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{{Aphthous ulcer}}
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==Overview==
==Overview==
The exact cause of aphthous ulcers is unknown. Factors that provoke them include [[stress (psychology)|stress]], [[fatigue (physical)|fatigue]], [[illness]], injury from accidental biting, [[hormone|hormonal]] changes, [[menstruation]], sudden [[weight loss]], [[food allergy|food allergies]], the foaming agent in toothpaste ([[Sodium lauryl sulfate|SLS]]), and deficiencies in [[vitamin B12]], [[iron]], and [[folic acid]].<ref>{{cite journal |author=Wray D, Ferguson M, Hutcheon W, Dagg J |title=Nutritional deficiencies in recurrent aphthae |journal=J Oral Pathol |volume=7 |issue=6 |pages=418–23 |year=1978 |pmid=105102}}</ref>Some drugs, such as [[nicorandil]], also have been linked with mouth ulcers.  In some cases they are thought to be caused by an overreaction by the body's own [[autoimmunity|immune system]].
The exact cause of aphthous ulcers is unknown. Factors that provoke them include [[stress (psychology)|stress]], [[fatigue (physical)|fatigue]], [[illness]], injury from accidental biting, [[hormone|hormonal]] changes, [[menstruation]], sudden [[weight loss]], [[food allergy|food allergies]], the foaming agent in toothpaste ([[Sodium lauryl sulfate|SLS]]), and deficiencies in [[vitamin B12]], [[iron]], and [[folic acid]].


== Causes ==
==Causes==
===Common Causes===
===Trauma===
Trauma to the mouth is the most common trigger of aphthous ulcers.[http://www.patient.co.uk/showdoc/40024908/][http://www.health-disease.org/skin-disorders/aphthous-ulcer.htm][http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Mouth_ulcers?OpenDocument] [[Physical trauma]], such as that caused by toothbrush abrasions, laceration with sharp foods or objects, accidental biting (particularly common with sharp canine teeth), or [[dental braces]] can cause mouth ulcers by breaking the mucous membrane.  Other factors, such as chemical irritants or thermal injury, may also lead to the development of ulcers.  The large majority of toothpastes sold in the U.S. contain [[Sodium dodecyl sulfate|Sodium lauryl sulfate]] (SLS), which is known to cause aphthous ulcers in certain individuals.  Using a [[toothpaste]] without SLS will reduce the frequency of aphthous ulcers in persons who experience aphthous ulcers caused by SLS.<!--
Trauma to the mouth is the most common trigger of aphthous ulcers and includes:<ref name="pmid8811135">{{cite journal| author=Herlofson BB, Barkvoll P| title=The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers. | journal=Acta Odontol Scand | year= 1996 | volume= 54 | issue= 3 | pages= 150-3 | pmid=8811135 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8811135  }} </ref><ref name="pmid7825393">{{cite journal| author=Herlofson BB, Barkvoll P| title=Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. | journal=Acta Odontol Scand | year= 1994 | volume= 52 | issue= 5 | pages= 257-9 | pmid=7825393 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7825393  }} </ref><ref name="pmidPMID 105102">{{cite journal| author=Wray D, Ferguson MM, Hutcheon WA, Dagg JH| title=Nutritional deficiencies in recurrent aphthae. | journal=J Oral Pathol | year= 1978 | volume= 7 | issue= 6 | pages= 418-23 | pmid=PMID 105102 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=105102  }} </ref>
  --><ref>{{cite journal | author = Herlofson B, Barkvoll P | title = Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. | journal = Acta Odontol Scand | volume = 52 | issue = 5 | pages = 257–9 | year = 1994 | pmid=7825393 | url=http://www.wealthpartners.net/pdf/0535.pdf | format=PDF}}</ref><!--
*Toothbrush abrasions
  --><ref>{{cite journal | author = Herlofson B, Barkvoll P | title = The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers. | journal = Acta Odontol Scand | volume = 54 | issue = 3 | pages = 150–3 | year = 1996 | pmid=8811135}}</ref><!--
*Laceration with sharp foods or objects
  --><ref>{{cite journal | author = Chahine L, Sempson N, Wagoner C | title = The effect of sodium lauryl sulfate on recurrent aphthous ulcers: a clinical study. | journal = Compend Contin Educ Dent | volume = 18 | issue = 12 | pages = 1238–40 | year = 1997 | pmid=9656847}}</ref>
*Accidental biting (particularly common with sharp canine teeth)
However, some studies find no connection between SLS in toothpaste and mouth ulcers.<!--
*[[Dental braces]]
  --><ref>{{cite journal | author = Healy C, Paterson M, Joyston-Bechal S, Williams D, Thornhill M | title = The effect of a sodium lauryl sulfate-free dentifrice on patients with recurrent oral ulceration. | journal = Oral Dis | volume = 5 | issue = 1 | pages = 39–43 | year = 1999 | pmid=10218040}}</ref>


