Materiały źródłowe

• #1 Recurrent Aphthous Stomatitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431059/

  Recurrent aphthous stomatitis (RAS) is a chronic oral mucosa inflammatory disorder with an uncertain etiology. […] The etiology of recurrent aphthous stomatitis remains imperfectly understood. The cause is believed to be multifactorial, involving a cell-mediated immunological reaction and a genetic predisposition. Histopathological changes are seen before ulceration occurs. Lymphocytes (mononuclear cells) infiltrate the oral epithelium, edema develops, and the keratinocytes (oral epithelial cells) undergo vacuolization and vasculitis. This results in localized swelling and later ulceration of the epithelium. Infiltration with neutrophils, lymphocytes, and plasma cells occurs before the epithelium heals and regenerates. The pathogenesis of RAS is a T-cell-mediated immunological reaction involving the inflammatory cytokine named tumor necrosis factor-alpha (TNF-). TNF- activates the chemotaxis of neutrophils, generating an acute inflammatory response and the expression of the major histocompatibility (MHC) complex.

• #2 Aphthous Stomatitis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1075570-overview

  Aphthous stomatitis (also known as recurrent aphthous ulcers or canker sores) is among the most common oral mucosal lesions observed by physicians and dentists. […] The precise etiology and the pathogenesis remain unclear. Many possibilities have been investigated. Recurrent aphthous ulcer is a multifactorial condition, and it is likely that immune-mediated destruction of the epithelium is the common factor in its pathogenesis. […] Although no unifying theory of the immunopathogenesis of recurrent aphthous ulcer has been established, immune dysregulation appears to play a significant role. Cytotoxic action of lymphocytes and monocytes on the oral epithelium may cause the ulceration, but the trigger remains unclear. […] Recurrent aphthous ulcer formation may be a T-cell-mediated response to antigens of Streptococcus sanguis that cross-react with the mitochondrial heat-shock proteins and induce damage to oral mucosa.

• #3 Recurrent Aphthous Stomatitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431059/

  Recurrent aphthous stomatitis (RAS) is a chronic oral mucosa inflammatory disorder with an uncertain etiology. […] The etiology of recurrent aphthous stomatitis remains imperfectly understood. The cause is believed to be multifactorial, involving a cell-mediated immunological reaction and a genetic predisposition. Histopathological changes are seen before ulceration occurs. Lymphocytes (mononuclear cells) infiltrate the oral epithelium, edema develops, and the keratinocytes (oral epithelial cells) undergo vacuolization and vasculitis. This results in localized swelling and later ulceration of the epithelium. Infiltration with neutrophils, lymphocytes, and plasma cells occurs before the epithelium heals and regenerates. The pathogenesis of RAS is a T-cell-mediated immunological reaction involving the inflammatory cytokine named tumor necrosis factor-alpha (TNF-). TNF- activates the chemotaxis of neutrophils, generating an acute inflammatory response and the expression of the major histocompatibility (MHC) complex.

• #4 Aphthous stomatitis – Wikipedia

  https://en.wikipedia.org/wiki/Aphthous_stomatitis

  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 (common in toothpaste). […] Evidence for the T cell-mediated mechanism of mucosal destruction is strong, but 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 a number of possible triggers, each of which is capable of producing the disease in different subgroups. […] The mucosal destruction is thought to be the result of a T cell (T lymphocyte) mediated immune response which involves the generation of interleukins and tumor necrosis factor alpha (TNF-). […] When early aphthous ulcers are biopsied, the histologic appearance shows a dense inflammatory infiltrate, 80% of which is made up of T cells.

• #5 Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8934078/

  The pathogenesis of recurrent aphthosis stomatitis (RAS) remains poorly defined. It likely involves a predominantly cell-mediated inflammation involving T-cells and TNF- (tumor necrosis factor-alpha) production. […] Light and electron-microscope examination of oral aphthous ulcers showed a penetrating, early, lympho-monocyte infiltration of the epithelium. […] According to a study by Lehner, under light microscopy, oral ulcer epithelium showed considerable intercellular edema and degenerative changes. […] There was epithelial hyperplasia and only the basement membrane adjacent to the ulcer was affected, the rest of the basement membrane appeared intact. […] Mononuclear cells normally infiltrate the basal-cell and prickle-cell layers of the epidermis and they are most commonly lymphocytes and monocytes, but superficial to and immediately adjacent to the ulcer neutrophil polymorphs were also found.

• #6 Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8934078/

  The pathogenesis of recurrent aphthosis stomatitis (RAS) remains poorly defined. It likely involves a predominantly cell-mediated inflammation involving T-cells and TNF- (tumor necrosis factor-alpha) production. […] Light and electron-microscope examination of oral aphthous ulcers showed a penetrating, early, lympho-monocyte infiltration of the epithelium. […] According to a study by Lehner, under light microscopy, oral ulcer epithelium showed considerable intercellular edema and degenerative changes. […] There was epithelial hyperplasia and only the basement membrane adjacent to the ulcer was affected, the rest of the basement membrane appeared intact. […] Mononuclear cells normally infiltrate the basal-cell and prickle-cell layers of the epidermis and they are most commonly lymphocytes and monocytes, but superficial to and immediately adjacent to the ulcer neutrophil polymorphs were also found.

• #7 Pediatric Aphthous Ulcers: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/909213-overview

  Recurrent aphthous ulcers (canker sores) may initially appear as erythematous, indurated papules that erode to form sharply circumscribed necrotic ulcers with a gray, fibrinous exudate and an erythematous halo. […] The pathophysiology of aphthous ulcers remains incompletely understood. The primary disorder appears to be the result of activation of the cell-mediated immune system. Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring. […] Patients with recurrent aphthous ulcers (canker sores) have increased numbers of cytotoxic CD8+ cells and decreased numbers of helper CD4+ cells in peripheral blood. […] Lesions have elevated levels of interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-4, and IL-5; they have a functional deficit of IL-10.

• #8 Pediatric Aphthous Ulcers: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/909213-overview

  Recurrent aphthous ulcers (canker sores) may initially appear as erythematous, indurated papules that erode to form sharply circumscribed necrotic ulcers with a gray, fibrinous exudate and an erythematous halo. […] The pathophysiology of aphthous ulcers remains incompletely understood. The primary disorder appears to be the result of activation of the cell-mediated immune system. Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring. […] Patients with recurrent aphthous ulcers (canker sores) have increased numbers of cytotoxic CD8+ cells and decreased numbers of helper CD4+ cells in peripheral blood. […] Lesions have elevated levels of interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-4, and IL-5; they have a functional deficit of IL-10.

• #9 Pediatric Aphthous Ulcers: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/909213-overview

  Some lesions have also had mast-cell activation and degranulation. […] Aphthous ulcers may have abnormalities in cell communication and epithelial integrity. […] The oral flora likely plays a role in recurrent aphthous ulcers (canker sores), and a dysbiosis of the microbiota has been suggested. […] Factors predisposing patients to recurrent aphthous ulcers (canker sores) may include trauma, emotional stress, poor nutritional status, thiamine deficiency, vitamin B12 and D deficiency, zinc deficiency, malabsorption, celiac disease, regional enteropathy, menstruation, food hypersensitivity (eg, cow’s milk), allergic reaction, low antioxidant levels, and exposure to toxins (eg, nitrates in drinking water).

