Differential diagnostics of diseases of the tongue and lips. Treatment and prevention. Supervision of patients. Using of physical methods for treatment and diagnostics.
Glossitis
Glossitis can mean soreness of the tongue, or more usually inflammation with depapillation of the dorsal surface of the tongue (loss of the lingual papillae), leaving a smooth and erythematous (reddened) surface, (sometimes specifically termed atrophic glossitis). In a wider sense, glossitis can mean inflammation of the tongue generally. Glossitis is often caused by nutritional deficiencies and may be painless or cause discomfort. Glossitis usually responds well to treatment if the cause is identified and corrected. Tongue soreness caused by glossitis is differentiated from burning mouth syndrome, where there is no identifiable change in the appearance of the tongue, and there are no identifiable causes.
Fissured tongue
Fissured tongue (also known as “scrotal tongue,” “lingua plicata,” “Plicated tongue,” and “furrowed tongue”) is a benign condition characterized by deep grooves (fissures) in the dorsum of the tongue. Although these grooves may look unsettling, the condition is usually painless. Some individuals may complain of an associated burning sensation however.
Prevalence
It is a relatively common condition, with an estimated prevalence of 2-5% of the general population. Males are more commonly affected. The condition may be seen at any age, but generally affects older people more frequently. The condition also generally becomes more accentuated with age.
Clinical features
The clinical appearance is considerably varied in both the orientation, number, depth and length of the fissure pattern. There are usually multiple grooves/furrows 2-6mm in depth present. Sometimes there is a large central furrow, with smaller fissures branching perpendicularly. Other patterns may show a mostly dorsolateral position of the fissures (i.e. sideways running grooves on the tongue’s upper surface). Some patients may experience burning or soreness.
Cause
The cause is unknown, but it may be partly a genetic trait. Aging and environmental factors may also contribute to the appearance.
Associated conditions
Fissured tongue is seen in Melkersson-Rosenthal syndrome, in most patients with Down syndrome, in association with geographic tongue, and in healthy, normal individuals.
Treatment
If the fissures are causing halitosis, then mechanical tongue cleansing should be introduced to the patients oral hygiene routine.
As the condition is otherwise entirely benign, no treatment is indicated and the patient should be reassured that it is a common variance of the normal appearance of the tongue.
Atrophic glossitis
Atrophic glossitis, also known as bald tongue, smooth tongue, Hunter glossitis, Moeller glossitis, or Möller-Hunter glossitis, is a condition characterized by a smooth glossy tongue that is often tender/painful, caused by complete atrophy of the lingual papillae (depapillation). The dorsal tongue surface may be affected totally, or in patches, and may be associated with a burning sensation, pain and/or erythema. Atrophic glossitis is a non-specific finding, and has a great many causes, usually related to various nutritional deficiencies or other factors such as xerostomia (dry mouth) or anemia. Although the terms Möller and Hunter glossitis were originally used to refer to sepcifically the glossitis that occurs in vitamin B12 deficiency secondary to pernicious anemia, they are now used as synonyms for atrohpic glossitis generally.
Candidiasis may be a concurrent finding or an alternative cause of erythema, burning, and atrophy.
Geographic tongue
Geographic tongue (also known as benign migratory glossitis, BMG, erythema migrans, erythema migrans lingualis, glossitis areata exfoliativa, glossitis areata migrans, lingua geographica, stomatitis areata migrans, wandering rash of the tongue, and transitory benign plaques of the tongue), is an inflammatory condition of the mucous membrane of the tongue, usually on the dorsal surface. It is a common condition, affecting approximately 2-3% of the general population. It is characterized by areas of smooth, red depapillation (loss of lingual papillae) which migrate over time. The name comes from the map-like appearance of the tongue, with the patches resembling the islands of an archipelago. The cause is unknown, but the condition is entirely benign (importantly, it does not represent oral cancer), and there is no curative treatment. Uncommonly, geographic tongue may cause a burning sensation on the tongue, for which various treatments have been described with little formal evidence of efficacy.
Signs and symptoms
The appearance of geographic tongue is variable from one person to the next and changes over time. The bottom image shows fissured tongue combined with geographic tongue more posteriorly. It is common for these two conditions to coexist.
In health, the dorsal surface of the tongue is covered in tuft like projections called lingual papillae (some of which are associated with taste buds), which give the tongue an irregular surface texture and a white-pink color. Geographic tongue is characterized by areas of atrophy and depapillation (loss of papillae), leaving an erythematous (darker red) and smoother surface than the unaffected areas. The depapillated areas are usually well demarcated, and bordered by a slightly raised, white, yellow or grey, serpingious (snaking) peripheral zone. A lesion of geographic tongue may start as a white patch before the depapillation occurs. Sometimes there may be only one lesion, but this is uncommon, and more usually the lesions may start at multiple different locations on the tongue, and then over time the areas coalesce to form the typical map-like appearance. The lesions usually change in shape, size and migrate to other areas, sometimes within hours. The condition may affect only part of the tongue, with a predilection for the tip and the sides of the tongue, or the entire dorsal surface at any one time. The condition goes through periods of remission and relapse. Loss of the white peripheral zone is thought to signify periods of mucosal healing.
