Tobacco use is associated with an increase in keratinization of the oral mucosa. In extreme forms, this may manifest as leukoplakia or stomatitis nicotina (smokers 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.
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.