These lesions must be differentiated from melanosis, which is extremely common in individuals with dark skin and generally appears in a symmetric pattern. Also in the differential are oral melanotic macules. These are darkly pigmented benign macules that occur on the lips and on the oral mucosa [17]. These lesions are typically symmetric with sharp borders, present in adulthood, and are stable.

Surgery is the first choice of therapy for mucosal melanomas of the head and neck. Whenever possible the lesion should be resected with negative margins. Radiation therapy may be used to achieve local control if the lesion cannot be resected with negative margins. (See "Initial surgical management of melanoma of the skin and unusual sites".)

Granular cell tumor — The granular cell tumor is a benign neoplasm of neural origin composed of cells with granular cytoplasm. Most often, they present as solitary nodules affecting the dorsum of the tongue (picture 5), but may also occur in the skin, breasts, and internal organs [18]. Histologically, granular cell tumors are characterized by sheets or cords of large polygonal cells with small, round, central nuclei and an eosinophilic, coarse, and granular cytoplasm (picture 6). Occasionally, larger eosinophilic granules surrounded by a clear halo called pustulo-ovoid bodies of Milian can be seen. Treatment is surgical excision.

Amalgam tattoos — Amalgam tattoos are blue-black macules seen in the adjacent gingival margin or proximal buccal mucosa near amalgam dental fillings (picture 7). They are caused by inadvertent placement of dental silver amalgam restorative material into the oral soft tissues. The most common site for amalgam tattoos is the mandibular arch [19]. Their appearance may mimic oral melanomas. Visualization of the amalgam dental filling is the key to making the correct diagnosis.

Fordyce spots — Fordyce spots are benign neoplasms of sebaceous gland etiology. They present as isolated to scattered, white to yellow, 1 to 2 mm discrete papules, particularly prominent on the vermilion/buccal mucosal border (picture 8A-B).

Mucoceles — Mucoceles are fluid filled cavities with mucous glands lining the epithelium. They typically are seen after mild oral trauma as a result of disruption of the salivary gland duct, most frequently of the lower lip (as a result of biting of the lip), but they may also present on the labia. Seen most frequently in patients younger than age 20, mucoceles are variable in size, and may have a gelatinous fluid within that presents clinically as pinkish/blue soft papules or nodules (picture 9A-B).

Spontaneous rupture can result in complete resolution [20]. Removal with cryotherapy or excision of the entire cyst can also be performed if the lesions are symptomatic [21]. CO2 laser vaporization has also shown good results with a low rate of recurrence, and is an option for clinicians experienced in this modality [22]. Aspiration alone may initially relieve symptoms, but is rarely indicated except to aid in diagnosis or for short-term relief of irritation, as recurrence is common.

Torus palatinus — Torus palatinus is an exostosis located on the midline of the hard palate. It presents as a bony hard, nodular, lobular, or spindle-shaped mass covered with normal mucosa (picture 10) [23-25]. Torus palatinus is common, with a prevalence of approximately 20 to 30 percent in the general population.

The lesion appears during childhood, enlarges slowly over many years, and is asymptomatic. Torus palatinus is typically an incidental finding during routine physical examination. The diagnosis is clinical. However, referral for biopsy and imaging studies may be warranted if the mass is rapidly growing (over weeks or months), is not located on the midline, or has an atypical appearance.

In most cases, torus palatinus does not require treatment. Surgical removal may be an option if patients develop symptoms or the lesion precludes proper fitting of dentures or prosthetic devices.

INFECTIONS

Candidiasis — Oropharyngeal candidiasis or thrush is a common local infection seen in young infants, older adults who wear dentures, diabetics, patients treated with antibiotics, chemotherapy, or radiation therapy, and those with cellular immune deficiency states, such as the acquired immunodeficiency syndrome (AIDS). Patients receiving inhaled glucocorticoids for asthma or rhinitis are also subject to this complication.

