Aphthous stomatitis caused by a reduction in numbers of CD4+ T cells may be implicated in RAS-type ulceration in HIV infection. 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
Aphthous stomatitis 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 suffer from 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, which is also associated with aphthous-like ulceration. Gastrointestinal disorders are sometimes associated with aphthous-like stomatitis, e.g. most commonly Celiac disease, but also inflammatory bowel disease such as Crohn's disease or ulcerative colitis. The link between gastrointestinal disorders