• #10 Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8934078/

  An immunofluorescent examination couldn’t detect specific globulin binding to salivary gland tissue in the oral aphthous lesion. […] Major aphthous ulcers do not differ much from minor aphthous ulcers, but they have an increase in the degree of severity of the pathological changes. […] There were no vascular abnormalities and fibrinous necrosis noticed in recurrent oral ulcers. […] A three-fold rise in mast cells was found in recurrent oral aphthous, in contrast to a decreased count in non-specific ulcers. […] Mast cell count was present in all three groups of oral ulcers when it was compared with that in other oral lesions and normal tissue. […] Leukocytes have a normal chemotactic function in oral aphthosis but in Behcet’s disease, they showed hyperactive function. […] There’s a chance that a few immunologically arbitrated mechanisms are playing an important role in the pathogenesis of oral aphthosis. […] It may be due to an unopposed or excessive production of IL (interleukin)-1 or IL-6, which is essential for its development, a concept that may explain why ulceration worsens after local injury, or cessation of smoking, or both.

• #11 What’s the biology of canker sore formation – It’s an immune system response.

  https://www.animated-teeth.com/canker_sores/canker-sore-formation-biology.htm

  A characteristic of the immune response that leads to canker sore formation is that an inflammatory mediator (chemical) named TNF-alpha is involved. […] The presence of TNF-alpha triggers neutrophils (another kind of white blood cell thats been drawn to the site of the antigens) to release mediators (chemical compounds) that cause tissue destruction. The result of this carnage is the ulceration that forms. […] Once an offending antigen has been identified, a cell-mediated (white blood cells) immune system response is begun that leads to a win-at-all-costs outcome that results in the formation of an ulceration (a canker sore). […] In your immune systems zeal to eradicate what it interprets as an invading compound, it destroys both the detected antigens and the tissue in which they resided (a compromise between preserving tissue integrity yet eradicating the invading substance). The carnage that results is the aphthous ulceration you experience.

• #12 Aphthous Stomatitis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1075570-overview

  Aphthous stomatitis (also known as recurrent aphthous ulcers or canker sores) is among the most common oral mucosal lesions observed by physicians and dentists. […] The precise etiology and the pathogenesis remain unclear. Many possibilities have been investigated. Recurrent aphthous ulcer is a multifactorial condition, and it is likely that immune-mediated destruction of the epithelium is the common factor in its pathogenesis. […] Although no unifying theory of the immunopathogenesis of recurrent aphthous ulcer has been established, immune dysregulation appears to play a significant role. Cytotoxic action of lymphocytes and monocytes on the oral epithelium may cause the ulceration, but the trigger remains unclear. […] Recurrent aphthous ulcer formation may be a T-cell-mediated response to antigens of Streptococcus sanguis that cross-react with the mitochondrial heat-shock proteins and induce damage to oral mucosa.

• #13 Recurrent Aphthous Stomatitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431059/

  It has also been suggested that the T-cell-mediated reaction seen in RAS is in response to Streptococcus sanguis antigens that cross-react with mitochondrial heat shock proteins, causing damage to the oral mucosa. […] There is a genetic predisposition to RAS; a family history of the condition is seen in 24% to 46% of patients. These patients usually develop more rapid and severe ulceration. A link to HLA-B51 and genes that control cytokines or heat shock proteins has been described.

• #14 What’s the biology of canker sore formation – It’s an immune system response.

  https://www.animated-teeth.com/canker_sores/canker-sore-formation-biology.htm

  Biologically, why do these ulcerations develop? | What takes place at the cellular level and why? (Its an immune system response.) […] While the full mechanism of aphthous ulcer formation is not been precisely determined, the current predominating theory states that its due to the response of a persons own immune system to what can be a wide range of different triggering agents or events. […] So, the whole process of aphthous ulcer formation begins when your bodys immune system first detects the presence of a foreign molecule of some sort (the antigen) in the tissues where your canker sore will form. […] With aphthous ulcer development, the defensive action that the persons immune system responds with involves the attraction of various types of white blood cells (neutrophils, lymphocytes, macrophages, mast cells, etc) to the tissues where the antigens have been detected.

• #15 Recurrent Aphthous Stomatitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431059/

  Recurrent aphthous stomatitis (RAS) is a chronic oral mucosa inflammatory disorder with an uncertain etiology. […] The etiology of recurrent aphthous stomatitis remains imperfectly understood. The cause is believed to be multifactorial, involving a cell-mediated immunological reaction and a genetic predisposition. Histopathological changes are seen before ulceration occurs. Lymphocytes (mononuclear cells) infiltrate the oral epithelium, edema develops, and the keratinocytes (oral epithelial cells) undergo vacuolization and vasculitis. This results in localized swelling and later ulceration of the epithelium. Infiltration with neutrophils, lymphocytes, and plasma cells occurs before the epithelium heals and regenerates. The pathogenesis of RAS is a T-cell-mediated immunological reaction involving the inflammatory cytokine named tumor necrosis factor-alpha (TNF-). TNF- activates the chemotaxis of neutrophils, generating an acute inflammatory response and the expression of the major histocompatibility (MHC) complex.

• #16 Pediatric Aphthous Ulcers: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/909213-overview

  Some lesions have also had mast-cell activation and degranulation. […] Aphthous ulcers may have abnormalities in cell communication and epithelial integrity. […] The oral flora likely plays a role in recurrent aphthous ulcers (canker sores), and a dysbiosis of the microbiota has been suggested. […] Factors predisposing patients to recurrent aphthous ulcers (canker sores) may include trauma, emotional stress, poor nutritional status, thiamine deficiency, vitamin B12 and D deficiency, zinc deficiency, malabsorption, celiac disease, regional enteropathy, menstruation, food hypersensitivity (eg, cow’s milk), allergic reaction, low antioxidant levels, and exposure to toxins (eg, nitrates in drinking water).

• #17 Recurrent Aphthous Stomatitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431059/

  It has also been suggested that the T-cell-mediated reaction seen in RAS is in response to Streptococcus sanguis antigens that cross-react with mitochondrial heat shock proteins, causing damage to the oral mucosa. […] There is a genetic predisposition to RAS; a family history of the condition is seen in 24% to 46% of patients. These patients usually develop more rapid and severe ulceration. A link to HLA-B51 and genes that control cytokines or heat shock proteins has been described.

• #18 Recurrent Aphthous Stomatitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431059/

  It has also been suggested that the T-cell-mediated reaction seen in RAS is in response to Streptococcus sanguis antigens that cross-react with mitochondrial heat shock proteins, causing damage to the oral mucosa. […] There is a genetic predisposition to RAS; a family history of the condition is seen in 24% to 46% of patients. These patients usually develop more rapid and severe ulceration. A link to HLA-B51 and genes that control cytokines or heat shock proteins has been described.

