Soft tissue lesions commonly seen in the oral cavity tend to overlap in their onset, presentation, and location making it difficult to appreciate their etiology. In some instances, common oral soft tissue lesions can create confusion due to similar clinical appearance or unusual presentation; therefore, proper diagnosis of the lesion is key in pharmacologic management. In ulcerative conditions, topical steroids can decrease the symptoms and improve healing time, but do not affect the recurrence rate. Always be suspicious of soft tissue lesions that are nonresolving or recurrent lesions as they may warrant further investigation to rule out malignancy or associated systemic conditions. This article discusses key clinical presentations and the proper topical and systemic pharmacologic treatments.
The diagnosis of soft tissue lesions in the oral cavity requires a thorough clinical evaluation; therefore, avoiding confusion between similar appearing lesions.
Topical medications have been proven to be the most effective management of certain oral mucosal lesions.
When managing candidiasis it is important to address any underlying factor when possible.
Patients with ulcerative diseases may have superimposed candidiasis altering the clinical appearance of a lesion.
The overall objective of steroidal therapy is to decrease the number, size, and discomfort of lesions.
Lesions of the oral cavity can arise from many different etiologies, inflammatory, infection, traumatic, immunologic, or neoplastic. Obtaining a detailed patient history and physical examination of the lesion may give us suspicion of associated conditions or diseases; whether or not there is a triggering factor; new or recurrent lesion; pain or painless, length of time the lesion has been present; and rate of growth of the lesion over time. Neoplastic ulcerated lesions are notorious in the oral cavity for their ability to mimic benign ulcerative lesions, highlighting the essential nature of biopsy to establish a diagnosis in cases that are not clinically identifiable or do not respond as expected to treatment. Additional physical evaluations, laboratory tests, or adjunctive tests may be required for final diagnosis. This article divulges a selection of the most common oral lesions providers are likely to encounter and the recommended pharmacologic management.
Common soft tissue oral lesions
Recurrent aphthous stomatitis
Aphthous lesions are one of the most common oral lesions, they can affect up to 25% of the general population. Three month recurrence rates are as high as 50% with a predilection for women. Although it is unclear what causes aphthous ulcers, factors such as trauma, nutritional deficiency, stress, tobacco, food hypersensitivity, hormonal changes, and drugs, can contribute to the disease. , These lesions can occur as a single, isolated event, or in groups of 2 or more that may reoccur at intervals. In such cases, the condition is known as recurrent aphthous ulcers or recurrent aphthous stomatitis (RAS). The lesions emerge in 4 stages, in first stage or prodromal stage, the individual will experience tingling and burning in the normal-appearing site; during the second stage or preulcerative stage, red oval papules appear that intensifies; in the third stage or ulcerative stage, classic ulcer appear. The 4 stages are the healing stage, in which granulation tissue followed by epithelialization occurs.
Minor aphthae is the most common form of RAS and approximately 85% of patients have lesions of this type. Minor aphthae are superficial mucosal ulcers with variable shape and size typically 4 to 5 mm diameter but less than 1 cm. Minor aphthae involve the nonkeratinized movable oral mucosa of the oral cavity (the labial and buccal mucosa ( Fig. 1 ), the floor of the mouth and the ventral, or lateral surface of the tongue). ( Fig. 2 ) They tend to heal within a period of 10 to 14 days, at this stage, granulation tissue followed by epithelial migration and epithelial migration incurs in healing without a scar.
Major aphthae have identical developmental stages in their general appearance except that are larger (exceeding 10 mm), deeper (extending to submucosal layers and underlying muscle at times), and longer lasting (can last up to 6 weeks).
Herpetiform ulcerations are characterized by multiple recurrent small size ulcers from 2 to 3 mm in diameter. Multiple lesions may coalesce to form large irregular ulcers that last for about 10 to 14 days. These herpetiform ulcers, unlike herpetic lesions, are not preceded by vesicles and do not contain virally infected cells. Herpetiform aphthae are more common in women and have a later age of onset than other clinical variants.
The treatment of aphthous ulcers is palliative, the goal being to reduce the duration, size, and recurrence of lesions. Most individuals can endure minor levels of discomfort and are preferable to risking therapy with agents that can have potential side effects.
