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CHRONIC RECURRENT AFTHOUS STOMATITIS. MODERN TREATMENT APPROACHES (REVIEW ARTICLE) Akbarov A.N.1, Ziyadullaeva N.S.2, Irismetova B.D.3 Email: Akbarov460@scientifictext.ru
1Akbarov Avzal Nigmatullaevich - Doctor of Medical Sciences, Professor;
2Ziyadullaeva Nigora Saidullaevna - Candidate of Medical Sciences, Associate Professor; 3Irismetova Barno Dilshodovna - Assistant, FACULTY PROSTHETIC DENTISTRY, TASHKENT STATE DENTAL INSTITUTE, TASHKENT, REPUBLIC OF UZBEKISTAN
Abstract: the article provides a review of the literature, reflects the methods of diagnosis and treatment of chronic recurrent aphthous stomatitis. The issues of improving the treatment and prevention tactics of chronic recurrent aphthous stomatitis are one of the most urgent and unresolved problems of modern dentistry. In this regard, targeted research is needed to find, develop, clinical and biochemical evaluation, as well as to introduce into the practice of dentistry more reliable methods of local therapy of erosive and inflammatory processes in the oral mucosa, aimed at correcting morphological and microbiomic disorders in chronic recurrent aphthous stomatitis. Keywords: methods of treatment of recurrent aphthous stomatitis, HRAS, diseases of the oral mucosa.
ХРОНИЧЕСКИЙ РЕЦИДИВИРУЮЩИЙ АФТОЗНЫЙ СТОМАТИТ. СОВРЕМЕННЫЕ ПОДХОДЫ К ЛЕЧЕНИЮ (ОБЗОРНАЯ СТАТЬЯ) Акбаров А.Н.1, Зиядуллаева Н.С.2, Ирисметова Б.Д.3 (Республика Узбекистан)
1 Акбаров Авзал Нигматуллаевич - доктор медицинских наук, профессор;
2Зиядуллаева Нигора Саидуллаевна - кандидат медицинских наук, доцент;
3Ирисметова Барно Дильшодовна - ассистент, кафедра факультетской ортопедической стоматологии, Ташкентский государственный стоматологический институт, г. Ташкент, Республика Узбекистан
Аннотация: в статье приведен обзор литературы, отражены методы диагностики и лечения хронического рецидивирующего афтозного стоматита. Вопросы совершенствования лечебно-профилактической тактики хронического рецидивирующего афтозного стоматита относятся к одной из актуальных и до конца нерешённых проблем современной стоматологии. В связи с этим, необходимы целенаправленные исследования по поиску, разработке, клинической и биохимической оценке, а также внедрению в практику стоматологии более надежных методов местной терапии эрозивно-воспалительных процессов в слизистой полости рта, направленной на коррекцию морфологических и микробиомных нарушений при хроническом рецидивирующем афтозном стоматите.
Ключевые слова: методы лечения рецидивирующего афтозного стоматита, ХРАС, заболевания слизистой оболочки полости рта.
Diseases of the oral mucosa take a special point among dental diseases, for which timely diagnosis and selection of an appropriate method and treatment plan are extremely difficult.
The World Health Organization defines oral health as a condition characterized by the absence of chronic pain in the oral cavity and in the facial area, cancer of the mouth and throat, infections and oral ulcers, periodontal (gum) diseases, decayes, tooth loss and other diseases and disorders of health conditions that limit a person's ability to bite, chew, speak and their psychosocial well-being [28]. The Global Burden of Disease Survey (2018) estimates that at least 3.58 billion people worldwide suffer from oral diseases [14].
One of the most common diseases of the oral mucosa is chronic recurrent aphthous stomatitis (HRAS), characterized by recurrent and painful benign ulcerative lesions, unclear etiology, still controversial differential diagnostic criteria and treatment. The etiopathogenesis of this lesion of the oral mucosa remains unclear, which is often multifactorial, suggesting an underlying genetic susceptibility with possible triggers, including viral or bacterial microbial agents, food, drugs, hormones, stress, malnutrition and systemic diseases. In this case, the leading role is assigned to the infectious-allergic etiology.
