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 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 (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 apthous 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 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.

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. Some have argued that since SLS is almost ubiquitously used in oral hygiene products, there is unlikely to be a true predisposition for aphthous stomatitis caused by SLS.

Treatment includes fluid intake, good oral hygiene and gentle debridement of the mouth, as well as oral acyclovir. In healthy individuals the lesions heal spontaneously in 7–14 days without scarring.

Gingivostomatitis (also known as primary herpetic gingivostomatitis or orolabial herpes) is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of greater severity than herpes labialis (cold sores) which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.

Primary herpetic gingivostomatitis (PHGS) represents the clinically apparent pattern of primary herpes simplex virus (HSV) infection, since the vast majority of other primary infections are symptomless. PHGS is caused predominantly by HSV-1 and affects mainly children. Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. The disease presents as numerous pin-head vesicles, which rupture rapidly to form painful irregular ulcerations covered by yellow–grey membranes. Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings.

Following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve's cell body. HSV latency is static; no virus is produced; and is controlled by a number of viral genes, including latency-associated transcript.

Many HSV-infected people experience recurrence within the first year of infection. Prodrome precedes development of lesions. Prodromal symptoms include tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop and are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four or five times a year when not using antiviral therapy.

The causes of reactivation are uncertain, but several potential triggers have been documented. A 2009 study showed the protein VP16 plays a key role in reactivation of the dormant virus. Changes in the immune system during menstruation may play a role in HSV-1 reactivation. Concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to other infections is the likely source of the historic terms 'cold sore' and 'fever blister'.

Other identified triggers include local injury to the face, lips, eyes, or mouth; trauma; surgery; radiotherapy; and exposure to wind, ultraviolet light, or sunlight.

The frequency and severity of recurrent outbreaks vary greatly between people. Some individuals' outbreaks can be quite debilitating, with large, painful lesions persisting for several weeks, while others experience only minor itching or burning for a few days. Some evidence indicates genetics play a role in the frequency of cold sore outbreaks. An area of human chromosome 21 that includes six genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals experience fewer outbreaks and outbreak symptoms often become less severe. After several years, some people become perpetually asymptomatic and no longer experience outbreaks, though they may still be contagious to others. Immunocompromised individuals may experience longer, more frequent, and more severe episodes. Antiviral medication has been proven to shorten the frequency and duration of outbreaks. Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs.

HSV-2-infected individuals are at higher risk for acquiring HIV when practicing unprotected sex with HIV-positive persons, in particular during an outbreak with active lesions.

Herpes labialis is common throughout the world. A large survey of young adults on six continents reported that 33% of males and 28% of females had herpes labialis on two or more occasions during the year before the study. The lifetime prevalence in the United States of America is estimated at 20–45% of the adult population. Lifetime prevalence in France was reported by one study as 32% in males and 42% in females. In Germany, the prevalence was reported at 32% in people aged between 35 and 44 years, and 20% in those aged 65–74. In Jordan, another study reported a lifetime prevalence of 26%.

Many infections can cause oral ulceration (see table). The most common are herpes simplex virus (herpes labialis, primary herpetic gingivostomatitis), varicella zoster (chicken pox, shingles), and coxsackie A virus (hand, foot and mouth disease). Human immunodeficiency virus (HIV) creates immunodeficiencies which allow opportunistic infections or neoplasms to proliferate. Bacterial processes leading to ulceration can be caused by "Mycobacterium tuberculosis" (tuberculosis) and "Treponema pallidum" (syphilis).

Opportunistic activity by combinations of otherwise normal bacterial flora, such as aerobic streptococci, "Neisseria", "Actinomyces", spirochetes, and "Bacteroides" species can prolong the ulcerative process. Fungal causes include "Coccidioides immitis" (valley fever), "Cryptococcus neoformans" (cryptococcosis), and "Blastomyces dermatitidis" ("North American Blastomycosis"). Entamoeba histolytica, a parasitic protozoan, is sometimes known to cause mouth ulcers through formation of cysts.

