Oral Manifestations of Behcet’s Syndrome: Case Report

Behcet’s syndrome is an autoimmune disease of the seronegative vasculitic type, with a disease of vessels of variable caliber. It is mainly characterized by oral ulcers, genital ulcers and uveitis. The purpose of this case is to describe the oral manifestations and therapeutic behavior to be followed before a patient with Behcet syndrome. For our purpose, the case of a 20-year-old patient, female, black race, urban origin, who goes to the emergency departments of Maxillofacial Surgery of the body of guard of the Provincial Hospital Dr. Gustavo Aldereguía Lima in the province of Cienfuegos, referred by the specialist in Comprehensive General Stomatology who provided services in the area of health corresponding to the patient for presenting multiple ulcerated lesions throughout the oral cavity and lips. It was concluded that oral ulcers in Behcet’s disease are the first clinical manifestation, which in most cases, lead the patient to seek medical help and are considered by countless authors as the cornerstone to reach the diagnosis of this disease. A total of 14 bibliographies were consulted.


Introduction
Systemic diseases may be preceded or spread, with oral manifestations. The lesions of the oral cavity are attended, for the most part, by Stomatology Specialists, so that knowledge of the oral manifestations of systemic diseases contributes to correct behavior in the face of these conditions that, finally, must be referred to the specialist in the attention of each one of them [1]. Behcet's syndrome is an autoimmune disease of the seronegative vasculitic type, with a disease of vessels of variable caliber [2]. Although the etiology of Behcet's Syndrome is unknown, there are numerous investigations that indicate the participation of genetic, infectious (viral and bacterial) and immunological factors. Among the most important are the association with the HLA genotype of the patients, the cross-reactivity with human peptides and the activation of the vascular endothelium [3]. This disease is more common and severe along the old "silk road", which extended from East Asia to the Mediterranean, Turkey's current territory. 80 to 370 cases are reported per 100,000 inhabitants in Turkey, while the prevalence ranges from 13.5 to 35 per 100,000 in Japan, Korea, China, Iran, Iraq and Saudi Arabia; being a more severe manifestation in Japan [4].
In relation to sex, a predominance of female sex in countries of America and male sex in Asia is described, mainly between the ages of 20 and 40 [5]. In Cuba there are no prevalence studies of this entity [3]. The first description made of this pathology arises may have been described by Hippocrates in his third book of endemic diseases [4]. In 1930, the Greek ophthalmologist Benediktos Adamantiades reported to a patient with arthritis, oral and genital ulcers, phlebitis, and iritis but it was not until 1936 that the Turkish dermatologist Hulsui Behcet determined the description of this disease of more accurate way [6]. The clinical spectrum of this disease, characterized by a symptomatic triad (recurrent oral and genital ulcers with uveitis and hypotension) in addition to the fact that the histopathological study of the affected organs and the analytical data are nonspecific, makes its diagnosis based on the clinical method of description and grouping of signs and symptoms [7]. In 1990, the criteria for the diagnosis of this entity were established for the first time by the International Study Group for Behçet's Disease [8].
In 2006, new diagnostic criteria of the International Group for the study of Behcet's disease were established [9], which declared a major or mandatory criterion: recurrent oral ulcers and minor criteria: recurrent genital ulcers, eye lesions, skin lesions, vascular lesions and positive patergia test [10]. In 2013, the international criteria for the diagnosis of the disease were reviewed, as a result of the analysis they proposed to award 2 points to ocular lesions and oral and genital aphthous lesions and assign 1 point to skin lesions, of the Central Nervous System, vascular manifestations and the positive patergia test. According to these criteria, a patient with a score ≥ 4 points is classified as a Behcet disease [3]. At present it is known that it is not curable, but treatable [4]. The goals of therapy are to: suppress inflammation, reduce the frequency and severity of recurrences. To be effective, treatment must be implemented early [11]. Objective: Describe the oral manifestations and therapeutic behavior to be followed before a patient with Behcet syndrome.

Case Presentation
Patient of 20 years of age, female sex, black race, urban origin,

Anamnesis
During the interrogation, the patient was referred to as inflammation of the entire oral cavity, pain during food intake and difficulty swallowing (dysphagia), burning sensation and burning of the mouth, halitosis, recurrent episodes (7 to 8 times a year) ulcerated bleeding lesions, which previously healed spontaneously until their total disappearance but during the last episode the lesions persist. It also refers to the presence of genital ulcers, skin rash in the frontal region and persistent joint pain.

Physical Exam
Multiple ulcers were detected in the oral cavity of approximately

Complementary Exams
The following complements were indicated:  (a) yellowish-green pseudo membrane located in the tongue and oropharynx; (b) Skin rash in the frontal region; (c) Irregular and rough surface in the left axillary and subaxillary region. According to this current classification criterion it is only necessary to accumulate a score ≥ 4 points, in this case the patient added a total of 6 points.

