Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com




Recurrent aphthous stomatitis: genetic aspects of etiology
Zuzanna Ślebioda,corresponding author1 Elżbieta Szponar,1 and Anna Kowalska2


Abstract
Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers – RAU; canker sores) is a chronic inflammatory, ulcerative condition of the oral mucosa. Its prevalence in the general population ranges between 5% and 20%, depending on the method and group studied. The etiopathogenesis of the disease is considered to be multifactorial, but remains still not fully understood. In patients with RAS, an enhanced immunologic response occurs to some trigger factors that may include: mechanical injury, stress or bacterial and viral antigens. Higher prevalence of aphthae in relatives may also indicate the genetic background of the condition. The inheritance of some specific gene polymorphisms, especially those encoding proinflammatory cytokines, which play a role in the formation of aphthous ulcer, may predispose family members to RAS. The purpose of this paper was to present the main clinical features of recurrent aphthous stomatitis, epidemiologic data and crucial etiopathogenetic factors with a special emphasis on genetic background of the condition.

Keywords: recurrent aphthous stomatitis, genetic background, etiology
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Introduction
Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers – RAU; canker sores) belongs to a group of chronic, inflammatory, ulcerative diseases of the oral mucosa [1–4]. The condition was initially described by a superb surgeon of Polish origin, Johann von Mikulicz-Radecki, in 1898 [5]. To honor the author, a great professor and scientist, a pioneer in many surgical techniques, small aphthae are traditionally called the Mikulicz's aphthae [5, 6]. Multifactorial etiopathogenesis of RAS remains still not fully understood. The genetic background and the disturbed immunologic mechanisms of this condition have not been clearly defined so far [7–10]. In the course of RAS, a recurrent onset of single or multiple painful erosions and ulcers in various regions of the oral mucosa is observed. These eruptions are surrounded by erythematous halo, while the other regions of the oral mucosa remain unchanged. Most common locations of the lesions include the areas covered with non-keratinized oral mucosa: the lips, cheeks, floor and vestibule of the mouth, palatal arches and soft palate [2, 7, 8, 10, 11]. Severe pain, which often disturbs speaking and swallowing, may accompany the development of the lesions. The treatment of the disease is not very effective and mainly symptomatic. Aphthous ulcers occur as a result of enhanced immunologic response and the activation of pro-inflammatory cytokines’ cascade, directed against the selected regions of the oral mucosa [12, 13]. Histologic observations of the oral mucosa affected by RAS revealed the presence of massive, leukocytic infiltration, which evolves with time. In the initial stage of the disease, before the ulcer is formed, monocytes, lymphocytes (mainly T type) with single mast and plasmatic cells accumulate under the basal layer. In the advanced stages, polynuclear lymphocytes dominate in the center of the ulcer, while the massive infiltrate of mononuclear cells surrounds the aphtha [14, 15]. Considering the clinical features, three main types of recurrent aphthous stomatitis can be defined: minor aphthae (Mikulicz's aphthae; MiRAS), major aphthae (Sutton's aphthae; MaRAS) and herpetiform aphthae (HeRAS) [1, 2, 16].

The most common type of RAS is the minor aphtha, which can be described as an erosion smaller than 1 cm in diameter, surrounded by erythematous halo. It heals with no scar formation and lasts no longer than 2 weeks. Mikulicz's aphtha on the upper lip in a female patient of the Department of Oral Mucosa Diseases, Poznan University of Medical Sciences is presented in (Figure 1).

Figure 1
Figure 1
Mikulicz’s aphtha on the upper lip in female patient of the Department of Oral Mucosa Diseases, Poznan University of Medical Sciences
Sutton's aphthae are typical ulcers – they are observed less frequently than MiRAS, larger and extend deeper. They are very painful and may significantly disturb speaking and swallowing. Lesions heal slowly (they may last up to 1 month) and very often with scaring. Herpetiform aphthae are very small and multiple – up to 100 lesions may be observed simultaneously during one episode of the disease. In no type of aphthae, vesicles or gingivitis – typical symptoms of viral infections – can be observed [1–3, 16]. The most crucial clinical signs of aphthae are presented in Table 1.

Table 1
Table 1
Clinical features of aphthae depending on type
Recurrent aphthous stomatitis may be also one of the symptoms of the Behçet's syndrome

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