• #19 Canker Sore – Aphthous Stomatitis/Aphthous Ulcer | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/canker-sore-aphthous-stomatitisaphthous-ulcer

  Canker Sores (Aphthous Ulcers): Painful sores of the oral mucosa which have the propensity to recur (Plewa Chatterjee). […] Recurrent aphthous stomatitis (RAS): A chronic inflammatory condition in which patients develop recurrent Canker Sores (Scully Porter, 2008). […] The etiology of recurrent aphthous stomatitis is not perfectly understood. In susceptible individuals, the development of aphthous ulcers is related to the bodys lymphocytic response which is mediated by TNF-alpha (Taylor et al.). TNF-alpha causes a cytokine-mediated inflammatory reaction driving the expression of MHC complexes (Savage et al.). Increased MHC expression culminates with CD8+ T-cells targeting epithelial cells leading to ulceration. […] Although the genetic etiology is not fully understood at this time, it has been estimated that 46% of patients with recurrent aphthous stomatitis ulcers have a positive family history (Chiang et al., 2019). It has also been suggested that there could be a genetic association between RAS and HLA-B51 (Shohat Zabarski et al.).

• #20 Canker Sore – Aphthous Stomatitis/Aphthous Ulcer | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/canker-sore-aphthous-stomatitisaphthous-ulcer

  Local trauma has been shown to be a trigger for recurrent aphthous ulcers in susceptible individuals (Huling et al., 2012). Stress and food sensitivities are also believed to increase the likelihood of aphthous ulcer recurrence in susceptible individuals (Pedersen, 1989; Nolan et al., 1991). Additionally, hormonal changes and tobacco usage have been associated with RAS onset (Ferguson et al., 1978; Axell Henricsson, 1985; Dorsey, 1964). […] Aphthous ulcers are associated with conditions such as Behcet disease, cyclic neutropenia, MAGIC syndrome, PFAPA syndrome, and HIV.

• #21 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Mouth ulcers, which include canker sores, are small sores that develop within the mouth. There are no definite causes of mouth ulcers, but some injuries, allergies, or sensitivities may trigger them. […] Theres no definite cause behind mouth ulcers, but certain risk factors and triggers have been identified. […] Triggers include: minor mouth injury from dental work, hard brushing, sports injury, or an accidental bite, dental braces, toothpaste or mouthwash that contains sodium lauryl sulfate (SLS), an allergic response to oral bacteria, bacterial, viral, or fungal infections in the mouth, such as hand, foot, and mouth disease, sensitivities to acidic foods and beverages like strawberries, citrus fruits, pineapple, chocolate, and coffee, certain nutrient deficiencies, especially vitamin B9 (folate), vitamin B12, zinc, and iron, hormonal changes, such as those that occur during menstruation or pregnancy, emotional stress, lack of sleep.

• #22 Canker Sore – Aphthous Stomatitis/Aphthous Ulcer | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/canker-sore-aphthous-stomatitisaphthous-ulcer

  Local trauma has been shown to be a trigger for recurrent aphthous ulcers in susceptible individuals (Huling et al., 2012). Stress and food sensitivities are also believed to increase the likelihood of aphthous ulcer recurrence in susceptible individuals (Pedersen, 1989; Nolan et al., 1991). Additionally, hormonal changes and tobacco usage have been associated with RAS onset (Ferguson et al., 1978; Axell Henricsson, 1985; Dorsey, 1964). […] Aphthous ulcers are associated with conditions such as Behcet disease, cyclic neutropenia, MAGIC syndrome, PFAPA syndrome, and HIV.

• #23 Canker Sores (Aphthous Ulcers) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/canker.html

  Canker sores are small sores that happen inside the cheeks and lips, at the base of the gums, and on or under the tongue. […] No one knows exactly what causes canker sores, also known as aphthous (AF-thiss) ulcers. Many things are thought to put a person at risk for them. Diet may play a part. People whose diets are low in folic acid, vitamin B12, and iron seem to develop canker sores more often, as do people with food allergies. […] Mouth injuries (like biting the inside of the lip or even brushing too hard and damaging the delicate lining inside the mouth) also seem to bring on canker sores. Sodium lauryl sulfate (SLS), an ingredient in many toothpastes and mouthwashes, has been linked to canker sores, and sometimes the sores can be a sign of an immune system problem. […] Even emotional stress could be a factor. One study of college students showed that they had more canker sores during stressful periods, such as around exam time.

• #24 HOW STRESS CONTRIBUTES TO THE OCCURRENCE OF CANKER SORES? | Isotekindo

  https://www.isotekindo.co.id/article/details/319

  Canker sores, or oral ulcers, are small lesions that appear inside the mouth, causing pain and discomfort. Stress can weaken the immune system and trigger inflammatory reactions within the mouth. This mechanism can increase the risk of developing canker sores or worsen existing conditions. […] Some studies indicate that stress plays a role in the development of canker sores. When an individual is stressed, the immune system may weaken, making them more susceptible to infections and inflammation. This can trigger the onset of canker sores or exacerbate existing conditions. […] Stress can lead to the release of stress hormones, such as cortisol, which can inhibit the immune system’s response. This can make it harder for the body to fight infections or maintain normal balance, including within the mouth.

• #25 Canker Sore – Aphthous Stomatitis/Aphthous Ulcer | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/canker-sore-aphthous-stomatitisaphthous-ulcer

  Local trauma has been shown to be a trigger for recurrent aphthous ulcers in susceptible individuals (Huling et al., 2012). Stress and food sensitivities are also believed to increase the likelihood of aphthous ulcer recurrence in susceptible individuals (Pedersen, 1989; Nolan et al., 1991). Additionally, hormonal changes and tobacco usage have been associated with RAS onset (Ferguson et al., 1978; Axell Henricsson, 1985; Dorsey, 1964). […] Aphthous ulcers are associated with conditions such as Behcet disease, cyclic neutropenia, MAGIC syndrome, PFAPA syndrome, and HIV.

• #26 Canker sores: Causes, remedies, and prevention

  https://www.medicalnewstoday.com/articles/303311

  Researchers have not yet provided a scientific explanation of why canker sores develop; however, there are some factors that are known to be involved, including viral infection. […] The causes of recurrent cases of canker sore known as recurrent oral aphthous ulcers or recurrent aphthous stomatitis are also unclear, although there are links with a number of factors including a family history of aphthous ulcers, and allergies. […] Ulcers are sometimes associated with other conditions needing medical attention, such as inflammatory bowel disease, compromised immunity, allergies, and nutritional deficiency. […] The following factors are thought to be involved in the development of canker sores: Hormonal changes. Physical trauma (damage to the lining of the mouth, such as during dental treatment). Drugs. Food hypersensitivity for instance, citrus fruits and tomatoes can trigger or worsen a canker sore. Nutritional deficiencies, including iron, folic acid, zinc, and vitamin B12. Stress.

