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The most common infection and disease of the mouth is caries. Caries is a chronic, transmissible disease caused by bacteria using sugar to create an acidic environment that erodes the teeth.
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Candidiasis is an infection of the oral mucosa by the Candida species. The most prominent candida infection in humans is Candida albicans.
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Approximately 50% of children will have some form of gingivitis; for adults, it is as much as 90% when all types and causes are included. Gingivitis is very prevalent during pregnancy due to hormonal changes.
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Benign bony protuberances arise from the cortical plate and consist of lamellar bone. They are more common in the hard palate of the mouth but can also occur in the floor of the mouth. They are likely congenital but do not develop until adulthood.
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Clinicians should pay close attention to a history of nonhealing ulcer or mass in the mouth or on the lip, or any area that bleeds easily or has unexplained pain. Other concerning symptoms for oral cancer may include dysphagia/odynophagia, chronic sore throat or hoarseness, or unexplained ear pain.
Disease in the mouth can cause systemic diseases (eg, bacterial endocarditis), and systemic disease can also lead to complications in the mouth (eg, Behcet disease). Patients often present first to their primary care provider with oral symptoms. Medical clinicians often defer diseases of the mouth to dental professionals, oral surgeons, and otolaryngologists; however, medical professionals should be comfortable with the diagnosis and initial management of many common diseases of the oral cavity. This article discusses 3 major categories of disease within the mouth (excluding the tongue and salivary glands):
1.
Mouth infections (caries and complications, candidiasis)
2.
Inflammatory conditions (gingivitis, periodontitis, and stomatitis)
3.
Common benign and malignant lesions (bony tori, mucocele, lichen planus, leukoplakia, cancer).
Infections of the mouth
Caries
Description
The most common infection and disease of the mouth is caries. Caries is a chronic, transmissible disease caused by bacteria using sugar to create an acidic environment that erodes the teeth. Over time this process leads to holes (cavities) in the tooth’s structure. The predominant bacterium involved is Streptococcus mutans, although the disease may have more to do with a disruption of a complex biofilm on the teeth than the overpopulation of one species. Fluoride and saliva are protective factors.
The western developed countries tend to have more caries compared with lesser developed countries and this is thought to be second to the predominance of concentrated refined sweets in many countries.
Clinical implications
Untreated caries can lead to local and systemic infections. A cavity invades the pulp and root of the tooth, which includes the nerves and blood supply. This local infection can spread through surrounding gingival tissue, form an abscess, penetrate other layers of anatomy such as the cheek or airway, and ultimately infect the meninges or bloodstream. At a minimum, untreated cavities can cause pain and at worst has caused death through meningitis.
Diagnostic options and dilemmas
Routine screening examinations by medical and dental professionals can help identify caries early. Most professional organizations recommend an examination every 6 months. Mouth radiographs done periodically (common recommendation is every 2 years) can also help diagnose disease in the early stages.
Management
Prevention is the key. The patient should be advised to brush teeth twice daily with fluoridated toothpaste and floss daily.
Routine screening is suggested as above. Children and adolescents should also be considered for fluoride varnish treatments, supplemental fluoride if primary water supply is not fluoridated, and sealants of secondary molars. Early caries can be treated with restoration; deeper cavities will require root canal or extractions.
A delay in treatment can lead to spread of infection as outlined above. Initial antibiotics include penicillin (loading dose of 1000 mg, followed by 500 mg 3–4 times daily for 7–10 days) but broader antibiotics (such as clindamycin; loading dose of 600 mg, followed by 300 mg orally 3 times daily for 7–10 days) should be used if infection is spreading.
and consultation. Pain should be managed with acetaminophen and ibuprofen; depending on the degree of infection and pain, a short course of opioids may be necessary.
Candida species are normal inhabitants of the gastrointestinal tract. Those that are immunocompromised are more susceptible to oral candidal infections, including elderly, infants, HIV-positive individuals, patients with cancer, and diabetes or those with glucose intolerance.
Certain medications cause individuals to be more prone, including antibacterial therapy (especially broad-spectrum antibiotics, which disrupt normal protective flora), inhaled steroids,
and chemotherapy. Dentures also can get infected with Candida and the surrounding area may only be erythematous and not white.
