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Stomatitis is
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
of the mouth and lips. It refers to any inflammatory process affecting the
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
s of the mouth and lips, with or without
oral ulceration A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause ...
. In its widest meaning, stomatitis can have a multitude of different causes and appearances. Common causes include infections, nutritional deficiencies, allergic reactions, radiotherapy, and many others. When inflammation of the gums and the mouth generally presents itself, sometimes the term ''gingivostomatitis'' is used, though this is also sometimes used as a synonym for
herpetic gingivostomatitis Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of gre ...
. The term is derived from the
Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...
''stoma'' (), meaning "mouth", and the suffix ''-itis'' (), meaning "inflammation".


Causes


Nutritional deficiency

Malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
(improper dietary intake) or
malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...
(poor absorption of nutrients into the body) can lead to nutritional deficiency states, several of which can lead to stomatitis. For example, deficiencies of
iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...
, vitamin B2 (riboflavin),
vitamin B3 Vitamin B3, colloquially referred to as niacin, is a vitamin family that includes three forms or vitamers: niacin (nicotinic acid), nicotinamide (niacinamide), and nicotinamide riboside. All three forms of vitamin B3 are converted within the b ...
(niacin),
vitamin B6 Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., " vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosp ...
(pyridoxine), vitamin B9 (folic acid) or
vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
(cobalamine) may all manifest as stomatitis. Iron is necessary for the upregulation of transcriptional elements for cell replication and repair. Lack of iron can cause genetic downregulation of these elements, leading to ineffective repair and regeneration of epithelial cells, especially in the mouth and lips. Many disorders which cause malabsorption can cause deficiencies, which in turn causes stomatitis. Examples include
tropical sprue Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a more ...
.


Aphthous stomatitis

Aphthous stomatitis (canker sores) is the recurrent appearance of mouth ulcers in otherwise healthy individuals. The cause is not completely understood, but it is thought that the condition represents a
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
mediated immune response which is triggered by a variety of factors. The individual ulcers (aphthae) recur periodically and heal completely, although in the more severe forms, new ulcers may appear in other parts of the mouth before the old ones have finished healing. Aphthous stomatitis is one of the most common diseases of the
oral mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been de ...
, and is thought to affect about 20% of the general population to some degree. The symptoms range from a minor nuisance to being disabling in their impact on eating, swallowing, and talking, and the severe forms can cause people to lose weight. There is no cure for aphthous stomatitis, and therapies are aimed at alleviating the pain, reducing the inflammation and promoting healing of the ulcers, but there is little evidence of efficacy for any treatment that has been used.


Angular stomatitis

Inflammation of the corners (angles) of the lips is termed angular stomatitis or angular cheilitis. In children a frequent cause is repeated lip-licking, and in adults it may be a sign of underlying
iron deficiency anemia Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, sho ...
, or vitamin B deficiencies (''e.g.'', B2-
riboflavin Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved i ...
, B9-
folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing an ...
, or B12-
cobalamin Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
, which in turn may be evidence of poor diets or malnutrition such as
celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...
). Also, angular cheilitis can be caused by a patient's jaws at rest being 'overclosed' due to edentulousness or
tooth wear Tooth wear refers to loss of tooth substance by means other than dental caries. Tooth wear is a very common condition that occurs in approximately 97% of the population. This is a normal physiological process occurring throughout life; but with i ...
, causing the jaws to come to rest closer together than if the complete/unaffected
dentition Dentition pertains to the development of teeth and their arrangement in the mouth. In particular, it is the characteristic arrangement, kind, and number of teeth in a given species at a given age. That is, the number, type, and morpho-physiolo ...
were present. This causes skin folds around the angle of the mouth which are kept moist by saliva, which in turn favours infection; mostly by ''Candida albicans'' or similar species. Treatment usually involves the administration of topical nystatin or similar
antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...
agents. Another treatment can be to correct the jaw relationship with dental treatment (''e.g.'', dentures or occlusal adjustment).


