Aphthous Stomatitis
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Aphthous stomatitis, or recurrent aphthous stomatitis (RAS), is a common condition characterized by the repeated formation of
benign Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
and non- contagious
mouth ulcer 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 ca ...
s (aphthae) in otherwise healthy individuals. The informal term ''canker sore'' is also used, mainly in North America, although it may also refer to other types of mouth ulcers. The cause is not completely understood but involves 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 An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
triggered by a variety of factors which may include
nutritional deficiencies 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 ...
, local
trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...
,
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
,
hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required f ...
influences,
allergies Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermat ...
, genetic predisposition, certain foods,
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
, some food additives, or some hygienic chemical additives like SDS (common in toothpaste). These ulcers occur periodically and heal completely between attacks. In the majority of cases, the individual ulcers last about 7–10 days, and ulceration episodes occur 3–6 times per year. Most appear on the non-keratinizing epithelial surfaces in the mouth – i.e. anywhere except the attached gingiva, the
hard palate The hard palate is a thin horizontal bony plate made up of two bones of the facial skeleton, located in the roof of the mouth. The bones are the palatine process of the maxilla and the horizontal plate of palatine bone. The hard palate spans t ...
and the dorsum of the
tongue The tongue is a muscular organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive process, and is the primary organ of taste. The tongue's upper surface (dorsum) is covered by taste ...
– although the more severe forms, which are less common, may also involve keratinizing epithelial surfaces. Symptoms range from a minor nuisance to interfering with eating and drinking. The severe forms may be debilitating, even causing
weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...
due to
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 ...
. The condition is very common, affecting about 20% of the general population to some degree. The onset is often during childhood or adolescence, and the condition usually lasts for several years before gradually disappearing. There is no cure, and treatments such as corticosteroids aim to manage pain, reduce healing time and reduce the frequency of episodes of ulceration.


Signs and symptoms

Persons with aphthous stomatitis have no detectable systemic symptoms or signs (i.e., outside the mouth). Generally, symptoms may include
prodromal In medicine, a prodrome is an early sign or symptom (or set of signs and symptoms) that often indicates the onset of a disease before more diagnostically specific signs and symptoms develop. It is derived from the Greek word ''prodromos'', meaning ...
sensations such as burning, itching, or stinging, which may precede the appearance of any lesion by some hours; and pain, which is often out of proportion to the extent of the ulceration and is worsened by physical contact, especially with certain foods and drinks (e.g., if they are acidic or abrasive). Pain is worst in the days immediately following the initial formation of the ulcer, and then recedes as healing progresses. If there are lesions on the tongue, speaking and chewing can be uncomfortable, and ulcers on the
soft palate The soft palate (also known as the velum, palatal velum, or muscular palate) is, in mammals, the soft tissue constituting the back of the roof of the mouth. The soft palate is part of the palate of the mouth; the other part is the hard palate. ...
, back of the throat, or
esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
can cause painful swallowing. Signs are limited to the lesions themselves. Ulceration episodes usually occur about 3–6 times per year. However, severe disease is characterized by virtually constant ulceration (new lesions developing before old ones have healed) and may cause debilitating chronic pain and interfere with comfortable eating. In severe cases, this prevents adequate nutrient intake leading to
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 ...
and weight loss. Aphthous ulcers typically begin as
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 assoc ...
tous
macule A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sy ...
s (reddened, flat area of
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 is ...
) which develop into ulcers that are covered with a yellow-grey
fibrin Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...
ous
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
that can be scraped away. A reddish "halo" surrounds the ulcer. The size, number, location, healing time, and periodicity between episodes of ulcer formation are all dependent upon the subtype of aphthous stomatitis.