Prevalence
Candidiasis is not common in the general public; annual estimates are 50 in 100,000. However, in high-risk populations the numbers are more prevalent: 5% to 7% of babies less than 1 month old; 9% to 31% of AIDS patients; nearly 20% of patients with cancer.
Oral candidiasis statistics. Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases, Division of Foodborne, Waterborne, and Environmental Diseases. Available at: www.cdc.gov/fungal/candidiasis/thrush/statistics.html. Accessed February 20, 2013.
The diagnosis for candidiasis is usually made through a history of risk factors and symptoms (including painless white patches in the mouth). Physical examination of white patches confirms the diagnosis. The white layer can be partially wiped off and there can be an erythematous mucosa underlying. Complications include a descending spread of the infection along the gastrointestinal tract causing esophageal and gastric candidiasis. Candida of the mouth can also present solely as angular cheilitis at the corners of the mouth, resulting in cracks in the skin. Candidiasis of dentures may present as only erythema of the mucosa.
Diagnostic options and dilemmas
Diagnosis can be aided with a slide preparation looking for hyphae. If pH is checked, it should be less than 4.5. If there is any doubt of a diagnosis, a culture can be obtained. A culture can also be helpful for recalcitrant infection to confirm species and sensitivities. Differential diagnosis includes leukoplakia, lichen planus, geographic tongue, and milk or other white foods.
Management
Prevention includes modifying risk factors (avoid antibiotics, use narrow spectrum antibiotics, consider probiotics when using antibiotics, rinse after inhaled steroid use). For treatment, Nystatin suspension, 100,000 U/mL given 4 to 6 times daily, is a common, effective treatment. It also comes as a pastille.
Clotrimazole (Mycelex), 10 mg troche, sucked on 20 minutes 5 times a day for 7 to 14 days is an alternative. For angular cheilitis, Nystatin ointment can be prescribed: 100,000 U/g to corners of mouth 2 to 3 times daily for 3 weeks. If dentures are involved, proper cleaning is important
; one technique is to clean with diluted (1:20) bleach. For infants with thrush, be sure to boil all pacifiers and bottle nipples. Infants should be treated with nystatin suspension 0.5 mL in each cheek 4 times daily until better, which is usually 7 to 10 days. Mother’s breasts should be treated as needed in breastfed babies with topical antifungals such as nystatin to the nipples of the breasts for the same duration. Oral agents (fluconazole or equivalent) can be used as second-line treatment or in cases of esophageal candidiasis.
Inflammatory conditions of the mouth
Gingivitis
Description
Gingivitis is a reversible form of inflammation of the gingival (Fig. 2). It is a mild form of periodontal disease. Classifications include plaque-induced, non-plaque-induced, and then gingivitis secondary to medications and systemic diseases.
Vitamin C deficiency (scurvy); coenzyme Q10 deficiency
Possible genetic link (up to 30% of population)
Hereditary gingival fibromatosis (rare)
Prevalence
Approximately 50% of children will have some form of gingivitis; for adults it is as much as 90% when all types and causes are included. Gingivitis is very prevalent during pregnancy due to hormonal changes. Other changes in hormonal activity can also increase prevalence of gingivitis in women, including menarche, menstruation, and use of contraceptives.
Gingivitis is often acute but can be intermittent and relapsing; some patients do get chronic gingivitis. Prognosis is generally favorable because it does respond well to appropriate treatment. Some experts think that if left untreated, gingivitis may progress to periodontitis over months to years, which can lead to other issues (see Periodontitis below). There is a condition called acute necrotizing ulcerative gingivitis that includes a necrotic slough of the gingival and is caused by a compromised immune system and malnutrition seen mostly in undeveloped countries.
Diagnostic options and dilemmas
Patients report painful gums that bleed easily especially with brushing, flossing, and eating. A thorough history should explore risk factors. Physical examination reveals swollen and erythematous gums that are tender to palpation. Plaque and calculus may be present. Differential includes periodontitis, pericoronitis (a flap of gum tissue growing over a tooth), and other oral ulcerative diseases and infections.