Artificial sugars, such as those found in diet cola and sugarless gum, have been reported as causes of aphthous ulcers as well.  They can also be linked to an increased intake of acids such as [[ascorbic acid]] (one form of [[Vitamin C]]) or [[citric acid]].  In this case the sores disappear after intake decreases (for example, by substituting [[ascorbate]] [[salt]]s for ascorbic acid).
===Drugs===
Common medications, that can result in recurrent aphthous stomatitis, include:
*[[Beta blockers]]
*[[NSAIDs]]
*[[Cidofovir]]
*[[Pergolide]]
*[[Nicorandil]]
*[[Alendronate]]


According to small-scale experiments by one [[patent]] applicant Hau, ({{US patent|6248718|6,248,718}}), topical preparations of high doses of [[penicillin]] resulted in accelerated healing of mouth ulcers.
===Genetic Factors===
The role of genetic factors is the best-defined underlying cause of aphthous ulcer.
Certain genetically specific [[HLAs]] which have been identified in aphthous ulcer patients include:<ref name=HLA-Aphthous> Albanidou‐Farmaki, E., et al. "HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance?." International journal of immunogenetics 35.6 (2008): 427-432.</ref>
*HLA-A2
*HLA-B5, B12, B44, B51, B52
*HLA-DR2 and HLA-DR7
*HLA-DQ series


There is a commonly held belief that another cause of aphthous ulcers is gluten intolerance ([[Celiac disease]]), whereby consumption of [[wheat]], rye, barley and sometimes oats can result in chronic mouth ulcers. However, two small studies of patients with Celiac disease have demonstrated no link between the disease and aphthous ulcers.<ref name="bucci">{{cite journal | author = Bucci P, Carile F, Sangianantoni A, D'Angio F, Santarelli A, Lo Muzio L. | title = Oral aphthous ulcers and dental enamel defects in children with celiac disease. | journal = Acta Paediatrica | volume = 95 | issue = 2 | pages = 203–7 | year = 2006 | pmid=16449028}}</ref><ref>{{cite journal | author = Sedghizadeh PP, Shuler CF, Allen CM, Beck FM, Kalmar JR. | title = Celiac disease and recurrent aphthous stomatitis: a report and review of the literature. | journal = Oral Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics | volume = 94 | issue = 4 | pages = 474–8 | year = 2002 | pmid=12374923}}</ref> If patients with aphthous ulcers do happen to have gluten intolerance, they may experience benefit in eliminating breads, pastas, cakes, pies, scones, biscuits, beers and so on from their diet and substituting gluten-free varieties where available.<ref name="bucci"/>
===Nutritional Factors===
Aphthous ulcers are commonly seen in nutritional deficiencies.
Low serum levels of following elements may result in recurrent aphthous ulcer:<ref name=Nutritional-Aphthous> Nolan A, McIntosh WB, Allam BF, Lamey PJ. Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy. J Oral Pathol Med 1991; 20: 389–91.</ref>
*[[Iron]]
*[[Folate]]
*[[Zinc]]
*[[Vitamin B1|Vitamins B1]], [[Vitamin B2|B2]], [[Vitamin B6|B6]], and [[Vitamin B12|B12]]


