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Common Oral Lesions in the Dental Setting

Strategies for a differential diagnoses of immune-related oral mucosal diseases.

This course was published in the April/May 2024 issue and expires May 2027. The author has no commercial conflicts of interest to disclose. This 2 credit hour self-study activity is electronically mediated.

AGD Subject Code: 730

Educational ­Objectives

After reading this course, the participant should be able to:

  1. Discuss the etiologics and presentations of common oral lesions.
  2. Define differential diagnosis.
  3. Develop effective management strategies for patients presenting with these lesions.

Multiple ulcerations, erosions, erythema, or desquamative lesions that present as chronic or recurring lesions can prove to be a diagnostic challenge for clinicians. A comprehensive history and physical examination are key in creating a reasonable differential diagnosis. Although similar in clinical presentation, recurrent aphthous stomatitis, oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris are distinct conditions that require proper and timely diagnosis and management. Each condition has a unique etiology, pathogenesis, clinical presentation, diagnostic work-up, treatment, prognosis, and patient considerations. Oral healthcare providers should be knowledgeable about these diseases in order to optimize patient health outcomes.

Recurrent Aphthous Stomatitis

Recurrent aphthous stomatitis is an inflammatory condition defined by recurring ulcers in the oral cavity. These lesions appear as pseudomembranous ulcers with an erythematous border.1,2 They may be characterized as major, minor, or herpetiform type (Figure 1). The condition affects approximately 20% of the general population.3 The etiology is multifactorial in nature with genetic, hematologic, and immunologic factors often contributing. A genetic component is the most documented causative factor. However, certain triggers, such as hormonal changes or stress, may also contribute to the development of lesions. Trauma or contact allergies may incite ulcer development.1–3

Aphthous ulcers can be seen in a number of systemic conditions such as nutritional deficiencies, most commonly iron, folate, or vitamin B12. They may also present in gastrointestinal conditions, such as celiac or Crohn disease, and in children as a part of a condition known as periodic fever, aphthous stomatitis, pharyngitis, and adenopathy (or PFAPA) syndrome.4 Therefore, recurrent aphthous stomatitis is considered a diagnosis of exclusion with no other known cause.1

Symptoms of recurrent aphthous stomatitis may include prodromal burning prior to the onset of the ulcers. Clinically, the ulcers tend to be round and shallow, similar to those seen in herpes simplex virus, which is why many practitioners mistake aphthous ulcers for herpetic ones.2 However, the location of the lesion and potential symptoms can help differentiate the condition.

Aphthous ulcers typically occur on the buccal or labial, nonkeratinized mucosa and, rarely, on heavily keratinized gingiva or palatal tissue. Aphthous ulcers do not typically cause erosions resulting from ruptured vesicles, which can help differentiate it from other vesicular conditions such as pemphigoid or pemphigus.1–3

Diagnosis is primarily completed through history and physical examination. Rarely, laboratory testing for hematologic abnormalities, such as deficiencies in iron, vitamin B12, and folate, or biopsy is conducted to rule out granulomatous conditions. Cases with severe minor ulcers or major aphthae may also require further testing.1,3

Treatment for mild cases involves a protective emollient or topical anesthetic agents such as lidocaine or benzocaine. For severe cases, topical steroids (eg, fluocinonide, clobetasol) may be helpful in decreasing the duration of the ulcer. No topical treatment, however, is known to reduce the frequency of ulcer development. Finding the underlying cause may be helpful in these situations. In severe cases or those recalcitrant to topical treatment, systemic medications, such as colchicine, pentoxifylline, dapsone, or steroids, may be considered.1–3

Oral Lichen Planus and Oral Lichenoid Lesions

Oral lichen planus is a T-cell mediated, chronic inflammatory condition with a poorly understood etiology that is likely multifactorial in nature.5 The condition appears to target epithelial cells, mainly in the basal layer. Stress and certain foods, such as mint, cinnamon, and tomatoes, may trigger the inflammation. The condition most commonly affects women in their 50s to 60s and is considered an oral potentially malignant disorder, with a relative risk of approximately 1%.6


Oral lichen planus has several subtypes, including reticular, atrophic, plaque-like, erosive, and bullous. The condition may appear as ulcerations, erythema, or desquamation, with Wickham striae (lacelike pattern) being a hallmark of the condition (Figure 2A and B).5 Symptoms may include soreness and burning, though many patients are asymptomatic. Cutaneous lesions may occur and are typically polygonal, purple, pruritic papules. Scratching may provide symptomatic relief; however, trauma can aggravate the condition, leading to more lesions (ie, the Koebner phenomenon). Genital involvement is seen in approximately a quarter of women with oral lichen planus.5

The clinical impression of lichen planus is easier to discern when the condition presents as a reticular or papular appearance. Differential diagnoses include oral lichenoid mucositis; oral lichenoid lesions seen in oral lichenoid contact reactions to dental materials, such as amalgam; or oral lichenoid drug eruptions to common medications (eg, nonsteroidal anti-inflammatory drugs). Lichenoid-type lesions also occur in patients with chronic graft-vs-host disease and systemic and discoid lupus erythematosus; therefore, a thorough medical history intake is essential.5 Note that lichenoid mucositis and lichenoid-type lesions are separate entities from lichen planus.