There are usually no symptoms, but in some cases persons may experience pain or burning e.g. when eating hot, acidic, spicy or other kinds of foods (e.g. cheese, tomatoes, fruit). Where there is a burning symptom, other causes of a burning sensation on the tongue are considered, such as oral candidiasis.
Causes
The cause is unknown. Geographic tongue does not usually cause any symptoms, and in those cases where there are symptoms, an oral parafunctional habit may be a contributory factor. Persons with parafunctional habits related to the tongue may show scalloping on the sides of the tongue. Some suggest that hormonal factors may be involved, because one reported case in a female appeared to vary in severity in correlation with oral contraceptive use. People with geographic tongue frequently claim that their condition worsens during periods of psychologic stress. Geographic tongue is inversely associated with smoking and tobacco use. Sometimes geographic tongue is said to run in families, and it is reported to be associated with several different genes, though studies show family association may also be caused by similar diets. Some have reported links with various human leukocyte antigens, such as increased incidence of HLA-DR5, HLA-DRW6 and HLA-Cw6 and decreased incidence in HLA-B51. Vitamin B2 deficiency (ariboflavinosis) can cause several signs in the mouth, possibly including geographic tongue, although other sources state that geographic tongue is not related to nutritional deficiency. Fissured tongue often occurs simultaneously with geographic tongue, and some consider fissured tongue to be an end stage of geographic tongue.
In the past, some research suggested that geographic tongue was associated with diabetes, seborrheic dermatitis and atopy, however more modern research does not corroborate these findings. Some studies have reported a link between geographic tongue and psoriasis, although 90% of children who are diagnosed with geographic tongue do not contract psoriasis. Again however, modern research studies do not support any link between psoriasis and geographic tongue. Lesions that are histologically indistinguishable from geographic tongue may also be diagnosed in Reiter’s syndrome (arthritis, uveitis/conjunctivitis and urethritis).
Diagnosis
The differential diagnosis includes oral lichen planus, erythematous candidiasis, leukoplakia, lupus erythematosus, glossitis, and chemicl burns. Atrophic glossitis is usually distinguished from benign migratory glossitis on the basis of the migrating pattern of the lesions and the presence of a whitish border, features which are not present in atrophic glossitis, which instead shows lesions which enlarge rather than migrate. Rarely, blood tests may be required to distinguish from glossitis associated with anemia or other nutritional deficiencies. Since the appearance and the history of the condition (i.e. migrating areas of depapillation) are so striking, there is rarely any need for biopsy. When biopsy is taken, the histopathologic appearance is quite similar to psoriasis one of:
Hyperparakeratosis.
Acanthosis.
Subepithelial T lymphocyte inflammatory infiltrate.
Migration of neutrophilic granulocytes into the epithelial layer, which may create superficial microabscesses, similar to the Munro’s microabscesses described in pustular psoriasis.
Treatment
Since most cases cause no symptoms, reassuring the person affected that the condition is entirely benign is usually the only treatment.
When symptoms are present, topical anesthetics can be used to provide temporary relief. Other drugs that have been used to manage the symptoms include antihistamines, corticosteroids or anxiolytics, but these drugs have not been formally assessed for efficacy in geographic tongue. If some foodstuffs exacerbate or trigger the symptoms, then cutting these foods out of the diet may benefit. One uncontrolled trial has shown some benefit in controlling the symptoms of geographic tongue.
The condition may disappear over time, but it is impossible to predict if or when this may happen.
Median rhomboid glossitis
Median rhomboid glossitis (MRG, also known as central papillary atrophy, or glossal central papillary atrophy) is a condition characterized by an area of redness and loss of lingual papillae, situated on the dorsum of the tongue in the midline immediately in front of the circumvallate papillae. Median rhomboid glossitis is thought to be created by a chronic fungal infection, and usually is a type of oral candidiasis.
Signs and symptoms
Rarely is any soreness associated with the condition. Apart from the appearance of the lesion, there are usually no other signs or symptoms. The typical appearance of the lesion is an oval or rhomboid shaped area located in the midline of the dorsal surface of the tongue, just anterior (in front) of the sulcus terminalis. The lesion is usually symmetric, well demarcated, erythematous and depapillated, which has a smooth, shiny surface. Less typically, the lesion may be hyperplastic or lobulated and exophytic. There may be candidal lesions at other sites in the mouth, which may lead to a diagnosis of chronic multifocal oral candidiasis. Sometimes an approximating erythematous lesion is present on the palate (a “kissing lesion”). The lesion is typically 2 – 3 cm in its longest dimension.
Causes
Predisposing factors include smoking, denture wearing, use of corticosteroid sprays or inhalers and human immunodeficiency virus (HIV) infection.[2] Candida species even in healthy people mainly colonizes the posterior dorsal tongue. Median rhombiod glossitis is thought to be a type of chronic atrophic (or erythematous) candidiasis. Microbiological culture of the lesion usually shows Candida mixed with bacteria.
Diagnosis
The diagnosis is usually made on the clinical appearance, and tissue biopsy is not usually needed. The histologic picture is one of superficial candidal hyphal infiltration and a polymorphonuclear leukocytic inflammatory infiltrate present in the epithelium. The rete ridges are elongated and hyperplastic (pseudoepitheliomatous hyperplasia, which may be mistaken for carcinoma).
Treatment and prognosis
Treatment may involve smoking cessation and prescription of topical or systemic antifungal medication. Usually the mucosal changes resolve with antifungal therapy, but sometimes the lesion is resistant to complete resolution.