Although the exact cause is not known, aphthous ulcers are thought to form when the body becomes aware of and attacks [[molecules]] which it does not recognize.<ref name="Lewkowicz">{{cite journal |author=Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchorzewski H.|title=Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. |journal=Immunol Lett. |volume=99 |issue=1 |pages=57-62 |year=2005 |pmid=15894112}}</ref> The presence of the unrecognized [[molecule]]s garners a reaction by the [[T-cell]]s, which trigger a reaction that causes the damage of a mouth ulcer. People who get these ulcers have lower numbers of regulatory [[T-cell]]s.<ref name="Lewkowicz">{{cite journal |author=Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchorzewski H.|title=Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. |journal=Immunol Lett. |volume=99 |issue=1 |pages=57-62 |year=2005 |pmid=15894112}}</ref>
===Allergic Factors===
It is thought that aphthous ulcer may be caused by [[hypersensitivity]] to certain a[[llergens]] such as:<ref name=Allergens-aphthous>Wray D, Vlagopoulos TP, Siraganian RP. Food allergens and basophil histamine release in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982; 54(4):388–95.</ref><ref name=Allergens-Aphthous-2>Pacor ML, Di Lorenzo G, Martinelli N, et al. Results of double-blind placebo- controlled challenge with nickel salts in patients affected by recurrent aphthous stomatitis. Int Arch Allergy Immunol 2003;131(4):296–300.</ref>
*Environmental allergens
*Food allergens
**Milk
**Chocolate
**Cheese
**Nuts
**Tomatoes
**Wheat


Repeat episodes of aphthous ulcers can be indicative of an [[immunodeficiency]], signalling low levels of [[immunoglobulin]] in the mucous membrane of the mouth. Certain types of [[chemotherapy]] cause mouth ulcers as a side effect.<!--
===SLS containing Toothpaste===
  --><ref name="nonhodgkinsAdvice">{{cite web | title=Non Hodgkin's Lymphoma Cyberfamily — Side effects | url=http://www.nhlcyberfamily.org/effects.htm | publisher=NHL Cyberfamily | accessdate=2006-08-10}}</ref>
The large majority of toothpastes sold in the U.S. contain [[Sodium dodecyl sulfate|Sodium lauryl sulfate]] (SLS), which is known to cause aphthous ulcers in certain individuals.<ref name="pmidPMID 7825393">{{cite journal| author=Herlofson BB, Barkvoll P| title=Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. | journal=Acta Odontol Scand | year= 1994 | volume= 52 | issue= 5 | pages= 257-9 | pmid=PMID 7825393 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7825393  }} </ref><ref name="pmidPMID 8811135">{{cite journal| author=Herlofson BB, Barkvoll P| title=The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers. | journal=Acta Odontol Scand | year= 1996 | volume= 54 | issue= 3 | pages= 150-3 | pmid=PMID 8811135 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8811135  }} </ref>
Mouth ulcers may also be symptoms or complications of several diseases listed in the following section. The treatment depends on the believed cause.
 
===Microbial Factors===
It is thought that aphthous ulcers may be caused by microbial factors such as:<ref name=Microbial-aphthous> Lindemann RA, Riviere GR, Sapp JP. Serum antibody responses to indigenous oral mucosal antigens and selected laboratory-maintained bacteria in recurrent aphthous ulceration. Oral Surg Oral Med Oral Pathol 1985;59:585.</ref><ref name=CMV-Aphthous> Leimola-Virtanen R, Happonen RP, Syrjanen S. Cytomegalovirus (CMV) and Hel- icobacter pylori (HP) found in oral mucosal ulcers. J Oral Pathol Med 1995;24: 14–7. </ref><ref name=Varicella-Aphthous> Pedersen A, Hornsleth A. Recurrent aphthous ulceration: a possible clinical mani- festation of reaction of varicella zoster of cytomegalovirus infection. J Oral Pathol Med 1993;22:64–8.</ref>
*[[Streptococcus|Streptococcus sanguis]]
*[[Helicobacter pylori]]
*[[Varicella zoster]]
*[[Cytomegalovirus]]
*[[Coxsackie A]]
*[[Herpes simplex]]
*[[Epstein-Barr]]
*[[HIV]]
*[[Tuberculosis]]
*[[Syphilis]]
*[[Coccidioides immitis]]
*[[Cryptococcus neoformans]]
*[[Blastomyces dermatidis]]<ref name="pmid28360966">{{cite journal| author=Edgar NR, Saleh D, Miller RA| title=Recurrent Aphthous Stomatitis: A Review. | journal=J Clin Aesthet Dermatol | year= 2017 | volume= 10 | issue= 3 | pages= 26-36 | pmid=28360966 | doi= | pmc=5367879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28360966  }} </ref>
 
