Ⅰ. INTRODUCTION

The oral and maxillofacial region is a diverse area of disease. Several syndromes encompass these conditions. Among them, Behçet's disease (BD) is a clinical condition characterized by common recurrent aphthous stomatitis. BD is an autoimmune disorder, also known as Behçet's syndrome, due to its characteristic three or more symptoms. The three most common symptoms of BD include recurrent oral ulcers, genital ulcers, and ocular diseases such as uveitis.

Behçet's disease (BD) was first described in 1937 by Professor Hulusi Behçet as a triple symptom complex (oral ulcers, genital ulcers, and uveitis) ⁽¹⁾. Alibaz-Oner et al. ⁽²⁾ reported that BD is a systemic inflammatory disease of unknown etiology, presenting with recurrent mucocutaneous, ocular, neurologic, gastointestinal, and vascular lesions. Kim et al. ⁽³⁾ reported that local factors may influence the recurrence and delayed healing of oral ulcers in BD, and that the treatment of oral ulcers requires not only systemic treatment but also the removal of local factors.

Bang et al. ⁽⁴⁾ reported the epidemiologic and clinical survey of Behçet's disease in Koreans as the First Multicenter Study between 1997 and 1999, reporting that oral ulcers were present in 98.8% of patients, genital ulcers in 83.2%, skin lesions in 84.3%, and ocular lesions in 50.9%. This suggests that among patients visiting the dental clinic with recurrent aphthous stomatitis, it is important to conduct a more detailed interview to check for genital ulcers, ocular diseases such as uveitis, and skin lesions. This is because among patients who are not yet aware of the onset or possibility of Behçet's disease, if a detailed interview is conducted during the diagnosis, treatment, and continuous follow-up of recurrent aphthous stomatitis in the oral cavity in dental clinics, the discovery of genital ulcers, ocular diseases, and skin lesions will be helpful in the early diagnosis and treatment of Behçet's disease.

Behçet's disease (BD) is one of the diseases classified as a rare disease in Korea. However, it is considered incurable, causing significant suffering for patients. If dentists pay more attention to BD and conduct more thorough dental clinical interviews to identify additional lesions in other organs in patients with recurrent aphthous stomatitis, this will contribute to the early diagnosis and treatment of this rare and intractable condition.

However, research on the incidence of Behçet's disease is still insufficient. The aim of this study is to use big data to examine the recent incidence of Behçet's disease in Koreans, thereby understanding the current status of the disease and helping dentists gain a deeper understanding of the possibility that patients with Behçet's disease may visit their clinics.

Ⅱ. SUBJECTS and METHODS

Big data for this study was used for academic purposes in the 2019 to 2022 rare disease patient statistics from the Korea Disease Control and Prevention Agency (public domain source). In recent years, the number of newly registered Behçet's disease patients with the Korea Disease Control and Prevention Agency was 1,031, 935, 1,028, and 892 for 2019 through 2022, respectively.

Table 1 shows the big data of newly registered Behçet's disease patients at the Korea Disease Control and Prevention Agency by age and gender from 2019 to 2022. The annual total population of South Korea (male/female) from 2019 to 2022 is as follows: 2019 - 51,849,861 (25,864,816/25,985,045), 2020 - 51,829,023 (25,841,029/25,987,994), 2021 - 51,638,809 (25,746,684/25,892,125), 2022 - 51,628,117 (25,790,370/25,837,747).

The annual incidence rates in recent years were analyzed by gender and age for Behçet's disease patients newly registered with the Korea Disease Control and Prevention Agency from 2019 to 2022. In addition, the annual incidence rates of Behçet's disease in the overall population (male/female) were analyzed. The incidence of Behçet's disease was analyzed using Excel.

Ⅲ. RESULTS

The recent incidence of Behçet's disease among Koreans from 2019 to 2022 shows that among patients with Behçet's disease, the proportion of men was 36.7%, 36.6%, 36.4%, and 34.6%, while that of women was 63.3%, 63.4%, 63.6%, and 65.4% (Fig. 1). The incidence rate in men was in the 30% range, and in women, it was in the 60% range.

Table 2 shows the incidence of Behçet's disease patients by age from 2019 to 2022 and presents the average rate over the past four years. In 2019, it appeared in the order of 24% in their 40s, 21% in their 50s, and 19% in their 30s. In 2020, it appeared in the order of 25% in their 40s, 24% in their 50s, and 18% in their 30s. In 2021, it was 23% in their 50s, 22% in their 40s, and 16% in their 30s in that order. In 2022, it appeared in the order of 23% in their 40s, 21% in their 50s, and 17% in their 30s.