Thrush can manifest in several ways. The pseudomembranous form is the most common and appears as white plaques on the buccal mucosa, palate, tongue, or oropharynx (picture 11A-C). The atrophic form, which is often found under dentures, is characterized by erythema without plaques (picture 11D) [26]. Candidiasis may also present with a beefy red tongue and associated soreness. In addition, Candida species can cause angular cheilitis or perlèche, a painful fissuring at the corners of the mouth. (See "Clinical manifestations of oropharyngeal and esophageal candidiasis".)

Recurrent, recalcitrant, or extensive disease warrants immune status evaluation and HIV testing. The diagnosis is confirmed by obtaining a KOH prep, scraping the white patches or erosive areas of the mucosa; budding yeasts with or without pseudohyphae are seen.

Most studies of therapies for oral candidiasis have been performed in patients with HIV or malignancy. Topical therapy is usually effective although relapses in immunosuppressed patients are common. Nystatin suspension (400,000 to 600,000 units four times per day), nystatin troche (200,000 to 400,000 units four to five times per day), or clotrimazole troche (10 mg troche dissolved five times per day) for 7 to 14 days can be used. Nystatin suspension is the least expensive option; clotrimazole troches are probably more palatable and possibly more effective.

Options for patients with refractory disease or inability to tolerate topical therapy are discussed in detail elsewhere. (See "Treatment of oropharyngeal and esophageal candidiasis".)

Older adult patients with dentures should be reminded to clean their dentures carefully and frequently to reduce the likelihood of developing candidiasis [27].

Herpes simplex virus — Herpes simplex virus type 1 (HSV-1) can infect multiple sites of the body, including the oral cavity and perioral area. Herpetic gingivostomatitis is the most common clinical manifestation of primary herpes simplex infection in childhood. The primary infection is often asymptomatic; when symptoms occur they typically include the sudden onset of multiple intraoral vesicular lesions and erosions bordered by an inflammatory, erythematous base (picture 12A-B). (See "Clinical manifestations and diagnosis of herpes simplex virus type 1 infection".)

HSV is able to enter, undergo latency, and survive in neural ganglia, thereby preventing elimination of the virus by immune responses. Thus, recurrent infection is common. Most patients (>85 percent) develop prodromal symptoms (eg, pain, burning, tingling) about 24 hours before the appearance of painful lesions at the lip borders [28]. Precipitating factors include exposure to sunlight, trauma, and emotional stress [29]. Because primary infection with HSV-1 is often asymptomatic, a recurrence may be the first manifestation of infection.

Primary episodes of oral HSV tend to involve the buccal mucosa, while recurrent disease is usually confined to the cutaneous surface or keratinized areas [30]. Young children may have associated fever, lymphadenopathy, drooling, and decreased oral intake. In one study, 3 out of 36 children with herpes gingivostomatitis became dehydrated, requiring hospitalization for intravenous rehydration [31]. Immunosuppressed individuals can have extensive and persistent intraoral ulcerations due to herpetic infection.

The diagnosis is confirmed by identifying multinucleated giant cells on a Tzanck smear (these are also seen with varicella zoster virus infection), direct immunofluorescence smear, or by viral culture. The alcohol-wiped vesicle should be gently "unroofed" with a sterile needle; the vesicular fluid can be removed with a sterile cotton swab for viral culture and cells from the base of the lesion may be scraped off gently and placed onto a slide for the Tzanck prep. Slides prepared from scrapings may be examined for herpes antigens via immunofluorescence microscopy. This technique has been made possible by the generation of HSV type-specific monoclonal antibodies that permit identification and typing of isolates in tissue samples. (See "Dermatologic procedures", section on 'Tzanck smear' and "Clinical manifestations and diagnosis of herpes simplex virus type 1 infection", section on 'Immunofluorescence staining'.)

The standard treatment regimen involves systemic antiviral therapy (eg, acyclovir), pain, and fluid management (see "Treatment of herpes simplex virus type 1 infection in immunocompetent patients"). For comfort care, consider suggesting patients use ice, popsicles, or rinse and expectorate every two hours with diphenhydramine 12.5/5 cc mixed with magnesia-alumina 1:1.