Desquamative gingivitis, ulcerations, or erythema in erosive oral lichen planus may mirror autoimmune conditions such as mucous membrane pemphigoid or pemphigus vulgaris. Therefore, diagnosis should be established through incisional biopsy with both routine histology and direct immunofluorescence (DIF) studies to rule out such autoimmune conditions.


Histopathologic analysis with hematoxylin-eosin (H&E) staining often reveals atrophic epithelium, saw-toothing of the rete ridges, hydropic degeneration of the basal cell layer with cytoid bodies, and a band-like inflammatory infiltrate, consisting of predominantly T-lymphocytes. (Figure 3A and B). DIF may reveal linear pattern of fibrinogen along the basement membrane.5,6

Management may involve avoidance of triggering foods or products, such as mint, cinnamon, spicy, citrus, or acidic foods. First-line treatment primarily includes topical corticosteroids (eg, fluocinonide or clobetasol) or in severe cases, systemic steroids (eg, prednisone). In cases recalcitrant to steroid therapy, second-line treatment includes topical calcineurin inhibitors (eg, tacro­limus).5,7

Mucous Membrane Pemphigoid

A rare, autoimmune vesiculobullous disease, mucous membrane pemphigoid is part of the subepithelial bullous diseases, which also includes bullous pemphigoid, linear IgA disease, and epidermolysis bullosa acquisita.5 Mucous membrane pemphigoid typically affects white women, with 55 to 65 being the average age of onset. Autoantibodies are targeted against structural proteins in the basement membrane, including BP180 and BP230, resulting in subepithelial blistering.8


Clinically, mucous membrane pemphigoid most commonly manifests as desquamative gingivitis, though lesions may be seen in the palate, buccal mucosa, and tongue (Figure 4). In addition to the oral cavity, which is affected in approximately 85% of patients with mucous membrane pemphigoid, the disease also impacts the conjunctiva, upper digestive tract, and anogenital tissues, with occasional cutaneous involvement.8,9

The clinical differential diagnosis can include other erosive conditions such as oral lichen planus or pemphigus vulgaris. Diagnosis is achieved through incisional biopsy for routine H&E staining and DIF. Histopathologic analysis reveals subepithelial


split with a mild, chronic inflammatory infiltrate (Figure 5A and B). Direct DIF staining reveals linear accumulation of IgG, IgA, or C3 along the basement membrane zone.5,8,9

Treatment typically occurs in a multidisciplinary fashion, with an emphasis on oral hygiene practices and topical medication use. Topical corticosteroids are primarily used in the oral cavity for mild disease. Moderate or severe disease may require concurrent topical and systemic treatment. Medicine trays with topical steroid use can be helpful for patients who present with predominantly gingival involvement.

Systemic treatment may involve corticosteroids in conjunction with an immunosuppressant such as cyclophosphamide or azathioprine. Dapsone and tetracycline may also be used to manage lesions. Recalcitrant lesions can be treated with rituximab or intravenous immunoglobulin. Co-management may be seen with dermatologists. As the conjunctiva may be affected if left untreated, resulting in symblepharon or even blindness, a referral to an ophthalmologist is critical as soon as the diagnosis is confirmed.8,9

Pemphigus Vulgaris

Pemphigus is a group of autoimmune, blistering conditions, characterized by epithelial acantholysis and intraepithelial clefting.10 Pemphigus vulgaris is the most common subtype, accounting for more than 80% of cases.10 Other types of pemphigus include vegetans, foliaceus, erythematosus, paraneoplastic, drug-induced, and IgA.10 Pemphigus vulgaris is a chronic, mucocutaneous, autoimmune vesiculobullous disease in which autoantibodies are directed against structural components of the desmosome, which are cell-cell adhesion molecules, specifically Desmoglein (Dsg) 1 and 3.5,10,11

Pemphigus vulgaris tends to affect women aged 50 to 60.5,10,11 Although the etiology is poorly understood, several genetic and environmental factors have been identified. Those of Ashkenazi Jewish descent are at increased risk and environmental factors, such as viruses, dietary factors, and psychological stresses, may play a role in the disease.11 Medications may also trigger pemphigus vulgaris-like drug induced reactions, including -thiol and -phenol drugs, NSAIDs, and calcium channel blockers.


