates gingival around may extend into the , with associ- a tooth, with or without purulence (FIGURE 7). ated chronic pain and compromised intake.2 z Acute necrotizing ulcerative gingi- RAS associated with systemic conditions is vitis (ANUG) and periodontitis (ANUP) are reviewed below. severe conditions that are typically associ- ated with psychological stress, severe malnu- trition, and immunosuppression in patients Uninsured How to spot signs with preexisting gingivitis or periodontitis.6 individuals may of common dental diseases ANUG is associated with intense gingival neglect a dental In 2010 in the United States, close to 1.4 mil- pain, halitosis, generalized erythema, and problem until lion emergency department visits and about destruction of the gingival papilla, often with it becomes $1 billion in hospital charges were due to bleeding.7 ANUP is a more advanced condi- a medical dental problems.4 Approximately 40% of tion associated with damage and loss of the emergency. these visits were made by individuals without periodontium (including bone), often with insurance.4 Due to a lack of dental insurance, loose teeth (FIGURE 8).8 patients may present to a medical profession- z Trauma. can be limited al rather than a dental professional. Addition- to the teeth and soft tissues, while more se- ally, uninsured individuals may neglect their vere can also affect the jaw bone.9 dental problem until it becomes a medical Accidental falls, assault, and motor vehicle emergency. Family physicians need to rec- traffic accidents are the most common causes ognize dental disease and be able to provide of facial fractures in the United States, and are basic management of emergencies.5 often associated with dentoalveolar trauma z Dental . A can (FIGURE 9). The most commonly fractured arise from pulpal infection (due to progres- facial bone is the , characterized by sion of caries) or periodontal infection (due painful opening and closing and an incom- to progression of ). Pain plete or altered bite.10 symptoms are variable; however, intense, spontaneous cyclical pain is generally char- acteristic of a dental abscess of pulpal etiol- Oral symptoms may be ogy, whereas a can have the first sign of systemic disease less obvious symptoms. Swelling intraorally Inflammatory bowel disease. Crohn’s dis- or extraorally indicates the spread of a local- ease may affect the ized infection (FIGURE 5). anywhere from the mouth to the anus and Severe infection and swelling can limit may initially present with oral findings that mouth opening and function, and in extreme may not correlate with abdominal symp- cases may obstruct swallowing and even toms. Oral Crohn’s disease may present as breathing (eg, Ludwig’s angina). Affected mucosal cobblestoning, mucosal tags, deep teeth may or may not demonstrate obvious linear ulcerations, gingival , lip findings of advanced dental disease, such as fissuring, aphthous ulcers, and angular chei-

jfponline.com Vol 64, No 7 | JULY 2015 | The Journal of Family Practice 393 FIGURE 1 FIGURE 2 HSV-1 infection Erythema multiforme

Primary 1 infection character- Erythema multiforme limited to the , with ized by painful diffuse, irregular, crop-like ulcerations diffuse, extensive ulceration of the entire lower labial throughout the oral cavity and lips, with focal mucosa and patchy ulceration of the floor of mouth. ulceration of the gingiva. Note that the gingiva is spared.

Intense, FIGURE 3 FIGURE 4 spontaneous Minor aphthous ulcers Major aphthous ulcer cyclical pain is generally characteristic of a dental abscess from a pulpal infection.

Multiple minor aphthous ulcers of the ventrolateral Major aphthous ulcer of the maxillary right labial in a patient with complex aphthous stomatitis. mucosa with slightly irregular borders.

FIGURE 5 FIGURE 6 Dental abscess Parulis

Left sided extraoral and submandibular swelling Multiple decayed and broken down teeth with an secondary to an abscessed left mandibular molar. associated gingival swelling that represents a draining sinus tract.

394 The Journal of Family Practice | JULY 2015 | Vol 64, No 7 oral health

FIGURE 7 FIGURE 8 Pericoronitis Ulcerative periodontitis

Pericoronitis associated with a partially erupted left Acute nectrotizing ulcerative periodontitis in a mandibular third molar with gingival swelling and patient with advanced human immunodeficiency virus erythema. infection. Note the crater-like gingival defects with complete loss of interdental papillae.