Denture-related stomatitis

This is a common condition present in denture wearers. It appears as reddened but painless mucosa beneath the denture. 90% of cases are associated with ''Candida'' species, and it is the most common form of
oral candidiasis Oral candidiasis, also known as oral thrush among other names, is candidiasis that occurs in the mouth. That is, oral candidiasis is a mycosis (yeast/fungal infection) of ''Candida'' species on the mucous membranes of the mouth. ''Candida albic ...
. Treatment is by
antifungal medication An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryp ...
and improved dental hygiene, such as not wearing the denture during sleep.


Allergic contact stomatitis

Allergic contact stomatitis (also termed "allergic gingivostomatitis" or "allergic contact gingivostomatitis") is a type IV (delayed) hypersensitivity reaction that occurs in susceptible atopic individuals when
allergen An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. In technical t ...
s penetrate the skin or
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
. Allergens, which may be different for different individuals, combine with
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
-derived
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, forming haptens which bind with
Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...
s in the mucosa, which in turn present the antigen on their surface to
T lymphocyte A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
s, sensitizing them to that antigen and causing them to produce many specific clones. The second time that specific antigen is encountered, an inflammatory reaction is triggered at the site of exposure. Allergic contact stomatitis is less common than
allergic contact dermatitis Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance; the other type being irritant contact dermatitis (ICD). Although less common than ICD, ACD is ...
because the mouth is coated in saliva, which washes away antigens and acts as a barrier. The oral mucosa is also more vascular (has a better blood supply) than skin, meaning that any antigens are more quickly removed from the area by the circulation. Finally, there is substantially less
keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up Scale (anatomy), scales, hair, Nail ...
in
oral mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been de ...
, meaning that there is less likelihood that haptens will form. Allergic contact stomatitis appears as non-specific inflammation, so it may be mistaken for chronic physical irritation. There may be burning or soreness of the mouth and ulceration. Chronic exposure to the allergen may result in a lichenoid lesion. Plasma cell gingivitis may also occur, which may be accompanied by
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 atro ...
and
cheilitis Cheilitis is a medical condition characterized by inflammation of the lips. The inflammation may include the perioral skin (the skin around the mouth), the vermilion border, or the labial mucosa. The skin and the vermilion border are more common ...
. Allergens that may cause allergic contact stomatitis in some individuals include
cinnamaldehyde Cinnamaldehyde is an organic compound with the formula(C9H8O) C6H5CH=CHCHO. Occurring naturally as predominantly the ''trans'' (''E'') isomer, it gives cinnamon its flavor and odor. It is a phenylpropanoid that is naturally synthesized by the shi ...
, Balsam of Peru,
peppermint Peppermint (''Mentha'' × ''piperita'') is a hybrid species of mint, a cross between watermint and spearmint. Indigenous to Europe and the Middle East, the plant is now widely spread and cultivated in many regions of the world.Euro+Med Plantb ...
, mercury,
gold Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile ...
,
pyrophosphate In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among othe ...
s,
zinc citrate Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic ta ...
, free
acrylic Acrylic may refer to: Chemicals and materials * Acrylic acid, the simplest acrylic compound * Acrylate polymer, a group of polymers (plastics) noted for transparency and elasticity * Acrylic resin, a group of related thermoplastic or thermosett ...
monomer,
nickel Nickel is a chemical element with symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive but large pieces are slow t ...
,
fluoride Fluoride (). According to this source, is a possible pronunciation in British English. is an inorganic, monatomic anion of fluorine, with the chemical formula (also written ), whose salts are typically white or colorless. Fluoride salts ty ...
, and
sodium lauryl sulfate Sodium dodecyl sulfate (SDS) or sodium lauryl sulfate (SLS), sometimes written sodium laurilsulfate, is an organic compound with the formula . It is an anionic surfactant used in many cleaning and hygiene products. This compound is the sodium s ...
. These allergens may originate from many sources, including various foods and drink, chewing gum, toothpaste, mouthwash, dental floss, dental fillings, dentures, orthodontic bands or wires, and many other sources. If the substance containing the allergen comes into contact with the lips,
allergic contact cheilitis Cheilitis is a medical condition characterized by inflammation of the lips. The inflammation may include the perioral skin (the skin around the mouth), the vermilion border, or the labial mucosa. The skin and the vermilion border are more common ...
can occur, together with allergic contact stomatitis. The diagnosis is confirmed by patch test, and management is by avoidance of exposure to the allergen.