Most immunocompetent individuals with recurrent herpes labialis do not require treatment other than the occasional use of local analgesics. Attempts to treat recurrent episodes with both topical and oral acyclovir have largely been unsuccessful [32,33]. This is mostly due to the difficulty of determining the earliest time of recurrence, since antiviral medication works only during the period of viral replication and thus has little effect if begun after the appearance of lesions. Nevertheless, some patients with an identifiable prodrome may benefit from treatment. In one randomized trial, a single application of acyclovir 50 mg buccal tablets at the first occurrence of prodromal symptoms was more effective than placebo in reducing the rate of recurrence (64 percent versus 74 percent) and the time to recurrence (205 days versus 165 days) [34].

Chronic suppression has proven helpful in preventing HSV recrudescence in individuals with frequently recurrent lesions. (See "Treatment of herpes simplex virus type 1 infection in immunocompetent patients".)

Varicella-zoster virus — Vesicles and erosions are commonly seen in patients with varicella (chickenpox) (picture 13A-B). In patients with herpes zoster, grouped vesicles or erosions may be seen unilaterally on the hard palate (picture 13C). Other oral areas that may be involved include the buccal mucosa, tongue, and gingiva. (See "Epidemiology and pathogenesis of varicella-zoster virus infection: Herpes zoster".)

Coxsackie virus — Infections with coxsackie virus produce both intraoral and palmar/plantar lesions. Coxsackie virus infections most commonly occur in children as oval shaped pale papules with a rim of erythema on the palms and soles, and small aphthae intraorally, otherwise known as hand, foot, and mouth disease (picture 14A-E). Fever is common along with sore throat and a malaise that often precedes the onset of lesions. Lesions tend to spare the lips and gingiva, in contrast to HSV. Treatment is typically supportive. (See "Clinical manifestations and diagnosis of enterovirus and parechovirus infections".)

HIV infection — Painful mucocutaneous ulceration is one of the most distinctive manifestations of primary HIV-1 infection. Shallow, sharply demarcated ulcers may be found on the oral mucosa, anus, penis, or esophagus [35]. These lesions may reflect mucocutaneous disease associated with primary HIV infection or coincident sexually transmitted infections, such as herpes simplex virus, syphilis, or chancroid [36,37]. (See "Acute and early HIV infection: Pathogenesis and epidemiology".)

Oral manifestations of established HIV disease are most commonly due to candidal infections, but many other opportunistic pathogens also can cause oral ulcerations. Antiretroviral treatment has decreased the frequency of HIV-associated oral lesions [38].

●Oral cryptococcosis and histoplasmosis are non-characteristic and the diagnosis must be made on biopsy.

●Mucormycosis (zygomycosis), aspergillosis, and penicilliosis are less common.

●Bacterial ulcerations are most commonly caused by bacillary epithelioid angiomatosis, and biopsy is needed to rule out Kaposi's sarcoma. (See "Epidemiology and clinical manifestations of Bartonella infections in HIV-infected patients".)

●Oral ulcerations have been reported secondary to syphilis, mycobacterium avium intracellulare, Helicobacter pylori, amoeba, and leishmaniasis.

●Viral induced ulcerations may erupt due to infection by HSV, cytomegalovirus (CMV), or herpes zoster. Patients with HIV infection tend to have more extensive HSV, while oral ulcers due to CMV are rare. (See "Clinical manifestations and diagnosis of herpes simplex virus type 1 infection".)

●Ulceration in oral neoplasia is seen with Kaposi's sarcoma and non-Hodgkin lymphoma. Involvement of the oral cavity occurs in approximately one-third of patients with Kaposi's sarcoma; the intraoral site most commonly affected is the palate followed by the gingiva [39]. (See "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis".)

●Drug reactions (eg, foscarnet, interferon, dideoxycytidine) may cause oral ulcerations, agranulocytosis, and toxic epidermal necrolysis in rare cases.