Ulceration of the oral mucosa is often a symptom of a wide range of diseases associated with many etiological factors. These lesions can represent a complex therapeutic and diagnostic search due to the overlap of clinical and histological characteristics between different types of ulcerative lesions in the oral cavity, most of which can be divided into four categories: infectious, immune, traumatic and neoplastic [9, 15, 17].
Benign oral ulcers include aphthous ulcers or chronic recurrent aphthous stomatitis (HRAS), characterized by an unclear etiology, still controversial treatment and differential diagnosis requiring proper attention and clinical experience from dentists [11, 19].
Unfortunately, many studies face difficulties in conducting an epidemiological study in relation to HRAS [20, 21, 27]. So, according to B.W. Neville et al. (2016) HRAS is one of the most common diseases of the oral mucosa with a frequency of occurrence in the general population from 5% to 66%, an average of 20% [15].
Slebioda et al. (2020) explain such significant differences in the incidence of HRAS depending on the origin of the studied groups and populations, as well as on the design and methodology of the study [24]. So in one of the latest similar studies SIML Queiroz et al. (2018) reported a prevalence of HRAS of 1.4% over 11 years.
The authors conclude that the lower statistical data they obtained may indicate that many people suffering from this disease do not seek dental care, since most patients often have a short and self-limiting clinical course of the disease [19].
The fact that HRAS is one of the most frequent lesions of the oral mucosa in young patients is confirmed in the reports of American scientists K. Shah et al. (2016), who also proposed a classification of ASD, dividing three forms of the disease (minor, major, and herpetiformis) and noting the importance of localization, number of lesions, duration, recurrence rate, and severity.
Also, the authors separately distinguish the so-called "complex ASD", manifested by frequent or permanent lesions of the oral cavity and possible lesions of the genital organs in the absence of a systemic disease [22].
To date, the etiopathogenesis of HRAS remains unclear and is often multifactorial, suggesting an underlying genetic susceptibility with possible triggers, including viral or bacterial microbial agents, foods, drugs, hormones, stress, malnutrition, and systemic diseases [18, 22, 24 , 25, 30].
According to the existing literature on the pathogenesis of HRAS, the leading role is assigned to infectious-allergic etiology (changes in reactivity, hypersensitization of the body as a whole with increased sensitivity to Proteus, Staphylococcus, Streptococcus, E. coli).
The viral theory of HRAS is also well known, suggesting that patients have a latent viral infection that mainly affects the capillaries of the oral mucosa and is accompanied by aphthous eruptions. Other theories of the occurrence of HRAS are considered violations of vitamin metabolism, in particular, B1, B2, B6, B12, hypovitaminosis C, an increase in the levels of lysosomal hydrolases in the secretion of the salivary glands and lipid peroxidation [2].
A number of authors are conducting studies aimed at identifying the role of autoimmune processes in the pathogenesis of HRAS, the results of which indicate the role of tissue damage against the background of the influence of immune complexes consisting of antigens of various microorganisms and antibodies - immunoglobulins [2, 15].
The diagnosis of ASD requires a patient-reported history and a thorough oral examination [18]. Family history, frequency of occurrence, duration, number, location (keratinized or non-keratinized tissue), size and shape of ulcers are also important for diagnosis [11, 26].
It is important to note that there is no specific laboratory test for diagnosing ASD and that histopathologic findings are nonspecific, but additional tests such as complete blood count, dosage of inflammatory and hematologic markers and vitamins, and serologic testing are useful tools. to exclude possible systemic conditions that can cause mouth ulcers [2, 6, 7, 12, 26].
Y.J. Shim et al. (2012) in their publications note that patients with HRAS should be evaluated for possible association with potential triggers of ASD (food and supplements, topical agents or drugs, malnutrition and underlying systemic diseases) [23].