Migratory stomatitis

Migratory stomatitis (or geographic stomatitis) is an atypical presentation of a condition which normally presents on the tongue, termed geographic tongue. Geographic tongue is so named because there are atrophic,
erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...
tous areas of
depapillation Lingual papillae (singular papilla) are small structures on the upper surface of the tongue that give it its characteristic rough texture. The four types of papillae on the human tongue have different structures and are accordingly classified as c ...
that migrate over time, giving a map-like appearance. In migratory stomatitis, other mucosal sites in the mouth, such as the ventral surface (undersurface) of the tongue, buccal mucosa, labial mucosa, soft palate, or floor of mouth may be afflicted with identical lesions, usually in addition to the tongue. Apart from not being restricted to the tongue, migratory stomatitis is an identical condition in every regard to geographic tongue. Another synonym for geographic tongue which uses the term stomatitis is "stomatitis areata migrans".


Herpetic gingivostomatitis

This is inflammation of the mouth caused by
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names '' Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral in ...
.


Irradiation and chemotherapy

Stomatitis may also be caused by chemotherapy, or radiation therapy of the oropharyngeal area. The term '' mucositis'' is sometimes used synonymously with stomatitis, however the former usually refers to mucosal reactions to
radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
or
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...
, and may occur anywhere in the gastrointestinal tract and not just in the mouth.


Necrotizing ulcerative gingivostomatitis

The term ''necrotizing ulcerative gingivostomatitis'' is sometimes used as a synonym of the necrotizing periodontal disease more commonly termed necrotizing ulcerative gingivitis, or a more severe form (also termed necrotizing stomatitis). The term ''necrotizing gingivostomatitis'' is also sometimes used.


Stomatitis nicotina

Also called smoker's palatal keratosis, this condition may occur in smokers, especially pipe smokers. The palate appears dry and cracked, and white from keratosis. The minor
salivary gland The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary ...
s appear as small, red and swollen bumps. It is not a
premalignant condition A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increase ...
, and the appearance reverses if the smoking is stopped.


Chronic ulcerative stomatitis

Chronic ulcerative stomatitis is a condition with specific immunopathologic features, which was first described in 1990. It is characterized by erosions and
ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
s which relapse and remit. Lesions are located on the buccal mucosa (inside of the cheeks) or on the
gingiva The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health. Structure The gums are part of the soft tissue lin ...
(gums). The condition resembles
oral lichen planus Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, and is only named that because it looks like one. It is characterized by polygonal, fl ...
when biopsied. The diagnosis is made by microscopic examination of biopsy tissue: direct immunofluorescence can reveal the presence of antinuclear antibodies specifically directed against the ΔNp63α form of the p63 protein, which is normally expressed within the
basal layer The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...
of stratified epithelium. Treatment with
hydroxychloroquine Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, an ...
can be effective.


Plasma cell gingivostomatitis

Terms such as ''plasma cell gingivostomatitis'', ''atypical gingivostomatitis'' and ''idiopathic gingivostomatitis'' are sometimes a synonym for plasma cell gingivitis, or specifically to refer to a severe form of plasma cell gingivitis.


Other forms of stomatitis

*
Periodic fever, aphthous stomatitis, pharyngitis and adenitis Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome is a medical condition, typically occurring in young children, in which high fever occurs periodically at intervals of about 3-5 weeks, frequently accompanied by aphthous-like ...
(PFAPA) syndrome—occurs in children. * Uremic stomatitis—a rare form of stomatitis that occurs with
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. * Pyostomatitis vegetans *
Bovine papular stomatitis Bovine papular stomatitis is a farmyard pox caused by ''Bovine papular stomatitis virus'' (BPSV), which can spread from infected cattle to cause disease in milkers, farmers and veterinarians. Generally there is usually one or a few skin lesions ty ...


References


External links

{{Oral pathology Inflammations Oral mucosal pathology