• #27 Pediatric Aphthous Ulcers: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/909213-overview

  Some lesions have also had mast-cell activation and degranulation. […] Aphthous ulcers may have abnormalities in cell communication and epithelial integrity. […] The oral flora likely plays a role in recurrent aphthous ulcers (canker sores), and a dysbiosis of the microbiota has been suggested. […] Factors predisposing patients to recurrent aphthous ulcers (canker sores) may include trauma, emotional stress, poor nutritional status, thiamine deficiency, vitamin B12 and D deficiency, zinc deficiency, malabsorption, celiac disease, regional enteropathy, menstruation, food hypersensitivity (eg, cow’s milk), allergic reaction, low antioxidant levels, and exposure to toxins (eg, nitrates in drinking water).

• #28 Canker sores: Causes, remedies, and prevention

  https://www.medicalnewstoday.com/articles/303311

  Researchers have not yet provided a scientific explanation of why canker sores develop; however, there are some factors that are known to be involved, including viral infection. […] The causes of recurrent cases of canker sore known as recurrent oral aphthous ulcers or recurrent aphthous stomatitis are also unclear, although there are links with a number of factors including a family history of aphthous ulcers, and allergies. […] Ulcers are sometimes associated with other conditions needing medical attention, such as inflammatory bowel disease, compromised immunity, allergies, and nutritional deficiency. […] The following factors are thought to be involved in the development of canker sores: Hormonal changes. Physical trauma (damage to the lining of the mouth, such as during dental treatment). Drugs. Food hypersensitivity for instance, citrus fruits and tomatoes can trigger or worsen a canker sore. Nutritional deficiencies, including iron, folic acid, zinc, and vitamin B12. Stress.

• #29 Recurrent Aphthous Stomatitis – Mouth and Dental Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/mouth-and-dental-disorders/symptoms-of-oral-and-dental-disorders/recurrent-aphthous-stomatitis

  Recurrent aphthous stomatitis (RAS) is very common. The cause is unclear but probably involves multiple factors, including disorders or abnormal function of the immune system, exposure to preservatives and toothpaste ingredients, and a genetic predisposition. […] Many factors seem to predispose to or trigger attacks, but allergic reactions do not seem to be involved. Such factors include injury to the mouth, stress (for example, a college student may get canker sores during final exam week), and certain foods (particularly chocolate, coffee, peanuts, eggs, cereals, almonds, strawberries, cheese, and tomatoes). […] If the corticosteroids that are applied directly to the affected area do not work, prednisone tablets may be taken by mouth. However, before prescribing a corticosteroid, a doctor must ensure that the person does not have oral herpes simplex infection, which would be made worse by taking corticosteroids.

• #30 Canker Sores in the Throat: 7 Causes & How to Treat – Tua Saúde

  https://www.tuasaude.com/en/throat-canker-sores/

  To help heal canker sores in the throat, some precautions should be considered, such as rinsing your mouth with mouthwash after brushing your teeth, as this can help to eliminate bacteria and cleanse the area. […] Avoiding acidic foods like lemon, pineapple, tomato, kiwi and orange, as the acidity can increase pain. […] Eating more foods rich in B complex vitamins, folic acid and iron such as banana, mango, low-fat yogurt or apple juice (vitamin deficiency can cause throat ulcers). […] Gargling warm water with salt or gargling hydrogen peroxide diluted in water, as they are antiseptic and clean the area. […] When canker sores appear frequently in the throat (e.g. more than 6 times a year) you should see a doctor for assessment, especially if you have other symptoms.

• #31 Canker Sores (Aphthous Ulcers) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/canker.html

  Canker sores are small sores that happen inside the cheeks and lips, at the base of the gums, and on or under the tongue. […] No one knows exactly what causes canker sores, also known as aphthous (AF-thiss) ulcers. Many things are thought to put a person at risk for them. Diet may play a part. People whose diets are low in folic acid, vitamin B12, and iron seem to develop canker sores more often, as do people with food allergies. […] Mouth injuries (like biting the inside of the lip or even brushing too hard and damaging the delicate lining inside the mouth) also seem to bring on canker sores. Sodium lauryl sulfate (SLS), an ingredient in many toothpastes and mouthwashes, has been linked to canker sores, and sometimes the sores can be a sign of an immune system problem. […] Even emotional stress could be a factor. One study of college students showed that they had more canker sores during stressful periods, such as around exam time.

• #32

  https://www.sharonalbrightdds.com/canker-sores-apthous-ulcers

  Canker sores, also known as apthous ulcers, mouth ulcers and more formally as apthous stomatitis, are oval or round reddened swellings in the mouth that if elevated usually burst within 24 hours. […] Their occurrence is thought to be related to immune system mediated conditions such as ulcerative colitis, HIV, autoimmune disorders and crohns disease. […] Sodium Lauryl Sulfate (SLS), the foaming agent found in most toothpastes and mouthwashes, also increases the occurrence of canker sores in susceptible individuals because it dries the protective layer of oral tissues allowing underlying tissues to be traumatized.

• #33 A Guide to Treating and Avoiding Canker Sores | TIME

  https://time.com/7261601/canker-sores-how-to-treat-prevent/

  Most times, we dont know why they come, says Dr. Alessandro Villa, chief of oral medicine and oral oncology at Miami Cancer Institute at Baptist Health South Florida. […] Although a single cause hasnt been identified, we do know that these sores, also known as ulcers, can coincide with serious health problems. […] Canker sores seem related to immune system activity, and stress activates the immune system. […] The sores are also associated with sleep deprivation, another challenge to immunity. […] A surprising factor in some cases is toothpaste. A foaming agent called sodium lauryl sulfate is a common ingredient that can disrupt the cheeks protective barrier in people susceptible to mouth ulcers, some research shows. […] Poor nutrition is sometimes involved. Theres pretty strong data to support that nutritional deficiencies could be a causative factor for canker sores, Villa says.

• #34 Mouth ulcer – Wikipedia

  https://en.wikipedia.org/wiki/Mouth_ulcer

  Stomatitis is a general term meaning inflammation within the mouth, and often may be associated with ulceration. […] Pathologically, the mouth represents a transition between the gastrointestinal tract and the skin, meaning that many gastrointestinal and cutaneous conditions can involve the mouth. […] The high bacterial load in the mouth means that ulcers may become secondarily infected. […] Repeat episodes of mouth ulcers can be indicative of an immunodeficiency, signaling low levels of immunoglobulin in the oral mucous membranes. […] Autoimmunity is also a cause of oral ulceration. […] Numerous aphthous ulcers could be indicative of an inflammatory autoimmune disease called Behet’s disease. […] Vitamin C deficiency may lead to scurvy which impairs wound healing, which can contribute to ulcer formation.

• #35 Canker Sore – Aphthous Stomatitis/Aphthous Ulcer | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/canker-sore-aphthous-stomatitisaphthous-ulcer

  Local trauma has been shown to be a trigger for recurrent aphthous ulcers in susceptible individuals (Huling et al., 2012). Stress and food sensitivities are also believed to increase the likelihood of aphthous ulcer recurrence in susceptible individuals (Pedersen, 1989; Nolan et al., 1991). Additionally, hormonal changes and tobacco usage have been associated with RAS onset (Ferguson et al., 1978; Axell Henricsson, 1985; Dorsey, 1964). […] Aphthous ulcers are associated with conditions such as Behcet disease, cyclic neutropenia, MAGIC syndrome, PFAPA syndrome, and HIV.