●Recurrent aphthous ulcers occur in 0.6 to 13.6 percent of patients with HIV infection, the vast majority of whom will have CD4 cell counts below 100 cells per mm3 [40]. Healing of oral ulcers has been reported with antiretroviral therapy [41]. Treatment of aphthous ulcers in HIV disease includes topical antibiotics, glucocorticoids, or analgesics, and oral thalidomide. The efficacy of topical treatments for oral aphthous ulcers in patients with HIV infection has not been evaluated in randomized trials [42]. In two small randomized trials, oral thalidomide, at the dose of 200 mg/day for four to eight weeks, was more effective than placebo in inducing healing of RAS in HIV-infected patients [43,44].

 

Syphilis — Mucosal involvement may occur with syphilis as split, fissured papules of the oral commissures or oral erosions (picture 15A-C). Look for the more classic papulosquamous eruption involving the palms and soles and condyloma lata involving the anal region. Multiple spirochetes are found in the lesions. (See "Pathogenesis, clinical manifestations, and treatment of early syphilis".)

APHTHOUS ULCERATIONS

Recurrent aphthous stomatitis — Aphthae (also called canker sores) are painful oral lesions that appear as localized, shallow, round to oval ulcers with a grayish base (picture 16). Recurrent aphthous stomatitis (RAS) is the most common cause of mouth ulcers [45]. RAS may be seen in patients with celiac disease and inflammatory bowel disease and in patients with human immunodeficiency virus (HIV) infection.

Etiology and pathogenesis — The pathogenesis of RAS is not well defined. One hypothesis is that RAS results from a dysregulation in local cell-mediated immunity, with accumulation of subsets of T cells and proinflammatory cytokines [46].

Factors that may predispose to the development of RAS include familial tendency, trauma, hormonal factors, and emotional stress [47]. Vitamin and mineral deficiencies have also been implicated in the pathogenesis of recurrent oral aphthae, particularly deficiency of vitamin B12. However, in a randomized trial involving 120 patients with RAS, multivitamin supplementation did not reduce the number or duration of RAS episodes [48].

Other causes of aphthae include use of antimetabolites such as methotrexate and neutropenia of any cause. (See "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults" and "Major side effects of low-dose methotrexate" and "Overview of neutropenia in children and adolescents" and "Approach to the adult with unexplained neutropenia", section on 'Signs of an underlying disorder'.)

Clinical presentation and course — The most common presentation of RAS is the presence of round, clearly defined, small, painful ulcers that heal within 10 to 14 days without scarring [45]. More severe disease, with larger lesions (>5 mm) that can last for six weeks, is less common. Herpetiform ulcers, which present as multiple small clusters of pinpoint lesions that coalesce to form large irregular ulcers lasting 7 to 10 days, can also occur. Sodium lauryl sulfate, a toothpaste detergent, may prolong the ulcer healing time [49].

Some people have only two to four outbreaks per year, while others may have almost continuous eruptions. Aphthae occur more commonly in childhood and adolescence and become less frequent in adulthood.

Treatment — The most common treatment for aphthous ulcers includes symptomatic relief with agents such as triamcinolone acetonide in Orabase, fluocinonide gel covered by Orabase, and topical analgesics. These are applied to the ulcer two to four times daily until the ulcer is healed. Early initiation of treatment may result in more rapid healing [50].

Chemical cautery can also be used for aphthous ulcers [51]. Randomized trials with silver nitrate [52], or with sulfuric acid with sulfonated phenolics [53], suggest that cautery can lead to more rapid improvement in pain, although it does not appear to speed overall healing. Lesions can be numbed with topical lidocaine prior to chemical cautery, and patients should rinse with water for several minutes after the procedure.

Intralesional or oral glucocorticoids are indicated for recalcitrant lesions or severe disease. Colchicine, dapsone, pentoxifylline, interferon alpha, and levamisole also may have therapeutic value in severe cases of RAS [54-57].

Thalidomide has been studied in patients with severe RAS [43,44,58-60]. In a randomized trial of HIV-infected patients with RAS, treatment with thalidomide, 200 mg/day for four weeks, resulted in healing in 16 of 29 patients in the thalidomide group (55 percent) compared with 2 of 28 patients receiving placebo (7 percent) [43]. A retrospective study of 92 non-HIV infected patients with RAS (including 16 with Behçet's syndrome) reported efficacy of lower doses; at a mean initial dose of 50 mg/day, thalidomide induced complete remission in 85 percent of subjects within 14 days [60]. Recurrence is common following cessation of therapy [58]; low maintenance doses of thalidomide may reduce recurrences [59,60].

