Continuing Education Activity

White lesions discovered upon routine oral examination can range from benign processes to invasive malignancies. It is prudent for the clinician to collect the patient’s complete medical history, to include any potential carcinogenic habits they may have, i.e., smoking, to formulate an appropriate differential diagnosis. The clinical examination is among the most crucial aspects of patient care, emphasizing appropriate and complete documentation of findings. This activity reviews the most found benign chronic white lesions of the oral mucosa and their etiologies and highlights the role of the healthcare team in evaluating, managing, and potentially treating patients with these described conditions.

Objectives:

• Describe the clinical presentation of common benign chronic white lesions found on the oral mucosa.
• Review the potential etiologies of the most common benign chronic white lesions found on the oral mucosa.
• Identify ways to differentiate the most common benign chronic white lesions from one another and formulate appropriate differential diagnoses.
• Summarize the appropriate treatment modalities for the most common benign chronic white lesions found on the oral mucosa.

Introduction

The discovery of a white lesion on the oral mucosa can present a variety of challenges to the practitioner, as they can range from benign to malignant processes. The most common benign chronic white lesions are pseudomembranous candidiasis, erythema migrans, morsicatio buccarum, linea alba, leukoedema, and lichen planus. White lesions can be found anywhere in the oral cavity, but the above-mentioned lesions typically present either on the dorsal aspect of the tongue or on the buccal mucosa.

Etiology

Pseudomembranous candidiasis is an opportunistic infection with the primary etiology being an overgrowth of the fungal species Candia albicans. Pseudomembranous candidiasis results from a disturbance of the normal oral microbiota, allowing Candida species to dominate.[1][2]

Erythema migrans is an inflammatory condition of unknown etiology but has been found more frequently in patients with psoriasis.[3]

Morsicatio buccarum, commonly known as “cheek biting,” can present on the buccal mucosa or the lateral surface of the tongue (morsicatio linguarum). This lesion is the result of repeated trauma from occlusion on the mucosa.[4]

Linea alba can present either unilaterally or bilaterally and is attributed to the negative pressure associated with sucking on the cheeks.

Leukoedma presents on either the buccal or labial mucosa. Its etiology is unknown but has been suggested to appear in areas of irritation.[5]

Lichen planus is a chronic inflammatory condition. This condition involves the epithelium and underlying lamina propria of the oral mucosa.[6] It is a T-cell mediated disorder of unknown etiology.[7]

Epidemiology

Pseudomembranous candidiasis can be present in any patient but is most frequently found in immunocompromised patients.[8] There is no gender predilection.[9]

Erythema migrans affect 1% to 2% of individuals, with more frequent cases in younger individuals.[3] This condition has a slightly higher predilection for females over males.[10]

Morsicatio buccarum can be present in any patient, likely patients undergoing stressful situations or with adverse habits. Amadori et al. discovered cheek biting to be present in 4.7% of a cohort of teenagers aged 13 to 18. There is no gender predilection.[11]

Linea alba can be present with any patient, especially those undergoing stressful situations. Amadori et al. identified linea alba to be present in 5.3% of a cohort of teenagers aged 13 to 18, while Gonçalves Vieira-Andrade et al. found it to be present in 33.9% of a cohort of adults, with a female predilection.[11][12]

Leukoedema’s prevalence varies in different ethnic groups, with Martin et al. discovering it in 58% of African American patients with no predilection for gender.[13][14]

Oral lichen planus affects 1 to 2% of patients, with the highest incidence seen with middle-aged females. Globally, its incidence is estimated at 0.5% to 1.5%. Oral involvement is found between 70-77% of patients with systemic lichen planus.[15]

Pathophysiology

Pseudomembranous candidiasis is a fungal infection in the oral cavity. These infections usually arise due to a shift in the oral microbiota that allows Candida species to grow uninhibited. Commonly, this lesion is identified by the thick, white plaque that can easily be wiped off, oftentimes to reveal erythematous tissue underneath.

Erythema migrans may present with immunogenetic patterns similar to psoriasis [16]. These lesions can present with inflammatory infiltrates, which can result in the loss of normal papillae on the tongue. The inflammatory response is also responsible for the erythematous color of the tissue.

Morsicatio buccarum is a result of a self-destructive habit of chewing on one's cheek or tongue in the case of morsicatio linguarum. Oftentimes, patients are unaware of these destructive habits, which often manifest subconsciously in times of stress.

Linea alba is a result of negative pressure, created by sucking in on one's cheek. This pressure will lead the tissue to stretch and appear less vascular, giving the white color to the lesion. This lesion is a result of habit, typically induced subconsciously in times of stress.

Leukoedema is an acquired condition by local irritation [5]. These lesions arise due to intracellular edema, causing the tissue to appear blanched or white. Upon being stretched, this edema resolves, giving the tissue its normal appearance. 

Oral lichen planus is a chronic inflammatory condition impacting mucosal surfaces [6]. Oral lesions can be triggered by many stimuli, from stress, infections, or cell-mediated inflammatory autoimmune responses. As the inflammatory response is against the existing cellular components, their atrophy in an inflamed environment makes their replacement by normal, healthy cells difficult. This chronic inflammatory response is the link between the potential malignant transformation of untreated oral lichen planus lesions [6].