• #36 Canker Sore – Aphthous Stomatitis/Aphthous Ulcer | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/canker-sore-aphthous-stomatitisaphthous-ulcer

  Local trauma has been shown to be a trigger for recurrent aphthous ulcers in susceptible individuals (Huling et al., 2012). Stress and food sensitivities are also believed to increase the likelihood of aphthous ulcer recurrence in susceptible individuals (Pedersen, 1989; Nolan et al., 1991). Additionally, hormonal changes and tobacco usage have been associated with RAS onset (Ferguson et al., 1978; Axell Henricsson, 1985; Dorsey, 1964). […] Aphthous ulcers are associated with conditions such as Behcet disease, cyclic neutropenia, MAGIC syndrome, PFAPA syndrome, and HIV.

• #37 Canker Sore – Aphthous Stomatitis/Aphthous Ulcer | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/canker-sore-aphthous-stomatitisaphthous-ulcer

  Local trauma has been shown to be a trigger for recurrent aphthous ulcers in susceptible individuals (Huling et al., 2012). Stress and food sensitivities are also believed to increase the likelihood of aphthous ulcer recurrence in susceptible individuals (Pedersen, 1989; Nolan et al., 1991). Additionally, hormonal changes and tobacco usage have been associated with RAS onset (Ferguson et al., 1978; Axell Henricsson, 1985; Dorsey, 1964). […] Aphthous ulcers are associated with conditions such as Behcet disease, cyclic neutropenia, MAGIC syndrome, PFAPA syndrome, and HIV.

• #38 Management of Aphthous Ulcers | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0701/p149.html

  The pathophysiology of aphthous ulcers is poorly understood. Histologically, aphthae contain a mononuclear infiltrate with a fibrin coating. Patients with recurrent aphthae may have alteration of local cell-mediated immunity. Systemic T- and B-cell responses have also been reported as altered in patients with recurrent aphthae. […] The lack of clarity regarding etiology has resulted in treatments that are largely empiric and aimed at symptom reduction. […] Immune modulators used for the management of aphthous ulcers have been investigated most thoroughly in patients infected with HIV. Aphthous ulcers in HIV-infected patients may have extremely protracted healing times, up to months. Thalidomide (Thalomid) is the agent most frequently used for management of aphthous ulcers that cause severe pain with eating. Thalidomide in a dosage of 200 mg once to twice daily for three to eight weeks yields a faster healing rate than placebo.

• #39 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Mouth ulcers can also be a sign of conditions that are more serious and require medical treatment, such as celiac disease, inflammatory bowel disease (IBD), including ulcerative colitis, diabetes, HIV, some autoimmune diseases, including lupus, oral lichen planus, Behets disease, a rare condition that causes inflammation throughout the blood vessels. […] Canker sores are the most common type of mouth ulcer, with 20% of people having a canker sore at least once. There are three main types of canker sores: minor, major, herpetiform. […] Minor canker sores are small oval or round ulcers measuring under 5 millimeters (mm). They heal within 1 to 2 weeks and dont cause scars. […] Major canker sores are larger and deeper than minor ones. They often measure over 10 mm. They have irregular edges and can take weeks or months to heal. Major canker sores can result in long-term scarring.

• #40 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Mouth ulcers can also be a sign of conditions that are more serious and require medical treatment, such as celiac disease, inflammatory bowel disease (IBD), including ulcerative colitis, diabetes, HIV, some autoimmune diseases, including lupus, oral lichen planus, Behets disease, a rare condition that causes inflammation throughout the blood vessels. […] Canker sores are the most common type of mouth ulcer, with 20% of people having a canker sore at least once. There are three main types of canker sores: minor, major, herpetiform. […] Minor canker sores are small oval or round ulcers measuring under 5 millimeters (mm). They heal within 1 to 2 weeks and dont cause scars. […] Major canker sores are larger and deeper than minor ones. They often measure over 10 mm. They have irregular edges and can take weeks or months to heal. Major canker sores can result in long-term scarring.

• #41 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Mouth ulcers can also be a sign of conditions that are more serious and require medical treatment, such as celiac disease, inflammatory bowel disease (IBD), including ulcerative colitis, diabetes, HIV, some autoimmune diseases, including lupus, oral lichen planus, Behets disease, a rare condition that causes inflammation throughout the blood vessels. […] Canker sores are the most common type of mouth ulcer, with 20% of people having a canker sore at least once. There are three main types of canker sores: minor, major, herpetiform. […] Minor canker sores are small oval or round ulcers measuring under 5 millimeters (mm). They heal within 1 to 2 weeks and dont cause scars. […] Major canker sores are larger and deeper than minor ones. They often measure over 10 mm. They have irregular edges and can take weeks or months to heal. Major canker sores can result in long-term scarring.

• #42 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Mouth ulcers can also be a sign of conditions that are more serious and require medical treatment, such as celiac disease, inflammatory bowel disease (IBD), including ulcerative colitis, diabetes, HIV, some autoimmune diseases, including lupus, oral lichen planus, Behets disease, a rare condition that causes inflammation throughout the blood vessels. […] Canker sores are the most common type of mouth ulcer, with 20% of people having a canker sore at least once. There are three main types of canker sores: minor, major, herpetiform. […] Minor canker sores are small oval or round ulcers measuring under 5 millimeters (mm). They heal within 1 to 2 weeks and dont cause scars. […] Major canker sores are larger and deeper than minor ones. They often measure over 10 mm. They have irregular edges and can take weeks or months to heal. Major canker sores can result in long-term scarring.

• #43 Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8934078/

  An immunofluorescent examination couldn’t detect specific globulin binding to salivary gland tissue in the oral aphthous lesion. […] Major aphthous ulcers do not differ much from minor aphthous ulcers, but they have an increase in the degree of severity of the pathological changes. […] There were no vascular abnormalities and fibrinous necrosis noticed in recurrent oral ulcers. […] A three-fold rise in mast cells was found in recurrent oral aphthous, in contrast to a decreased count in non-specific ulcers. […] Mast cell count was present in all three groups of oral ulcers when it was compared with that in other oral lesions and normal tissue. […] Leukocytes have a normal chemotactic function in oral aphthosis but in Behcet’s disease, they showed hyperactive function. […] There’s a chance that a few immunologically arbitrated mechanisms are playing an important role in the pathogenesis of oral aphthosis. […] It may be due to an unopposed or excessive production of IL (interleukin)-1 or IL-6, which is essential for its development, a concept that may explain why ulceration worsens after local injury, or cessation of smoking, or both.

• #44 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Mouth ulcers can also be a sign of conditions that are more serious and require medical treatment, such as celiac disease, inflammatory bowel disease (IBD), including ulcerative colitis, diabetes, HIV, some autoimmune diseases, including lupus, oral lichen planus, Behets disease, a rare condition that causes inflammation throughout the blood vessels. […] Canker sores are the most common type of mouth ulcer, with 20% of people having a canker sore at least once. There are three main types of canker sores: minor, major, herpetiform. […] Minor canker sores are small oval or round ulcers measuring under 5 millimeters (mm). They heal within 1 to 2 weeks and dont cause scars. […] Major canker sores are larger and deeper than minor ones. They often measure over 10 mm. They have irregular edges and can take weeks or months to heal. Major canker sores can result in long-term scarring.