Thalidomide is teratogenic (pregnancy class X). In the United States, thalidomide can only be prescribed through a special distribution program designed to minimize the chance of fetal exposure to the drug (S.T.E.P.S. program; access at www.thalomid.com/steps_program.aspx).

Behçet's syndrome — Behçet's syndrome is a neutrophilic inflammatory disorder that presents with recurrent oral and genital ulcerations.

●Most, but not all, patients initially manifest oral aphthae that are grossly and histologically similar to common oral ulcers; however, they tend to be more extensive and often multiple (picture 17). Healing of the oral ulcerations is typically spontaneous within one to three weeks; although with recurrent lesions, many patients will have ulcers present almost constantly.

●Genital lesions occur in about 75 percent of patients with Behçet's syndrome. They are similar in appearance to the oral aphthae.

 

Recurrent oral ulcers (three times per year) are required for the diagnosis of Behçet's syndrome, in addition to two other clinical findings (recurrent genital ulcers, eye lesions, skin lesions, or a positive pathergy test [24 to 48 hours after oblique insertion of a 20 to 25 gauge needle]) (table 1) [61]. (See "Clinical manifestations and diagnosis of Behçet’s syndrome".)

The mucocutaneous manifestations of Behçet's syndrome can be treated with oral colchicine, topical anesthetics, topical or intralesional corticosteroids, or systemic glucocorticoids [62]. Thalidomide and dapsone have also been shown to be effective. (See "Treatment of Behçet’s syndrome".)

Complex aphthosis — Complex aphthosis is the term used to describe the occurrence of recurrent large oral ulcers in conjunction with genital lesions in the absence of other criteria for Behçet's syndrome [63,64]. Other syndromes associated with both oral and genital lesions are the MAGIC syndrome (mouth and genital ulcers with inflamed cartilage), FAPA (fever, aphthosis, pharyngitis, and adenitis) syndrome, and cyclic neutropenia (see "Cyclic neutropenia"). Infectious cases of oral and vulvar aphthae include Yersinia enterocolitis, tuberculous enterocolitis, and typhoid fever.

Nicorandil-induced ulceration — Nicorandil is a potassium channel activator used in the treatment of angina pectoris. Its use has been associated with the development of skin and mucosal ulcerations [65,66]. Painful oral ulcerations have been reported in 0.4 to 5 percent of patients taking nicorandil [66,67]. The mechanism by which nicorandil induces cutaneous or mucosal ulcerations is unknown. Oral ulcers can occur weeks to months after starting treatment with any dose of the drug. Lesions resolve spontaneously in a few weeks upon withdrawal of the offending drug [66,68,69].

AUTOIMMUNE DISEASES

Systemic lupus erythematosus — Mucus membrane involvement occurs in up to 50 percent of patients with systemic lupus erythematosus (SLE) [70]. Oral disease can involve the lips and oral mucosa. Discoid lip lesions, characterized as keratotic papules or plaques with pigment alteration, scale, photosensitivity, and atrophy, may be present in up to 25 percent of patients with discoid or subacute lupus erythematosus. Irregularly shaped raised white plaques, silvery white scarred lesions, areas of erythema, and punched out erosions or ulcers with surrounding erythema may appear on the soft or hard palate (picture 18). (See "Mucocutaneous manifestations of systemic lupus erythematosus".)

In contrast with the discoid lesions that tend to be painful, the oral ulcers are usually painless. There is no apparent association between the presence of such ulcers and systemic activity.

The diagnosis is based upon the histologic finding on of a lesion biopsy of hyperkeratosis, focal liquefaction degeneration of the basal layer, and a lichenoid infiltrate [71,72]. Treatment of lip lesions includes topical or intralesional glucocorticoids; antimalarials are used for oral ulcerations [73]. New oral lesions that develop on the buccal mucosa in a patient with SLE who is being treated with an antimalarial drug may represent a lichenoid drug eruption secondary to the antimalarial agent. (See "Mucocutaneous manifestations of systemic lupus erythematosus" and "Lichenoid drug eruption (drug-induced lichen planus)".)