Causes

The cause is not entirely clear, but is thought to be multifactorial. It has been suggested that aphthous stomatitis is not a single entity, but rather a group of conditions with different causes. Multiple research studies have attempted to identify a causative organism, but aphthous stomatitis appears to be non-contagious, non-infectious, and not sexually transmissible. The mucosal destruction is thought to be the result of 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 ...
(T lymphocyte) mediated immune response which involves the generation of
interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
s and
tumor necrosis factor alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
(TNF-α).
Mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
s and
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s are also involved, secreting TNF-α along with the T cells. When early aphthous ulcers are
biopsied A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...
, the
histologic Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
appearance shows a dense inflammatory infiltrate, 80% of which is made up of T cells. Persons with aphthous stomatitis also have circulating lymphocytes which react with
peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...
s 91–105 of
heat shock protein Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...
65–60, and the ratio of
CD4+ T cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...
to
CD8+ T cells A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
in the peripheral blood of individuals with aphthous stomatitis is decreased. Aphthous stomatitis has been associated with other autoimmune diseases, namely
systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
,
Behçet's disease Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the e ...
and inflammatory bowel diseases. However, common autoantibodies are not detected in most patients, and the condition tends to resolve spontaneously with advancing age rather than worsen. Evidence for the T cell-mediated mechanism of mucosal destruction is strong, but the exact triggers for this process are unknown and are thought to be multiple and varied from one person to the next. This suggests that there are a number of possible triggers, each of which is capable of producing the disease in different subgroups. In other words, different subgroups appear to have different causes for the condition. These can be considered in three general groups, namely primary immuno-dysregulation, decrease of the mucosal barrier and states of heightened antigenic sensitivity (see below). Risk factors in aphthous stomatitis are also sometimes considered as either host-related or environmental.


Immunity

At least 40% of people with aphthous stomatitis have a positive family history, suggesting that some people are genetically predisposed to developing oral ulceration.
HLA-B12 HLA-B12 (B12) is an HLA- B serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on t ...
,
HLA-B51 HLA-B51 (B51) is an HLA- B serotype. The serotype identifies the more common HLA-B*51 gene products. B51 is a split antigen of the broad antigen B5, and is a sister serotype of B52. There are many alleles within the B*51 allele group. B51 is ...
, HLA-Cw7,
HLA-A2 HLA-A*02 (A*02) is a human leukocyte antigen serotype within the HLA-A serotype group. The serotype is determined by the antibody recognition of the α2 domain of the HLA-A α-chain. For A*02, the α chain is encoded by the HLA-A*02 gene and the ...
,
HLA-A11 HLA-A11 (A11) is a human leukocyte antigen serotype within HLA-A "A" serotype group. The serotype is determined by the antibody recognition of α11 subset of HLA-A α-chains. For A11, the alpha "A" chain are encoded by the HLA-A allele grou ...
, and
HLA-DR2 HLA-DR2 (DR2) of the HLA- DR serotype system, is a broad antigen serotype that is now preferentially covered by HLA-DR15 and HLA-DR16 serotype group. This serotype primarily recognizes gene products of the HLA-DRB1*15 and HLA-DRB1*16 allele gro ...
are examples of
human leukocyte antigen The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of th ...
types associated with aphthous stomatitis. However, these HLA types are inconsistently associated with the condition, and also vary according to ethnicity. People who have a positive family history of aphthous stomatitis tend to develop a more severe form of the condition, and at an earlier age than is typical. Stress has effects on the immune system, which may explain why some cases directly correlate with stress. It is often stated that in studies of students with the condition, ulceration is exacerbated during examination periods and lessened during periods of vacation. Alternatively, it has been suggested that oral parafunctional activities such as lip or cheek chewing become more pronounced during periods of stress, and hence the mucosa is subjected to more minor trauma. Aphthous-like ulceration also occurs in conditions involving systemic immuno-dysregulation, e.g.
cyclic neutropenia Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It ...
and
human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...
infection. In cyclic neutropenia, more severe oral ulceration occurs during periods of severe immuno-dysregulation, and resolution of the underlying neutropenia is associated with healing of the ulcers. The relative increase in percentage of CD8+ T cells, caused by a reduction in numbers of CD4+ T cells may be implicated in RAS-type ulceration in HIV infection.


