JADA Continuing Education
Mucosal Lesions in Older Adults
Sol Silverman Jr., DDS, MA
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ABSTRACT
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Background and Overview. Many oral diseases/conditions associated with aging are complex and can have a significant effect on the quality of life for ambulatory older adults. Among these are oral cancers and premalignant lesions, vesiculoerosive diseases, candidiasis, aphthous ulcers and herpes virus reactivation. The practitioner should establish the diagnosis so that appropriate management can be instituted.
Conclusions. The challenge to the practitioner is to formulate a differential diagnosis from oral mucosal signs and symptoms, arrange tests and referrals as needed, and establish a definitive diagnosis so that appropriate management can be instituted.
Clinical Implications. Recognition of benign and malignant muosal lesions will accelerate proper treatment that will help control a variety of oral diseases and conditions. It also will improve the quality of life for many elderly patients who experience associated pain and altered oral functions.
Key Words: Mucosal lesions; older patients; oral medicineAbbreviations: EM: Erythema multiforme • HPV: Human papillomavirus • HSV: Herpes simplex virus • LP: Lichen planus • MMP: Mucous membrane pemphigoid • RAS: Recurrent aphthous stomatitis • VED: Vesiculoerosive disease
The specialty of oral medicine provides important services for oral health problems in older adults. These oral health conditions and diseases associated with aging often are complex and can affect the quality of life adversely.
Three of the most common causes for referrals include suspected premalignant and cancerous lesions, oral inflammatory vesiculoerosive changes and candidiasis. The use of medications increases significantly in elderly people; therefore, the clinician must consider a patient’s potential drug reactions in the differential diagnosis of signs and symptoms. Additionally, when a patient has severe aphthae and herpetic reactivation, the clinician may have difficulty in both recognition and management of the conditions. The practitioner’s challenge is to establish a diagnosis so that he or she can institute appropriate treatment.
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ORAL CANCER
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Epidemiology and control.
Oral and pharyngeal cancer are estimated to exceed 34,000 new cases in the United States in 2007.1 Controlling these types of cancer depends on identifying and modifying etiologic factors, such as tobacco and alcohol use, diets low in fruits and vegetables, the potential role of the human papillo-mavirus (HPV), the influence of immunosuppression, genetic mutations and precancerous conditions (primarily leukoplakia).2 Ninety-five percent of oral and pharyngeal cancers occur after the age of 40 years.3
Treatment and survival.
In spite of advancements in surgery, radiation and chemotherapy, the overall five-year survival rate for oral and pharyngeal cancer is approximately 59 percent.3 It is conclusively apparent that early diagnosis combined with adequate treatment of oral cancers is the most effective way of reducing morbidity and mortality. Treatment is preceded with accurate staging, use of clinical findings and imaging with magnetic resonance imaging techniques. Positron-emission computerized tomography can be helpful.
Delay in diagnosis.
Early diagnosis requires both patient (public) and professional education. People must seek professional help when signs or symptoms in the mouth persist for more than three weeks so that clinicians can assess the seriousness as well as treatment of their problems. Clinicians must perform an appropriate oral screening examination to detect the cause of the complaints and findings. An oral cancer examination involves palpation of the neck and assessment of the lips, entire oral mucosa and oropharynx for any deviations from normal. Clinicians should conduct routine periodic oral cancer examinations with all adult patients.
Signs and symptoms.
Oral carcinomas can be mistaken for benign lesions, which in turn can lead to delays in diagnosis (Figures 1
–3). The most frequent chief complaint is that of a "sore" in the mouth. Both cancerous and premalignant lesions may appear as white, red, or white and red changes with or without ulceration. There may be associated firmness (induration) owing to an increase in the number of cells, inflammation or both. These lesions may be painless or associated with only slight irritation and, therefore, lead to a false sense of safety, use of empirical treatments and delay in diagnosis and treatment.
As a general rule, clinicians must consider all lesions that persist or do not respond to treatment as possibly premalignant or cancerous until proven otherwise.