Bullous pemphigoid — Bullous pemphigoid is an autoimmune blistering disorder. Lesions commonly occur in the flexural areas, groin, and axillae. Oral involvement consisting of intact bullae or erosions occurs in about one-third of cases but is rarely the presenting feature. Skin lesions may consist of bullae or urticarial plaques. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Bullous pemphigoid'.)

The diagnosis is made on routine and direct immunofluorescence testing of lesional and perilesional skin, respectively. Standard therapy remains oral glucocorticoids, although many other agents are also effective.

Mucous membrane pemphigoid — Mucous membrane pemphigoid includes a heterogeneous group of chronic inflammatory blistering diseases that affect oral, ocular, pharyngeal, laryngeal, genital, or anal mucosa. Oropharyngeal involvement predominates. Oral lesions include desquamative gingivitis and bullae with a tendency to scar (picture 19). Significant ocular and upper airway involvement also can occur.

The diagnosis is made on routine and direct immunofluorescence testing of lesional and perilesional skin, respectively, along with the appropriate clinical findings. Potent immunosuppressants are often necessary to control this disease. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Mucous membrane pemphigoid'.)

Epidermolysis bullosa acquisita — Epidermolysis bullosa acquisita is a rare autoimmune bullous disease presenting with blisters that are localized predominantly at sites of trauma and heal with scarring and milia. Erosions and blisters may occur in the mouth, larynx, and esophagus. (See "Epidermolysis bullosa acquisita".)

Pemphigus vulgaris — Pemphigus vulgaris is characterized by flaccid bullae that typically begin in the oropharynx and then may spread to involve the skin, with a predilection for the scalp, face, chest, axillae, and groin (picture 20). The bullae rupture easily, so that the patient often presents with only painful erosions and no intact bullae. One variant, paraneoplastic pemphigus, tends to markedly involve the oral and ocular mucosa.

The pathogenesis, clinical manifestations, diagnosis, and treatment of pemphigus vulgaris are discussed separately. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus" and "Initial management of pemphigus vulgaris and pemphigus foliaceus" and "Management of refractory pemphigus vulgaris and pemphigus foliaceus".)

Paraneoplastic pemphigus — Paraneoplastic pemphigus (PNP) is a severe paraneoplastic mucocutaneous blistering disorder most often associated with lymphoproliferative disorders [74,75]. Erosive, painful mucositis is uniformly present in patients with PNP, and in its absence, the diagnosis should not be considered. Oral involvement is most common, and patients develop a painful, erosive stomatitis that characteristically involves the tongue (picture 21A-C). Oral erosions are the initial disease manifestation in almost one-half of patients [76].

Paraneoplastic pemphigus is discussed separately. (See "Paraneoplastic pemphigus".)

ERYTHEMA MULTIFORME AND STEVENS-JOHNSON SYNDROME — Erythema multiforme and Stevens-Johnson syndrome are hypersensitivity reactions that often present with both skin lesions and mucosal involvement (picture 22A-E). Erythema multiforme is frequently related to herpes simplex infections, but also may be caused by other infections (eg, Mycoplasma pneumoniae) or medications, or may be idiopathic. Stevens-Johnson syndrome is most commonly induced by drugs. Target skin lesions are a characteristic feature of erythema multiforme; erythematous, purpuric macules and skin detachment may occur in Stevens-Johnson syndrome. (See "Pathogenesis, clinical features, and diagnosis of erythema multiforme", section on 'Clinical manifestations' and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)

Mucosal involvement is seen in more than 90 percent of patients with erythema multiforme and Stevens-Johnson syndrome [77]. When oral lesions are the primary feature, erythema and edema of the lips along with intraoral bullae may occur. The bullae often rupture, leaving painful friable raw surfaces and even hemorrhagic crusts. Pain is a prominent feature when oral lesions are present.

The management of these disorders is discussed separately. (See "Treatment of erythema multiforme" and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae".)