First-line treatment options comprise antiseptics, such as chlorhexidine, antiinflammatory drugs, and analgesics for as long as the lesions persist. A mixture often called magic mouthwash, which often consisting of diphenhydramine hydrochloride, viscous lidocaine, Kaopectate, and corticosteroids may be useful in controlling the number, frequency, and duration of lesions. The patient is instructed to use 1 tsp at a time and swish, hold the solution in his or her mouth as long as possible, and swallow, three times daily.
Topical steroids can decrease the symptoms and improve healing time, but do not affect the recurrence rate. If multiple lesions are present, an aqueous solution is preferred. A dexamethasone rinse can be considered or in isolated lesions, a high potency topical steroid (kenalog, clobetasol, or fluocinonide) for no more than 2 weeks , ( Table 1 ). A trial with the antibiotic minocycline, which has immunomodulatory effects suppressing neutrophils, T lymphocytes, and collagenase activity, can be used. A blind crossover study shows a significant reduction in duration and severity of pain compared with placebo.
|Topical Medications for the Treatment of Aphthous Lesions|
|Chlorhexidine 0.12%||5 mL swish and spit TID for 14 d|
|Dexamethasone 0.2%||5 mL swish and spit TID for 10 d|
|Kenalog 0.1%||Apply to affected areas TID for 10 d|
|Minocycline 0.5%||5 mL swish and spit QID for 10 d|
|Fluocinonide 0.05%||Apply ointment to affected areas TID for 10 d|
In severe cases, whereby these regimens fail and the number, size, and discomfort of the lesions increases, and lesions, an injectable or systemic steroid, such as prednisone, are recommended. It is started at 1 mg/kg/d as a single dose in patients with severe lesions and tapered after 1 to 2 weeks. The recommendation is to use less than 50 mg per day, preferably in the morning, for 5 days. ,
When managing patients with RAS, a thorough medical history and further work-up should be conducted to rule out any systemic conditions associated with aphthous ulcers. Systemic conditions such as Behcet syndrome, hand-foot-and-mouth, cyclic neutropenia, periodic fever with aphthae, pharyngitis and adenitis syndrome, Reiter syndrome, and Sweet syndrome, gluten-sensitive enteropathy, Crohn’s disease, ulcerative colitis, and immune deficiencies, may all have oral manifestations; thus, need to be considered at the time of diagnosis. ,
Oral herpes (herpes simplex virus)
Primary herpetic gingivostomatitis
Primary herpetic gingivostomatitis are caused by herpes simplex virus (HSV) and can be seen most commonly in children and young adults. Infection can be asymptomatic or can cause painful vesicular lesions on all mucosal surfaces and rupture and produce foul smell. Patients can become febrile and have significant malaise and tender cervical lymphadenopathy. Lesions and acute illness can last from 5 to 10 days and resolve with scar formation. The clinical course is limited by the synthesis of viral-specific antibodies (IgM, days 3–5; IgG, days 5–21). HSV gains access via direct or airborne water-droplet transmission. The lesions in mucosal membranes represent direct viral infection and the virus then ascends along the epineurium of the trigeminal nerve, establishing latency in the Gasserian ganglion, where it develops dormant existence within ganglion cell bodies ( Fig. 3 ). It can become reactivated under various stimuli: stress, fever, ultraviolet light, trauma, or menstruation.
Recurrent herpes infection
On reactivation of herpes lesions, the patient first experiences the prodromal symptoms of pain, itching, burning, or paresthesia. Viral shedding occurs mostly during the time of active lesions and therefore, the time of greatest transmissibility. Recurrent secondary lesions may be more frequent and intense within the initial few years after primary infection and decrease in severity and increased intervals as time passes.
Herpes labialis is frequently occurring and self-limiting thus, many patients do not consult their general practitioners and use over-the-counter medication. Treatment with indifferent (zinc oxide and zinc sulfate), anesthetic, or antiviral cream has a small favorable effect on the duration of the symptoms, if applied promptly. A randomized controlled study with zinc oxide as a treatment showed that after 5 days, 50% of the patients in the treatment group were symptom-free compared with 35% in the placebo group.