Mucosal barrier

The thickness of the mucosa may be an important factor in aphthous stomatitis. Usually, ulcers form on the thinner, non-keratinizing mucosal surfaces in the mouth. Factors which decrease the thickness of the mucosa increase the frequency of occurrence, and factors which increase the thickness of the mucosa correlate with decreased ulceration. The nutritional deficiencies associated with aphthous stomatitis (vitamin B12, folate, and iron) can all cause a decrease in the thickness of the oral mucosa (
atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
). Local trauma is also associated with aphthous stomatitis, and it is known that trauma can decrease the mucosal barrier. Trauma could occur during injections of local anesthetic in the mouth, or otherwise during dental treatments, frictional trauma from a sharp surface in the mouth such as broken tooth, or from tooth brushing. Hormonal factors are capable of altering the mucosal barrier. In one study, a small group of females with aphthous stomatitis had fewer occurrences of aphthous ulcers during the
luteal phase The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...
of the
menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
or with use of the
contraceptive pill Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. Female Two types of female oral contraceptive pill, taken once per day, are widely available: * The combin ...
. This phase is associated with a fall in
progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...
levels, mucosal proliferation and keratinization. This subgroup often experiences remission during pregnancy. However, other studies report no correlation between aphthous stomatitis and menstrual period, pregnancy or menopause. Aphthous stomatitis is more common in people who smoke, and there is also a correlation between habit duration and severity of the condition. Tobacco use is associated with an increase in keratinization of the oral mucosa. In extreme forms, this may manifest as
leukoplakia Oral leukoplakia is a ''potentially malignant disorder'' affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque th ...
or
stomatitis nicotina Stomatitis nicotina is a diffuse white patch on the hard palate, usually caused by tobacco smoking, usually pipe or cigar smoking. It is painless, and it is caused by a response of the palatal oral mucosa to chronic heat. A more pronounced appeara ...
(smoker's keratosis). This increased keratinization may mechanically reinforce the mucosa and reduce the tendency of ulcers to form after minor trauma, or present a more substantial barrier to microbes and antigens, but this is unclear. Nicotine is also known to stimulate production of adrenal steroids and reduce production of TNF-α, interleukin-1 and interleukin-6.
Smokeless tobacco Smokeless tobacco is a tobacco products, tobacco product that is used by means other than smoking. Their use involves chewing, sniffing, or placing the product between gum and the cheek or lip. Smokeless tobacco products are produced in various f ...
products also seem to protect against aphthous stomatitis. Cessation of smoking is known to sometimes precede the onset of aphthous stomatitis in people previously unaffected, or exacerbate the condition in those who were already experiencing aphthous ulceration. Despite this correlation, starting smoking again does not usually lessen the condition.


Antigenic sensitivity

Various antigenic triggers have been implicated as a trigger, including L forms of streptococci,
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 inf ...
,
varicella-zoster virus Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...
,
adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
, and
cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
. Some people with aphthous stomatitis may show herpes virus within the epithelium of the
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 is ...
, but without any productive infection. In some persons, attacks of ulceration occur at the same time as asymptomatic
viral shedding Viral shedding is the expulsion and release of virus progeny following successful reproduction during a host cell infection. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruse ...
and elevated viral titres. In some instances, recurrent mouth ulcers may be a manifestation of an
allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
. Possible allergens include certain foods (e.g., chocolate, coffee, strawberries, eggs, nuts, tomatoes, cheese, citrus fruits,
benzoate Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, wh ...
s,
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 shik ...
, and highly acidic foods), toothpastes, and mouthwashes. Where dietary allergens are responsible, mouth ulcers usually develop within about 12–24 hours of exposure. Sodium lauryl sulphate (SLS), a
detergent A detergent is a surfactant or a mixture of surfactants with cleansing properties when in dilute solutions. There are a large variety of detergents, a common family being the alkylbenzene sulfonates, which are soap-like compounds that are more ...
present in some brands of toothpaste and other oral healthcare products, may produce oral ulceration in some individuals. It has been shown that aphthous stomatitis is more common in people using toothpastes containing SLS, and that some reduction in ulceration occurs when a SLS-free toothpaste is used. Some have argued that since SLS is almost ubiquitously used in oral hygiene products, there is unlikely to be a true predisposition for aphthous stomatitis caused by SLS.