• #45 Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8934078/

  An immunofluorescent examination couldn’t detect specific globulin binding to salivary gland tissue in the oral aphthous lesion. […] Major aphthous ulcers do not differ much from minor aphthous ulcers, but they have an increase in the degree of severity of the pathological changes. […] There were no vascular abnormalities and fibrinous necrosis noticed in recurrent oral ulcers. […] A three-fold rise in mast cells was found in recurrent oral aphthous, in contrast to a decreased count in non-specific ulcers. […] Mast cell count was present in all three groups of oral ulcers when it was compared with that in other oral lesions and normal tissue. […] Leukocytes have a normal chemotactic function in oral aphthosis but in Behcet’s disease, they showed hyperactive function. […] There’s a chance that a few immunologically arbitrated mechanisms are playing an important role in the pathogenesis of oral aphthosis. […] It may be due to an unopposed or excessive production of IL (interleukin)-1 or IL-6, which is essential for its development, a concept that may explain why ulceration worsens after local injury, or cessation of smoking, or both.

• #46 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Herpetiform canker sores are pinpoint-sized, occur in clusters, and often appear on the tongue. Sometimes the clusters can merge to form one large sore. […] Herpetiform canker sores have irregular edges and often heal, without scarring, within 1 month. Theyre called herpetiform because they may resemble the sores caused by herpes. Herpetiform canker sores are not otherwise associated with herpes infection. […] A cold sore is another common type of oral lesion. Although mouth ulcers and cold sores share some causes and symptoms, its usually easy to tell the two apart. […] Mouth ulcers only appear inside the mouth. […] Most mouth ulcers are not contagious. Cold sores are typically caused by the herpes virus and are always contagious. […] Aphthous ulcer is another name for a canker sore. The medical term aphtha has a few definitions but is mostly used to refer to a small ulcer.

• #47 Oral Aphthous: Pathophysiology, Clinical Aspects and Medical Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8934078/

  According to Lehner, the Intra-nuclear inclusion bodies were found in 3 out of the 25 biopsies examined by electron microscopy. […] The affected nuclei were slightly larger and the nucleoli were uneven in shape. […] Inclusion bodies were not seen in the cytoplasm. […] Herpetiform ulcers differ from recurrent aphthous ulcers in that they showed epithelial vesicles and intra-nuclear inclusion bodies, suggesting a virus etiology. […] The immuno-fluorescent studies showed predominantly IgG and IgM binding only in autologous tissues from patients with aphthous ulcers. […] This reaction could indicate blood group antigens, trapped globulins due to the inflammatory reaction, non-immunological physicochemical binding of the fluorescent conjugate, or normal immunoglobulin transport through the oral mucosa.

• #48 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Herpetiform canker sores are pinpoint-sized, occur in clusters, and often appear on the tongue. Sometimes the clusters can merge to form one large sore. […] Herpetiform canker sores have irregular edges and often heal, without scarring, within 1 month. Theyre called herpetiform because they may resemble the sores caused by herpes. Herpetiform canker sores are not otherwise associated with herpes infection. […] A cold sore is another common type of oral lesion. Although mouth ulcers and cold sores share some causes and symptoms, its usually easy to tell the two apart. […] Mouth ulcers only appear inside the mouth. […] Most mouth ulcers are not contagious. Cold sores are typically caused by the herpes virus and are always contagious. […] Aphthous ulcer is another name for a canker sore. The medical term aphtha has a few definitions but is mostly used to refer to a small ulcer.

• #49 Canker sore – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/canker-sore/symptoms-causes/syc-20370615

  The precise cause of canker sores remains unclear, though researchers suspect that a combination of factors contributes to outbreaks, even in the same person. […] Canker sores may also occur because of certain conditions and diseases, such as: […] A faulty immune system that attacks healthy cells in your mouth instead of pathogens, such as viruses and bacteria. […] Unlike cold sores, canker sores are not associated with herpes virus infections.

• #50 Canker sore // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/canker-sore

  The precise cause of canker sores remains unclear, though researchers suspect that a combination of factors contributes to outbreaks, even in the same person. […] Canker sores may also occur because of certain conditions and diseases, such as a faulty immune system that attacks healthy cells in your mouth instead of pathogens, such as viruses and bacteria. […] Unlike cold sores, canker sores are not associated with herpes virus infections.

• #51 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Herpetiform canker sores are pinpoint-sized, occur in clusters, and often appear on the tongue. Sometimes the clusters can merge to form one large sore. […] Herpetiform canker sores have irregular edges and often heal, without scarring, within 1 month. Theyre called herpetiform because they may resemble the sores caused by herpes. Herpetiform canker sores are not otherwise associated with herpes infection. […] A cold sore is another common type of oral lesion. Although mouth ulcers and cold sores share some causes and symptoms, its usually easy to tell the two apart. […] Mouth ulcers only appear inside the mouth. […] Most mouth ulcers are not contagious. Cold sores are typically caused by the herpes virus and are always contagious. […] Aphthous ulcer is another name for a canker sore. The medical term aphtha has a few definitions but is mostly used to refer to a small ulcer.

• #52 Mouth Ulcer: Causes, Symptoms, Diagnosis, and Treatment

  https://www.healthline.com/health/mouth-ulcers

  Herpetiform canker sores are pinpoint-sized, occur in clusters, and often appear on the tongue. Sometimes the clusters can merge to form one large sore. […] Herpetiform canker sores have irregular edges and often heal, without scarring, within 1 month. Theyre called herpetiform because they may resemble the sores caused by herpes. Herpetiform canker sores are not otherwise associated with herpes infection. […] A cold sore is another common type of oral lesion. Although mouth ulcers and cold sores share some causes and symptoms, its usually easy to tell the two apart. […] Mouth ulcers only appear inside the mouth. […] Most mouth ulcers are not contagious. Cold sores are typically caused by the herpes virus and are always contagious. […] Aphthous ulcer is another name for a canker sore. The medical term aphtha has a few definitions but is mostly used to refer to a small ulcer.

• #53 Aphthous Ulcers (Canker Sore): Sing and Treatments | Ada

  https://ada.com/conditions/aphthous-ulcers/

  To lessen the likelihood of an ulcer outbreak, especially for those with a history of recurrent aphthous ulcers (aphthae), a number of measures can be taken. […] Aphthous ulcers (aphthae) are generally non-serious and will go away without any particular treatment. […] If an ulcer or group of ulcers does not heal within three weeks, or lasts for longer than three weeks, the affected person should see a doctor as soon as possible for a proper diagnostic workup. […] A mouth ulcer that does not clear up is sometimes a sign of oral cancer. However, very few mouth ulcers are a sign of cancer.