According to K. Shah et al. (2016) any drugs, including non-steroidal anti-inflammatory drugs, antibiotics, beta-blockers, angiotensin-converting enzyme inhibitors and antianginal drugs, can cause ASD-like lesions [22]. In this case, the contributing factors can be a deficiency of iron, B vitamins, vitamin C or folic acid [10, 13, 29].
There have been many attempts to find the ideal treatment for HRAS, however some patients do not need treatment due to the mild nature of the disease, while others who experience several episodes over a period of months and / or have severe pain symptoms and difficulty eating should be treated. palliative [11].
The first line of therapy for HRAS is topical corticosteroids, although complex or severe cases may require systemic steroids or alternative immunosuppressive drugs [8]. Topical drugs are the first choice because they are safe and effective, have few side effects and are less likely to interact with drugs [19, 26].
In terms of the treatments used, A. Chattopadhyay in 2011 named local or intralesional corticosteroids and local anesthetics as the most commonly used palliative treatment for HRAS to relieve symptoms, control pain and reduce future ulcers, as there is no specific treatment for ASD that addresses to heal lesions [3].
The use of laser therapy as a strategy to support standard dental treatment regimens has recently become very popular [24]. In dental surgery and endodontic treatment, high-power lasers such as carbon dioxide (CO2), neodymium-doped yttrium-aluminum garnet (Nd: YAG) or erbium-doped yttrium aluminum garnet (Er: YAG) are commonly used. Meanwhile, low-power semiconductor lasers are used in physiotherapy of the oral mucosa and periodontium [16].
N. Zand et al. (2012) concluded, after conducting a randomized, blind, controlled clinical trial, that CO2 laser can be used to accelerate minor healing of ASD without visible side effects, although its analgesic effect is more important than its therapeutic effect [32]. The authors highlight the fact that their study is still a pilot study and that larger samples are needed for subsequent studies.
In addition to topical treatments, there are systemic treatments such as thalidomide, prednisone, and dapsone. According to the literature, the best therapy for HRAS is to control oral ulcers for as long as possible with minimal side effects. Even in the absence of a proven etiology, identifying factors associated with relapse episodes is
important to check for possible risks of increased pain symptoms for each patient. The differential diagnosis of ASD with other oral ulcerations is already well known and is an important clinical aspect for a thorough examination, since its diagnosis in many cases is made after excluding other conditions [15, 24].
Some patients with HRAS have anemia, hematin deficiency and positive serum GPCA, TGA and TMA [5, 7, 12, 13, 25, 29, 30, 31]. Therefore, it is important to evaluate CBC, serum iron, ferritin, vitamin B12, folate, and homocysteine levels, and the presence or absence of serum GPCA, TGA, and TMA positive results before starting any treatment.
If patients with HRAS are diagnosed with nutritional deficiencies and / or systemic disorders, the addition of iron, zinc, folic acid and vitamins B1, B2, B6 and B12, as well as referral of patients to doctors for the treatment of specific systemic diseases is a prerequisite [1, 30].
Long-term clinical experience of Wu YH (2018) and Chiang CP (2019) also showed that supplemental therapy with a complex of vitamins B and C together with the preparation of iron, vitamin B12 and / or folic acid can significantly reduce the severity and frequency of recurrence of HRAC [5, 30] ...
The clinical management of HRAS using local and systemic therapies is based on symptom severity, size and number of lesions [2, 6]. The goals of therapy are to reduce pain, reduce the size and number of ulcers, heal ulcers, and reduce the pain of recurrent ulcers. Medicines used for topical or systemic therapy usually include corticosteroids, antimicrobials, analgesics, anti-inflammatories, immunomodulators, etc.
Topical corticosteroids are the most commonly used drugs for the treatment of HRAC. Some patients with HRAS may have prodromal symptoms such as tingling or burning sensation in the area of the oral mucosa where ulceration subsequently develops. In this situation, the use of a topical corticosteroid can prevent the onset of aphthous ulcer [2].
