Micro-organisms
Candida in its pathogenic hyphal form is occasionally seen in biopsies of idiopathic leukoplakia. It is debated whether candida infection is a primary cause of leukoplakia with or without dysplasia, or a superimposed (secondary) infection that occurs after the development of the lesion. It is known that Candida species thrive in altered tissues. Some leukoplakias with dysplasia reduce or disappear entirely following use of antifungal medication. Smoking, which as discussed above can lead to the development of leukoplakia, can also promote oral candidiasis. Candida in association with leukoplakia should not be confused with white patches which are primarily caused by candida infection, such as chronic hyperplastic candidiasis ("candidal leukoplakia").The involvement of viruses in the formation of some oral white lesions is well established, e.g. Epstein-Barr virus in oral hairy leukoplakia (which is not a true leukoplakia). Human papilloma virus (HPV), especially HPV 16 and 18, is sometimes found in areas of leukoplakia, however, since this virus can be coincidentally found on normal, healthy mucosal surfaces in the mouth, it is unknown if this virus is involved in the development of some leukoplakias. In vitro experimentation has demonstrated that HPV 16 is capable of inducing dysplastic changes in previously normal squamous epithelium. Epithelial atrophy
Leukoplakia is more likely to develop in areas of epithelial atrophy. Conditions associated with mucosal atrophy include iron deficiency, some vitamin deficiencies, oral submucous fibrosis, syphilis and sideropenic dysphagia. Trauma
Another very common cause of white patches in the mouth is frictional or irritational trauma leading to keratosis.
Causes
The causes of ORS are unknown. It is thought that significant negative experiences may trigger the development of ORS. These have been considered as two types: key traumatic experiences related to smell, and life stressors present when the condition developed but which were unrelated to smell. In one review, 85% of reported cases had traumatic, smell-related experiences, and 17% of cases had stress factors unrelated to smell. Reported smell-related experiences usually revolve around family members, friends, co-workers, peers or other people making comments about an odor from the person, which causes embarrassment and shame. Examples include accusation of flatulence during a religious ceremony, or being bullied for flatulence such at school, accidental urination in class, announcements about a passenger needing to use deodorant over speaker by a driver on public transport, sinusitis which caused a bad taste in the mouth, mockery about a fish odor from a finger which had been inserted into the persons vagina in the context of a sexual assault, and revulsion about menarche and brothers sexual intimacy. It has been suggested that a proportion of such reported experiences may not have been real, but rather early symptom of ORS (i.e. referential thoughts). Examples of non smell-related stressful periods include guilt due to a romantic affair, being left by a partner, violence in school, family illness when growing up (e.g. cancer), and bullying.The importance of a family history of mental illness or other conditions in ORS is unclear, because most reported cases have lacked this information.