===Systemic Disease===
Common systemic conditions that may be caused in aphthous ulcer are include:<ref name=Behcet’s-disease> Klein P, Weinberger A, Altmann VJ, et al. Prevalence of Behcet’s disease among adult patients consulting three major clinics in a Druze town in Israel. Clin Rheu- matol 2010;29(10):1163–6.</ref><ref name="pmidPMID 15894112">{{cite journal| author=Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchórzewski H| title=Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. | journal=Immunol Lett | year= 2005 | volume= 99 | issue= 1 | pages= 57-62 | pmid=PMID 15894112 | doi=10.1016/j.imlet.2005.01.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15894112  }} </ref>
*[[Behcet syndrome]]
*MAGIC syndrome
*[[Cyclic neutropenia]]
*[[Crohn’s disease]]
*[[Ulcerative colitis]]
*[[Celiac disease]]
*[[HIV]]
*[[Cyclic neutropenia]]
*[[PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis)]]
*[[Sweet syndrome Familial Mediterranean fever]]
*[[Hyperimmunoglobulinemia D]] with periodic fever syndrome
*[[Anemia]]
*[[Neutropenia]]
*[[Hypereosinophilic syndrome]]
*[[Lichen planus]]
*[[Linear IgA bullous dermatosis]]
*[[Epidermolysis bullosa]]
*[[Chronic granulomatous disease]]
*[[Wegener’s granulomatosis]]<ref name="pmid28360966">{{cite journal| author=Edgar NR, Saleh D, Miller RA| title=Recurrent Aphthous Stomatitis: A Review. | journal=J Clin Aesthet Dermatol | year= 2017 | volume= 10 | issue= 3 | pages= 26-36 | pmid=28360966 | doi= | pmc=5367879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28360966  }} </ref>
 
===Others===
*[[Stress (psychology)|Stress]]
*[[Fatigue (physical)|Fatigue]]
*[[Illness]]
*Smoking
*[[Hormone|Hormonal]] changes
*[[Menstruation]]
*Sudden [[weight loss]]
*[[Pemphigus vulgaris]]
*[[Linear IgA disease]]
*[[Erythema multiforme]]<ref name="pmid28360966">{{cite journal| author=Edgar NR, Saleh D, Miller RA| title=Recurrent Aphthous Stomatitis: A Review. | journal=J Clin Aesthet Dermatol | year= 2017 | volume= 10 | issue= 3 | pages= 26-36 | pmid=28360966 | doi= | pmc=5367879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28360966  }} </ref>


==References==
==References==
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[[uk:Афти]]
[[zh:口疮]]


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Latest revision as of 22:26, 12 January 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2] José Eduardo Riceto Loyola Junior, M.D.[3]

Overview

The exact cause of aphthous ulcers is unknown. Factors that provoke them include stress, fatigue, illness, injury from accidental biting, hormonal changes, menstruation, sudden weight loss, food allergies, the foaming agent in toothpaste (SLS), and deficiencies in vitamin B12, iron, and folic acid.