Geometric glossitis
Geometric glossitis, also termed herpetic geometric glossitis, is a term used by some to refer to a chronic lesion associated with herpes simplex virus (HSV) type I infection, in which there is a deep fissure in the midline of the tongue and gives off multiple branches. The lesion is usually very painful, and there may be erosions present in the depths of the fissures. Similar fissured lesions which are not associated with HSV, as may occur in fissured tongue, do not tend to be painful. The name comes from the geometric pattern of the fissures which are longitudinal, crossed or branched. It is described as occurring in immunocompromized persons, e.g. who have leukemia. However, the association between herpes simplex and geometric glossitis is disputed by some due to a lack of gold standard techniques for diagnosis of intraoral herpetic lesions, and the high prevalence of asymptomatic viral shedding in immunocompromized individuals. Treatment is with systemic aciclovir.
Strawberry tongue
Strawberry tongue (also called raspberry tongue), refers to glossitis which manifests with hyperplastic (enlarged) fungiform papillae, giving the appearance of a strawberry. White strawberry tongue is where there is a white coating on the tongue through which the hyperplastic fungiform papillae protrude. Red strawberry tongue is where the white coating is lost and an dark red, erythematous surface is revealed, interspaced with the hyperplastic fungiform papillae. White strawberry tongue is seen in early scarlet fever (a systemic infection of group A β- hemolytic streptococci), and red strawberry tongue occurs later, after 4–5 days. Strawberry tongue is also seen in Kawasaki disease (a common vasculitic disorder often occurring in children under 5), and toxic shock syndrome. It may mimic other types of glossitis or Vitamin B12 deficiency.
Black hairy tongue
Black hairy tongue (BHT, also termed lingua villosa nigra) refers to a condition of the tongue where the filiform papillae elongate with black or brown discoloration, giving a black and hairy appearance. The appearance may be alarming, but it is a harmless condition. Predisposing factors include smoking, xerostomia (dry mouth), soft diet, poor oral hygiene and certain medications. Management is by improving oral hygiene, especially scraping or brushing the tongue.
Classification
Black discoloration on the dorsal surface of the tongue. Black hairy tongue is characterized by a hairy and discolored tongue.
Hairy tongue (lingua villosa) refers to a marked accumulation of keratin on the filiform papillae on the dorsal surface of the tongue, giving a hair-like appearance. Black tongue (lingua nigra) refers to a black discoloration of the tongue, which may or may not be associated with hairy tongue. However, the elongated papillae of hairy tongue usually develop discoloration due to growth of pigment producing bacteria and staining from food. Hence the term black hairy tongue, although hairy tongue may also be discolored yellow or brown. Transient, surface discoloration that is not associated with hairy tongue can be brushed off. Drug induced black hairy tongue specifically refers to BHT that develops because of medication.
Signs and symptoms
Hairy tongue largely occurs in the central part of the dorsal tongue, just anterior (in front) of the circumvallate papillae, although sometimes the entire dorsal surface may be involved. Discoloration usually accompanies hairy tongue, and may be yellow, brown or black. Apart from the appearance, the condition is typically asymptomatic, but sometimes people may experience a gagging sensation or a bad taste. There may also be associated oral malodor (intra-oral halitosis).
Causes
The cause is uncertain, but it is thought to be caused by accumulation of epithelial squames and proliferation of chromogenic (color producing) micro-organisms. There may be an increase in keratin production or a decrease iormal desquamation (shedding of surface epithelial cells). Many people with BHT are heavy smokers. Other possible associated factors are poor oral hygiene, general debilitation, hyposalivation (decreased salivary flow rate), radiotherapy, overgrowth of fungal or bacterial organisms, and a soft diet. Occasionally, BHT may be caused by the use of antimicrobial medications e.g. tetracyclines, or oxidizing mouthwashes or antacids. A soft diet may be involved as normally food has an abrasive action on the tongue, which keeps the filiform papillae short. Pellagra, a condition caused by a vitamin deficiency, may cause a thick greyish fur to develop on the dorsal tongue, along with other oral signs.
Transient surface discoloration of the tongue and other soft tissues in the mouth can be occur in the absence of hairy tongue. Causes include smoking (or betel chewing), some foods and beverages (e.g. coffee, tea or liquorice), and certain medications e.g. chlorhexidine, iron salts, or bismuth subsalicylate (Pepto-Bismol).
Diagnosis
Diagnosis is usually made on the clinical appearance without the need for a tissue biopsy. However, when biopsies have been taken, the histologic appearance is one of marked elongation and hyperparakeratosis of the filiform papillae and numerous bacteria growing on the epithelial surface.
Hairy tongue may be confused with hairy leukoplakia, however the latter usually occurs on the sides of the tongue and is associated with an opportunistic infection with Epstein-Barr virus on a background immunocompromise (almost always human immunodeficiency virus infection but rarely other conditions which suppress the immune system).
Treatment
Treatment is by reassurance, as the condition is benign, and then by correction of any predisposing factors. This may be cessation of smoking or cessation/substitution of implicated medications or mouthwashes. Generally direct measures to return the tongue to its normal appearance involve improving oral hygiene, especially scraping or brushing the tongue before sleep. This promotes desquamation of the hyperparakeratotic papillae. Keratolytic agents (chemicals to remove keratin) such as podophyllin are successful, but carry safety concerns. Other reported successful measures include sodium bicarbonate mouthrinses, eating pineapple, sucking on a peach stone and chewing gum.
