Aphthous stomatitis
Aphthous stomatitis, or recurrent aphthous stomatitis, commonly referred to as a canker sore or salt blister, is a common condition characterized by the repeated formation of benign and non-contagious mouth ulcers in otherwise healthy individuals.
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.
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. However, 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, but treatments such as corticosteroids aim to manage pain, reduce healing time and reduce the frequency of episodes of ulceration.
Signs and symptoms
Individuals with aphthous stomatitis typically exhibit no detectable systemic symptoms or signs. 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. 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. 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 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 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 mediated immune response which involves the generation of interleukins and tumor necrosis factor alpha. 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. 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 several 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. 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. Hence, the mucosa is subjected to less 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 can all cause a decrease in the thickness of the oral mucosa.
Local trauma is also associated with aphthous stomatitis. 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 a broken tooth, or from tooth brushing.
Hormonal factors can alter 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 less 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. This increased keratinization may mechanically reinforce the mucosa and reduce the tendency for 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 the production of adrenal steroids and reduce the 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, toothpastes, and mouthwashes. Where dietary allergens are responsible, mouth ulcers usually develop within about 12–24 hours of exposure.
Sodium lauryl sulphate, 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 an SLS-free toothpaste is used.