Diseases of the Mouth and Salivary Glands

Aphthous Stomatitis (“Canker Sores”)

These idiopathic recurrent ulcers are common, afflicting up to 20% of the population and can be found on nonkeratinized mucosa: the buccal mucosa, ventral tongue, lips, and alveolar mucosa ( Fig. 393-1 ). They form well-defined, usually shallow, circular ulcers that may be single or multiple. There are three clinical forms: (1) minor, which are flat and less than 0.5 cm in diameter and last 5 to 10 days; (2) major, which have raised borders, are deeper, solitary, greater than 0.5 cm, and often last for weeks or months; and (3) herpetiform, which are usually clusters of very small ulcers that resemble recurrent herpetic lesions but are not preceded by vesicles and do not occur on keratinized mucosa. A viral or bacterial pathogenesis has not been established for any of these forms. Lesions clinically indistinguishable from minor aphthae occur in Behçet syndrome ( Chapter 249 ). Aphthae are rarely associated with anemias or gluten-sensitive enteropathy ( Chapter 126 ) and may become more frequent and severe in association with human immunodeficiency virus (HIV) infection ( Table 393-2 ).

Minor or herpetiform aphthous ulcers are generally self-limiting within a week or two and may not require treatment unless they occur frequently. Topical steroids, such as fluocinonide gel or ointment, can reduce the severity and duration of the lesions only if applied with prodromal symptoms or earliest signs. A freshly prepared suspension of tetracycline or doxycycline in water used as a mouth rinse at the onset of symptoms also reduces the severity and duration of disease. Unfortunately, none of these treatments prevent recurrent ulcers. Major aphthae usually require treatment with prednisone (e.g., 40 mg daily for 3 days); failure to respond significantly should prompt incisional biopsy to exclude neoplasia. Unfortunately, no treatment will cure a patient of recurrent aphthous stomatitis. Laser therapy may promote healing and pain relief in patients with recurrent aphthous stomatitis, although this approach has not been proven in clinical trials.

Viral Ulcers

Several types of virus (most commonly herpes simplex type 1; Chapter 345 ) cause multiple oral mucosal vesicles that last only a few hours or days and then become irregular shallow ulcers. In the initial infection by herpes simplex virus, usually in children, numerous vesicles may appear on any oral mucosal site (called primary herpetic gingivostomatitis), accompanied by malaise, headache, fever, and cervical lymphadenopathy. Patients previously exposed to this virus may develop recurrent (secondary) lesions that appear as clusters of small vesicles, most commonly on the lips (herpes labialis) and less commonly on the keratinized mucosa of the gingiva or hard palate ( Fig. 393-2 ). Such lesions contain live virus and tend to recur at the same site but less frequently with increasing age.

Although widespread vaccination has reduced the incidence, similar mucosal vesicles may also accompany the initial infection by the varicella-zoster virus in children with chickenpox ( Chapter 346 ), and unilateral lesions may occur if herpes zoster ( Chapter 346 ) affects branches of the trigeminal nerve. Uncommonly, oral mucosal ulcers may be caused by different types of coxsackievirus ( Chapter 349 ), appearing on any oral site in hand-foot-and-mouth disease or on the soft palate or pharynx in herpangina. After infection by the measles (rubeola) virus, small ulcers (Koplik spots; see Fig. 338-2 in Chapter 338 ) may form on the inside of the cheeks 1 to 2 days before development of the skin rash ( Chapter 338 ). Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ( Chapter 336 ) may have a variety of oral manifestations, including erosions, ulcers, bullae, vesicles, and pustules.

Mucositis Associated with Cancer Treatment

Patients who receive radiation therapy for cancers where the radiation fields include the oral cavity are at risk for the development of oral mucositis ( Chapters 18 and 176 ). Oral mucositis is also common in patients who receive intensive chemotherapy for malignancies, such as patients who have leukemia ( Chapter 167, Chapter 170 ) or undergo hematopoietic stem cell transplantation ( Chapter 163 ). Oral mucositis also occurs in about 20 to 40% of patients treated with chemotherapy for other solid tumors. Risk factors include smoking, poor oral hygiene, a lower pretreatment neutrophil count, and the depth of treatment-induced neutropenia. Agents with higher risks include anti-angiogenic tyrosine kinase inhibitors (e.g., axitinib, cabozantinib, pazopanib, sorafenib, and sunitinib) and mammalian target of rapamycin (mTOR) inhibitors (e.g., everolimus), as well as etoposide, fluorouracil, and methotrexate. The pathobiology is cytotoxic damage to rapidly dividing cells, predominantly basal cells of the mucosal epithelium, by chemotherapy and radiation.

Patients can develop pain and sensitivity to irritating substances, which can be avoided by the patient. Mild mucositis may be difficult to confirm on examination, but oral ulceration is the hallmark of the condition. Bleeding occurs with more severe mucositis. A complete blood count with differential is helpful, and the patient should also be assessed for any signs of dehydration ( Chapter 7 ).

For patients with mild symptoms, a bland mouthrinse (e.g., normal saline or sodium bicarbonate in water) as a “swish and spit” can be symptomatically helpful. For moderate pain that does not interfere with oral intake, patients should avoid hard-consistency, rough, or sharp foods; alcohol; and smoking. A 2% oral lidocaine solution can be added to a normal saline or sodium bicarbonate mouthrinse. For more severe mucositis, topical agents include a doxepin mouthrinse and “Magic” mouthwashes. For more severe pain that interferes with eating, dehydration, neutropenia, or suspected systemic infection, expert consultation and typically hospitalization must be considered. For radiation-induced mucositis, a diphenhydramine/lidocaine/antacid mouthwash can reduce the incidence and severity of mucositis, and dexamethasone mouthwash can provide analogous benefits for patients receiving mTOR inhibitors.

Erythema Multiforme

In this potentially recurrent disease, painful oral mucosal ulcerations develop rapidly, with or without target-like skin lesions. It may be associated with a previous viral infection or hypersensitivity to a food or drug. The affected patients, usually young adults with minimal or no systemic symptoms, have irregularly shaped ulcers that can be small and few or involve large areas of the mucosa; the most common sites are the lower labial mucosa and vermilion. On the vermilion of the lips, bilateral hemorrhagic crusting is a characteristic finding. These lesions can be distinguished from those of primary herpes by the absence of oral vesicles and systemic symptoms or by the presence of characteristic skin lesions ( Chapter 406 ). A major variant of this disease is Stevens-Johnson syndrome, in which ocular, genital, and other lesions may accompany the oral lesions.

Venereal Infections

Primary syphilis may arise as a solitary, indurated, painless ulcer on the oral mucosa that resolves spontaneously in 4 to 6 weeks ( Chapter 295 ). Uncommonly, Neisseria gonorrhoeae ( Chapter 275 ) may cause oral ulcers, usually in the soft palate and pharynx, which may be confused with oral ulcers of other causes.

Lichen Planus

Oral lesions of lichen planus ( Chapter 405 ) occur in about 1% of the population, usually as multiple, bilaterally symmetrical reticular (lattice-like) white lesions, with or without adjacent areas of erythema (atrophy or erosion) or irregular ulcers ( Fig. 393-4 ). The presence of mucosal atrophy, erosion, or ulceration usually causes pain and sensitivity to certain foods. Most lesions can be adequately controlled by topical application of fluocinonide or clobetasol gel or ointment (0.05%, three times a day) for periods of several weeks, although recurrence is common.