aphthous stomatitis aphthous stomatitis aphthous stomatitis, or recurrent aphthous stomatitis (ras), is a common condition characterized by the repeated formation of benign and non-contagious mouth ulcers (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-mediated immune response triggered by a variety of factors which may include nutritional deficiencies, local trauma, stress, hormonal influences, allergies, genetic predisposition, certain foods, dehydration, some food additives, or some hygienic chemical additives like sds (common in toothpaste). aphthous stomatitisother namesrecurrent aphthous stomatitis (ras), recurring oral aphthae, recurrent aphthous ulcerationcanker sore on the lower lipspecialtyoral medicine, dermatologysymptomsa round, often painful sore inside the mouth that is white or gray with a red border; tingling or burning sensation prior to sore development; fever, sluggishness, and/or swollen lymph nodes (severe cases only)complicationscellulitis (a bacterial skin infection); fever; sores that appear outside of the mouth; pain while brushing teeth, eating, and/or talkingusual onset1 to 2 days, before visual appearanceduration7–10 dayscausesbehçet's disease; celiac disease; food allergies; hiv infection; lupus; oral injuries; poor oral hygiene; stress; vitamin deficiencyrisk factorsanyone can develop canker sores.preventionavoiding foods that irritate the mouth, including acidic, hot or spicy foods; avoid irritation from gum chewing; avoiding oral hygiene products containing sodium lauryl sulfate, brushing with a soft-bristled brush after meals and flossing daily.treatmentmouth rinses; nutritional supplements; oral medicationmedicationgood oral hygiene, topical agentsfrequency~20% of people to some degreedeathsnone reported. 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 and the dorsum of the tongue – 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 due to malnutrition. 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 the lower lip is retracted, revealing aphthous ulcers on the labial mucosa (note erythematous "halo" surrounding ulcers) ulcers can take many shapes and sizes. this one is long and narrow persons with aphthous stomatitis have no detectable systemic symptoms or signs (i.e., outside the mouth). generally, symptoms may include prodromal 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, back of the throat, or esophagus 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 and weight loss. aphthous ulcers typically begin as erythematous macules (reddened, flat area of mucosa) which develop into ulcers that are covered with a yellow-grey fibrinous membrane 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 (t lymphocyte) mediated immune response which involves the generation of interleukins and tumor necrosis factor alpha (tnf-α). mast cells and macrophages are also involved, secreting tnf-α along with the t cells. when early aphthous ulcers are biopsied, the histologic 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 peptides 91–105 of heat shock protein 65–60, and the ratio of cd4+ t cells to cd8+ t cells in the peripheral blood of individuals with aphthous stomatitis is decreased. aphthous stomatitis has been associated with other autoimmune diseases, namely systemic lupus erythematosus, behçet's disease 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-b51, hla-cw7, hla-a2, hla-a11, and hla-dr2 are examples of human leukocyte antigen 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 and human immunodeficiency virus 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). 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 of the menstrual cycle or with use of the contraceptive pill. this phase is associated with a fall in progestogen 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 or stomatitis nicotina (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 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, varicella-zoster virus, adenovirus, and cytomegalovirus. some people with aphthous stomatitis may show herpes virus within the epithelium of the mucosa, but without any productive infection. in some persons, attacks of ulceration occur at the same time as asymptomatic viral shedding and elevated viral titres. in some instances, recurrent mouth ulcers may be a manifestation of an allergic reaction. possible allergens include certain foods (e.g., chocolate, coffee, strawberries, eggs, nuts, tomatoes, cheese, citrus fruits, benzoates, cinnamaldehyde, 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 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. systemic disease systemic disorders associated with aphthous-like ulceration behçet's disease celiac disease cyclic neutropenia nutritional deficiencies iga deficiency immunocompromised states, e.g. hiv/aids inflammatory bowel disease magic syndrome pfapa syndrome reactive arthritis sweet's syndrome ulcus vulvae acutum main article: oral ulceration 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 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. 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 (between the mediterranean and the far east). it tends to be rare in other countries such as the united states and the united kingdom. magic syndrome 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). pfapa syndrome is a rare condition that tends to occur in children. the name stands for "periodic fever, aphthae, pharyngitis (sore throat) and cervical adenitis" (inflammation of the lymph nodes in the neck). the fevers occur periodically about every 3–5 weeks. the condition appears to improve with tonsillectomy or immunosuppression, suggesting an immunologic cause. in cyclic