Management
Care should include removing any offending agents (medications, tobacco products) and modify diet if malnutrition is a concern. Dental referrals may be necessary for cleaning and plaque removal or dental appliance refitting. General measures can include warm saline rinses, better oral hygiene, and analgesics if necessary. Chlorhexidine rinses, mouth rinses with essential oils, and fluoridated hydrogen peroxide-based mouth rinses have all been shown to reduce gingivitis significantly.
Antibiotics are only necessary for acute necrotizing ulcerative gingivitis and include penicillin, metronidazole, and/or erythromycin. Prevention includes good oral hygiene, including daily high-quality flossing
healthy well-rounded diet, and regular dental checkups.
Periodontitis
Description
Periodontitis is a deep inflammation of the gingiva, including the ligaments and supporting structure of the teeth. It is caused by persistent exposure of the mouth to bacteria and plaque, leading to chronic inflammation. (Therefore, like many conditions of the mouth, it is not simply inflammatory but inflammatory and infectious.) Over time this leads to periodontal ligament destruction, loss of supporting alveolar bone, and loosening of teeth. Two major types are chronic and aggressive.
Risk factors
Poor oral hygiene (lack of brushing and flossing) and lack of dental cleanings lead to chronic plaque accumulation. Other contributing factors include tobacco exposure, HIV, pregnancy, and diabetes.
Local infection may also occur resulting in abscess formation. Multiple studies have shown an association between periodontitis and cardiovascular disease, preterm labor, and worsening diabetes among other disease states (although interventions may not improve outcomes making prevention a key goal).
Interventions to treat periodontitis are not always helpful for the systemic condition (ie, cardiovascular disease, preterm labor) in many studies, raising the question of whether prevention of periodontitis would have a more profound effect.
Diagnostic options and dilemmas
Clinical examination and history reveal painful gums that bleed easily. Advanced disease includes loose teeth. Radiographs show bone loss. Dental assessments to categorize disease will include probing depth of gingiva, attachment loss, and bone loss.
Management
Periodontitis is treated by dental professionals with deep root scaling and planing of bacteria and calculus to address the inflammation deep into the root. Topical antibiotics (metronidazole, minocycline, and doxycycline) and systemic antibiotics (doxycycline 100 mg daily, metronidazole 500 mg twice daily) are also used.
Chlorhexidine rinses may also be prescribed. Oral hygiene is an essential aspect of management and can be supported by medical professionals. Oral hygiene should include brushing twice daily with fluoridated toothpaste, ideally using an electric oscillating toothbrush, flossing daily, avoiding sugary snacks and drinks, avoiding tobacco products, and regular dental visits and cleanings.
Stomatitis
Description
Stomatitis is an inflammation of the mucous lining of the mouth, which can include the tongue, gingiva, lips, buccal surface, and floor of the mouth. It is usually erythematous and can be ulcerated and usually painful.
Risk factors
Stomatitis can have many causes and therefore there can be many risks, including poor oral hygiene, malnutrition, dietary deficiencies (ie, iron, folic acid, vitamin B6 and B12), chronic systemic disease (ie, inflammatory bowel disease, Behcet disease), immune deficiencies (ie, leukemia, AIDS), poor fitting dentures, smoking, and cancer therapies.
There are no specific estimates of these conditions but the following is a general guideline: very common: herpetic stomatitis (Fig. 3), hand-foot-mouth disease, and recurrent aphthous stomatitis; common: herpangina, nicotinic stomatitis, and denture-related stomatitis. The remaining causes are uncommon or rare.
Fig. 3Herpes simplex stomatitis.
(From Fatahzadeh M, Schwartz R. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol 2007;57(5):737–63; with permission.)
Resolution is expedited when offending agents are removed (eg, nicotine for nicotinic stomatitis or refitting poorly fitted dentures for denture-related stomatitis).
Complications
Complications include intraoral scarring and possible restriction of oral mobility if stomatitis is severe or chronic. Infectious causes can have systemic effects (eg, gangrenous stomatitis leading to facial disfigurement and even death; herpetic stomatitis can be associated with ocular or central nervous system involvement). Systemic disease can also have other systemic effects (eg, Behçet disease may result in vision loss, colitis, vasculitis, large-artery aneurysms, or encephalitis).