• #54 Mouth Ulcers: Types, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/21766-mouth-ulcer

  Canker sores (aphthous ulcers). These are the most common type of mouth ulcers. Healthcare providers arent exactly sure what causes them or why some people get them more than others do. Causes include minor trauma (like biting your cheek), acidic foods and even stress. Canker sores are usually white or yellow with red around the edges. […] You might get a canker sore if you have a folate, vitamin B or iron deficiency. But in most cases, canker sores appear without a known cause and for no apparent reason. They can also recur (return), meaning they come and go over the course of your lifetime. […] A mouth ulcer that doesnt go away could be a sign of oral cancer. In most cases of mouth cancer, mouth ulcers appear on or under the tongue.

• #55 Pediatric Aphthous Ulcers: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/909213-overview

  Recurrent aphthous ulcers (canker sores) may initially appear as erythematous, indurated papules that erode to form sharply circumscribed necrotic ulcers with a gray, fibrinous exudate and an erythematous halo. […] The pathophysiology of aphthous ulcers remains incompletely understood. The primary disorder appears to be the result of activation of the cell-mediated immune system. Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring. […] Patients with recurrent aphthous ulcers (canker sores) have increased numbers of cytotoxic CD8+ cells and decreased numbers of helper CD4+ cells in peripheral blood. […] Lesions have elevated levels of interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-4, and IL-5; they have a functional deficit of IL-10.

• #56 Pediatric Aphthous Ulcers: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/909213-overview

  Recurrent aphthous ulcers (canker sores) may initially appear as erythematous, indurated papules that erode to form sharply circumscribed necrotic ulcers with a gray, fibrinous exudate and an erythematous halo. […] The pathophysiology of aphthous ulcers remains incompletely understood. The primary disorder appears to be the result of activation of the cell-mediated immune system. Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring. […] Patients with recurrent aphthous ulcers (canker sores) have increased numbers of cytotoxic CD8+ cells and decreased numbers of helper CD4+ cells in peripheral blood. […] Lesions have elevated levels of interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-4, and IL-5; they have a functional deficit of IL-10.

• #57 Recurrent Aphthous Stomatitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431059/

  Recurrent aphthous stomatitis (RAS) is a chronic oral mucosa inflammatory disorder with an uncertain etiology. […] The etiology of recurrent aphthous stomatitis remains imperfectly understood. The cause is believed to be multifactorial, involving a cell-mediated immunological reaction and a genetic predisposition. Histopathological changes are seen before ulceration occurs. Lymphocytes (mononuclear cells) infiltrate the oral epithelium, edema develops, and the keratinocytes (oral epithelial cells) undergo vacuolization and vasculitis. This results in localized swelling and later ulceration of the epithelium. Infiltration with neutrophils, lymphocytes, and plasma cells occurs before the epithelium heals and regenerates. The pathogenesis of RAS is a T-cell-mediated immunological reaction involving the inflammatory cytokine named tumor necrosis factor-alpha (TNF-). TNF- activates the chemotaxis of neutrophils, generating an acute inflammatory response and the expression of the major histocompatibility (MHC) complex.

• #58 Management of Aphthous Ulcers | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0701/p149.html

  The pathophysiology of aphthous ulcers is poorly understood. Histologically, aphthae contain a mononuclear infiltrate with a fibrin coating. Patients with recurrent aphthae may have alteration of local cell-mediated immunity. Systemic T- and B-cell responses have also been reported as altered in patients with recurrent aphthae. […] The lack of clarity regarding etiology has resulted in treatments that are largely empiric and aimed at symptom reduction. […] Immune modulators used for the management of aphthous ulcers have been investigated most thoroughly in patients infected with HIV. Aphthous ulcers in HIV-infected patients may have extremely protracted healing times, up to months. Thalidomide (Thalomid) is the agent most frequently used for management of aphthous ulcers that cause severe pain with eating. Thalidomide in a dosage of 200 mg once to twice daily for three to eight weeks yields a faster healing rate than placebo.

• #59 Treating cold sores in two days and canker sores through glutathione antioxidation | Perio Implant Advisory

  https://www.perioimplantadvisory.com/periodontics/oral-pathology/article/55087903/treating-cold-sores-in-two-days-and-canker-sores-through-glutathione-antioxidation

  Cold sores and canker sores are common oral health issues that affect 50%80% of the US population. On the other hand, canker sores (or aphthous ulcers) are noncontagious lesions that occur inside the oral cavity and are believed to be caused by various factors, including stress, inflammation, gut dysbiosis, nutritional deficiencies, and immune system dysregulation. […] The ability of glutathione to modulate oxidative stress makes it a valuable therapeutic agent for conditions characterized by elevated ROS, such as cold sores and canker sores. […] Canker sores, or aphthous ulcers, are characterized by the presence of painful, recurring lesions within the oral cavity. Although the exact etiology is not well understood, oxidative stress is believed to play a significant role in their development. Factors such as trauma, nutritional deficiencies, irritable bowel disorders, leaky gut, microbiome dysbiosis, and immune dysregulation can all contribute to the generation of ROS, leading to tissue damage and ulcer formation.

• #60 Treating cold sores in two days and canker sores through glutathione antioxidation | Perio Implant Advisory

  https://www.perioimplantadvisory.com/periodontics/oral-pathology/article/55087903/treating-cold-sores-in-two-days-and-canker-sores-through-glutathione-antioxidation

  Glutathiones ability to neutralize ROS and protect against oxidative damage makes it a successful therapeutic option for canker sores. […] Moreover, glutathiones anti-inflammatory properties can further aid in the treatment of canker sores. Inflammation is a key component of ulcer pathogenesis, and reducing the inflammatory response can alleviate pain and promote healing. Glutathione has been shown to inhibit the production of pro-inflammatory cytokines, such as TNF- and IL-6, which are elevated in patients with RAS. By dampening the inflammatory response, glutathione can facilitate faster resolution of canker sores. […] The antioxidative and anti-inflammatory properties of glutathione make it a promising therapeutic agent for these conditions. By neutralizing ROS, protecting against oxidative damage, and modulating the immune response, glutathione can potentially reduce the severity and frequency of cold sore and canker sore outbreaks.

• #61 Canker sores: Causes, remedies, and prevention

  https://www.medicalnewstoday.com/articles/303311

  The management of canker sores is focused on treating symptoms, reducing inflammation, and promoting the healing process by countering secondary effects that could slow this down, such as bacterial infection. […] Antibiotics may be prescribed to minimize inflammatory irritation whether or not a bacterial infection is present. […] Some medicines designed for other conditions can sometimes be used. The American Academy of Oral Maxillofacial Pathology, for example, cites an association between recurrent cases of canker sores and an overactive immune system, so topical immunosuppressant medications may help, such as locally applied cortisone. […] With a similar mode of action, topical corticosteroids are often considered by doctors; these include clobetasol ointment, dexamethasone rinse, and fluocinonide gel (Lidex). One possible side effect of using corticosteroids against canker sores is a fungal infection in the mouth. […] Particularly severe or recurrent cases of canker sores may be referred to an oral specialist who might consider systemic rather than locally applied (topical) drugs.