Prognosis
BHT is a benign condition, but people who are affected may be distressed at the appearance and possible halitosis, and therefore treatment is indicated.
Cheilitis glandularis
Cheilitis glandularis (CG) is a clinically descriptive diagnosis that refers to an uncommon, poorly understood inflammatory disorder of the lower lip. Its etiology remains obscure. Cheilitis glandularis is characterized by progressive enlargement and eversion of the lower labial mucosa that results in obliteration of the mucosal-vermilion interface. With externalization and chronic exposure, the delicate lower labial mucous membrane is secondarily altered by environmental influences, leading to erosion, ulceration, crusting, and, occasionally, infection. Most significantly, susceptibility to actinic damage is increased. Therefore, cheilitis glandularis can be considered a potential predisposing factor for the development of actinic cheilitis and squamous cell carcinoma.
Historically, cheilitis glandularis has been subclassified into 3 types: simple, superficial suppurative, and deep suppurative. The deep suppurative type has also been variously referred to as myxadenitis labialis or cheilitis apostematosa, and the superficial suppurative type has been termed Baelz disease. Many believe these subtypes represent a continuum of disease, where the simple type, if not treated, could become secondarily infected and progress to become the superficial or eventually, the deeply suppurative type.
Treatment
The approach to treatment for cheilitis glandularis is based on diagnostic information obtained from histopathologic analysis, the identification of likely etiologic factors responsible for the cheilitis glandularis, and attempts to alleviate or eradicate those causes. Given the relatively small number of reported cases of cheilitis glandularis, neither sufficient nor reliable data exist with regard to medical approaches to cheilitis glandularis. Therefore, treatment for cheilitis glandularis varies accordingly for each patient.
For cases attributable to angioedema, administration of an antihistamine may effect temporary reduction in acute nonpurulent swelling.
Suppurative cases of cheilitis glandularis require management with appropriate antimicrobial treatment as determined by culture and sensitivity testing. Concomitant intralesional or oral corticosteroid treatment may potentiate the effectiveness of antimicrobial therapy in cases with nodularity; however, the potential systemic adverse effects of long-term corticosteroid treatment, plus its propensity for promoting local fibrosis and scarring, limit its potential use either as an adjunct to antibiotic treatment or as a single therapeutic modality for cheilitis glandularis.
Topical 5-fluorouracil is useful for treatment of dysplastic actinic cheilitis and to curtail its progression. In conjunction with clinical supervision, it can be prescribed as an alternative to vermilionectomy or as a prophylactic measure following vermilionectomy.
In cheilitis glandularis cases in which lip biopsy demonstrates chronic inflammation without evidence of epithelial atypia or dysplasia and no suggestion of deep infection, Bovenschen reported successful treatment using combined oral minocycline (100 mg once per day) plus tacrolimus ointment 0.1% twice daily for 6 weeks. Another case report describes successful palliative treatment with topical tacrolimus and pimecrolimus in cheilitis glandularis superimposed on oral lichen planus.
Cheilitis exfoliativa
Cheilitis exfoliativa, or exfoliative cheilitis, is an inflammatory condition of the lips, in which they may be covered with crusts. The condition has not yet been attributed to any particular cause. Its indefinite persistence and resistance to measures taken for its management may take a toll on the psychological well-being of the persons affected. Management consists mostly of keeping the lips moist and the application of topical corticosteroids ranging from hydrocortisone to clobetasol. There have also been reports of using topical tacrolimus ointment.
Allergic Contact Cheilitis
Contact cheilitis is a term used to describe inflammation of the lips, most often caused by either irritant contact cheilitis (ICC) or allergic contact cheilitis (ACC). This inflammation can cause a variety of signs and symptoms, such as dryness, scaling, crusting, fissuring, erythema, edema and/or angular cheilitis, as well as burning or itching.
Contact allergy of the oral mucosa, allergic contact stomatitis (ACS), is less common than contact allergy of skin of the lips. A potential explanation regarding this phenomenon involves saliva’s cleansing effect, washing away antigens that are presented to the mucosa, where antigen-presenting cells may also be less prevalent. The vascularity of the buccal mucosa also aids in the dispersal of antigens; however, despite this, the mucosa can become sensitized, with a subsequent inflammatory reaction, most often to dental materials and appliances, such as metals, acrylics fillings, crowns and dentures. Cheilitis and circumoral dermatitis usually accompany primary allergic stomatitis, although stomatitis does not necessarily always accompany primary allergic cheilitis. Of interest, early allergen exposure to the oral mucosa may actually be a means to creating tolerance. For example, it is well documented that wearing metal dental braces prior to nickel exposure (ear piercing) confers a lower risk of developing nickel allergy than the reverse of first piercing then being braced.
Actinic cheilitis
Actinic cheilitis (also known as “Actinic cheilosis”) is a form of cheilitis which is the counterpart of actinic keratosis of the skin and can develop into squamous cell carcinoma. In actinic cheilitis, there is thickening whitish discoloration of the lip at the border of the lip and skin. There is also a loss of the usually sharp border between the red of the lip and the normal skin, known as the vermillion border. The lip may become scaly and indurated as actinic cheilitis progresses. The lesion is usually painless, persistent, more common in older males, and more common in individuals with a light complexion with a history of chronic sun exposure.