Diagnostic options and dilemmas
Patients usually present with complaints of a burning sensation or localized pain (minimal to severe pain), intolerance to temperature changes, and irritation with certain foods. Constitutional symptoms may include low-grade fever, malaise, and headache. Nutrition deficiencies, exposures to medications, foods, or oral products, recent cancer or cancer treatments, nicotine exposure, and systemic symptoms, such as fever, other lesions, or rashes, should be inquired about.
The physical examination should include comprehensive oral examination of all mucosal surfaces. Erythema and edema are the usual oral manifestations. Ulceration can occur in some cases. If Candida is involved, a white patch can also be present. Usually no tests are needed. If the diagnosis is in question, the following tests may be helpful: herpes simplex virus culture; serologic testing for syphilis; complete blood count, and cultures to determine secondary infection. A biopsy may be needed for persistent or recurrent lesions. Immunofluorescence is useful in the differential diagnostic between recurrent aphthous stomatitis and bullous skin diseases.
Management
Treatment of stomatitis depends on the cause. If cause is allergic, removal of the agent is critical. For infectious causes, antibiotic or antifungal medications are best. Steroidal anti-inflammatory drugs can help for systemic conditions with stomatitis manifestation. If the cause of stomatitis is due to medical treatment or cancer therapy, therapies may need to be altered.
There are many approaches to providing relief topically in the mouth. See Box 3.
Miracle mouth rinses: various combinations of the following in equal parts (swish and spit) multiple times daily:
Maalox or Mylanta, diphenhydramine, lidocaine
Maalox or Mylanta, diphenhydramine, Carafate
Nystatin, diphenhydramine, hydrocortisone
Steroids, colchicine, and cytotoxic drugs can be used for Behçet disease. Antibiotics are necessary for gangrenous stomatitis (penicillin and metronidazole are reasonable first-line agents; often started intravenously). For candidiasis, Nystatin oral suspension (swish and swallow) should be tried. Acyclovir 200 to 800 mg 5 times a day for 7 to 14 days for herpetic stomatitis.
For prevention or reducing severity of mucositis with cancer treatments, these agents have some evidence of benefit: allopurinol, aloe vera, amifostine, cryotherapy, glutamine (intravenous), honey, keratinocyte growth factor, laser, and polymixin/tobramycin/amphotericin antibiotic pastille/paste.
They are more common in the hard palate of the mouth but can also occur in the floor of the mouth. They are likely congenital but do not develop until adulthood.
Fig. 4Bony tori.
(From Swartz MH. Textbook of physical diagnosis: history and examination. Philadelphia: Saunders; p. 324–61.)
Bony tori do not usually cause any symptoms. On occasion, they can cause mechanical interference with eating or denture placement.
Diagnostic options and dilemmas
Tori are usually painless and go unnoticed. Medical personnel can sometimes confuse them for cancerous growths.
Management
No management is necessary unless the tori are interfering with oral function or denture fabrication. An oral surgery consult would be appropriate in these situations.
Mucocele
Description
Mucoceles are benign fluid-filled sacs within the lining of the epithelium (Fig. 5). They contain mucous glands.
Fig. 5Mucocele.
(From Wu CW, Kao YH, Chen CM, et al. Mucoceles of the oral cavity in pediatric patients. Kaohsiung J Med Sci 2011;27(7):276–9; with permission.)
Risk includes mild oral trauma, which leads to disruption of the salivary gland duct.
Prevalence
The prevalence of mucoceles is common and is usually seen in patients under the age of 20.
Clinical implications
The lesions are seldom symptomatic, but often are aggravating because a person will continue to retraumatize them when eating. Patients will present with pinkish/blue soft papules or nodules. Palpation reveals a gelatinous sac usually. Most frequently they occur on the lower lip (ie, result of biting of the lip). They vary in size.
Diagnostic options and dilemmas
Mucoceles are usually easy to diagnose. If there is a lack of gelatinous material, it may simply be gingivitis. Any lesion that does not heal in the mouth over 4 to 6 weeks should be followed up for further assessment and possible biopsy or excision for pathologic evaluation.
Management
Lesions will often rupture spontaneously, which should lead to complete resolution.