The pathophysiology of the condition is caused by loss of cell-cell adhesion in the epithelial keratinocytes, a phenomenon called acantholysis. Clinical signs include vesicles that easily rupture (Figure 6A and B). Oral lesions typically precede cutaneous lesions. Approximately 80% to 90% of patients with pemphigus vulgaris will develop oral lesions at some point.10,11 A positive Nikolsky sign, the development of a lesion after application of manual pressure in an area, is characteristic of the condition. In severe cases, pemphigus vulgaris may also impact other mucosal tissues, such as conjunctival, nasopharyngeal, laryngeal, esophageal, and anogenital tissue.

The gold standard for diagnosis is determined through incisional biopsy of the skin or oral tissue for both routine H&E and DIF staining. Histopathologic analysis reveals acantholysis with suprabasal, or intraepithelial clefting (Figure 7A and B). DIF staining reveals intercellular binding of IgG, C3, or both, at the intracellular junctions of keratinocytes within the epithelium.11,12

Treatment typically involves systemic medications, often involving a combination of corticosteroids with an immunosuppressant such as rituximab. Co-management with dermatology is commonly seen. Indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA) may be helpful in monitoring disease activity/progression in patients undergoing treatment. IIF is used to quantify circulating levels of anti-Dsg1 and anti-Dsg3 in patient serum. ELISA is a highly sensitive tool to detect autoantibodies against both Dsg1 and 3. If left untreated, pemphigus vulgaris can result in sepsis, impaired thermoregulation, fluid or electrolyte imbalance, and cardiac and renal failure.11,12

Clinical Considerations

Oral health professionals play a critical role in the recognition, diagnosis, and management of chronic mucosal diseases. Special considerations should be implemented when treating patients with such conditions.

In patients who present with aphthous ulcers, the dentist must be aware of the underlying cause. Dentists may need to work collaboratively with other clinicians, such as gastroenterologists, rheumatologists, and hematologists, to ensure that the ulcers or underlying conditions are managed appropriately. When providing dental care, oral health professionals should be mindful of reducing trauma to an area with an existing ulcer. Recurrent trauma can delay healing of the ulcer.

In patients with lichenoid lesions, oral health professionals should determine if the lesion is a contact reaction, drug eruption, oral lichenoid mucositis, or oral lichen planus. Oral lichenoid contact reactions may require a deeper look into common dental materials such as gold or amalgam. Drug eruptions require proper history taking to determine temporal correlation with medications such as antihypertensives or anti-inflammatories. Patients with lichen planus should be advised to avoid common triggers, such as but not limited to mint and cinnamon. During dental appointments, using topical anesthetics or prophy paste without these flavorings may be prudent. Patients may be advised to eliminate mint in oral hygiene products, including toothpastes, mouthrinses, and floss. Some patients may benefit from a toothpaste without sodium lauryl sulfate and mouthrinses without alcohol to reduce symptoms.

In cases of mucous membrane pemphigoid and pemphigus vulgaris, patients should focus on thorough oral hygiene practices. Many patients also undergo more routine prophylaxis every 3 to 4 months to reduce the bacterial component of inflammation, given the most commonly affected intraoral site in mucous membrane pemphigoid is the gingiva. Avoiding triggering flavors, such as mint or cinnamon, can also help reduce symptoms in some patients. Atraumatic treatment of tissue can also reduce risk of new blisters, ulcers, or other manifestations of the condition. Referral to necessary specialists is also recommended, which may include dermatologists or ophthalmologists.13


Immune-mediated and autoimmune oral mucosal diseases can present as diagnostic and management challenges in the clinic. The conditions described in this article can all present in various forms of erythema, ulceration, and even pain to the patient. However, each also has its own unique characteristics that are important for clinicians to identify. Early and accurate diagnosis and management can prevent long-term complications and improve the overall health of the patient. Oral healthcare providers should be equipped to understand the distinct factors of chronic oral mucosal diseases in order to manage their patients accordingly.


The author would like to thank Faizan Alawi, DDS, of the University of Pennsylvania, for supplying the histopathology images for this article.


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  7. Sun SL, Liu JJ, Zhong B, et al. Topical calcineurin inhibitors in the treatment of oral lichen planus: a systematic review and meta-analysis. Br J Dermatol. 2019;181:1166-1176.
  8. Setterfield J, Carey B. Mucous membrane pemphigoid and oral blistering diseases. Clin Exp Dermatol. 2019;44:732-739.
  9. Alrashdan MS, Kamaguchi M. Management of mucous membrane pemphigoid: A literature review and update. Eur J Dermatol. 2022;32:312-321.
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From Decisions in Dentistry. April/May 2024; 10(3):32-35

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