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      Etiopathogenesis of Recurrent Aphthous Stomatitis and the Role of Immunologic Aspects: Literature Review

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          Abstract

          Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers; canker sores) belongs to the group of chronic, inflammatory, ulcerative diseases of the oral mucosa. Up to now, the etiopathogenesis of this condition remains unclear; it is, however, considered to be multifactorial. The results of currently performed studies indicate that genetically mediated disturbances of the innate and acquired immunity play an important role in the disease development. Factors that modify the immunologic response in RAS include: food allergies, vitamin and microelement deficiencies, hormonal and gastrointestinal disorders (e.g., celiac disease, Crohn’s disease, ulcerative colitis), some viral and bacterial infections, mechanical injuries and stress. In this paper, we presented the main etiopathogenetic factors of RAS with a special emphasis on the mechanisms of the immune response modification. Moreover, we discussed the crucial clinical symptoms and types of RAS together with epidemiologic data based on the current medical literature reports and our own observations.

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          Most cited references135

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          Inflamm-aging. An evolutionary perspective on immunosenescence.

          In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.
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            Innate immunity in aging: impact on macrophage function.

            Innate and adaptive immune functions decline with age, leading to increased susceptibility to infectious diseases and cancer, and reduced responses to preventive vaccination in the elderly population. Macrophages function as 'pathogen sensors' and play an important role in the initiation of inflammatory responses, elimination of pathogens, manipulation of the adaptive immune response and reparation of damaged tissue. In this paper, we review the literature addressing the impact of aging on the macrophage population.
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              Oral mucosal disease: recurrent aphthous stomatitis.

              Recurrent aphthous stomatitis (RAS; aphthae; canker sores) is common worldwide. Characterised by multiple, recurrent, small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow or grey floors, it usually presents first in childhood or adolescence. Its aetiology and pathogenesis is not entirely clear, but there is genetic predisposition, with strong associations with interleukin genotypes, and sometimes a family history. Diagnosis is on clinical grounds alone, and must be differentiated from other causes of recurrent ulceration, particularly Behçet disease - a systemic disorder in which aphthous-like ulcers are associated with genital ulceration, and eye disease (particularly posterior uveitis). Management remains unsatisfactory, as topical corticosteroids and most other treatments only reduce the severity of the ulceration, but do not stop recurrence.
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                Author and article information

                Contributors
                zuzia_slebioda@o2.pl
                Journal
                Arch Immunol Ther Exp (Warsz)
                Arch. Immunol. Ther. Exp. (Warsz.)
                Archivum Immunologiae et Therapiae Experimentalis
                Springer Basel (Basel )
                0004-069X
                1661-4917
                12 November 2013
                12 November 2013
                2014
                : 62
                : 205-215
                Affiliations
                [ ]Department of Oral Mucosa Diseases, University of Medical Sciences, Bukowska 70, 60-812 Poznan, Poland
                [ ]Institute of Human Genetics in Poznan, Polish Academy of Sciences, Poznan, Poland
                [ ]Division Biology of Civilization Diseases, Department of Chemistry and Clinical Biochemistry, University of Medical Sciences, Poznan, Poland
                Article
                261
                10.1007/s00005-013-0261-y
                4024130
                24217985
                3b80a59c-ef52-499f-a230-2766c7085215
                © The Author(s) 2013

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 31 May 2013
                : 28 October 2013
                Categories
                Review
                Custom metadata
                © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2014

                Immunology
                recurrent aphthous stomatitis,etiopathogenesis,immunologic factors,cytokines
                Immunology
                recurrent aphthous stomatitis, etiopathogenesis, immunologic factors, cytokines

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