Systemic disease

Aphthous-like ulceration may occur in association with several systemic disorders (see table). These ulcers are clinically and histopathologically identical to the lesions of aphthous stomatitis, but this type of oral ulceration is not considered to be true aphthous stomatitis by some sources. Some of these conditions may cause ulceration on other mucosal surfaces in addition to the mouth such as the
conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...
or the genital mucous membranes. Resolution of the systemic condition often leads to decreased frequency and severity of the oral ulceration. Behçet's disease is a triad of mouth ulcers, genital ulcers and anterior
uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
. The main feature of Behçet's disease is aphthous-like ulceration, but this is usually more severe than seen in aphthous stomatitis without a systemic cause, and typically resembles major or herpetiforme ulceration or both. Aphthous-like ulceration is the first sign of the disease in 25–75% of cases. Behçet's is more common in individuals whose ethnic origin is from regions along the
Silk Road The Silk Road () was a network of Eurasian trade routes active from the second century BCE until the mid-15th century. Spanning over 6,400 kilometers (4,000 miles), it played a central role in facilitating economic, cultural, political, and reli ...
(between the
Mediterranean The Mediterranean Sea is a sea connected to the Atlantic Ocean, surrounded by the Mediterranean Basin and almost completely enclosed by land: on the north by Western and Southern Europe and Anatolia, on the south by North Africa, and on the e ...
and the
Far East The ''Far East'' was a European term to refer to the geographical regions that includes East and Southeast Asia as well as the Russian Far East to a lesser extent. South Asia is sometimes also included for economic and cultural reasons. The ter ...
). It tends to be rare in other countries such as the United States and the United Kingdom.
MAGIC syndrome Magic or Magick most commonly refers to: * Magic (supernatural), beliefs and actions employed to influence supernatural beings and forces * Ceremonial magic, encompasses a wide variety of rituals of magic * Magical thinking, the belief that unrela ...
is a possible variant of Behçet's disease, and is associated with aphthous-like ulceration. The name stands for "mouth and genital ulcers with inflamed cartilage" (
relapsing polychondritis Relapsing polychondritis is a multi-systemic condition characterized by repeated episodes of inflammation and deterioration of cartilage. The often painful disease can cause joint deformity and be life-threatening if the respiratory tract, heart v ...
).
PFAPA syndrome 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 ...
is a rare condition that tends to occur in children. The name stands for "periodic
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, aphthae,
pharyngitis Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoarse voice ...
(sore throat) and cervical adenitis" (inflammation of the
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s in the neck). The fevers occur periodically about every 3–5 weeks. The condition appears to improve with
tonsillectomy Tonsillectomy is a list of surgical procedures, surgical procedure in which both palatine tonsils are fully removed from the back of the throat. The procedure is mainly performed for recurrent tonsillitis, throat infections and obstructive sleep ...
or immunosuppression, suggesting an immunologic cause. In
cyclic neutropenia Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It ...
, there is a reduction in the level of circulating
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s in the blood that occurs about every 21 days.
Opportunistic infection An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...
s commonly occur and aphthous-like ulceration is worst during this time.
Hematinic A hematinic is a nutrient required for the formation of blood cells in the process of hematopoiesis. The main hematinics are iron, B12, and folate. Deficiency in hematinics can lead to anaemia. In cases of hematinic deficiency, hematinics can be ...
deficiencies (
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. It ...
,
folic acid 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 and ...
and
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 f ...
), occurring singly or in combination, and with or without any underlying gastrointestinal disease, may be twice as common in people with RAS. However, iron and vitamin supplements only infrequently improve the ulceration. The relationship to vitamin B12 deficiency has been the subject of many studies. Although these studies found that 0–42% of those with recurrent ulcers have a vitamin B12 deficiency, an association with deficiency is rare. Even in the absence of deficiency, vitamin B12 supplementation may be helpful due to unclear mechanisms. Hematinic deficiencies can cause
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
, which is also associated with aphthous-like ulceration.
Gastrointestinal disorder Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the Human gastrointestinal tract, gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory org ...
s are sometimes associated with aphthous-like stomatitis, e.g. most commonly
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 barl ...
, but also
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
such as
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
or
ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...
. The link between gastrointestinal disorders and aphthous stomatitis is probably related to nutritional deficiencies caused by
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 ...
. Less than 5% of people with RAS have celiac disease, which usually presents with severe malnutrition, anemia,
abdominal pain Abdominal pain, also known as a stomach ache, is a symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
,
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
and
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 ...
(inflammation of the tongue). Sometimes aphthous-like ulcerations can be the only sign of celiac disease. Despite this association, a
gluten-free diet A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of proteins found in wheat (and all of its species and hybrids, such as spelt, kamut, and triticale), as well as barley, rye, and oats. The incl ...
does not usually improve the oral ulceration. Other examples of systemic conditions associated with aphthous-like ulceration include
reactive arthritis Reactive arthritis, also known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can ...
, and recurrent
erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...
.


