Aphthous ulcer pathophysiology
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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]
Overview
The exact pathophysiology of aphthous ulcers is not fully understood. The pathogenesis of recurrent aphthous ulcer is varies based on underlying medical conditions.
Pathophysiology
Pathogenesis
The exact pathogenesis of aphthous ulcer in not clear. Contributing factors include:
- Allergies
- Genetic predisposition
- Hormonal influences
- Hematologic abnormalities
- Immunologic factors
- Infectious agents
- Nutritional deficiencies
- Smoking cessation
- Stress
- Trauma
The exact pathophysiology of aphthous ulcers is not fully understood. The pathogenesis of recurrent aphthous ulcer is varies based on underlying medical conditions.
Microbial factors
- The exact pathogenesis of aphthous ulcer caused by microbial factors is not fully understood. It is thought that oral mucosal damage in aphthous ulcer is caused by either direct pathogens or by the cross reactivity between microbial antigens and mitrocondrial heat shock protein which may lead to T-cell mediated response to the antigens and result in mucosal damage.[1][2][3]
Immune System
It is thought that aphthous ulcer is the result of the cross reactivity between Staphylococcus sanguis and 60kDa Heat shock protein (HSP60)
- The exact pathogenesis of recurrent aphthous ulcer in immunocompromised patients is not fully understood. It is thought that aphthous ulcer in immunocompromised patients may occur by following mechanisms:[4][5]
Abnormality in immunologic response may result in aphthous ulcer by following mechanisms:
- Deposition of immune complexes within the oral epithelium
- Elevated level of salivary immunoglobulin A
- Alteration of the CD41/CD81 ratio
- Increased levels of several cytokines such as interleukin-2, interferon-g, and tumor necrosis factor-a (TNF-a)
Underlying Disease
- The exact pathogenesis of aphthous ulcer caused by different systemic conditions is not fully understood. It is though that recurrent aphthous ulcer in Behcet’s syndrome may be caused by abnormal inflammatory respond in patients which is mediated by T lymphocytes and plasma cells.[6]
- Aphthous ulceration may occasionally arise in HIV disease as initial sign. However, it is a common sing in AIDS patients with CD4+ lymphocyte counts below 100cells⁄mm3
The exact pathogenesis of aphthous ulcer in HIV is remain unclear.[7][8]
- The exact pathogenesis of aphthous ulcer following Crohn’s disease is not fully understood. It is though aphthous ulcer in patients with Crohn’s disease is a result of inflammation of minor salivary glands.[9]
- 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.[10][11] 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.[10]
Associated conditions
- Systemic disease
- Behcet disease
- Mouth and genital ulcers with inflamed cartilage (MAGIC syndrome)
- Crohn disease
- Ulcerative colitis
- Human immunodeficiency virus infection
- Cyclic neutropenia
- Marshall syndrome
- Microbial
- Bacterial (streptococci, Helicobacter pylori,)
- Viral (varicella zoster and cytomegalovirus)
- Genetics
- Ethnicity
- Human leukocyte antigen haplotypes (HLA B51)
- Allergic/Immunologic
- Local T-lymphocyte cytotoxicity
- Sodium lauryl sulfate sensitivity (in tooth paste)
- Abnormal CD4/CD8 ratio
- Microbe-induced hypersensitivity
- Food sensitivity
- Others
- Antioxidants
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Beta blockers
- Immunosuppressive drugs
- Stress
- Psychological imbalance
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Pekiner FN, Aytugar E, Demirel GY, et al. Interleukin-2, interleukin-6 and T reg- ulatory cells in peripheral blood of patients with Behcet’s disease and recurrent aphthous ulcerations. J Oral Pathol Med 2012;41(1):73–9.
- ↑ Hasan A, Shinnick T, Mizushima Y, et al. Defining a T-cell epitope within HSP 65 in recurrent aphthous stomatitis. Clin Exp Immunol 2002;128(2):318–25.
- ↑ Klein P, Weinberger A, Altmann VJ, et al. Prevalence of Behcet syndrome among adult patients consulting three major clinics in a Druze town in Israel. Clin Rheu- matol 2010;29(10):1163–6.
- ↑ Di Alberti L, Porter SR, Speight P, et al. Detection of human herpesvirus-8 DNA in oral ulcer tissues of HIV infected individuals. Oral Dis 1997;3(Suppl 1):S133–4.
- ↑ Ramos-Gomez FJ, Flaitz C, Catapano P, Murray P, Milnes AR, Dorenbaum A. Classification, diagnostic criteria, and treatment recommendations for orofacial manifestations in HIV-infected pediatric patients. Collaborative Workgroup on Oral Manifestations of Pediatric HIV Infection. J Clin Pediatr Dent 1999; 23: 85–96.
- ↑ Schnitt SJ, Antonioli DA, Jaffe B, Peppercorn MA. Granulomatous inflammation of minor salivary gland ducts: a new oral manifestation of Crohn’s disease. Hum Pathol 1987; 18: 405–7.
- ↑ 10.0 10.1 Bucci P, Carile F, Sangianantoni A, D'Angio F, Santarelli A, Lo Muzio L. (2006). "Oral aphthous ulcers and dental enamel defects in children with celiac disease". Acta Paediatrica. 95 (2): 203–7. PMID 16449028.
- ↑ Sedghizadeh PP, Shuler CF, Allen CM, Beck FM, Kalmar JR. (2002). "Celiac disease and recurrent aphthous stomatitis: a report and review of the literature". Oral Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics. 94 (4): 474–8. PMID 12374923.