FIGURE 9 FIGURE 10 Dentoalveolar trauma Crohn’s disease Crohn's disease may initially present with oral findings that may not correlate with abdominal symptoms.

Dentoalveolar trauma of the anterior mandible with Oral Crohn’s disease showing fissure-like ulcerations of an fracture involving 3 teeth. The right the mandibular buccal vestibule. lateral incisor is completely avulsed and missing.

FIGURE 11 FIGURE 12 Crohn’s disease

Oral Crohn’s disease characterized by angular Pyostomatitis vegetans in a patient with ulcerative and marked fissuring and erythema of the labial colitis, characterized by typical serpentine pustules that mucosa and maxillary gingiva. coalesce in a “snail track” pattern. continued

jfponline.com Vol 64, No 7 | JULY 2015 | The Journal of Family Practice 395 FIGURE 13 FIGURE 14 vulgaris emphigoid

Erosion of the lower lip in a patient with pemphigus Ulceration of the buccal mucosa with an intact bulla in vulgaris. a patient with mucous membrane .

FIGURE 15 FIGURE 16 Systemic erythematosus Erosion of the enamel on the lingual surface of the teeth may be a sign of gastro­ esophageal disease or bulimia.

Oral lichen planus with characteristic radiating white Characteristic lichenoid inflammation of the buccal striations and associated erythema of the buccal mucosa in a patient with systemic . mucosa.

FIGURE 17 FIGURE 18 Enamel erosion Candidiasis

Erosion of the palatal aspects of the anterior maxillary Pseudomembranous candidiasis of the buccal mucosa in teeth secondary to severe and uncontrolled gastro- an immunosuppressed patient. esophageal reflux disease Note that the teeth restored with full crowns are unaffected due to the porcelain material.

396 The Journal of Family Practice | JULY 2015 | Vol 64, No 7 oral health

FIGURE 19 FIGURE 20 Oral Thrombocytopenia purpura

Oral hairy leukoplakia characterized by asymptomatic Multiple ecchymoses and thrombus formation in a corrugated white plaques of the lateral tongue. patient with idiopathic thrombocytopenia purpura.

FIGURE 21 FIGURE 22 Squamous cell Leukoplakia Recurrent candidiasis and oral hairy leukoplakia may indicate HIV infection.

Squamous cell carcinoma of the posterior buccal Oral leukoplakia with well-defined borders and an mucosa with well-defined, raised borders and a central exophytic verrucous growth pattern. A healing punch area of irregular ulceration. biopsy site is evident at the anterior aspect of the .

FIGURE 23 FIGURE 24 Acute myelogenous leukemia

Mucoepidermoid carcinoma of the minor salivary Acute myelogenous leukemia with characteristic glands within the maxillary labial mucosa. erythematous overgrowth of the gingiva with focal hemorrhage.