Diagnosis

Diagnosis is mostly based on the clinical appearance and the medical history. The most important diagnostic feature is a history of recurrent, self healing ulcers at fairly regular intervals. Although there are many causes of oral ulceration, ''recurrent'' oral ulceration has relatively few causes, most commonly aphthous stomatitis, but rarely
Behçet's disease Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the e ...
,
erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...
, ulceration associated with gastrointestinal disease, and recurrent intra-oral herpes simplex infection. A systemic cause is more likely in adults who suddenly develop recurrent oral ulceration with no prior history. Special investigations may be indicated to rule out other causes of oral ulceration. These include
blood test A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholester ...
s to exclude anemia, deficiencies of iron, folate or vitamin B12, or celiac disease. However, the nutritional deficiencies may be latent and the peripheral blood picture may appear relatively normal. Some suggest that screening for celiac disease should form part of the routine work up for individuals complaining of recurrent oral ulceration. Many of the systemic diseases cause other symptoms apart from oral ulceration, which is in contrast to aphthous stomatitis where there is isolated oral ulceration. Patch testing may be indicated if allergies are suspected (e.g. a strong relationship between certain foods and episodes of ulceration). Several drugs can cause oral ulceration (e.g.
nicorandil Nicorandil is a vasodilatory drug used to treat angina. Angina is chest pain that results from episodes of transient myocardial ischemia. This can be caused by diseases such as atherosclerosis, coronary artery disease and aortic stenosis. An ...
), and a trial substitution to an alternative drug may highlight a causal relationship. Tissue
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
is not usually required, unless to rule out other suspected conditions such as oral
squamous cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
. The
histopathologic Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
appearance is not
pathognomonic Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doub ...
(the microscopic appearance is not specific to the condition). Early lesions have a central zone of ulceration covered by a fibrinous membrane. In the
connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
deep to the ulcer there is increased
vascularity Vascularity, in bodybuilding, is the condition of having many highly visible, prominent, and often extensively-ramified superficial veins. The skin appears "thin"—sometimes virtually transparent—due to an extreme reduction of subcutaneous fat ...
and a mixed inflammatory infiltrate composed of lymphocytes,
histiocyte A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s and
polymorphonuclear leukocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They hav ...
s. The
epithelium 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 intercellul ...
on the margins of the ulcer shows
spongiosis Spongiosis is mainly intercellular edema (abnormal accumulation of fluid) in the epidermis,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. Page 1230. . and is characteristic of ...
and there are many mononuclear cells in the basal third. There are also lymphocytes and
histiocyte A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s in the connective tissue surrounding deeper blood vessels near to the ulcer, described histologically as "perivascular cuffing".


Classification

Aphthous stomatitis has been classified as a type of non-infectious
stomatitis Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...
(inflammation of the mouth). One classification distinguishes "common simple aphthae", accounting for 95% of cases, with 3–6 attacks per year, rapid healing, minimal pain and restriction of ulceration to the mouth; and "complex aphthae", accounting for 5% of cases, where ulcers may be present on the genital mucosa in addition to mouth, healing is slower and pain is more severe. A more common method of classifying aphthous stomatitis is into three variants, distinguished by the size, number and location of the lesions, the healing time of individual ulcers and whether a scar is left after healing (see below).


Minor aphthous ulceration

This is the most common type of aphthous stomatitis, accounting for about 80–85% of all cases. This subtype is termed minor aphthous ulceration (MiAU), or minor recurrent aphthous stomatitis (MiRAS). The lesions themselves may be referred to as minor aphthae or minor aphthous ulcers. These lesions are generally less than 10 mm in diameter (usually about 2–3 mm), and affect non-
keratinized 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 scales, hair, nails, feathers, h ...
mucosal surfaces (i.e. the
labial The term ''labial'' originates from '' Labium'' (Latin for "lip"), and is the adjective that describes anything of or related to lips, such as lip-like structures. Thus, it may refer to: * the lips ** In linguistics, a labial consonant ** In zoolog ...
and
buccal 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 des ...
,
lateral Lateral is a geometric term of location which may refer to: Healthcare *Lateral (anatomy), an anatomical direction *Lateral cricoarytenoid muscle *Lateral release (surgery), a surgical procedure on the side of a kneecap Phonetics *Lateral cons ...
borders of the tongue and the floor of the mouth). Usually several ulcers appear at the same time, but single ulcers are possible. Healing usually takes seven to ten days and leaves no scar. Between episodes of ulceration, there is usually an ulcer-free period of variable length.