From 2019 to 2022, the incidence rate in individuals in their 60s ranked fourth each year from 2019 to 2022, showing 13%, 12%, 16%, and 16%, respectively. From 2019 to 2022, over the past four years, the average incidence rate was highest in people in their 40s at 24%, followed by 22% in their 50s, 17% in their 30s, and 14% in their 60s (Table 2).

The incidence rate of Behçet's disease in the total population of South Korea was 0.001988%, 0.001804%, 0.00199%, and 0.001727% from 2019 to 2022 (Fig. 2). In this study, from 2019 to 2022, Behçet's disease occurred in 1.9, 1.8, 1.8, and 1.7 per 1,000 people, respectively, and over the past four years, an average of 1.8 cases per 1,000 people were reported.

The incidence rates of Behçet's disease among men and women were analyzed from 2019 to 2022 based on the total population each year. In men, the rates were 0.000729%, 0.00066%, 0.000724%, and 0.000598% from 2019 to 2022, respectively (Fig. 2). In women, the rates were 0.001259%, 0.001144%, 0.001266%, and 0.001129% from 2019 to 2022, respectively (Fig. 2). When analyzing the incidence of Behçet's disease in men and women based on the total population by year from 2019 to 2022, women showed a higher incidence than men in all of the past four years.

An analysis of the annual incidence of male Behçet's disease patients per year in South Korea from 2019 to 2022, based on the total male population, showed rates of 0.001461%, 0.001323%, 0.001452%, and 0.001198%, respectively. This corresponds to 1.4, 1.3, 1.4, and 1.1 cases per 1,000 men, and over the past four years, an average of 1.3 men per 1,000 has developed Behçet's disease. An analysis of the annual incidence of female Behçet's disease patients per year in South Korea from 2019 to 2022, based on the total female population, showed rates of 0.0025%, 0.0022%, 0.0025%, and 0.0022%, respectively. This corresponds to 2.5, 2.2, 2.5 and 2.2 cases per 1,000 female, and over the past four years, an average of 2.3 female per 1,000 has developed Behçet's disease.

Ⅳ. Discussion

There are various syndromes associated with diseases in the oral and maxillofacial region. Among them, Behçet's disease (Behçet's syndrome) is an autoimmune disorder that manifests with recurrent aphthous ulcers in the mouth, ulcers in the genital area, ocular diseases such as uveitis, and systemic vasculitis. As modern society ages, a significant proportion of dental patients are elderly. When a patient with recurrent aphthous ulcers in the oral and maxillofacial region visits a dental clinic, it is considered important for dentists to check for the relevance to Behçet's disease through interviews to see if there are other symptoms. This is not only meaningful for the early diagnosis of Behçet's disease but also for its prevention.

In a big data study (394,827 patients) on systemic autoimmune diseases (SADs), Behçet's disease was reported to occur in young people ⁽⁵⁾. However, in our study, the occurrence of Behçet's disease was reported across various age groups, most frequently in people in their 40s at 24%, followed by 22% in their 50s, 17% in their 30s, and 14% in their 60s.

Oshima et al. ⁽⁶⁾ classified 85 patients in clinical and laboratory studies of Behçet's syndrome according to their clinical symptoms (oral ulcers, genital ulcers, ocular symptoms, skin lesions). They categorized them into four types: Complete (all four main symptoms: cutaneous, oral, genital, and ocular), Incomplete (three main symptoms, or ocular symptoms plus one main symptom), Suspective (two main symptoms), and Possible type (one main symptom).

The criteria most commonly used recently for diagnosing Behçet's disease are those established by the International Study Group (ISG) in 1990, which are as follows. Oral ulcers must appear, and if two or more of the secondary criteria are present, it is diagnosed as Behçet's disease. The essential criterion is recurrent oral ulcers (aphthous ulcers recurring three or more times within 12 months, major aphthous ulcers, or herpetiform ulcers). The ancillary items for diagnosis include recurrent vulvar ulcers, eye lesions, skin lesions (such as erythema nodosum), and skin hypersensitivity reactions (positive Pathergy test: formation of a red papule or pustule confirmed by a doctor 24–48 hours after pricking the skin with a needle smaller than 20 gauge under sterile conditions).