If the lesions are symptomatic, they can be excised, which must include the entire cyst to prevent recurrence. Aspiration alone is not recommended because it will provide short-term relief but recurrence is common. Alternative treatments include cryosurgery or laser, which also has shown good results with low recurrence rates and the latter being well tolerated.
Ther are no risk factors, possibly age. There may be a genetic link. One proposed theory is that lichen planus is a response to an infection, medication, or trauma.
Lichen planus affects 1% to 2% of the population and can occur at any age but is more predominant over age 40; there is a female-to-male ratio of 1.4:1.
Clinical implications are benign; however, if not exhibiting classical features or not responding to therapy, they may require a biopsy to confirm diagnosis. Lichen planus occurs at other sites in the body including skin and genitals.
Diagnostic options and dilemmas
Lichen planus are asymptomatic. Usually they will appear like white lace-like striations in the buccal surface. Alternative presentation is an erythematous atropic-appearing lesion; these lesions can be more painful. There is a third type that is more erosive.
Goals of management are to decrease pain if present and to prevent scarring. Good oral hygiene, avoiding irritating foods/drinks and tobacco, and removing any appliances that irritate the area may be helpful. Secondary treatments that have some proven benefit include intralesional corticosteroids, cyclosporine, and pimecrolimus and tacrolimus.
Leukoplakia (and Erythroplakia)
Description
Leuokoplakia are premalignant lesions that present as white patches or mucosal thickening (Fig. 7). Erythroplakia are similar lesions that have a red or red and white appearance. The lesions are hyperplasia of the squamous epithelium and although they begin as a benign reactive, inflammatory process can also evolve to transformative dysplasia.
Fig. 7Leukoplakia and erythroplakia.
(From Wu CW, Kao YH, Chen CM, et al. Mucoceles of the oral cavity in pediatric patients. Kaohsiung J Med Sci 2011;27(7):276–9; with permission.)
The risk factors are similar to oral squamous cell cancers (see Oral Cancer below). Biggest risk factors are carcinogens, especially smokeless tobacco products and repeat trauma. More evidence is emerging about the role of human papilloma virus (HPV) and leukoplakia.
Benign leukoplakia is common. Erythroplakia is less common. It is estimated that between 1% and 20% of benign lesions become malignant within 10 years.
White and red lesions in the mouth can be simple trauma, gingivitis, or lichen planus. Areas of the mouth where trauma is common (eg, inside of cheek) have thicker linings and therefore lesions in this area are less likely to be dysplastic. However, traumatic or nontraumatic lesions that do not resolve within 4 weeks should be biopsied. (Note that oral hairy leukoplakia is a different form of mucosal thickening and is not a premalignant lesion. It usually involves the tongue in HIV-infected patients and is not covered in this article.)
Diagnostic options and dilemmas
Usually lesions are asymptomatic and noticed by patients incidentally. (This is the reason periodic examinations by dental and medical professionals can find such lesions before they become more serious.) Lesions will often begin as white or red patches and then progress to thicker plaques or even erosions. Ulcerated lesions are more likely to be cancerous. Clinicians may visualize lesions at any of these stages.
Management
All white or erythematous lesions that cannot be explained or persist should be biopsied.
Depending on local expertise, dentists, oral surgeons, and otolaryngologists can perform this procedure. If moderate or severe dysplasia is identified, then surgical excision is the treatment of choice. Mild lesions can be treated with cryotherapy or laser ablation but do not allow for pathologic confirmation of complete removal. Prevention should include advising all patients to avoid tobacco products.
Oral Cancer
Description
Malignancies arising from the lips, tongue, floor of the mouth, salivary glands, buccal mucosa, gums, hard and soft palate, oropharynx, nasopharynx, and hypopharynx or other ill-defined sites within the lip, oral cavity, or pharynx. Ninety percent are squamous cell carcinomas; the others include lymphomas and adenocarcinomas from minor salivary gland origin and sarcomas.
Risk factors
Seventy-five percent of head and neck cancers are linked to tobacco (smokeless or smoked, including cigars and pipes) and alcohol.