Major aphthous ulceration

This subtype makes up about 10% of all cases of aphthous stomatitis. It is termed major aphthous ulceration (MaAU) or major recurrent aphthous stomatitis (MaRAS). Major aphthous ulcers (major aphthae) are similar to minor aphthous ulcers, but are more than 10 mm in diameter and the ulceration is deeper. Because the lesions are larger, healing takes longer (about twenty to thirty days), and may leave scars. Each episode of ulceration usually produces a greater number of ulcers, and the time between attacks is less than seen in minor aphthous stomatitis. Major aphthous ulceration usually affects non-keratinized mucosal surfaces, but less commonly keratinized mucosa may also be involved, such as the dorsum (top surface) of the
tongue The tongue is a muscular organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive process, and is the primary organ of taste. The tongue's upper surface (dorsum) is covered by taste ...
or 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 lini ...
(gums). The soft palate or the fauces (back of the throat) may also be involved, the latter being part of the
oropharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
rather than the
oral cavity In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on ...
. Compared to minor aphthous ulceration, major aphthae tend to have an irregular outline.


Herpetiform ulceration

Herpetiform ulcers, (also termed stomatitis herpetiformis, or herpes-like ulcerations) is a subtype of aphthous stomatitis so named because the lesions resemble a primary infection with
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 inf ...
(
primary 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 greate ...
). However, herpetiform ulceration is not caused by herpes viruses. As with all types of aphthous stomatitis, it is not contagious. Unlike true herpetic ulcers, herpetiforme ulcers are not preceded by
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
(small, fluid-filled blisters). Herpetiforme ulcers are less than 1 mm in diameter and occur in variably sized crops up to one hundred at a time. Adjacent ulcers may merge to form larger, continuous areas of ulceration. Healing occurs within fifteen days without scarring. The ulceration may affect keratinized mucosal surfaces in addition to non keratinized. Herpetiform ulceration is often extremely painful, and the lesions recur more frequently than minor or major aphthous ulcers. Recurrence may be so frequent that ulceration is virtually continuous. It generally occurs in a slightly older age group than the other subtypes, and females are affected slightly more frequently than males.


RAS type ulceration

Recurrent oral ulceration associated with systemic conditions is termed "RAS-type ulceration", "RAS-like ulceration", or "aphthous-like ulcers". Aphthous stomatitis occurs in individuals with no associated systemic disease. Persons with certain systemic diseases may be prone to oral ulceration, but this is secondary to the underlying medical condition (see the
systemic disease A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Examples * Mastocytosis, including mast cell activation syndrome and eosinophilic esophagitis * Chronic fatigue syndrome * Systemic vasculi ...
section). This kind of ulceration is considered by some to be separate from true aphthous stomatitis. However, this definition is not strictly applied. For example, many sources refer to oral ulceration caused by anemia and/or nutritional deficiencies as aphthous stomatitis, and some also consider
Behçet's disease Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the e ...
to be a variant.


Treatment

The vast majority of people with aphthous stomatitis have minor symptoms and do not require any specific therapy. The pain is often tolerable with simple dietary modification during an episode of ulceration such as avoiding spicy and acidic foods and beverages. Many different
topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
and systemic medications have been proposed (see table), sometimes showing little or no evidence of usefulness when formally investigated. Some of the results of interventions for RAS may in truth represent a
placebo effect A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...
. No therapy is curative, with treatment aiming to relieve pain, promote healing and reduce the frequency of episodes of ulceration.


Medication

The first line of therapy for aphthous stomatitis are topical agents rather than systemic medication, with topical corticosteroids being the mainstay treatment. Systemic treatment is usually reserved for severe disease due to the risk of adverse side effects associated with many of these agents. A
systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
found that no single systemic intervention was found to be effective. Good
oral hygiene Oral hygiene is the practice of keeping one's mouth clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and cleaning between the teeth. It is important that oral hygiene be carried out ...
is important to prevent secondary infection of the ulcers. Occasionally, in females where ulceration is correlated to the menstrual cycle or to birth control pills, progestogen or a change in birth control may be beneficial. Use of nicotine replacement therapy for people who have developed oral ulceration after stopping smoking has also been reported. Starting smoking again does not usually lessen the condition. Trauma can be reduced by avoiding rough or sharp foodstuffs and by brushing teeth with care. If sodium lauryl sulfate is suspected to be the cause, avoidance of products containing this chemical may be useful and prevent recurrence in some individuals. Similarly patch testing may indicate that food allergy is responsible, and the diet modified accordingly. If investigations reveal deficiency states, correction of the deficiency may result in resolution of the ulceration. For example, there is some evidence that vitamin B12 supplementation may prevent recurrence in some individuals.