Causes
Actinic cheilitis is caused by chronic and excessive exposure to ultraviolet radiation in sunlight. Additional factors may also play a role, including tobacco use, lip irritation, poor oral hygiene, and ill-fitting dentures.
Treatment options
This condition is considered premalignant because it may lead to squamous cell carcinoma in about 10% of all cases. It is not possible to predict which cases will progress into SCC, so the current consensus is that all lesions should be treated.
Treatment options include 5-fluorouracil, imiquimod, scalpel vermillionectomy, chemical peel, electrosurgery, and carbon dioxide laser vaporization. These curative treatments attempt to destroy or remove the damaged epithelium. All methods are associated with some degree of pain, edema, and a relatively low rate of recurrence.
Medication
Topical 5-fluorouracil (5-FU, Efudex, Carac) has been shown to be an effective therapy for diffuse, but minor actinic cheilitis. 5-fluorouracil works by blocking DNA synthesis. Cells that are rapidly growing need more DNA, so they accumulate more 5-fluorouracil, resulting in their death. Normal skin is much less affected. The treatment usually takes 2-4 weeks depending on the response. The typical response includes an inflammatory phase, followed by redness, burning, oozing, and finally erosion. Treatment is stopped when ulceration and crusting appear. There is minimal scarring. Complete clearance has been reported in about 50% of patients.
Imiquimod (Aldara) is an immune response modifier that has been studied for the treatment of actinic cheilitis. It promotes an immune response in the skin leading to apoptosis (death) of the tumor cells. It causes the epidermis to be invaded by macrophages, which leads to epidermal erosion. T-cells are also activated as a result of imiquimod treatment. Imiquimod appears to promote an “immune memory” that reduces the recurrence of lesions. There is minimal scarring. Complete clearance has been demonstrated in up to 45% of patients with actinic keratoses. However, the dose and duration of therapy, as well as the long-term efficacy, still need to be established in the treatment of actinic cheilitis.
Procedures
Both cryosurgery and electrosurgery are effective choices for small areas of actinic cheilitis. Cryosurgery is accomplished by applying liquid nitrogen in an open spraying technique. Local anesthesia is not required, but treatment of the entire lip can be quite painful. Cure rates in excess of 96% have been reported. Cryosurgery is the treatment of choice for focal areas of actinic cheilitis. Electrosurgery is an alternate treatment, but local anesthesia is required, making it less practical than cryosurgery. With both techniques, adjacent tissue damage can delay healing and promote scar formation.
More extensive or recurring areas of actinic cheilitis may be treated with either a shave vermillionectomy or a carbon dioxide laser. The shave vemillionectomy removes a portion of the vermillion ridge but leaves the underlying muscle intact. Considerable bleeding can occur during the procedure due to the vascular nature of the lip. A linear scar may also form after treatment, but this can usually be minimized with massage and steroids. Healing time is short, and effectiveness is very high.
A newer procedure uses a carbon dioxide laser to ablate the vermillion border. This treatment is relatively quick and easy to perform, but it requires a skilled operator. Anesthesia is usually required. Secondary infection and scarring can occur with laser ablation. In most cases, the scar is minimal, and responds well to steroids. Pain can be a progressive problem during the healing phase, which can last three weeks or more. However, the carbon dioxide laser also offers a very high success rate, with very few recurrences.
Chemical peeling with 50% trichloroacetic acid has also been evaluated, but results have been poor. Healing usually takes 7-10 days with very few side effects. However, limited studies show that the success rate may be lower than 30%.
Angular cheilitis
Angular cheilitis, (AC, and also called perlèche, cheilosis, angular cheilosis, commissural cheilitis, or angular stomatitis), is inflammation of one, or more commonly both, of the corners of the mouth. It is a type of cheilitis (inflammation of the lips). Angular cheilitis often represents an opportunistic infection of fungi and/or bacteria, with multiple local and systemic predisposing factors being involved in the initiation and persistence of the lesion. Such factors include nutritional deficiencies, overclosure of the mouth, dry mouth, a lip-licking habit, drooling, immunosuppression, and others. Treatment for angular cheilitis varies based on the exact causes of the condition in each case, but often an antifungal cream is used among other measures. It is a fairly common problem, and is more prevalent in people without any natural teeth who wear dentures, and in elderly people, although it may also occur in children.
Classification
Angular cheilitis could be considered to be a type of stomatitis. Where Candida species are involved, angular cheilitis is classed as a type of oral candidiasis, specifically a primary (group I) Candida-associated lesion. This form angular cheilitis which is caused by Candida is sometimes termed “Candida-associated angular cheilitis”, or less commonly, “monilial perlèche”. Angular cheilitis can also be classified as acute or chronic and refractory to attempts to treat it.
Signs and symptoms
A fairly mild case of angular cheilitis extending onto the facial skin in a young person (affected area within the black oval).
A mild case of angular cheilitis, confined to a small split in the labial mucosa, in a young person.