MISCELLANEOUS

Lichen planus — Oral mucosal involvement may occur with lichen planus as an isolated event or in conjunction with cutaneous or genital disease. The presentation of oral lichen planus may vary from lace-like white patches (Wickham striae) on the buccal mucosa to erosions on the gingival margin (picture 23A-C). Lesions are often painful and interfere with oral intake. Oral lichen planus tends to be chronic, and may increase the risk for oral cancer. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis".)

Burning mouth syndrome — Burning mouth syndrome is an uncommon disorder affecting predominantly postmenopausal women, characterized by a persistent intraoral burning sensation for which no medical or dental cause can be found [78,79]. Before making the diagnosis, it is important to exclude other mucosal disease, including xerostomia and allergic contact stomatitis. (See "Overview of craniofacial pain", section on 'Burning mouth syndrome'.)

Telangiectasias secondary to hereditary hemorrhagic telangiectasia — In patients with hereditary hemorrhagic telangiectasia, mucosal telangiectasias can occur anywhere along the gastrointestinal tract and are frequently visible on the lips, tongue, and oral mucosa (picture 24A-B) [80,81]. They generally develop by the age of 30 years and increase in number over time. Bleeding can occur but rarely requires medical intervention. (See "Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)".)

Atrophic glossitis — Atrophic glossitis is an inflammatory disorder of the tongue that leads to the atrophy of the filiform papillae. The tongue appears smooth, glossy, and erythematous (picture 25A-B). Causes of atrophic glossitis include [82-84]:

●Nutritional deficiencies (iron, vitamin B12, folic acid) (see "Diagnosis and treatment of vitamin B12 and folate deficiency")

●Dry mouth (sicca symptoms) (see "Diagnosis and classification of Sjögren's syndrome", section on 'Dry eye and mouth in older adults'and "Diagnosis and classification of Sjögren's syndrome", section on 'Epidemiology')

●Sjögren syndrome (see "Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren's syndrome" and "Clinical manifestations of Sjögren's syndrome: Exocrine gland disease")

●Oral Candida infection (see 'Candidiasis' above)

●Protein-calorie malnutrition in older adults (see "Geriatric nutrition: Nutritional issues in older adults")

●Celiac disease (see "Diagnosis of celiac disease in adults")

 

Patients with atrophic glossitis often complain of a burning sensation and increased sensitivity when eating acidic or salty foods. Treatment is directed at the underlying condition.

Fissured tongue — Fissured tongue is a benign condition of unknown etiology usually seen in adults. Deep grooves are located on the midline or evenly distributed on the tongue surface (picture 26). Fissured tongue is also seen in patients with Down syndrome or Melkersson-Rosenthal syndrome (a rare syndrome characterized by the triad of fissured tongue, facial palsy, and granulomatous cheilitis) [85,86]. (See "Down syndrome: Clinical features and diagnosis", section on 'Skin disorders' and "Bell's palsy: Pathogenesis, clinical features, and diagnosis in adults", section on 'Melkersson-Rosenthal syndrome'.)

Patients with fissured tongue are generally asymptomatic. The condition is permanent and does not require treatment unless the patient gets irritation from entrapped debris in the fissures. In such cases, brushing the affected area or using an oral irrigator may provide benefit.

Black tongue — Hyperpigmentation of the tongue and oral mucosa is commonly seen in dark-skinned individuals. Less common causes of tongue hyperpigmentation include drugs (eg, tetracyclines, linezolid, bismuth subsalicylate, antidepressants, proton pump inhibitors, interferon), Addison disease (picture 27), Laugier-Hunziker disease, or pellagra [87-90].

Black hairy tongue — Black hairy tongue (lingua villosa nigra) is a benign condition associated with antibiotic use, candida albicans infection, or poor oral hygiene. Patients have elongated filiform papillae or, in pseudohairy tongue, a yellowish white to brown dorsal tongue surface (picture 28). Therapy consists of brushing that area of the tongue with a soft-bristle toothbrush and toothpaste two to three times per day [36].