jfponline.com Vol 64, No 7 | JULY 2015 | The Journal of Family Practice 397 litis (FIGURES 10 AND 11). Other features may candidiasis, and oral hairy leukoplakia (FIG- include diffuse, painless swelling of the lips URE 19). In the absence of known HIV infec- and mucosal erythema. tion, patients who present with any of these Pyostomatitis vegetans is an uncommon oral conditions should be evaluated for HIV condition typically associated with ulcerative infection.13 (For more on recognizing the colitis that is characterized by serpentine signs of HIV infection in patients without pustules that coalesce in a “snail track” pat- classic risk factors, see “HIV: 3 cases that hid tern (FIGURE 12).11 in plain site” (J Fam Pract. 2015;64:20-26). z Dermatologic/vesiculo-bullous diseases. Atrophic may indicate a Vesiculo-bullous lesions in the mouth may be B deficiency. Thrombocytopenia and leuke- seen in or bullous pem- mia may present with oral petechiae, pur- phigoid. Pemphigus vulgaris is an autoim- pura, oral hematomas, or hemorrhagic bullae mune intraepithelial blistering disease that (FIGURE 20).13 Painless pseudomembranous often first presents in the oral cavity as flaccid mucosal erosions may be a presentation for bullae or painful ulcerations, prior to the onset secondary .16 of skin lesions (FIGURE 13). Mucous membrane pemphigoid is an au- toimmune subepithelial disease that affects Look for signs mucous membranes and the skin. Charac- that suggest malignancy SCC of the oral teristic oral mucosal quickly rupture In the United States, oral and pharyngeal can- cavity usually and form ulcerations, which may be present cers account for approximately 40,000 cases occurs on the in the absence of other mucosal involvement of and 8000 deaths each year.17 More tongue but (eg, anus, genitalia, nose or throat) (FIGURE than 90% of these are squamous cell carcino- can develop 14).12 Painful aphthous ulcers are common. mas (SCCs); the remainder are mainly salivary at any site, When oral ulcerations are diffuse and recur- gland tumors, , and other infre- presenting as rent, they may be the first sign of Behçet’s dis- quent .18 mucosal ulcers, ease, a multisystem autoimmune .13 z SCC of the oral cavity most commonly plaques, or Oral lichen planus is a chronic immune- occurs on the tongue but can develop in any masses that mediated mucocutaneous disease that is of- site, presenting as mucosal ulcers, plaques, don't heal. ten limited to the oral cavity. It presents with or masses that do not heal (FIGURE 21). Tobac- characteristic radiating white striations of the co and alcohol use are associated with up to buccal mucosa and tongue, often with associ- 80% of cases of SCC of the head and neck.18 ated erythema and ulcerations (FIGURE 15).14 Some oropharyngeal SCCs are associated with z Rheumatologic conditions. Systemic human papillomavirus infection type 16.19 or discoid lupus erythematosus may present Potentially malignant oral lesions include with oral findings that largely resemble those leukoplakia and erythroplakia. Leukoplakia of oral lichen planus (FIGURE 16).15 Sjögren’s is a white patch or plaque of the oral mucosa syndrome is an with that can’t be explained by any other clinical characteristic xerostomia, which can lead to diagnosis (FIGURE 22). These lesions are at risk oral discomfort, , recurrent candi- for malignant transformation and may dem- diasis, and rampant dental caries. onstrate or frank SCC on biopsy.20 z Other conditions to watch for. Erosion Proliferative verrucous leukoplakia is a unique of the enamel on the lingual surface of the teeth form of leukoplakia that’s characterized by a may be a sign of gastroesophageal reflux dis- wrinkled appearance that is often multifocal; ease or bulimia (FIGURE 17). Examination of the the condition is associated with a higher risk oral mucosa can reveal typical white plaques of of malignant transformation. (FIGURE 18), which may be as- Erythroplakia is a red patch that similarly sociated with systemic immune suppression as can’t be explained by another diagnosis. It has well as salivary gland dysfunction. a very high risk of malignant transformation Oral conditions that have been associ- over time. All potentially malignant oral le- ated with human immunodeficiency virus sions, including leukoplakia and erythropla- infection include ANUG/ANUP, recurrent kia, require biopsy and careful monitoring.

398 The Journal of Family Practice | JULY 2015 | Vol 64, No 7 oral health

z Non-SCC cancers. Salivary gland tu- Hematologic malignancies may initially mors are rare and most commonly occur in present (or demonstrate evidence of relapse) patients ages 55 to 65 years. Most in the oral cavity. Leukemia typically pres- (70%-85%) occur in the parotid gland, while ents with sheet-like overgrowth and swelling 8% to 15% develop in the submandibular of the gingiva with associated erythema and salivary gland and less than 1% involve the bleeding (FIGURE 24), whereas lymphoma sublingual gland.21 Minor salivary gland tis- typically presents as a solitary mass or ulcer- sue, especially in the lips and , may also ation. Solid tumors that metastasize to the be affected FIGURE( 23). Patients present with oral cavity may present with localized unex- circumscribed, fixed or movable, painless, plained soft or hard tissue growths, with or soft or firm masses in a salivary gland. without associated neurologic symptoms (eg, Melanoma should be included in the dif- paresthesia). JFP ferential diagnosis of oral pigmented lesions that have any features of cutaneous melano- CORRESPONDENCE William D. Anderson, III, MD, DABFM FAAFP, University of ma, such as asymmetry, irregular borders, or South Carolina School of Medicine, 15 Medical Park, Suite variable or changing color.22 300, Columbia, SC 29203; [email protected]