Treatment
As part of the Stomatological treatment, the patient was

Discussion
Systemic diseases are those morbid processes that affect more than one organic system. The etiopathogenesis of many of these diseases is still not completely clear, but it is well known that, in large part of them, inflammatory processes and immune system disorders that give rise to the various manifestations are involved.
The majority of patients with recurrent oral aphthous ulcers have no other involvement, but in others the presence of chronic aphthous stomatitis lesions is associated with systemic processes [1]. Behcet's syndrome is a very rare autoimmune disease condition in these latitudes [4]. The most accepted concept so far defines it as: in a chronic, multisystemic, recurrent inflammatory process whose main alteration lies in a vasculitis that involves the arteries and veins of any caliber. It is characterized in the clinic by presenting patients with inflammation of the mucous membranes, translated by oral and genital ulcers; in addition to uveitis; digestive symptoms, skin lesions, arthritis and occasional neurological intake.
The etiology of Behcet's disease is unknown and although the majority of cases are sporadic, some studies support the possible genetic origin with evidence of autosomal recessive inheritance as it is reported that in 1 in 10 families there is another member with the disease or other autoimmune diseases in first-degree relatives such as hypothyroidism, scleroderma, discoid lupus erythematosus and juvenile idiopathic arthritis. Another of the arguments described in defense of this genesis is the increased risk of suffering from Behcet's disease when it is associated with the presence of the HLA-B51 main histocompatibility system antigen [12]. It is believed as for many autoimmune or auto-inflammatory syndromes, that certain infectious factors (in particular, Streptococcus antigens) and / or environmental factors are capable of triggering symptoms in individuals with certain genetic variants [13]. In some investigations, the herpes simplex virus type 1 and parvovirus B 19, among the triggers of Behcet's syndrome, other research reports that in this syndrome there is an alteration in the number and activation of lymphocytes, so the CD4 + / CD8 + index inversion has been observed.
The syndrome is usually more serious and frequent in men [3], however the case presented corresponds to a female patient.
The white skin color shows a predominance, although there is a great miscegenation in Cuba [12], this ailment is uncommon in the black population but when it appears they present greater complications and worse prognosis [14]. Over the years different  [10]. In 2013, an international group, composed of representatives from 27 countries, reviewed the international criteria, according to these criteria, a patient with a score ≥ 4 points is classified as a Behcet disease [3]. The presence of recurrent, painful, variable-sized canker sores that heal in 1-3 weeks usually without scarring in most cases are the first manifestation, as occurred in this case. The genital canker sores present in 72-94% of cases are morphologically similar to oral ones, usually heal at 2-4 weeks, but they do leave a scar [7]. There are no typical laboratory alterations of Behcet Syndrome.
Erythrosedimentation and C-reactive protein levels are often moderately high but do not correlate well with disease activity, in this case these values were kept within normal parameters.
Acute phase reactants may be elevated, mainly in patients with vasculitis of large vessels. Serum immunoglobulins are sometimes elevated and immunocomplex levels may be elevated, but autoantibodies such as rheumatoid factor, antinuclear antibodies, anticardiolipin and neutrophil antithoplasm (ANCA) are negative [3].
The patergia test is not 100% specific, only a proportion of patients with Behcet Syndrome have a positive response and the positivity in patients with the syndrome vary in different geographical areas (60-70% in Turkey and Japan, but rare in America and Europe) [11], however, the case presented is of a patient born in Cuba who is part of the American continent in which the test was positive, not coinciding with world statistics, where positivity is rare in the Americas. The differential diagnosis should be made with: Reiter's disease, Steven-Johnson syndrome, aphthous stomatitis, recurrent  although more recent studies report highly positive results with immunosuppressants [7]. It is described that all patients should use colchicine and steroids, with Metrotexate being the diseasemodifying drug most used in the treatment of this [5]. The majority of patients diagnosed with Behcet syndrome have a productive life.
The symptoms are controlled with a healthy diet, rest, physical exercises and drug treatment and the prognosis varies according to the affected organs [7]. Behcet's disease has a chronic course with exacerbations and unpredictable remissions, the frequency and severity of which may decrease over time. After the first five years, the disease acquires a stable course or towards improvement; after the fourth decade, clinical severity is decreased, with longer intervals of recurrence between exacerbations. The prognosis is good, unless there is commitment of vital organs. The presentation at the age of early onset (before age 25) has been associated with more severe manifestations of the disease and increased mortality [13].

Conclusion
While it is true that multiple systemic diseases present with aphthous oral manifestations, oral ulcers in Behcet's disease are the first clinical manifestation, which in most cases, lead the patient to seek medical help and constitute for countless authors the cornerstone to reach the diagnosis of this disease, so it is considered vital that the Comprehensive General Stomatologist putting into practice the knowledge acquired about the syndrome, consider it a possible differential diagnosis more before a patient with recurrent oral ulcerations. The timely management of a patient with an unusual and exceptional pathology can have an optimal evolution and reduction of complications in the quality of life. It is recommended to expand coverage and health education to be able to detect these cases in the first instance, thus avoiding underdiagnosis.