When using antiviral therapy, the aim is to block viral replication. Peak viral titers occur in the first 24 hours after lesion onset when most lesions reach the vesicular stage. Thus, for the treatment to be effective, it should be started at the first signs. Some topical agents include penciclovir 1% cream, acyclovir 5% cream, and docosanol cream. Penciclovir is inactive until it is phosphorylated within the virus, whereby it selectively inhibits herpes viral DNA synthesis and replication. Therefore, it has low toxicity and good selectivity. Acyclovir 200 mg oral for 5 days can be started at first prodromal signs. Antivirals are used in primary and recurrent infections to decrease pain, viral shedding, and duration of symptoms. Prophylactic use of antivirals has proven useful in decreasing the frequency of recurrences, especially in immunocompromised patients and immunocompetent persons who experience frequent recurrences of oral or genital HSV infections ( Table 2 ).
|Topical Medications for the Treatment of Oral Herpes|
|Zinc Oxide 1% gel||Apply to affected area q 2 h for 5 d|
|Acyclovir 5% Ointment||Apply to affected area q 3–4 h for 4 d|
|Penciclovir 1%||Apply to affected area q 2 h for 4 d|
For primary herpetic gingivostomatitis, the clinician might recommend only supportive care consisting of hydration, antipyretics, nutrition, and if secondary bacterial infections arise the use of antibiotics. However, severe cases may require systemic antiviral therapy.
Oral candidiasis is caused by an overgrowth of the normally present organism Candida albicans . The infection is associated with alterations in the host’s defense mechanisms. The incidence varies depending on age and certain predisposing factors. Some of the predisposing factors include impaired salivary gland function, drugs, dental prosthesis, high carbohydrate diet, and extremes of age, smoking, diabetes mellitus, Cushing’s syndrome, malignancies, prolonged antibiotic use, and immunosuppressive conditions or agents Oral candidiasis can have multiple clinical presentations that vary greatly according to the predisposing factors. , Classifications of oral candidosis include Pseudomembranous form, hyperplastic form, and atrophic form. The symptoms of the acute form are rather mild and the patients may complain only of a slight tingling sensation or foul taste, whereas the severe chronic forms may involve the esophageal mucosa leading to dysphagia. ,
Pseudomembranous candidiasis often referred to as thrush , can present as both acute and chronic forms. The affected mucosal surface becomes tender with red and white to whitish-yellow creamy plaques resembling milk curds or cottage cheese. These white plaques consist of cellular debris mixed with Candida organisms. The red areas correspond to the areas whereby organisms have invaded into the upper layers of the mucosa, resulting in parakeratinization, hyperemia, atrophy, and inflammation. The white plaques or pseudomembrane characteristically can be easily removed, leaving behind an underlying erythematous and hemorrhagic area. The oral surfaces frequently involved include labial and buccal mucosa, tongue, hard and soft palate, and oropharynx. The involvement of both oral and esophageal mucosa is prevalent in AIDS patients. Few lesions mimicking pseudomembranous, candidiasis could be white-coated tongue, thermal and chemical burns, lichenoid reactions, leukoplakia, secondary syphilis, and diphtheria.
Atrophic (erythematous) candidiasis
Clinically, atrophic candidiasis manifests as a painful localized erythematous area. The chronic form usually involves the dorsum of the tongue, palate, and occasionally the buccal mucosa. Red lesions are seen on the dorsum of the tongue typically presenting as depapillated areas. Other forms of atrophic candidiasis includes denture stomatitis , angular cheilitis, and median rhomboid glossitis ( Fig. 4 ).
Denture stomatitis, commonly known as “chronic atrophic candidiasis” is a chronic inflammation of mucosa that involves the denture area. Here the high-frequency, low-intensity trauma of the denture compressing the palatal mucosa alters the barrier mechanism allowing for the overgrowth of candida organisms. ,
Angular cheilitis, also known as perleche, presents as erythematous or ulcerated fissures affecting the commissures of the lip unilaterally or bilaterally. This form is commonly associated with patients with chronic lip-licking habit or loss of the occlusal vertical dimension. The constant moisture and cracking at the commissure and predispose the tissue to Candida proliferation and invasion.