Other

Surgical excision of aphthous ulcers has been described, but it is an ineffective and inappropriate treatment.
Silver nitrate Silver nitrate is an inorganic compound with chemical formula . It is a versatile precursor to many other silver compounds, such as those used in photography. It is far less sensitive to light than the halides. It was once called ''lunar caustic' ...
has also been used as a chemical cauterant. Apart from the mainstream approaches detailed above, there are numerous treatments of unproven effectiveness, ranging from herbal remedies to otherwise alternative treatments, including '' Aloe vera'', '' Myrtus communis'', ''
Rosa damascena Rosa or De Rosa may refer to: People *Rosa (given name) * Rosa (surname) *Santa Rosa (female given name from Latin-a latinized variant of Rose) Places *223 Rosa, an asteroid *Rosa, Alabama, a town, United States *Rosa, Germany, in Thuringia, Ge ...
'',
potassium alum Potassium alum, potash alum, or potassium aluminium sulfate is a chemical compound: the double sulfate of potassium and aluminium, with chemical formula KAl(SO4)2. It is commonly encountered as the dodecahydrate, KAl(SO4)2·12H2O. It crystalli ...
,
zinc sulfate Zinc sulfate is an inorganic compound. It is used as a dietary supplement to treat zinc deficiency and to prevent the condition in those at high risk. Side effects of excess supplementation may include abdominal pain, vomiting, headache, and ti ...
, nicotine,
polio virus A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species ''Enterovirus C'', in the family of ''Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3. Poliovirus is composed of an ...
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
and prostaglandin E2.


Prognosis

By definition, there is no serious underlying medical condition, and most importantly, the ulcers do not represent
oral cancer Oral cancer, also known as mouth cancer, is cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless white patch, that thickens, develops red patches, an ulcer, and continues to grow. When on ...
nor are they infectious. However, aphthae are capable of causing significant discomfort. There is a spectrum of severity, with symptoms ranging from a minor nuisance to disabling. Due to pain during eating, weight loss may develop as a result of not eating in severe cases of aphthous stomatitis. Usually, the condition lasts for several years before spontaneously disappearing in later life.


Epidemiology

Aphthous stomatitis affects between 5% and 66% of people, with about 20% of individuals in most populations having the condition to some degree. This makes it the most common disease of the oral mucosa. Aphthous stomatitis occurs worldwide, but is more common in developed countries. Within nations, it is more common in higher socioeconomic groups. Males and females are affected in an equal ratio, and the peak age of onset between 10 and 19 years. About 80% of people with aphthous stomatitis first developed the condition before the age of 30. There have been reports of ethnic variation. For example, in the United States, aphthous stomatitis may be three times more common in white-skinned people than black-skinned people.


