Recurrent aphthous stomatitis (RAS) is a chronic, ulcerative condition of the oral mucosa without a fully recognized etiology [1, 2]. The current research suggests that genetically conditioned abnormal immune response triggered by various local and systemic factors, plays an essential role in the disease [1, 3]. An abnormally initiated cascade of proinflammatory cytokines acting against the host mucosa leads to the formation of massive leukocytic infiltration and local tissue damage [1]. Disruption of the humoral and cellular immune response in patients with RAS results in an elevated concentration of a complement of species: increased number of NK (natural killer) cells and B lymphocytes, disrupted CD4/CD8 (cluster of differentiation 4/8) ratio, increased number of CD25 (cluster of differentiation 25) and TCR (T cell receptor) ɣδ cells in peripheral blood and hyper-reactivity of neutrophils [4,5,6].
RAS is characterized by the presence of painful, oval erosions or ulcers generally localized on the unattached oral mucosa of the lips, cheeks and tongue, which are surrounded by an erythematous halo. Lesions reappear frequently and to date now there has been no effective causative treatment available [1,2,3]. According to Stanley, the three main types of the disease can be described: major (MaRAS), minor (MiRAS) and herpetiform (HeRAS). The classification criteria include the size and the depth of the lesion, the number of lesions in one episode, their location and duration [1]. Most commonly observed type is minor, where the diameter of lesion varies between 5 and 10 mm. The number of eruptions per one flare-up in this type does not normally exceed 10, while the healing lasts for 10 to 14 days. This form affects from 75 to 90% of all patients with RAS. Major type is found in 10 to 15% of RAS subjects and usually develops as a single ulcer with a diameter over 1 cm, located on keratinized or non-keratinized oral mucosa. The healing phase lasts longer than in case of MiRAS and may take up to 1 month. This form is considered as the most severe one. The least common type is herpetiform RAS, where the crucial finding is the presence of multiple, small, short-lasting erosions that spread throughout the oral cavity, healing within 14 days without leaving a scar [1, 2]. The presence of recurrent oral aphthae accompanied by genital ulcers and uveitis is a characteristic of a systemic condition called Behçet’s disease, which may also involve some other visceral organs [7, 8].
Depending on the diagnostic criteria, the condition affects between 10 and 20% of the general population. The peak period of the RAS occurrence is the second life decade. A higher incidence among females, non-smokers, white races and people with a high socio-economic status has also been reported in some studies [1, 2].
Minor aphthae on the lower lip are presented on Fig. 1.
Zinc is an essential, biologically active, trace metal in the human body. It acts as co-enzymatic and activator of almost 100 human enzymes. It participates in the metabolism of lipids, proteins and carbohydrates, regulates RNA and DNA biosynthesis, modifies the growth and development of epithelium and helps to maintain the correct serum vitamin A concentration [9,10,11]. Zinc levels have been shown to affect the immune response; for example in Zn deficiency, interleukin 2 (IL-2) secretion is limited and the number of T1- helper lymphocytes (Th1) is reduced. Zinc exhibits anti-oxidative properties by inhibiting the oxidation of unsaturated fatty acids. Zinc deficiency is characterized by a broad spectrum of clinical symptoms that include: impaired growth and maturation, loss of appetite and insufficient body weight, pathologic skin lesions (eczema, stretch striae), impaired healing, vision disturbances, signs of accelerated aging, psychiatric and neurosensoric disturbances, reduced resistance to infections and elevated risk of diabetes due to increased glucose tolerance [9,10,11,12]. Zinc deficiency has been reported in patients with various systemic conditions such as: psoriasis, acne vulgaris, pernicious anemia, tuberculosis and cirrhosis [12,13,14,15,16].
A correlation of zinc levels in human body with some oral mucosa diseases has been already suggested, especially those with a potential autoimmune background, such as lichen planus and geographic tongue [16,17,18,19,20,21]. Although the etiology of RAS remains still not fully recognized, the presence of antibodies for different antigens of the epithelium in patients with aphthae also suggests an autoimmune character of the disease [3]. The role of several immunomodulators in the development of the condition has been recently considered. Primary immune abnormalities and immune system disruption observed in RAS patients may partially result from nutrient deficiencies that include iron, folic acid, and vitamin B group [1, 2, 11, 14]. The potential role of zinc deficiency as the modifier of the RAS course may result from the ability of zinc to stimulate the production of IL-1, IL-6 and TNF-α in peripheral blood mononuclear cells and separated monocytes. It was observed that the cytokines production becomes disrupted in zinc deficient subjects- low zinc serum levels correlate with a reduced production of Th1-type cytokines [9]. Meanwhile, the local tissue damage at the initial stage of aphtha formation occurs in the response to an abnormally stimulated cascade of cytokines [3, 4]. Several authors also suggest that Th1-type immunologic response plays an essential role in the etiopathogenesis of RAS [3]. Therefore recently, due to its proven immunoregulating and regenerating properties, zinc has raised a considerable interest as the potential trigger of the RAS development and modifier of its course. Deviations in serum zinc levels could on one hand influence the risk of the disease, but on the other hand it could also affect the course of RAS by promoting more severe forms like MaRAS in zinc deficient subjects.
The aim of the present study was to compare serum zinc levels in patients with RAS and in a group of healthy controls and to evaluate its effects on the disease severity.