Diagnosis.
Many times, clinical findings and judgments are equivocal and may result in a delay in appropriate testing to establish a diagnosis. The incisional biopsy is the gold standard for diagnosing lesions that may represent dysplastic (precancerous) or malignant transformation. Adjunctive techniques to clinical approaches are noninvasive and can be helpful in accelerating an incisional biopsy and the final diagnosis. These include several devices, all approved by the U.S. Food and Drug Administration: tolonium chloride stain (TBlue 630, Zila Pharmaceuticals, Phoenix), chemiluminescence (ViziLite, Zila Pharmaceuticals), fluorescence (Velscope, LED Dental, White Rock, British Columbia, Canada) and cytodiagnosis (brush biopsy) (Oral CDx, Suffern, N.Y.).
Routine oral cancer screening examinations and subsequent adjunctive techniques to accelerate obtaining a biopsy specimen are effective approaches to reducing the morbidity and mortality associated with oral and pharyngeal cancer. Through identification of premalignant lesions and appropriate treatment, clinicians even may prevent some cancers from occurring.4 Diets rich in fruits and vegetables are helpful in supplying both antioxidant and suppressor proteins that, along with other factors, may play a role in prevention. Genetic mutations and viruses are important, but our knowledge at this time does not allow clinical applications for controlling them. It is of critical importance that patients discontinue all tobacco use and minimize alcohol intake. Dental professionals, as a part of the health care team, play an important role in cancer control through prevention, early detection, managing complications of treatment and rehabilitation.
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VESICULOEROSIVE DISEASES
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Vesiculoerosive diseases (VEDs) are a group of mucocutaneous immunopathic inflammatory lesions that can affect any oral mucosal site.5,6 They are not readily associated with any identifiable causative factors. As research progresses, the basic explanation of their cause no doubt will be associated with chromosomal/genetic alterations or mutations that alter epithelial biology. VED mucosal changes are not recognized by host immune cells, which results in lymphocyte migration and cytokine release–induced reactions between connective tissue and the epithelium. The most common of these diseases that affect the mouth include lichen planus (LP),7 erythema multiforme (EM) and mucous membrane pemphigoid (MMP).8
Clinical features.
LP.
LP has three general oral forms: reticular (which has a white, lacelike keratotic pattern), atrophic (which has an erythematous component) and erosive (which has an ulcerative component) (Figure 4, page 44S).
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Figure 4. Painful lichen planus, present for three years, showing reticular keratosis, erythema and ulceration. Symptoms were controlled with daily corticosteroids.
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Pain, discomfort and irritation are the main complaints of patients with the condition, as well as concerns regarding infection and a small risk of malignant transformation.
EM.
Oral EM can appear as a red, red-white or red-white-ulcerative manifestation (Figure 5, page 44S). The outbreak can be chronic or cyclical and usually is associated with pain. EM represents a hypersensitivity reaction, but a causative agent often cannot be identified.
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Figure 5. Chronic idiopathic erythema multiforme manifested as painful palatal inflammation/ulceration. The condition was controlled with a combination of systemic and topical corticosteroids.
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MMP.
MMP usually occurs as a red or red-erosive change (Figure 6). The gingiva is the most common site in which it occurs, so the condition often is misrepresented as "desquamative gingivitis." In a small number of cases, MMP can affect the eyes, causing a symblepharon (a fibrous scar between the lower eye lid and the conjunctiva). Bullous pemphigoid manifests in the form of bullae and vesicles of the skin and, sometimes, oral lesions.
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Figure 6. Painful mucous membrane pemphigoid, present for 10 years in a 78-year-old woman. The condition was controlled with daily topical corticosteroids and occasional systemic steroid boost.
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Epidemiology.