Causes

Trauma

Trauma to the mouth is the most common trigger of aphthous ulcers and includes:[1][2][3]

  • Toothbrush abrasions
  • Laceration with sharp foods or objects
  • Accidental biting (particularly common with sharp canine teeth)
  • Dental braces

Drugs

Common medications, that can result in recurrent aphthous stomatitis, include:

Genetic Factors

The role of genetic factors is the best-defined underlying cause of aphthous ulcer. Certain genetically specific HLAs which have been identified in aphthous ulcer patients include:[4]

  • HLA-A2
  • HLA-B5, B12, B44, B51, B52
  • HLA-DR2 and HLA-DR7
  • HLA-DQ series

Nutritional Factors

Aphthous ulcers are commonly seen in nutritional deficiencies. Low serum levels of following elements may result in recurrent aphthous ulcer:[5]

Allergic Factors

It is thought that aphthous ulcer may be caused by hypersensitivity to certain allergens such as:[6][7]

  • Environmental allergens
  • Food allergens
    • Milk
    • Chocolate
    • Cheese
    • Nuts
    • Tomatoes
    • Wheat

SLS containing Toothpaste

The large majority of toothpastes sold in the U.S. contain Sodium lauryl sulfate (SLS), which is known to cause aphthous ulcers in certain individuals.[8][9]

Microbial Factors

It is thought that aphthous ulcers may be caused by microbial factors such as:[10][11][12]

Systemic Disease

Common systemic conditions that may be caused in aphthous ulcer are include:[14][15]

Others

References

  1. ↑ Herlofson BB, Barkvoll P (1996). "The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers". Acta Odontol Scand. 54 (3): 150–3. PMID 8811135.
  2. ↑ Herlofson BB, Barkvoll P (1994). "Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study". Acta Odontol Scand. 52 (5): 257–9. PMID 7825393.
  3. ↑ Wray D, Ferguson MM, Hutcheon WA, Dagg JH (1978). "Nutritional deficiencies in recurrent aphthae". J Oral Pathol. 7 (6): 418–23. PMID 105102 PMID 105102 Check |pmid= value (help).
  4. ↑ Albanidou‐Farmaki, E., et al. "HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance?." International journal of immunogenetics 35.6 (2008): 427-432.
  5. ↑ Nolan A, McIntosh WB, Allam BF, Lamey PJ. Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy. J Oral Pathol Med 1991; 20: 389–91.
  6. ↑ Wray D, Vlagopoulos TP, Siraganian RP. Food allergens and basophil histamine release in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982; 54(4):388–95.
  7. ↑ Pacor ML, Di Lorenzo G, Martinelli N, et al. Results of double-blind placebo- controlled challenge with nickel salts in patients affected by recurrent aphthous stomatitis. Int Arch Allergy Immunol 2003;131(4):296–300.
  8. ↑ Herlofson BB, Barkvoll P (1994). "Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study". Acta Odontol Scand. 52 (5): 257–9. PMID 7825393 PMID 7825393 Check |pmid= value (help).
  9. ↑ Herlofson BB, Barkvoll P (1996). "The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers". Acta Odontol Scand. 54 (3): 150–3. PMID 8811135 PMID 8811135 Check |pmid= value (help).
  10. ↑ Lindemann RA, Riviere GR, Sapp JP. Serum antibody responses to indigenous oral mucosal antigens and selected laboratory-maintained bacteria in recurrent aphthous ulceration. Oral Surg Oral Med Oral Pathol 1985;59:585.
  11. ↑ Leimola-Virtanen R, Happonen RP, Syrjanen S. Cytomegalovirus (CMV) and Hel- icobacter pylori (HP) found in oral mucosal ulcers. J Oral Pathol Med 1995;24: 14–7.
  12. ↑ Pedersen A, Hornsleth A. Recurrent aphthous ulceration: a possible clinical mani- festation of reaction of varicella zoster of cytomegalovirus infection. J Oral Pathol Med 1993;22:64–8.
  13. ↑ 13.0 13.1 13.2 Edgar NR, Saleh D, Miller RA (2017). "Recurrent Aphthous Stomatitis: A Review". J Clin Aesthet Dermatol. 10 (3): 26–36. PMC 5367879. PMID 28360966.
  14. ↑ Klein P, Weinberger A, Altmann VJ, et al. Prevalence of Behcet’s disease among adult patients consulting three major clinics in a Druze town in Israel. Clin Rheu- matol 2010;29(10):1163–6.
  15. ↑ Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchórzewski H (2005). "Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations". Immunol Lett. 99 (1): 57–62. doi:10.1016/j.imlet.2005.01.002. PMID 15894112 PMID 15894112 Check |pmid= value (help).

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