Herpes labialis infection occurs when the herpes simplex virus comes into contact with oral mucosal tissue or abraded skin of the mouth. Infection by the type 1 strain of herpes simplex virus (HSV-1) is most common; however, cases of oral infection by the type 2 strain are increasing. Specifically, type 2 has been implicated as causing 10–15% of oral infections.

Cold sores are the result of the virus reactivating in the body. Once HSV-1 has entered the body, it never leaves. The virus moves from the mouth to remain latent in the central nervous system. In approximately one-third of people, the virus can "wake up" or reactivate to cause disease. When reactivation occurs, the virus travels down the nerves to the skin where it may cause blisters (cold sores) around the lips, in the mouth or, in about 10% of cases, on the nose, chin, or cheeks.

Cold sore outbreaks may be influenced by stress, menstruation, sunlight, sunburn, fever, dehydration, or local skin trauma. Surgical procedures such as dental or neural surgery, lip tattooing, or dermabrasion are also common triggers. HSV-1 can in rare cases be transmitted to newborn babies by family members or hospital staff who have cold sores; this can cause a severe disease called neonatal herpes simplex.

The colloquial term for this condition, "cold sore" comes from the fact that herpes labialis is often triggered by fever, for example, as may occur during an upper respiratory tract infection (i.e. a cold).

People can transfer the virus from their cold sores to other areas of the body, such as the eye, skin, or fingers; this is called "autoinoculation". Eye infection, in the form of conjunctivitis or keratitis, can happen when the eyes are rubbed after touching the lesion. Finger infection (herpetic whitlow) can occur when a child with cold sores or primary HSV-1 infection sucks his fingers.

Blood tests for herpes may differentiate between type 1 and type 2. When a person is not experiencing any symptoms, a blood test alone does not reveal the site of infection. Genital herpes infections occurred with almost equal frequency as type 1 or 2 in younger adults when samples were taken from genital lesions. Herpes in the mouth is more likely to be caused by type 1, but (see above) also can be type 2. The only way to know for certain if a positive blood test for herpes is due to infection of the mouth, genitals, or elsewhere, is to sample from lesions. This is not possible if the afflicted individual is asymptomatic.

Many drugs can cause mouth ulcers as a side effect. Common examples are alendronate (a bisphosphonate, commonly prescribed for osteoporosis), cytotoxic drugs (e.g. methotrexate, i.e. chemotherapy), non-steroidal anti-inflammatory drugs, nicorandil (may be prescribed for angina) and propylthiouracil (e.g. used for hyperthyroidism). Some recreational drugs can cause ulceration, e.g. cocaine.

As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is about 8–11%.

This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is around 4–5% annually. Suppressive antiviral therapy reduces these risks by 50%. Antivirals also help prevent the development of symptomatic HSV in infection scenarios, meaning the infected partner will be seropositive but symptom-free by about 50%. Condom use also reduces the transmission risk significantly. Condom use is much more effective at preventing male-to-female transmission than "vice versa". Previous HSV-1 infection may reduce the risk for acquisition of HSV-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples.

However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom people will have of their own infections is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.

In October 2011, the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%.

In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the cutting, chewing or sucking of fingernail or thumbnail.

In adults, it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because of increased exposure to the herpes virus.

Contact sports are also a potential source of infection with herpetic whitlows.

There are many oral and maxillofacial pathologies which are not fully understood.

- Burning mouth syndrome (BMS) is a disorder where there is a burning sensation in the mouth that has no identifiable medical or dental cause. The disorder can affect anyone but tends to occur most often in middle aged women. BMS has been hypothesized to be linked to a variety of factors such as the menopause, dry mouth (xerostomia) and allergies. BMS usually lasts for several years before disappearing for unknown reasons. Other features of this disorder include anxiety, depression and social isolation. There is no cure for this disorder and treatment includes use of hydrating agents, pain medications, vitamin supplements or the usage of antidepressants.