History, society and culture

"Aphthous affectations" and "aphthous ulcerations" of the mouth are mentioned several times in the treatise "Of the Epidemics" (part of the
Hippocratic corpus The Hippocratic Corpus (Latin: ''Corpus Hippocraticum''), or Hippocratic Collection, is a collection of around 60 early Ancient Greek medical works strongly associated with the physician Hippocrates and his teachings. The Hippocratic Corpus cove ...
, in the 4th century BCE), although it seems likely that this was oral ulceration as a manifestation of some infectious disease, since they are described as occurring in
epidemic An epidemic (from Ancient Greek, Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time. Epidemics ...
-like patterns, with concurrent symptoms such as fever. Aphthous stomatitis was once thought to be a form of recurrent herpes simplex virus infection, and some clinicians still refer to the condition as "herpes" despite this cause having been disproven. The informal term "canker sore" is sometimes used, mainly in North America, either to describe this condition generally, or to refer to the individual ulcers of this condition, or mouth ulcers of any cause unrelated to this condition. The origin of the word "canker" is thought to have been influenced by Latin, Old English, Middle English and Old North French. In Latin, ''cancer'' translates to "malignant tumor" or literally "crab" (related to the likening of sectioned tumors to the limbs of a crab). The closely related word in Middle English and Old North French, ''
chancre A chancre ( )chancres
thefreedictionary
is a painless
'', now more usually applied to
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
, is also thought to be involved. Despite this etymology, aphthous stomatitis is not a form of cancer but rather entirely benign. An aphtha (plural ''aphthae'') is a non specific term that refers to an ulcer of the mouth. The word is derived from the Greek word ''aphtha'' meaning "eruption" or "ulcer". The lesions of several other oral conditions are sometimes described as aphthae, including
Bednar's aphthae Bednar's aphthae is a type of oral ulceration (mouth ulcers) which occurs in infants. The lesions are located on the palate and are caused by trauma. No treatment is required since the lesions heal within a few days. The condition was first descr ...
(infected, traumatic ulcers on the hard palate in infants),
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 ...
, and
foot-and-mouth disease Foot-and-mouth disease (FMD) or hoof-and-mouth disease (HMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids. The virus causes a high fever lasting two to six days, followe ...
. When used without qualification, ''aphthae'' commonly refers to lesions of recurrent aphthous stomatitis. Since the word aphtha is often taken to be synonymous with ulcer, it has been suggested that the term "aphthous ulcer" is redundant, but it remains in common use.
Stomatitis Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...
is also a non-specific term referring to any inflammatory process in the mouth, with or without oral ulceration. It may describe many different conditions apart from aphthous stomatitis such as angular stomatitis. The current most widely used medical term is "recurrent aphthous stomatitis" or simply "aphthous stomatitis". Historically, many different terms have been used to refer to recurrent aphthous stomatitis or its sub-types, and some are still in use. Mikulicz's aphthae is a synonym of minor RAS, named after
Jan Mikulicz-Radecki Jan Mikulicz-Radecki (german: Johann Freiherr von Mikulicz-Radecki) was a German-Polish-Austrian surgeon who worked mainly in the German Empire. He was born on 16 May 1850 in Czerniowce in the Austrian Empire (present-day Chernivtsi in Ukraine) ...
. Synonyms for major RAS include Sutton's ulcers (named after
Richard Lightburn Sutton Richard Lightburn Sutton Sr. M.D. FRSE FRGS LLD (July 9, 1878 – May 18, 1952) was an American dermatology, dermatologist. He gives the eponym for Sutton's disease (also known as aphthous ulceration, or canker sores), Sutton's naevus and Sutton's ...
), Sutton's disease, Sutton's syndrome and periadenitis mucosa necrotica recurrens. Synonyms for aphthous stomatitis as a whole include (recurrent) oral aphthae, (recurrent) aphthous ulceration and (oral) aphthosis. In
traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of action ...
, claimed treatments for aphthae focus on clearing heat and nourishing
Yin Yin may refer to: *the dark force in the yin and yang from traditional Chinese philosophy and medicine *Yīn (surname) (), a Chinese surname *Yǐn (surname) (), a Chinese surname *Shang dynasty, also known as the Yin dynasty **Yinxu or Yin, the S ...
. Rembrandt Gentle White toothpaste did not contain sodium lauryl sulfate, and was specifically marketed as being for the benefit of "canker sore sufferers". When the manufacturer
Johnson & Johnson Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...
discontinued the product in 2014, it caused a backlash of anger from long-term customers, and the toothpaste began to sell for many times the original price on the auction website
eBay eBay Inc. ( ) is an American multinational e-commerce company based in San Jose, California, that facilitates consumer-to-consumer and business-to-consumer sales through its website. eBay was founded by Pierre Omidyar in 1995 and became a ...
.


See also

*
Acute necrotizing ulcerative gingivitis Acute necrotizing ulcerative gingivitis (ANUG) is a common, non-contagious infection of the gums with sudden onset. The main features are painful, bleeding gums, and ulceration of inter-dental papillae (the sections of gum between adjacent teeth ...
, also known as "trench mouth"—another painful, non-contagious mouth infection with similar symptoms *
Mouth ulcer 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 ...


References


External links

* * {{DEFAULTSORT:Aphthous Ulcer Laryngology Conditions of the mucous membranes Oral mucosal pathology