Pigmented fungiform papillae of the tongue — Fungiform papillae are scattered on the tongue surface, predominantly on the anterior and lateral aspects, and are usually pink or red in color. Individuals with darker skin tones may show pigmented spots on the tongue due to melanin deposition on the tips of the fungiform papillae (picture 29) [91]. Lesions usually appear during the second or third decade of life and are typically asymptomatic [92-94]. Histologic examination reveals submucosal melanophages within the fungiform papillae in the absence of inflammation.

Geographic tongue — Geographic tongue (benign migratory glossitis) is a disorder of unknown etiology that affects the epithelium of the tongue [95]. Local loss of filiform papillae leads to ulcer-like lesions that appear as erythematous patches on the dorsal tongue with circumferential white polycyclic borders (picture 30A-B). Lesions can change location, pattern, and size within minutes to hours, and patients may have numerous exacerbations and remissions over time. Exacerbations are usually asymptomatic, although some patients complain of oral discomfort, burning, or foreign body sensations.

The differential diagnosis includes candidiasis, psoriasis, Reiter syndrome, lichen planus, leukoplakia, systemic lupus erythematosus, herpes simplex virus, and drug reaction [95]. The diagnosis is typically based on the clinical presentation and biopsy is not necessary. However, biopsy may be reassuring in unclear cases. The histology of involved areas is similar to pustular psoriasis.

No therapy is needed since patients are usually asymptomatic or have only mild symptoms. Symptomatic treatments that have been reported but are unproven include fluids, acetaminophen, mouth rinsing with a topical anesthetic agent, antihistamines, anxiolytics, tacrolimus, and corticosteroids [96-98]

Cheilitis — Cheilitis is an acute or chronic inflammation of the lips characterized by erythema, scaling, fissuring, and itching or burning. Factors that may precipitate or aggravate the condition include wind-burns, contact with irritants or allergens, and some medications, such as topical or systemic retinoids. Chronic lip licking is a common cause in young children as the saliva causes a repeated irritant dermatitis. Secondary infection resulting in impetigo is common in young children.

The clinical manifestations, diagnosis, and treatment of acute and chronic forms of cheilitis are reviewed in detail separately. (See "Cheilitis".)

Contact and irritant stomatitis — Contact or irritant stomatitis is a less common cause of oral lesions, but may present with a wide variety of manifestations, including erosions, ulcerations, lichenoid-like reactions, leukoplakic lesions, or only erythema (picture 31) [99]. Allergic reactions are primarily due to metallic mercury, cinnamon aldehyde, and gold salts, among others (table 2).

Lip and perioral involvement is seen when the offending agent is chewed or applied topically. Repetitive friction, particularly in relationship to dental appliances, may result in traumatic ulcers. Leukoplakic-like lesions can occur due to repeated friction from poorly fitting prostheses, cheek sucking, or with the use of oral tobacco. Lichenoid, lace-like, localized, buccal mucosal patches may occur secondary to amalgam. Symptoms usually outweigh clinical disease.

Burning mouth syndrome is most commonly seen in middle aged women and is not necessarily related to any allergies. Contact urticaria is seen most commonly due to allergies to dental materials or natural rubber latex, and anaphylaxis can occur. Food related inflammation may present with prominent lip swelling. (See "Overview of craniofacial pain", section on 'Burning mouth syndrome'.)

Dental erosions/gingival hyperplasia — It is important to perform a thorough dental examination even in the absence of oral complaints. Patients on chronic antiepileptic medications may develop gingival hyperplasia, particularly those on phenytoin, as can patients taking cyclosporine and nifedipine (picture 32). Dental erosions can occur from even mild systemic illness, such as chronic gastroesophageal reflux, and once established erosions can predispose to aspiration syndromes [100].

Inherited epidermolysis bullosa — Epidermolysis bullosa describes a group of rare inherited diseases with the common finding of epithelial fragility. Affected sites occur most commonly in areas of trauma and friction. Milder forms do not typically involve the mucosae, while more severe manifestations involve the oral, pharyngeal, and esophageal mucosa and tooth formation. (See "The genodermatoses", section on 'Epidermolysis bullosa'.)