- Aphthous stomatitis is a condition where ulcers (canker sores) appear on the inside of the mouth, lips and on tongue. Most small canker sores disappear within 10–14 days. Canker sores are most common in young and middle aged individuals. Sometimes individuals with allergies are more prone to these sores. Besides an awkward sensation, these sores can also cause pain or tingling or a burning sensation. Unlike herpes sores, canker sores are always found inside the mouth and are usually less painful. Good oral hygiene does help but sometime one may have to use a topical corticosteroid.

- Migratory stomatitis is a condition that involves the tongue and other oral mucosa. The common migratory glossitis (geographic tongue) affects the anterior two thirds of the dorsal and lateral tongue mucosa of 1% to 2.5% of the population, with one report of up to 12.7% of the population. The tongue is often fissured, especially. in elderly individuals. In the American population, a lower prevalence was reported among Mexican Americans (compared with Caucasians and African Americans) and cigarette smokers. When other oral mucosa, beside the dorsal and lateral tongue, are involved, the term migratory stomatitis (or ectopic geographic tongue) is preferred. In this condition, lesions infrequently involve also the ventral tongue and buccal or labial mucosa. They are rarely reported on the soft palate and floor of the mouth.

Dietary factors such as spice consumption, were hypothesized to cause ulcers until late in the 20th century, but have been shown to be of relatively minor importance. Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, appear to have little effect. Similarly, while studies have found that alcohol consumption increases risk when associated with "H. pylori" infection, it does not seem to independently increase risk. Even when coupled with "H. pylori" infection, the increase is modest in comparison to the primary risk factor.

Although it is a self-limited illness, oral or intravenous antiviral treatments, particularly acyclovir, have been used in the management of immunocompromised or severely infected patients. Topical acyclovir has not been shown to be effective in management of herpetic whitlow. Famciclovir has been demonstrated to effectively treat and prevent recurrent episodes. Lancing or surgically debriding the lesion may make it worse by causing a superinfection or encephalitis.

About 16 percent of Americans between the ages of 14 and 49 are infected with genital herpes, making it one of the most common sexually transmitted diseases. More than 80% of those infected are unaware of their infection. Annually, 776,000 people in the United States get new herpes infections.

Tests for herpes are not routinely included among STD screenings. Performers in the pornography industry are screened for HIV, chlamydia, and gonorrhea with an optional panel of tests for hepatitis B, hepatitis C and syphilis, but not herpes. Testing for herpes is controversial since the results are not always accurate or helpful. Most sex workers and performers will contract herpes at some point in their careers whether they use protection or not.

Stress due to serious health problems such as those requiring treatment in an intensive care unit is well described as a cause of peptic ulcers, which are termed stress ulcers.

While chronic life stress was once believed to be the main cause of ulcers, this is no longer the case. It is, however, still occasionally believed to play a role. This may be by increasing the risk in those with other causes such as "H. pylori" or NSAID use.

Chronic gastritis is a chronic inflammation of the gastric mucosa.

Bacterial

- (Plaque-induced) gingivitis—A common periodontal (gum) disease is Gingivitis. Periodontal refers to the area the infection affects, which include the teeth, gums, and tissues surrounding the teeth. Bacteria cause inflammation of the gums which become red, swollen and can bleed easily. The bacteria along with mucus form a sticky colorless substance called plaque which harbours the bacteria. Plaque that is not removed by brushing and flossing hardens to form tartar that brushing doesn't clean. Smoking is a major risk factor. Treatment of gingivitis is dependent on how severe and how far the disease has progressed. If the disease is not too severe it is possible to treat it with chlorhexidine rinse and brushing with fluoride toothpaste to kill the bacteria and remove the plaque, but once the infection has progressed antibiotics may be needed to kill the bacteria.

- Periodontitis—When gingivitis is not treated it can advance to periodontitis, when the gums pull away from the teeth and form pockets that harbor the bacteria. Bacterial toxins and the body's natural defenses start to break down the bone and connective tissues. The tooth may eventually become loose and have to be removed.

- Scarlet fever is caused by streptococci species, and starts as tonsilitis and pharyngitis before involving the soft palate and the tongue. It usually occurs in children where a fever occurs and a rash develops on the skin. It is treated with penicillin and the prognosis is generally excellent.

