The syndrome is named after the Turkish dermatologist Hulusi Behçet, who, in 1937, described a syndrome of aphthous ulcers and genital ulcers.
The Behçet syndrome is a multisystemic disease of unknown etiology, probably first described by Hippocrates in the fifth century.
Although the cause of the disease is still unknown, it has been recognized as a multisystem inflammatory disease with a heterogeneity of clinical manifestations. To complicate matters, clinical presentations vary according to geographic regions and manifestations tend to cluster.
Most cases of Behçet’s disease are sporadic; a small percentage of all cases have been reported to run in families; however, the condition does not have a clear inheritance pattern.
Pathophysiology of Behçet syndrome
Behçet syndrome is characterized by recurrent aphthous ulcers, genital ulcers and uveitis or retinal vasculitis.
Other manifestations of the disease include skin lesions, arthritis, gastrointestinal lesions, central nervous system involvement and vascular lesions, which include aneurysms and thrombosis.
In Behçet’s syndrome, the basic lesion is vasculitis . Biopsies have shown vasculitis near the affected lesions, including oral and genital ulcers and lesions of the central nervous system and eyes; the great vessels are affected by a vasa vasorum vasculitis.
Vascular lesions may overlap with the hypercoagulability observed in some patients.
Neutrophilic hyperfunction is observed in patients with Behçet syndrome with neutrophilic infiltration of the skin at the site of a puncture with a sterile needle (patergia test). The function of lymphocytes has also been reported as abnormal, with a clonal expansion of autoreactive T cells.
There is a wide range of phenotypic variations in Behçet syndrome, which may be due to genetic and ethnic differences.
Ocular : uveitis occurs in 60-80% of patients. The arterial and venous lesions of the retina are prognostic indicators of blindness, which is a major complication of Behçet’s syndrome.
Central nervous system : neurological involvement is one of the most severe manifestations of Behçet syndrome, which occurs in 10-30% of patients and has a poor prognosis.
Manifestations include meningitis or meningoencephalitis; psychiatric symptoms, including personality changes; neurological deficits, including hemiparesis; and the symptoms of the brainstem.
Neurological deficits may be progressive, and 30% of patients with neurological manifestations eventually develop dementia. Compared to adults, children tend to have dural sinus thrombosis more often than parenchymal disease.
Vascular : vascular involvement in Behçet’s syndrome is unique since it involves the arterial and venous systems.
Vascular complications, which occur in 7-40% of patients, include venous and arterial thrombosis, occlusions and vessel stenosis, and aneurysm formation . Venous involvement typically includes superficial thrombophlebitis or deep vein thrombosis, usually of the lower extremities.
Thrombosis of the vena cava can also occur, with extension to the hepatic vein, leading to Budd-Chiari syndrome and its associated morbidity and mortality.
Patients with arterial manifestations may present with thrombosis or aneurysm formation with possible fatal rupture, especially in the case of pulmonary arteries.
Gastrointestinal disease : it is associated with pyoderma gangrenosum and with papulopustular lesions, especially in children.
Gastrointestinal involvement consists of a disease of small vessels that affects the mucosa and produces ulcers or disease of large vessels that produces ischemia and infarction.
The ileocecal region is the area most commonly involved with ulcers; Ulcers may be superficial or more typically deep with an increased risk of perforation.
The cause of Behçet syndrome is unknown. The condition is probably the result of a combination of genetic and environmental factors, most of which have not been identified.
However, a particular variation in the HLA-B gene has been associated with the risk of developing Behçet’s disease.
The HLA-B gene provides instructions for producing a protein that plays an important role in the immune system. The HLA-B gene is part of a family of genes called the human leukocyte antigen (HLA) complex.
The HLA complex helps the immune system to distinguish proteins in the body from proteins produced by external invaders (such as viruses and bacteria).
A variation of the HLA-B gene called HLA-B51 increases the risk of developing Behçet’s disease by approximately a factor of six, although the mechanism is not well understood.
From one-third to two-thirds of people with Behçet’s disease have the HLA-B51 variation, but most people with this version of the HLA-B gene never develop the disorder.
Other genetic and environmental factors probably contribute to the risk of Behçet’s disease. Researchers are studying several genes related to the function of the immune system.
It also seems likely that environmental factors, such as certain bacterial or viral infections, play a role in triggering the disease in people who are at risk.
However, the influence of genetic and environmental factors on the development of this complex disorder remains unclear.
Frequency of Behçet syndrome
Behçet syndrome is more common in the Mediterranean countries, the Middle East, Japan and other parts of Asia. However, it has been found in populations around the world.
The highest prevalence of Behçet’s disease has been reported in northern Turkey, where the disorder affects up to 420 in 100,000 people. The disorder is rare in the countries of northern Europe and the United States, where it generally affects less than 1 in 100,000 people.
They usually start in the 20s or 30s, although they can appear at any age. Some affected people have relatively mild symptoms that are limited to sores around and inside the mouth and genitals.
Others have more severe symptoms that affect various parts of the body, including the eyes and vital organs. The characteristics of Behçet’s disease usually appear and disappear over a period of months or years.
In most people affected, the health problems associated with this disorder improve with age.
The onset generally occurs in patients in the late third and early fourth decades of life. The onset during the childhood years is well known, but the Behçet syndrome rarely occurs before school age.
The average age of onset for pediatric patients in a large Turkish series was 11.7 years, and the average age at onset of the Behçet neurological syndrome was 13 years.