Histopathology

Pseudomembranous candidiasis presents histologically with an inflammatory cell infiltrate, with irregular acanthotic changes in the epidermis. As this lesion is the result of a fungal infection, hyphae of Candida may be present in a Gomori methenamine silver (GMS) stain.

Erythema migrans has very characteristic findings, with a thickened spinous layer, swollen papillae, and a strong inflammatory infiltrate of T-lymphocytes, macrophages, and neutrophils - mimicking that of psoriasis [16]. 

Morsicatio buccarum presents histologically as normal tissue with a shredded appearance towards the outermost epithelium. Hyperkeratosis may be noted as a response to trauma. No evidence of dysplasia is noted.

Linea alba presents histologically as hyperkeratotic tissue and a potentially reduced granular layer [17]. No evidence of dysplasia is noted.

Leukoedema presents histologically with hyperkeratotic epithelium with irregular rete pegs [5]. No evidence of malignancy is noted. Intracellular edema is noted throughout the histological specimen. 

Oral lichen planus presents histologically with parakeratinized stratified squamous epithelium. Direct immunofluorescence reveals the distinctive linear fluorescence along the basement membrane and clefting of the epithelium-connective tissue junction [18].

History and Physical

Clinical photos of all lesions are present at the end of this activity.

Pseudomembranous candidiasis presents as either white or erythematous. The white presentation, commonly known as “thrush,” will present with thick, white, patchy lesions throughout the mouth, most often on the tongue and buccal mucosa.[19] These plaque-like deposits can be easily rubbed off with gauze or tactile pressure. Once removed, an erythematous surface is seen, which is the secondary presentation of this condition. These lesions may be symptomatic, with patients describing a burning sensation of the area.

Erythema migrans presents as annular transient patches that are white and/or red in color on the tongue, with alternating textures – either raised or smooth. The lesions are typically located on the dorsal or lateral aspect of the tongue and will change positions and sizes over time.[3]

Morsicatio buccarum presents as shredded oral mucosa, either on the cheek or tongue (linguarum).[20] This line of disrupted tissue is typically concurrent with the plane of occlusion.

Linea alba presents unilaterally or bilaterally, depending on the patient’s habits, as a white line on the buccal mucosa.

Leukoedema presents as a grayish-white lesion on the oral mucosa.[14] This lesion is generally believed to be a variation of normal anatomy instead of being associated with the disease.[21] Tissues associated with this lesion present in an edematous state and will resolve with stretching or manipulating the tissue.[5]

Lichen planus typically presents as white striations, known as Wickham’s striae, on the buccal mucosa or tongue but can also appear as white papules, plaques, or erosions.[18] Oral lichenoid reactions, which clinically resemble lichen planus, can result from a wide range of common medications, including but not limited to non-steroidal anti-inflammatory drugs and antihypertensive agents.[22][23]

Evaluation

Pseudomembranous candidiasis is likely easily managed from a clinical diagnosis; however, since this condition can occur in patients with underlying systemic diseases, a complete medical history should be gathered to rule out any underlying cause.

Erythema migrans is potentially an oral manifestation of psoriasis but is also seen as a variant of normal.[3] Patients observed with this condition should be evaluated by their primary care provider to rule out potential systemic involvement. Patients should also be evaluated for potential Lyme disease exposure, as this condition can be present 90% of the time.[24]

Morsicatio buccarum typically results from parafunctional habits, neurological dysfunction, or patients undergoing stressful situations, such as adolescence or pregnancy.[25]

Linea alba results from the negative pressure of sucking one’s cheeks. Discussion with the patient regarding their potential habits is prudent to the development of a differential diagnosis.

Leukoedema is an idiopathic condition, possibly associated with local irritation. Leukoedema has been found to be associated with smoking and diabetes mellitus.[21] Stretching the oral tissue surrounding the lesion can aid in the diagnosis, as leukoedema will resolve upon introducing tension.

Lichen planus is evaluated by histological examination and direct immunofluorescence (DIF) to obtain a definitive diagnosis. The histological findings consist of hyperkeratosis of the epithelium, obliteration of basal epithelial cells, loss of spinous epithelial cells, saw-tooth appearance to epithelial ridges, with a band of lymphocytic infiltrate within the lamina propria.[26] A negative DIF screening is used to differentiate oral lichen planus from other vesiculobullous lesions, such as pemphigus or pemphigoid.

Treatment / Management

Pseudomembranous candidiasis is treatable using the clinician’s antifungal medication of choice, likely fluconazole or clotrimazole.[27] It is paramount to emphasize to patients the need for regular oral hygiene, especially if the patient has a removable dental prosthesis, such as a denture, to prevent or limit recurrence.[2]

Erythema migrans has no specific treatment modalities recommended.[28] Since erythema migrans may be associated with underlying systemic disease, proper referral to the primary care provider to evaluate these conditions is indicated.

Morsicatio buccarum has no specific treatment modalities, though habit-changing and/or stress-reduction protocol can be beneficial to patients who present with cheek or tongue biting.