Angular cheilitis is a fairly non specific term which describes the presence of a lesion in a specific anatomic site (i.e. the corner of the mouth). As there are different possible causes and contributing factors from one person to the next, the appearance of the lesion is somewhat variable. The lesions are more commonly symmetrically present on both sides of the mouth, but sometimes only one side may be affected. In some cases, the lesion may be confined to the mucosa of the lips, and in other cases the lesion may extend past the vermilion border (the edge where the lining on the lips becomes the skin on the face) onto the facial skin. Initially, the corners of the mouth develop a gray-white thickening and adjacent erythema (redness). Later, the usual appearance is a roughly triangular area of erythema, edema (swelling) and maceration at either corner of the mouth. The mucosa of the lip may become fissured (cracked), crusted, ulcerated or atrophied. There is not usually any bleeding. Where the skin is involved, there may be radiating rhagades (linear fissures) from the corner of the mouth. Infrequently, the dermatitis (which may resemble eczema) can extend from the corner of the mouth to the skin of the cheek or chin. If Staphylococcus aureus is involved, the lesion may show golden yellow crusts. In chronic angular cheilitis, there may be suppuration (pus formation), exfoliation (scaling) and formation of granulation tissue.
Sometimes contributing factors can be readily seen, such as loss of lower face height from poorly made or worn dentures, which results in mandibular overclosure (“collapse of jaws”). If there is a nutritional deficiency underlying the condition, various other signs and symptoms such as glossitis (swollen tongue) may be present. In people with angular cheilitis who wear dentures, often there may be erythematous mucosa underneath the denture (normally the upper denture), an appearance consistent with denture-related stomatitis. Typically the lesions give symptoms of soreness, pain, pruritus (itching) or burning or a raw feeling.
Causes
Angular cheilitis is thought to be multifactorial disorder of infectious origin, with many local and systemic predisposing factors are known to be involved. The sores in angular cheilitis are often infected with fungi (yeasts), or sometimes bacteria, or a combination. This may represent a secondary, opportunistic infection by these pathogens, and some studies have linked the initial onset of angular cheilitis with nutritional deficiencies, especially of the B vitamins and iron (which causes iron deficiency anemia). which in turn may be evidence of malnutrition or malabsorption. Angular cheilitis can be a manifestation of contact dermatitis, which is considered in two groups; irritational and allergic.
Infection
The involved organisms are:
Candida species alone (usually Candida albicans), which accounts for about 20% of cases,
Bacterial species, either:
Staphylococcus aureus alone, which accounts for about 20% of cases,
β-hemolytic streptococci alone. These types of bacteria have been detected in between 8-15% of cases of angular cheilitis, but less commonly are they present in isolation,
Or a combination of the above organisms, (a polymicrobial infection) with about 60% of cases involving both C. albicans and S. aureus.
Candida can be detected in 93% of angular cheilitis lesions. This organism is found in in the mouths of about 40% of healthy individuals, and it is considered by some to be normal commensal component of the oral microbiota. However, Candida shows dimorphism, namely a yeast form which is thought to be relatively harmless and a pathogenic hyphal form which is associated with invasion of host tissues. Potassium hydroxide preparation is recommended by some to help distinguish between the harmless and the pathogenic forms, and thereby highlight which cases of angular cheilitis are truly caused by Candida. The mouth may act as a reservoir of Candida that reinfects the sores at the corners of the mouth and prevents the sores from healing.
A lesion caused by recurrence of a latent herpes simplex infection can occur in the corner of the mouth. Really this is herpes labialis (a cold sore), and is sometimes termed “angular herpes simplex”. A cold sore at the corner of the mouth behaves similarly to elsewhere on the lips, and follows a pattern of vesicle (blister) formation followed by rupture leaving a crusted sore which resolves in about 7–10 days, and recurs in the same spot periodically, especially during periods of stress. Rather than utilizing antifungal creams, angular herpes simplex is treated in the same way as a cold sore, with topical antiviral drugs such as aciclovir.
Irritation contact dermatitis
A famous sketch by Leonardo da Vinci in preparation to depict the face of Judas Iscariot in The Last supper. The subject shows overclosure of the jaws and loss of facial support around the mouth.
22% of cases of angular cheilitis are due to irritants. Saliva contains digestive enzymes, which may have a degree of digestive action on tissues if they are left in contact. The corner of the mouth is normally exposed to saliva more than any other part of the lips. Reduced lower facial height (vertical dimension or facial support) is usually caused by edentulism (tooth loss), or wearing worn down, old dentures or ones which are not designed optimally. This results in overclosure of the mandible (collapse of the jaws), which extenuates the angular skin folds at the corners of the mouth, in effect creating an intertriginous skin crease. The tendency of saliva to pool in these areas is increased, constantly wetting the area, which may cause tissue maceration and favors the development of a yeast infection. As such, angular cheilitis is more commonly seen in edentulous people (people without any teeth). It is by contrast uncommon in persons who retain their natural teeth. Angular cheilitis is also commonly seen in denture wearers. Angular cheilitis is present in about 30% of people with denture-related stomatitis. It is thought that reduced vertical dimension of the lower face may be a contributing factor in up to 11% of elderly persons with angular cheilitis and in up to 18% of denture wearers who have angular cheilitis. Reduced vertical dimension can also be caused by tooth migration, wearing orthodontic appliances, and elastic tissue damage caused by ultraviolet light exposure and smoking.