Davatchi ⁽⁷⁾ conducted a study on the diagnostic/classification criteria for Behçet's disease and reported that when comparing the criteria presented by the International Study Group (ISG) in 1990 with the criteria presented in 2006 (The International Criteria for Behçet’s Disease, ICBD), the ISG was more excellent in terms of specificity, while the ICBD was superior to the ISG in terms of sensitivity and accuracy. According to the ISG criteria, recurrent oral ulcers are a mandatory requirement, and the secondary items include recurrent genital ulcers, ocular lesions such as uveitis, skin lesions, and skin hypersensitivity reactions. ISG diagnoses Behçet's disease if the essential oral ulcers are present along with two or more of the secondary items. In ICBD, vascular lesions were added, and for the diagnosis of Behçet's disease, each lesion is scored (genital aphthous ulcer 2 points, eye lesions 2 points, each of the other lesions 1 point), and a total score of 3 or more leads to a diagnosis of Behçet's disease. Compared to ISG, ICBD did not require oral ulcers as a mandatory criterion.

When considering the ISG and ICBD criteria proposed by the International Society for Behçet's Disease, recurrent oral ulcers are an essential requirement, and it is clear that recurrent oral ulcers play an important role in the specificity of Behçet's disease diagnosis. For the early diagnosis of Behçet's disease, the role of dentists in diagnosing and treating patients with recurrent oral ulcers in clinical practice can be considered crucial.

Kim et al. ⁽⁸⁾ retrospectively studied the initial symptoms of 3,674 patients diagnosed with Behçet's disease at tertiary medical centers in Korea over a 30-year period (from 1983 to 2012). They reported a decrease in the occurrence of complete-type Behçet's disease, a reduction in the proportion of male patients, and a gradual increase in the average age of patients. Changes in organ involvement patterns were observed: major prominent symptoms such as genital ulcers, ocular involvement, and skin lesions decreased, while the frequency of joint, gastrointestinal, and central nervous system symptoms increased.

Therefore, as reported by various authors, Behçet's disease can be understood as a multi-organ vasculitis and a chronic, recurrent inflammatory disorder (9-¹⁴⁾. Behçet's disease is a chronic multisystem vasculitis that can cause symptoms not only in the mucous membranes, skin, and eyes, but also in the gastrointestinal tract, joints, and nervous system ⁽⁹⁾. The histopathological feature of Behçet's disease is systemic vasculitis accompanied by perivascular inflammatory cell infiltration ⁽¹²⁾. Although the exact pathogenesis is unknown, it has been reported to be an immunological abnormality that can be triggered by microbial pathogens( ¹²⁾. Wann et al. ⁽¹³⁾ reported that Behçet's disease is a systemic vasculitis characterized by three major symptoms: oral aphthosis, genital aphthosis, and uveitis, and that it may or may not be associated with organ involvement.

Bang et al. ⁽¹⁵⁾ conducted a multicenter study on Behçet's disease in Korea (1997–1999) and reported that 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions, and 50.9% had ocular lesions. Among the smaller-scale clinical symptoms, joint symptoms were the most common, and it was reported that females were more prevalent than males. Out of 3,497 patients, 1,527 were reported to have complete or incomplete types of Behçet's disease.

In this study, the incidence of Behçet's disease in Koreans from 2019 to 2022 was compared and analyzed on an annual basis, with the incidence being in the 30% range for men and in the 60% range for women. In this study, we analyzed the average incidence of Behçet's disease by age group over a four-year period from 2019 to 2022. The results showed that it was most common in people in their 40s, accounting for 24% over the past four years, followed by those in their 50s at 22%, 30s at 17%, 60s at 14%, 20s at 12%, and 10s and 70s at 3%, indicating that it occurs across various age groups.

In conclusion, the incidence of Behçet's disease was 16% in those under 30, 42% in people in their 30s and 40s, and 42% in those over 50 approaching old age. As modern society becomes an aging society, a large elderly population is receiving dental care. Therefore, for patients who exhibit recurrent aphthous ulcers during dental treatment or have a history of recurrent aphthous ulcers upon medical questioning, it is important to recognize that Behçet's disease can occur regardless of age, whether in younger or older individuals. Additionally, it is considered important to conduct further questioning to check for ulcers in genital organs or ocular diseases in order to diagnose Behçet's disease and take preventive measures.