Linea alba has no specific treatment modalities; however, habit-changing protocol or stress-reduction can benefit patients who present with this condition. 

Leukoedema is thought to be a variation of normal, resulting in no recommended treatment. Though it has been associated with smoking and diabetes mellitus, managing these underlying habits and conditions may aid in the lesion’s resolution.

Lichen planus is predominately treated with topical corticosteroids.[29] If the lesion is a lichenoid drug reaction, the lesion should resolve with the termination of the offending medication. Though corticosteroids are the mainstay treatment, hydroxychloroquine, calcineurin inhibitors, and retinoids can be utilized in recalcitrant cases.[30]

Differential Diagnosis

Pseudomembranous Candidiasis

• Oral hairy leukoplakia
• Nutritional deficiencies
• Lichen planus
• Trauma

Erythema Migrans

• Evaluation for psoriasis
• Lichen planus
• Fissured tongue
• Herpes simplex infection
• Candidiasis

Morsicatio Buccarum

• Oral lichen planus
• Candidiasis
• Leukoplakia
• Chemical burn
• White sponge nevus

Linea Alba

• Leukoedema
• Morsicatio buccarum
• Lichen planus

Leukoedema

• Leukoplakia
• Hyperkeratosis
• White sponge nevus
• Morsicatio buccarum

Lichen Planus

• Pemphigus
• Pemphigoid
• Leukoedema
• Leukoplakia

Prognosis

Pseudomembranous candidiasis overall has a good prognosis depending on patient compliance with the prescribed antifungal regimen and oral hygiene. It is rarely a condition that is life-threatening.[31]

The prognosis for erythema migrans is excellent and can be managed palliatively.[32]

Morsicatio buccarum has a good prognosis, granted the patient undergoes stress-reduction protocol or is made aware of their habits.

Linea alba has a good prognosis, granted the patient undergoes stress-reduction protocol or is made aware of their habits.

Leukoedema has an excellent prognosis, as it is a variation of normal.

Lichen planus has a good prognosis, though oral lesions may last for several years and heal with scarring. Oral lichen planus is considered potentially premalignant.[33]

Complications

Pseudomembranous candidiasis rarely presents with complications, though patients may complain of discomfort such as a burning sensation.[31]

Erythema migrans typically presents with few if any complications.[10]

Morsicatio buccarum may be difficult to manage, as it is completely patient-dependent. The clinician can aid by introducing stress-reduction protocols during visits to alleviate any patient anxiety.[34]

Linea alba may be difficult to manage or to fully resolve, as it is patient-dependent. This lesion does not present any complications, but it may be beneficial to the patient to undergo stress-reduction protocols.

Leukoedema itself does not present with any complications; however, since it can be a manifestation of local irritation, patients should be counseled on adverse habits or smoking cessation.

Lichen planus does present a risk of malignancy. Aghbari et al. discovered 1.1% of patients in a cohort of almost 20,000 patients developed squamous cell carcinoma from lichen planus.[35] Patients should be monitored and counseled on the risk for potential transformation to squamous cell carcinoma even though the risk is low. Clinical documentation, histological evaluation, and DIF are paramount for definitive diagnosis and therapy.

Deterrence and Patient Education

Patients presenting with pseudomembranous candidiasis should be encouraged to practice optimal oral hygiene, especially if they have an underlying systemic disease, such as diabetes, or are immunocompromised. Oral hygiene becomes even more paramount if the patient has a removable dental prosthesis.

Erythema migrans is a harmless inflammatory process, with no treatment necessary if there is no underlying condition.[36] Documentation of this lesion is recommended.

Morsicatio buccarum should be brought to the patient’s attention, as they may be unaware of the habit. Patients should be encouraged not to self-mutilate their tissue and to attempt to mitigate their habit. The lesion should be documented.

Linea alba should be brought to the patient’s attention, as they may be unaware they are sucking on their cheeks. Patients should be counseled on ways to reduce stress, and the lesion should be documented.

Leukoedema is a variation of normal but should be brought to the patient’s attention.

Lichen planus should be brought to the patient’s attention, as there is a risk for systemic involvement or possible impacts on the patient’s quality of life. It is the clinician’s responsibility to refer the patient to the appropriate specialist for evaluation.

Pearls and Other Issues

As this list is non-exhaustive, complete patient history and appropriate documentation are prudent for appropriate diagnosis and therapeutic intervention for any white lesion. Any lesion that does not correspond with the patient's medical history or adverse habits should be referred immediately for further evaluation.

Enhancing Healthcare Team Outcomes

Even for the trained dental clinician, the discovery of a white lesion on the oral mucosa can be intimidating and a diagnostic challenge. If a white lesion is discovered during routine care by a provider, gathering a complete medical history is a critical first step. All lesions noted should be appropriately documented by the discovering physician. If the lesion can be attributed to an obvious source, subsequent follow-up is appropriate; however, if there is any doubt regarding the lesion's etiology or presentation, appropriate referral to a dental provider is warranted. It is important to include the patient's medical history and any pertinent clinical information to provide the dental provider as much information as possible to draw appropriate conclusions, and therefore an appropriate diagnosis and treatment regimen.