Habits or conditions that keep the corners of the mouth moist might include chronic lip licking, thumb sucking (or sucking on other objects such as pens, pipes, lollipops), dental cleaning (e.g. flossing), chewing gum, hypersalivation, drooling and mouth breathing. Some consider habitual lip licking or picking to be a form of nervous tic, and do not consider this to be true angular cheilitis, instead calling it perlèche (derived from the French word pourlècher meaning “to lick one’s lips”), or “factitious cheilitis” is applied to this habit. The term “cheilocandidiasis” describes exfoliative (flaking) lesions of the lips and the skin around the lips, and is caused by a superficial candidal infection due to chronic lip licking. Less severe cases occur during cold, dry weather, and is a form of chapped lips. Individuals may lick their lips in an attempt to provide a temporary moment of relief, only serving to worsen the condition.
The sunscreen in some types of lip balm degrades over time into an irritant. Using expired lipbalm can initiate mild angular cheilitis, and when the person applies more lipbalm to alleviate the cracking, it only aggravates it. Because of the delayed onset of contact dermatitis and the recovery period lasting days to weeks, people typically do not make the connection between the causative agent and the symptoms.
Nutritional deficiencies
Several different nutritional deficiency states of vitamins or minerals have been linked to AC. It is thought that in about 25% of people with AC, iron deficiency or deficiency of B vitamins are involved. Nutritional deficiencies may be a more common cause of AC in third world countries. Chronic iron deficiency may also cause koilonychia (spoon shaped deformity of the fingernails) and glossitis (inflammation of the tongue). It is not completely understood how iron deficiency causes AC, but it is known that it causes a degree of immunocompromise (decreased efficiency of the immune system) which may in turn allow an opportunistic infection of candida. Vitamin B2 deficiency (ariboflavinosis) may also cause AC, and other conditions such as redness of mucous membranes, magenta colored glossitis (pink inflammation of the tongue). Vitamin B5 deficiency may also cause AC, along with glossitis, and skin changes similar to seborrhoeic dermatitis around the eyes, nose and mouth. Vitamin B12 deficiency is sometimes responsible for AC, and commonly occurs together with folate deficiency (a lack of folic acid), which also causes glossitis and megaloblastic anemia. Vitamin B3 deficiency (pellagra) is another possible cause, and in which other association conditions such as dermatitis, diarrhea, dementia and glossitis can occur. Biotin (vitamin B7) deficiency has also been reported to cause AC, along with alopecia (hair loss) and dry eyes. Zinc deficiency is known to cause AC. Other symptoms may include diarrhea, alopecia and dermatitis. Acrodermatitis enteropathica is an autosomal recessive genetic disorder causing impaired absorption of zinc, and is associated with AC.
In general, these nutritional disorders may be caused by malnutrition, such as may occur in alcoholism or in strict vegan diets, or by malabsorption secondary to gastrointestinal disorders (e.g. Celiac disease or chronic pancreatitis) or gastrointestinal surgeries (e.g. pernicious anemia caused by ileal resection in crohn’s disease).
Systemic disorders
Some systemic disorders are involved in angular cheilitis by virtue of their association with malabsorption and the creation of nutritional deficiencies described above. Such examples include people with anorexia nervosa. Other disorders may cause lip enlargement (e.g. orofacial granulomatosis), which alters the local anatomy and extenuates the skin folds at the corners of the mouth. More still may be involved because they affect the immune system, allowing normally harmless organisms like Candida to become pathogenic and cause an infection. Xerostomia (dry mouth) is thought to account for about 5% of cases of AC. Xerostomia itself has many possible causes, but commonly the cause may be side effects of medications, or conditions such as Sjögren’s syndrome. Conversely, conditions which cause drooling or sialorrhoea (excessive salivation) can cause angular cheilitis by creating a constant wet environment in the corners of the mouth. About 25% of people with Down syndrome appear to have AC. Other possible oral manifestations of down syndrome include macroglossia (a large tongue), which may protrude from the mouth constantly. Inflammatory bowel diseases (such as Crohn’s disease or ulcerative colitis) can be associated with angular cheilitis. In Crohn’s it is likely the result of malabsorption and immunosuppressive therapy which gives rise to the sores at the corner of the mouth. Glucagonomas are rare pancreatic endocrine tumors which secrete glucagon, and cause a syndrome of dermatitis, glucose intolerance, weight loss and anemia. AC is a common feature of glucagonoma syndrome. Infrequently, angular cheilitis may be one of the manifestations of chronic mucocutaneous candidiasis, and sometimes cases of oropharyngeal or esophageal candidiasis may accompany angular cheilitis. Angular cheilitis may be present in human immunodeficiency virus infection, neutropenia, or diabetes. Angular cheilitis is more common in people with eczema because their skin is more sensitive to irritants. Other conditions possibly associated include plasma cell gingivitis, Melkersson-Rosenthal syndrome, or sideropenic dysphagia (also called Plummer-Vinson syndrome or Paterson-Brown-Kelly syndrome).
Drugs
Several drugs may cause AC as a side effect, by various mechanisms, such as creating drug induced xerostomia. Various examples include isotretinoin, indinavir and sorafenib. Isotretinoin (Accutane), an analog of vitamin A, is a medication which dries the skin. Less commonly, angular cheilitis is associated with primary hypervitaminosis A, which can occur when large amounts of liver (including cod liver oil and other fish oils) are regularly consumed or as a result from an excess intake of vitamin A in the form of vitamin supplements. Recreational drug users may develop AC. Examples include cocaine, methamphetamines, heroin and hallucinogens.