Adequate population studies have not been done to establish incidence rates or occurrence of VEDs. LP is the most common of these diseases, possibly occurring in up to 1 percent of the adult population in the United States.9 VEDs occur in all ethnic groups, and the initial onset most often is beyond the third and fourth decades of life, with an increasing incidence beyond the age of 50 years. Clinical reports reflect a moderate predominance among women.9
Almost always, VEDs are chronic, and often they are characterized by flares and mild remissions. While these lesions can occur on any mucosal surface, LP most frequently occurs on the buccal mucosa and MMP on the gingiva. Occurrence is not related to either tobacco or alcohol use. There is no evidence of nutritional factors, although certain foods can cause flares. EM can be either cyclical or chronic.
Diagnosis.
Clinicians suspect the diagnosis of VEDs on the basis of clinical features and confirm it by means of biopsy. In classical LP and MMP cases, each entity has characteristic cell-tissue patterns, reflecting inflammatory patterns and sites of antigen-antibody reactions. In some cases in which specific patterns cannot be confirmed, clinicians may find immunofluorescence helpful; identifying sites of antigen-antibody reactions by means of this method requires special fixation and processing.
Since there is a slight increased risk of malignant transformation in LP, the clinician should closely follow patients with this condition and reestablish the diagnosis when changes occur in signs, symptoms or both. Since VEDs are chronic and lifelong, the differential diagnosis and biopsy are important if the clinician is to be certain that the clinical red-white-erosive changes do not represent a dysplastic or malignant process.
Treatment.
None of these conditions is curable; therefore, treatment is based on modifying the patient’s discomfort and pain. The treatment is directed toward the lymphocytes that are reacting with the epithelium and causing the symptoms. If mild over-the-counter medications are helpful, they are the first line of control. However, the most effective and predictive approach is modification of lymphocyte activity. Topical and systemic corticosteroids are the agents of choice for this.9
If clinicians select topical corticosteroids, they must be potent forms, since prolonged exposure is required for drug-lymphocyte interaction. Cortico-steroids of moderate-to-high potency, such as fluocinonide, are preferable. Applications can vary from single daily applications (most effective before bedtime) to as much as five times daily. Clinicians should follow up with these patients periodically. Long-term studies have not shown any pathophysiological adverse side effects. Occasionally, these topical agents might stimulate overgrowth of Candida, and the subsequent oral candidiasis must be treated with topical or systemic antifungal agents.
When the clinician uses systemic treatment, the strategy is high dose, short course to optimize efficacy and minimize side effects. In these situations, the clinician should coordinate treatment with the patient’s primary care physician. When using systemic routes, the clinician should use caution in patients with diabetes, gastrointestinal ulcers, hypertension and glaucoma.
Occasionally, when the patient’s signs and symptoms are not responding adequately, the clinician may find that a combination of prednisone and azathioprine, a synergistic cytotoxic drug, or other steroid-sparing agents may be helpful. The clinician must take care, since aza-thioprine can cause bone marrow suppression and alter liver function.
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CANDIDIASIS
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Diagnosis.
Candidal fungi are common residents of the oral flora. Overgrowth of these organisms will lead to candidiasis (thrush, moniliasis) manifested by white, red, or white and red surface changes10 (Figures 7 and 8). Angular cheilitis often is associated. These signs are accompanied by discomfort or pain, halitosis and alterations in taste. Some common causes of these conditions include hyposalivation (which causes xerostomia), high blood and salivary glucose, immunosuppression and the use of antibiotics and corticosteroids.
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Figure 7. Oropharyngeal pseudomembranous candidiasis associated with xerostomia and controlled with fluconazole.
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The clinician often can make the diagnosis by observing clinical signs and symptoms along with analyzing the patient’s history and taking a smear or culture, if necessary.
Treatment.
Topical (such as clotrimazole) and systemic (such as fluconazole) antifungal medications are effective in treating candidiasis. However, recurrence is certain if the initiating cause is not controlled.11
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RECURRENT APHTHOUS STOMATITIS
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Etiology and epidemiology.