References 1. Spruance SL. The natural history of recurrent oral-facial herpes 12. Xu HH, Werth VP, Parisi E, et al. Mucous membrane pemphigoid. Most salivary simplex virus infection. Semin Dermatol. 1992;11:200-206. Dent Clin North Am. 2013;57:611-630. gland tumors 2. Balasubramaniam R, Kuperstein AS, Stoopler ET. Update on oral 13. Chi AC, Neville BW, Krayer JW, et al. Oral manifestations of sys- herpes virus . Dent Clin North Am. 2014;58:265-280. temic disease. Am Fam Physician. 2010;82:1381-1388. (70%-80) occur 3. Lozada-Nur F, Gorsky M, Silverman S Jr. Oral erythema multi- 14. Lavanya N, Jayanthi P, Rao UK, et al. Oral lichen planus: An up- forme: clinical observations and treatment of 95 patients. Oral date on pathogenesis and treatment. J Oral Maxillofac Pathol. in the partoid Surg Oral Med Oral Pathol. 1989;67:36-40. 2011;15:127-132. gland. 4. Allareddy V, Rampa S, Lee MK, et al. Hospital-based emergency 15. Uva L, Miguel D, Pinheiro C, et al. Cutaneous manifesta- department visits involving dental conditions: profile and predic- tions of systemic lupus erythematosus. Autoimmune Dis. tors of poor outcomes and resource utilization. J Am Dent Assoc. 2012;2012:834291. 2014;145:331-337. 16. Ficarra G, Carlos R. Syphilis: The renaissance of an old disease 5. Allareddy V, Lin CY, Shah A, et al. Outcomes in patients hospi- with oral implications. Head Neck Pathol. 2009;3:195-206. talized for periapical abscess in the United States: an analysis 17. Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011: the im- involving the use of a nationwide inpatient sample. J Am Dent pact of eliminating socioeconomic and racial disparities on pre- Assoc. 2010;141:1107-1116. mature cancer deaths. CA Cancer J Clin. 2011;61:212-236. 6. Folayan MO. The epidemiology, etiology, and pathophysiology of 18. Licitra L, Locati LD, Bossi P, et al. Head and neck tumors other acute necrotizing ulcerative gingivitis associated with malnutri- than . Curr Opin Oncol. 2004;16:236- tion. J Contemp Dent Pract. 2004;5:28-41. 241. 7. Atout RN, Todescan S. Managing patients with necrotizing ulcer- 19. Gillison ML, Broutian T, Pickard RK, et al. Prevalence of oral HPV ative gingivitis. J Can Dent Assoc. 2013;79:d46. infection in the United States, 2009-2010. JAMA. 2012;307:693- 8. Todescan S, Nizar R. Managing patients with necrotizing ulcer- 703. ative periodontitis. J Can Dent Assoc. 2013;79:d44. 20. Silverman S Jr., Gorsky M, Lozada F. Oral leukoplakia and malig- 9. Allareddy V, Allareddy V, Nalliah RP. Epidemiology of facial frac- nant transformation: A follow‐up study of 257 patients. Cancer. ture injuries. J Oral Maxillofac Surg. 2011;69:2613-2618. 1984;53:563-568. 10. Nalliah RP, Allareddy V, Kim MK, et al. Economics of facial frac- 21. Spiro RH. Salivary neoplasms: overview of a 35-year experience ture reductions in the United States over 12 months. Dent Trau- with 2807 patients. Head Neck Surg. 1986;8:177-184. matol. 2013;29:115-120. 22. DeMatos P, Tyler DS, Seigler HF. Malignant melanoma of the 11. Padmavathi B, Sharma S, Astekar M, et al. Oral Crohn’s disease. J mucous membranes: a review of 119 cases. Ann Surg Oncol. Oral Maxillofac Pathol. 2014;18(suppl 1):S139-S142. 1998;5:733-742.

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