Allergic contact dermatitis
Allergic reactions may account for about 25-34% of cases of generalized cheilitis (i.e. not inflammation confined to the angles of the mouth). It is unknown how frequently allergic reactions are responsible for cases of angular cheilitis, but any substance capable of causing generalized allergic cheilitis may present involving the corners of the mouth alone. Examples of potential allergens include substances that may be present in some types of lipstick, toothpaste, acne products, cosmetics, chewing gum, mouthwash, foods, dental appliances, and materials from dentures or mercury containing amalgam fillings. It is usually impossible to tell the difference between irritant contact dermatitis and allergic contact dermatitis.
Diagnosis
Angular chielitis is normally a diagnosis made clinically. If the sore is unilateral rather than bilateral, this suggests a local factor (e.g. truama) or a split syphilitic papule. Angular cheilitis caused by mandibular overclosure, drooling and other irritants is usually bilateral.
The lesions are normally swabbed to detect if Candida or pathogenic bacterial species may be present. Persons with angular cheilitis who wear dentures often also will have their denture swabbed in addition. A complete blood count (full blood count) may be indicated, including assessment of the levels of iron, ferritin, vitamin B12 (and possibly other B vitamins), and folate.
Management
There are 4 aspects to the treatment of angular chieltis. Firstly, potential reservoirs of infection inside the mouth are identified and treated. Oral candidiasis, especially denture-related stomatitis is often found to be present where there is angular cheilitis, and if it is not treated, the sores at the corners of the mouth may often recur. This involves having dentures properly fitted and disinfected. Commercial preparations are marketed for this purpose, or simply the dentures are left in dilute (1:10 concentration) household bleach overnight, but only if they are plastic and do not contain any metal parts, and with rinsing under clean water before use. Improved denture hygiene is often required thereafter, including not wearing the denture during sleep and cleaning it daily.
Secondly, there may be a need to increase the vertical dimension of the lower face to prevent overclosure of the mouth and formation of deep skin folds. This may require the construction of a new denture with an adjusted bite. Rarely, in cases resistant to normal treatments, surgical procedures such as collagen injections (or other facial fillers such as autologous fat or crosslinked hyaluronic acid) are used in an attempt to restore the normal facial contour. Other measures which seek to reverse the local factors that may be contributing to the condition include improving oral hygiene, stopping smoking or other tobacco habits and use of a barrier cream (e.g. zinc oxide paste) at night.
Thirdly, treatment of the infection and inflammation of the lesion themselves is addressed. This is usually with topical antifungal medication, such as clotrimazole, amphotericin B, ketoconazole, or nystatin cream. Some antifungal creams are combined with corticosteroids such as hydrocortisone or triamcinolone to reduce inflammation, and some antifungals such as miconazole cream also have some antibacterial action. Diiodohydroxyquinoline is another topical therapy for angular cheilitis. If Staphylococcus aureus infection is demonstrated by microbiological culture to be responsible (or suspected), the treatment may be changed to fusidic acid cream, an antibiotic which is effective against this type of bacteria. Aside from fusidic acid, neomycin, mupirocin, metronidazole, and chlorhexidine, are alternative options for this scenario.
Finally, if the condition appears resistant to treatment, investigations for underlying causes such as anemia or nutrient deficiencies or HIV infection. Identification of the underlying cause is essential for treating chronic cases. The lesions may resolve when the underlying disease is treated, e.g. with a course of oral iron or B vitamin supplements. Patch testing is recommended by some in cases which are resistant to treatment and where allergic contact dermatitis is suspected.
Prognosis
Most cases of angular cheilitis respond quickly when antifungal treatment is used. In more long standing cases, the severity of the condition often follows a relapsing and remitting course over time. The condition can be difficult to treat and can be prolonged.
Melkersson–Rosenthal syndrome
Melkersson–Rosenthal syndrome is a rare neurological disorder characterized by recurring facial paralysis, swelling of the face and lips (usually the upper lip), and the development of folds and furrows in the tongue. Onset is in childhood or early adolescence. After recurrent attacks (ranging from days to years in between), swelling may persist and increase, eventually becoming permanent. The lip may become hard, cracked, and fissured with a reddish-brown discoloration. The cause of Melkersson–Rosenthal syndrome is unknown, but there may be a genetic predisposition. It can be symptomatic of Crohn’s disease or sarcoidosis.
Treatment
Treatment is symptomatic and may include nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids to reduce swelling, antibiotics and immunosuppressants. Surgery may be indicated to relieve pressure on the facial nerves and reduce swelling, but its efficacy is uncertain. Massage and electrical stimulation may also be prescribed.
Prognosis
Melkersson–Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. Follow-up care should exclude the development of Crohn’s disease or sarcoidosis.
References:
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6. http://emedicine.medscape.com/
7. http://www.rightdiagnosis.com/
8. http://rarediseases.info.nih.gov
9. http://en.wikipedia.org/wiki/Fissured_tongue
10. http://en.wikipedia.org/wiki/Glossitis
11. http://en.wikipedia.org/wiki/Black_hairy_tongue
12. http://en.wikipedia.org/wiki/Angular_cheilitis
Information was prepared by Sukhovolets I.O.