Viral

- Herpes simplex (infection with herpes simplex virus, or HSV) is very common in the mouth and lips. This virus can cause blisters and sores around the mouth (herpetic gingivostomatitis) and lips (herpes labialis). HSV infections tend to recur periodically. Although many people get infected with the virus, only 10% actually develop the sores. The sores may last anywhere from 3–10 days and are very infectious. Some people have recurrences either in the same location or at a nearby site. Unless the individual has an impaired immune system, e.g., owing to HIV or cancer-related immune suppression, recurrent infections tend to be mild in nature and may be brought on by stress, sun, menstrual periods, trauma or physical stress.

- Mumps of the salivary glands is a viral infection of the parotid glands. This results in painful swelling at the sides of the mouth in both adults and children. The infection is quite contagious. Today mumps is prevented by getting vaccinated in infancy. There is no specific treatment for mumps except for hydration and painkillers. Sometimes mumps can cause inflammation of the brain, testicular swelling or hearing loss.

Fungal

- Oral candidiasis is by far the most common fungal infection that occurs in the mouth. It usually occurs in immunocompromised individuals. Individuals who have undergone a transplant, HIV, cancer or use corticosteroids commonly develop candida of the mouth and oral cavity. Other risk factors are dentures and tongue piercing. The typical signs are a white patch that may be associated with burning, soreness, irritation or a white cheesy like appearance. Once the diagnosis is made, candida can be treated with a variety of anti fungal drugs.

This is inflammation of the mouth caused by herpes simplex virus.

Among those in the intensive care unit, ulceration resulting in bleeding is very rare.

Testing peoples blood, including those who are pregnant, who do not have symptoms for HSV is not recommended. This is due to concerns of greater harm than benefit such as relationship problems in the setting of a high rate of tests that may be falsely positive.

Treatment is usually supportive only, as the disease is self-limiting and usually runs its course in less than a week.

Allergic contact stomatitis (also termed "allergic gingivostomatitis" or "allergic contact gingivostomatitis") is a type IV (delayed) hypersensitivity reaction that occurs in susceptible atopic individuals when allergens penetrate the skin or mucosa.

Allergens, which may be different for different individuals, combine with epithelial-derived proteins, forming haptens which bind with Langerhans cells in the mucosa, which in turn present the antigen on their surface to T lymphocytes, sensitizing them to that antigen and causing them to produce many specific clones. The second time that specific antigen is encountered, an inflammatory reaction is triggered at the site of exposure. Allergic contact stomatitis is less common than allergic contact dermatitis because the mouth is coated in saliva, which washes away antigens and acts as a barrier. The oral mucosa is also more vascular (has a better blood supply) than skin, meaning that any antigens are more quickly removed from the area by the circulation. Finally, there is substantially less keratin in oral mucosa, meaning that there is less likelihood that haptens will form.

Allergic contact stomatitis appears as non-specific inflammation, so it may be mistaken for chronic physical irritation. There may be burning or soreness of the mouth and ulceration. Chronic exposure to the allergen may result in a lichenoid lesion. Plasma cell gingivitis may also occur, which may be accompanied by glossitis and cheilitis.

Allergens that may cause allergic contact stomatitis in some individuals include cinnamaldehyde, Balsam of Peru, peppermint, mercury, gold, pyrophosphates, zinc citrate, free acrylic monomer, nickel, fluoride, and sodium lauryl sulfate. These allergens may originate from many sources, including various foods and drink, chewing gum, toothpaste, mouthwash, dental floss, dental fillings, dentures, orthodontic bands or wires, and many other sources. If the substance containing the allergen comes into contact with the lips, allergic contact cheilitis can occur, together with allergic contact stomatitis.

The diagnosis is confirmed by patch test, and management is by avoidance of exposure to the allergen.

This is the most common form of chronic gastritis. Involvement tends to occur in either an antral-predominant or multifocal atrophic pattern. "H. pylori" infection is also associated with development of peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphomas.

Evidence does not support a role for specific foods including spicy foods and coffee in the development of peptic ulcers. People are usually advised to avoid foods that bother them.