According to I. Belenguer-Guallar et al. (2014) fluocinolone acetonide (0.025-0.05%) has medium to high efficacy, and clobetasol propionate (0.025%) is the most potent topical corticosteroid; thus, these two topical agents are intended for the treatment of severe or aggressive ASD lesions [1].
The most commonly used antimicrobial agent is chlorhexidine gluconate mouthwash (0.12%), which reduces bacteria in the mouth. It can protect the ulcer from bacterial infection and speed up the healing of aphthous ulcers. Benzydamine hydrochloride (1.5 mg / ml) oral spray is a local anesthetic that also has anti-inflammatory effects.
Also, to reduce pain, 3% diclofenac with 2.5% hyaluronic acid solution can be applied to the affected areas. Moreover, topical lidocaine (2% spray or gel) is also a local analgesic for the treatment of HRAC [1]. Studies have found that topical antibiotics such as tetracyclines and their derivatives (doxycycline and minocycline) in a gel or rinse form reduce pain and reduce ASD flare-ups. These drugs act by local inhibition of collagenases and metalloproteinases, which promote tissue destruction and ulceration [1].
If the lesions are large and the oral symptoms are severe, literature review has shown that topical spraying of corticosteroid powders (eg, a spray containing beclomethasone dipropionate) onto the affected areas of the oral mucosa 2-3 times daily is also effective. for the induction of healing of HRAS lesions.
Alternatively, large and severe lesions can also be treated with intralesional and submucosal injections of Kenacort A (40 mg triamcinolone acetonide for each ASD lesion once a week for 1-2 weeks) plus oral prednisolone (15-30 mg prednisolone after breakfast). once a day for a week; oral prednisolone is gradually reduced to 5 mg per day and stopped in the second week). This method of treatment can lead to accelerated healing of HRAC lesions.
If patients with HRAS suffer from oral candidiasis, especially in areas of lesions of the oral mucosa, due to prolonged use of corticosteroid ointment, patients should be prescribed antifungal drugs (for example, mycostatin) for at least two weeks to eliminate oral candidiasis [1, 4 ]. Patients with HRAS should be evaluated every 3-6 months until there has been a relapse for at least a year.
According to Belenguer-Guallar I (2014), Chavan M (2012), drugs with systemic immunosuppressive effects, including prednisolone, colchicine, levamisole, azathioprine (imuran), thalidomide, pantoxifylline and dapsone, can also be used to treat severe cases of HRAC [1 , four].
The immunosuppressant azathioprine (imuran) can be used as a corticosteroid-sparing agent for patients with HRAC associated with systemic diseases who may require large amounts of corticosteroids to suppress symptoms and signs of ASD lesions and associated systemic diseases [1, 4].
The authors recommend "if a patient with ASD is taking 50 mg of imuran per day, the amount of corticosteroids can be reduced by up to half to avoid side effects such as adrenal suppression, hypertension, hyperglycemia, weight gain, mood changes, insomnia, and gastrointestinal distress. irritation and osteoporosis due to long-term maintenance therapy with corticosteroids "[1, 4].
Thus, when studying the issues of treatment tactics in HRAS, the authors put forward several theories and it is believed that the first line of therapy is local drugs, since they are safe and effective, have few side effects and a lower likelihood of drug interactions, although in complex or severe cases, systemic steroids and/or alternative immunosuppressants.
Recently, the use of laser therapy has become very popular as a strategy to support standard endodontic treatment regimens in dental prosthetics in patients with HRAS.
Also, recently, methods of local therapy with the use of various gel and polymer compositions that help to reduce pain, foci of aphthosis and erosive-inflammatory process of the oral mucosa have been actively considered.
The analysis of the literature indicates that the issues of improving the treatment-and-prophylactic tactics of HRAS are one of the urgent and unresolved problems of modern dentistry. In this regard, targeted research is needed
to find, develop, clinical and biochemical assessment, as well as to introduce into dental practice more reliable methods of local therapy for erosive-inflammatory processes in the oral mucosa, aimed at correcting morphological and microbiome disorders in HRAS.
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