Recurrent aphthous stomatitis (RAS), also called "canker sores," is recognized as an immunopathic disorder influenced by genetics and external irritants (such as foods and trauma).12 Patients with RAS can have minor or major (> 6 millimeters) ulcers and single or multiple lesions (Figure 9). RAS probably affects more than 40 percent of the population in one form or the other, with variable presentations and duration. However, most aphthae are of the minor variety and heal within 10 days.
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Figure 9. A painful major aphthous ulcer of three weeks’ duration in an elderly immunocompromised patient. The signs and symptoms completely resolved with a regimen of 60 milligrams of prednisone daily for one week.
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Diagnosis and treatment.
Clinicians usually recognize RAS by clinical features and the patient’s history. In patients with competent immune systems, manifestations of RAS occur almost exclusively on unkeratinized epithelium. Pain is the chief complaint, which in elderly people can complicate quality of life. Since RAS is an immunopathic condition, clinicians direct treatment against the offending lymphocytes that are causing the reaction. While clinicians may choose from many treatment approaches, topical or systemic corticosteroids are reproducibly effective.
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HERPES VIRUS INFECTIONS
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Etiology and diagnosis.
There often is confusion between the cause of oral herpes simplex virus (HSV) infections and RAS. Unlike RAS (an immunological disorder), oral HSV is an infection due mainly to HSV1. The primary infection occurs when a patient with no HSV antibodies comes in contact with the virus and becomes infected. Initial infections are not always accompanied by signs or symptoms, but they can be acute and severe. About 90 percent of the population are exposed to HSV by early adulthood,13 and the virus then remains dormant in regional ganglia until reactivated.
Reactivation leads to herpes labialis (cold sores) or recurrent intraoral mucosal herpes.8 Reactivation can result from fever, outdoor exposure, nonspecific irritants, immunosuppression and stress. Opposite to RAS, recurrent HSV occurs on keratinized epithelium, which is helpful in the differential diagnosis. HSV can be bothersome to older adults, and it becomes more frequent as the immune system becomes less competent. The clinician often can make a diagnosis on the basis of clinical appearance and history (Figure 10). Cultures and smears can be used to confirm HSV, if necessary.
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Figure 10. Painful recurrent herpes simplex reactivation, shown on the third day. The lesions resolved without specific antiviral treatment in seven days.
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Treatment.
HSV most often is self-limiting. Topical and systemic antiviral medications can accelerate disappearance of signs and symptoms.13,14 Acyclovir and valacyclovir usually are effective. The patient’s partner should be alerted to the potential danger inherent in contact with the lesion and in the shedding of the virus during the first three to five days of infection. Identifying causative factors and future prevention are part of the management.
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VARICELLA ZOSTER VIRUS
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Etiology and diagnosis.
Reactivation of the herpes family varicella virus (chicken pox virus) often strikes medically compromised adults, causing "shingles." This condition is manifested by unilateral vesicles, ulcers and scabs (often associated with the branches of the trigeminal nerve), that can persist for many weeks. The important sequela is postzoster neuropathy, which can be quite debilitating.
Treatment.
Treatment requires medical monitoring of drug combinations that are not always successful in controlling the painful symptoms. Oral signs and symptoms may be the initial complaints, causing patients to first seek dental consultation.
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CONCLUSION
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Many oral diseases and conditions associated with aging are complex and can have a significant effect on the quality of life for ambulatory older adults. These include malignant, infectious and inflammatory lesions. The challenge to the practitioner is to establish the diagnosis to initiate treatment. Appropriate management and lesion control will have a positive impact on the health and well-being of patients.
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FOOTNOTES
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Dr. Silverman is a professor, Oral Medicine, Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, S-519B, Box 0422, 521 Parnassus Ave., San Francisco, Calif. 94143, e-mail "silvermans{at}dentistry.ucsf.edu". Address reprint requests to Dr. Silverman.
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- Al-Hashimi I, Schifter M, Lockhart PB, et al. Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103(supplement 1): S25–S31.[Medline]
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- Woo SB, Challacombe SJ. Management of recurrent oral herpes simplex infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103(supplement 1):S12–S18.[Medline]
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ABSTRACT
ORAL CANCER