• #62 Canker sores: Causes, remedies, and prevention

  https://www.medicalnewstoday.com/articles/303311

  The management of canker sores is focused on treating symptoms, reducing inflammation, and promoting the healing process by countering secondary effects that could slow this down, such as bacterial infection. […] Antibiotics may be prescribed to minimize inflammatory irritation whether or not a bacterial infection is present. […] Some medicines designed for other conditions can sometimes be used. The American Academy of Oral Maxillofacial Pathology, for example, cites an association between recurrent cases of canker sores and an overactive immune system, so topical immunosuppressant medications may help, such as locally applied cortisone. […] With a similar mode of action, topical corticosteroids are often considered by doctors; these include clobetasol ointment, dexamethasone rinse, and fluocinonide gel (Lidex). One possible side effect of using corticosteroids against canker sores is a fungal infection in the mouth. […] Particularly severe or recurrent cases of canker sores may be referred to an oral specialist who might consider systemic rather than locally applied (topical) drugs.

• #63 Management of Aphthous Ulcers | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0701/p149.html

  The pathophysiology of aphthous ulcers is poorly understood. Histologically, aphthae contain a mononuclear infiltrate with a fibrin coating. Patients with recurrent aphthae may have alteration of local cell-mediated immunity. Systemic T- and B-cell responses have also been reported as altered in patients with recurrent aphthae. […] The lack of clarity regarding etiology has resulted in treatments that are largely empiric and aimed at symptom reduction. […] Immune modulators used for the management of aphthous ulcers have been investigated most thoroughly in patients infected with HIV. Aphthous ulcers in HIV-infected patients may have extremely protracted healing times, up to months. Thalidomide (Thalomid) is the agent most frequently used for management of aphthous ulcers that cause severe pain with eating. Thalidomide in a dosage of 200 mg once to twice daily for three to eight weeks yields a faster healing rate than placebo.

• #64 Canker sores: Causes, remedies, and prevention

  https://www.medicalnewstoday.com/articles/303311

  The management of canker sores is focused on treating symptoms, reducing inflammation, and promoting the healing process by countering secondary effects that could slow this down, such as bacterial infection. […] Antibiotics may be prescribed to minimize inflammatory irritation whether or not a bacterial infection is present. […] Some medicines designed for other conditions can sometimes be used. The American Academy of Oral Maxillofacial Pathology, for example, cites an association between recurrent cases of canker sores and an overactive immune system, so topical immunosuppressant medications may help, such as locally applied cortisone. […] With a similar mode of action, topical corticosteroids are often considered by doctors; these include clobetasol ointment, dexamethasone rinse, and fluocinonide gel (Lidex). One possible side effect of using corticosteroids against canker sores is a fungal infection in the mouth. […] Particularly severe or recurrent cases of canker sores may be referred to an oral specialist who might consider systemic rather than locally applied (topical) drugs.

• #65 Mouth ulcer – Wikipedia

  https://en.wikipedia.org/wiki/Mouth_ulcer

  Stomatitis is a general term meaning inflammation within the mouth, and often may be associated with ulceration. […] Pathologically, the mouth represents a transition between the gastrointestinal tract and the skin, meaning that many gastrointestinal and cutaneous conditions can involve the mouth. […] The high bacterial load in the mouth means that ulcers may become secondarily infected. […] Repeat episodes of mouth ulcers can be indicative of an immunodeficiency, signaling low levels of immunoglobulin in the oral mucous membranes. […] Autoimmunity is also a cause of oral ulceration. […] Numerous aphthous ulcers could be indicative of an inflammatory autoimmune disease called Behet’s disease. […] Vitamin C deficiency may lead to scurvy which impairs wound healing, which can contribute to ulcer formation.

• #66 Recurrent Aphthous Stomatitis – Mouth and Dental Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/mouth-and-dental-disorders/symptoms-of-oral-and-dental-disorders/recurrent-aphthous-stomatitis

  Recurrent aphthous stomatitis (RAS) is very common. The cause is unclear but probably involves multiple factors, including disorders or abnormal function of the immune system, exposure to preservatives and toothpaste ingredients, and a genetic predisposition. […] Many factors seem to predispose to or trigger attacks, but allergic reactions do not seem to be involved. Such factors include injury to the mouth, stress (for example, a college student may get canker sores during final exam week), and certain foods (particularly chocolate, coffee, peanuts, eggs, cereals, almonds, strawberries, cheese, and tomatoes). […] If the corticosteroids that are applied directly to the affected area do not work, prednisone tablets may be taken by mouth. However, before prescribing a corticosteroid, a doctor must ensure that the person does not have oral herpes simplex infection, which would be made worse by taking corticosteroids.

• #67 Canker sores: An old enemy facing new treatment | Perio Implant Advisory

  https://www.perioimplantadvisory.com/clinical-tips/article/16412249/canker-sores-an-old-enemy-facing-new-treatment

  Aphthous ulcers, also known as canker sores, present as single or multiple ulcerations in the oral mucosa. Canker sore attacks can be brought on by a variety of factors including stress, medications, hormonal changes, vitamin deficiency (especially B12, folic acid, and iron), sensitivities to foods, and dental ingredients, such as sodium lauryl sulfate found in toothpaste. Genetics, immunologic factors, and microbial factors also play a role in recurrent aphthous ulcers. […] The following treatment has been shown to decrease severity of pain and duration of more painful canker sore lesions: Studies have shown that laser treatment can help to reduce the duration and intensity of aphthous ulcers. Lasers can be very effective in cases of major aphthous ulcers and herpetiform aphthous ulcers, where pain intensity can be high and the patient is looking to reduce lesion duration and scarring potential. This treatment has been shown to reduce both the duration and intensity of the canker sore lesion by 50% to 75%.

• #68 Aphthous Ulcers (Canker Sore): Sing and Treatments | Ada

  https://ada.com/conditions/aphthous-ulcers/

  A proper evaluation and diagnostic work-up of recurrent ulceration is important due to its links to other, more serious conditions such as celiac disease, inflammatory bowel diseases like Crohns disease or conditions causing a weakened immune system, such as HIV/AIDS. […] Although most mouth ulcers will clear up within two weeks, in very rare cases they may become infected with bacteria. […] There is no cure for aphthous ulcers, aphthae or canker sores, but there are ways to manage the symptoms. […] Other treatments may include topical or, rarely, oral steroids, typically used when the ulcers are unresponsive to other treatment methods; silver nitrate; other local anaesthetics/numbing agents; and nutritional supplements (containing folate, zinc or vitamin B-12, for example). […] Nutritional supplements such as Vitamin B-12 capsules, Vitamin D capsules, folate tablets, or zinc tablets can also reduce the risk of developing canker sores.

• #69 Recurrent aphthous stomatitis – UpToDate

  https://www.uptodate.com/contents/recurrent-aphthous-stomatitis/print

  Recurrent aphthous stomatitis (RAS), also known as „canker sores,” is a common disease of unknown etiology that affects the oral mucosa and is characterized by the repeated development of one to many discrete, painful ulcers that usually heal within 7 to 14 days. […] This topic will discuss the pathogenesis, clinical manifestations, and management of RAS.

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