Use of both alcohol and tobacco greatly increases risk as compared with those who use tobacco or alcohol alone (synergistic effect). HPV-positive oral cancers has increased by 225% recently and is now responsible for 2.8/100,000 individuals.
Ultraviolet light exposures increase risk for cancers of the lips. Radiation exposure from treatment of other facial cancers increases risk of salivary gland cancers. Chronic mechanical irritation (eg, sharp tooth edge, poor-fitting denture) and poor oral hygiene may also contribute. Other possible risk factors include HIV and betal nut chewing (other parts of the world).
Prevalence
Occurrence is 12/100,000/y for oral cancers and when head and neck cancers are taken collectively there are 53,000 new cases annually and 11,500 deaths per year,
representing 3% of all cancers in the United States, which is the sixth leading cause of cancer-related mortality. There is 30% to 50% higher incidence in African-Americans than in Caucasians; male > female (2:1); predominant age: >40 years. Oral cancer is the eighth most common cancer worldwide.
Clinical implications
Five-year survival rates have changed very little in the past decade; however, quality of life is much improved.
Unfortunately lesions are often detected late. If detected at an early stage, survival from oral cancer is better than 90% at 5 years, whereas late-stage disease survival is only 30%. HPV-related oral cancers have lower recurrence rates than non-HPV-related cancers after excision.
Complications
Complications from disease and treatments include functional and/or cosmetic disabilities proportional to the degree of surgery, location, and stage of tumor. Radiation therapy or chemotherapy can cause stomatitis with or without candidiasis, tissue hypoxia, tongue mucositis, and fibrosis. Xerostomia (dry mouth) is also a common side effect of treatments, which can lead to caries or dysphagia. Radiation may also cause new neoplasms.
Diagnostic options and dilemmas
Clinicians should pay close attention to a history of a nonhealing ulcer or mass in the mouth or on the lip, or any area that bleeds easily or has unexplained pain. Other concerning symptoms may include dysphagia/odynophagia, chronic sore throat or hoarseness, or unexplained ear pain. A thorough oral examination that includes visualization and palpation should be done (and also for those at high risk at regular intervals). Oral cancers can present in many forms. Most concerning are friable granular raised lesions or ulcers that can be confused with infection. Margins may be indurated and hard and extending beyond the borders of the ulcer. A firm neck mass may also suggest metastatic disease. White or red lesions that do not resolve should be biopsied, which is the gold standard for definitive diagnosis. Brush biopsy may be used for smaller oral lesions although, because some studies show brush biopsy to have low sensitivity/specificity, a negative result should be followed with transoral biopsy.
Further imaging is needed for staging. Differential includes stomatitis, infection, benign ulcers, leukoplakia, and lichen planus.
Management
Treatment varies depending on the location. Surgery and radiotherapy for early disease are comparable. Primary radiotherapy (and/or chemotherapy for palliation) is suggested for unresectable tumors and patients not amenable to surgery.
A dental consult should be obtained before any treatment to prevent serious complications later and to treat or eliminate questionable tooth and gum disease. The severity of mucositis during treatment can be lessened with aloe vera, amifostine, cryotherapy, granulocyte colony stimulating factor, intravenous glutamine, honey, keratinocyte growth factor, laser, polymyxin/tobramycin/amphotericin, antibiotic pastille/paste, and sucralfate.
There are a host of diseases that manifest in the mouth primarily or secondarily. Medical clinicians should become familiar with presentations for common and serious conditions as outlined above. Clinicians can often make initial diagnosis and management decisions and then refer as necessary. Often a team approach is needed for more complex or chronic conditions. Primary care providers can play an important role in prevention and early diagnosis by advising patients to perform proper hygiene and avoid tobacco and excess alcohol, have regular dental checkups, minimize prescribing medications with oral effects, promote a healthy diet, examine the oral cavity periodically, and make timely referrals.
References
Bouquot J.E.
Bond’s book of oral disease.
4th edition. The Maxillofacial Center for Diagnostic and Research,
2001 (Available at:)
Oral candidiasis statistics. Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases, Division of Foodborne, Waterborne, and Environmental Diseases. Available at: www.cdc.gov/fungal/candidiasis/thrush/statistics.html. Accessed February 20, 2013.
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