Median rhomboid glossitis appears as a well-demarcated, symmetric, depapillated area arising anterior to the circumvallate papillae typically located around the midline of the dorsum of the tongue. Although most cases are asymptomatic, some patients may report persistent pain, irritation, or pruritus. The lesion is believed to be a localized chronic infection by C. albicans . It is commonly seen in tobacco smokers and inhalation-steroid users.
Hyperplastic candidiasis also referred to as “candidal leukoplakia”, mainly presented in chronic form. Clinically, it will present as a well-demarcated, raised lesion that may vary from small translucent whitish areas to large opaque plaques less likely to be scraped off. Unlike the pseudomembranous type, the hyperplastic type seems to have a positive association with immunosuppression, malnutrition, smoking, and in addition, may present with varying degrees of dysplasia. The whitish lesion surface may often present localized erythematous areas.
Diagnosis of oral candidosis includes the physical examination of clinical signs and symptoms, presence of the candida organisms on the direct examination of a smear from the lesion or biopsy examination showing hyphae in the epithelium, positive culture, and serologic test. The concern of non–candida albican candida species is a concern in certain mucosal lesions, oral cancer, and elderly hospitalized patients, this is due to NCAC species to be naturally resistant to some of the common antifungal drugs.
When managing all forms of candidiasis, it is important to address any underlying factor when possible. Specific therapy for mild oral disease remains the standard nystatin oral suspension, 100,000 U/mL to be taken 5 mL (1 teaspoon) at a time as an oral swish and spit or swish and swallow 4 times daily. For chronic, candidiasis limited to the oral cavity and upper digestive tract, nystatin as noted above combined with clotrimazole troches, 10 mg five times daily, or the vaginal suppositories used as an oral troche three times daily, is very effective. In addition, the oral solution of itraconazole 10 mg/mL as 10-mL swish and swallow twice daily, is also effective, as is the oral solution of posaconazole 20 mg/mL as 5-mL swish and swallow twice daily ( Table 3 ). Regular dental evaluation is recommended as the clotrimazole troches contain sugars that may stimulate active caries, especially in xerostomic patients. Patients with dentures can also benefit from sprinkling nystatin powder into their dentures twice a day, and those with angular cheilitis may also want to apply nystatin cream to the skin 4 times a day.
|Nystatin Suspension 100,000 IU/mL||5 mL swish and spit for 14 d|
|Clotrimazole Troche 10 mg||Dissolve in 10 mL and swish and swallow BID for 14 d|
|Nystatin-Triamcinolone Acetonide 15g||Apply to corners of mouth after meals and at bedtime for 14 d|
For patients with refractory candidiasis, mucocutaneous candidiasis, women with concurrent candida vaginitis, or patients in whom compliance is a problem, a systemic antifungal therapy with ketoconazole or fluconazole 200 mg first day, followed by 100 mg daily for 2 weeks is recommended. ,
Autoimmune vesiculobullous and ulcerative diseases
Lichen planus (LP), the spectrum of pemphigus, pemphigoid, and lupus erythematosus are a gamut of autoimmune vesiculobullous and ulcerative diseases which are responsible for an onslaught of oral soft tissue lesions which affect the entire mucosa. It would behoove all practitioners to be well versed in recognizing and treating these lesions as they can prove to be difficult to differentiate. For that reason, it is imperative that the provider biopsy lesions when an autoimmune process is suspected. When selecting a site for biopsy, the target site should be a clinically involved area with an intact surface and some adjacent normal-appearing tissue.
LP is a mucocutaneous disease that manifests as a result of a delayed T cell-mediated hypersensitivity whereby the basal layer of skin and/or mucosa is attacked. This disease corporealizes as one of the 3 clinical forms which have a global prevalence of ∼0.1–2.2% and tend to present in patients older than 40 with a predilection for women. , All forms have a predilection for the buccal mucosa, tongue, and buccal surface of the attached gingiva. In order of advancing severity and symptomatology, LP has a reticular, plaque, and erosive form.
The reticular form ( Fig. 5 ) is most notably characterized by the pathognomonic Wickham’s striae which are lacy, white, interlacing lines found mostly on the characteristic sites of the posterior bilateral buccal mucosa, attached gingiva, and tongue. The aforementioned striae are usually asymptomatic; they wax and wane over a period of weeks to months while assuming a limited rather than disseminated territory of oral mucosa.