Behçet’s Disease
Behçet’s disease (BD) is a chronic inflammatory disorder that primarily affects blood vessels and follows a relapsing-remitting course¹. The condition is also referred to as Behçet syndrome because it can affect multiple organ systems, including the skin, mucous membranes, joints, nervous system and gastrointestinal tract².
Epidemiology
The prevalence of Behçet’s disease varies considerably worldwide⁴. The disease is most common in countries along the historical Silk Road¹,⁴. A recent study estimated the global prevalence at 10.3 per 100,000 people. Regional estimates include 119.8 per 100,000 in Turkey, 31.8 in the Middle East, 4.5 in Asia, 5.3 in Southern Europe, 2.1 in Northern Europe, and 3.8 in North America and the Caribbean⁵.
Pathophysiology
The cause of the disease remains unknown¹,⁶. There has been debate about whether BD should be classified as an autoimmune or autoinflammatory disease, but it has more recently been categorized as an MHC-I-opathy⁶. Genetic factors play an important role, with a clear association with the HLA-B51 antigen, higher prevalence in specific ethnic groups and a high sibling recurrence rate⁴,⁷,⁸.
Clinical Presentation
Vasculitis is the fundamental pathological process in Behçet’s disease and may involve blood vessels of any size. This explains the broad spectrum of manifestations, which may include:
Mucocutaneous involvement: Common manifestations include oral ulcers (aphthous stomatitis), genital ulcers, papulopustular eruptions, erythema-nodosum-like lesions, superficial thrombophlebitis and the pathergy phenomenon⁹.
Ocular involvement: Inflammatory conditions such as uveitis, vitritis, retinal infiltrates and occlusive vasculitis may occur. Ocular disease is the leading cause of severe functional impairment in people with BD¹⁰.
Musculoskeletal involvement: Arthritis, arthralgia, enthesopathy, avascular necrosis and myositis may occur⁹.
Vascular manifestations: These include deep-vein thrombosis, pulmonary aneurysms, Budd–Chiari syndrome and occlusion of major veins such as the vena cava⁹.
Cardiac involvement: May include pericarditis, myocarditis, endocarditis with valvular regurgitation, coronary arteritis and arrhythmias⁹.
Gastrointestinal involvement: Symptoms such as abdominal pain, nausea, diarrhea and gastrointestinal bleeding are common, and gastrointestinal complications may cause substantial morbidity and mortality¹¹,¹².
Neurological involvement: May present as focal or multifocal central-nervous-system disorders, cerebral venous thrombosis or increased intracranial pressure⁹. When neurological manifestations occur in combination with BD, the condition is referred to as neuro-Behçet’s disease (NBD), a serious manifestation associated with increased mortality risk, particularly in men¹³,¹⁴.
Pulmonary involvement: May include pulmonary artery aneurysm, infections, fibrosis, pleuritis and pulmonary embolism⁹.
Diagnostic Procedures
There is no specific biomarker that confirms Behçet’s disease, so diagnosis is based primarily on the clinical presentation⁴. Although more than fifteen different classification criteria have been proposed over time¹⁵, the criteria from the International Study Group (ISG) for Behçet’s Disease are among the most commonly used. These were established in 1990 and have demonstrated a sensitivity of 92% and specificity of 97%¹⁶,¹⁷.
According to the ISG criteria, the following requirements must be met for diagnosis:
Recurrent oral ulceration, with at least three episodes within one year. In addition, at least two of the following must be present:
Recurrent genital ulceration
Eye lesions
Skin lesions
Positive pathergy test¹⁸
Outcome Measures
A recent study⁴, based on a systematic review by the OMERACT Vasculitis Working Group¹⁹, summarized the most frequently used tools for measuring disease activity and quality of life in Behçet’s disease:
Behçet's Disease Current Activity Form (BDCAF)
Clinical Disease Activity Index
Clinical Manifestations Index
Iranian BD Dynamic Activity Measure
1994 Criteria for Disease Activity of BD
Krause's Total Severity Score
BD Quality of Life
Oral Ulcer Composite Index
However, the study highlighted several challenges:
Many outcome measures used in BD research have either not been sufficiently validated or lack standardized definitions for important outcomes such as response, relapse and remission.
Although Behçet-specific measurement tools have been developed, they are rarely used consistently in practice. For example, BDCAF, the most widely used disease-activity instrument, has been used in only about 10% of studies.
Internet-based surveys conducted by the OMERACT group among experts from different specialties and countries have emphasized the need for broadly accepted and well-validated outcome measures for Behçet’s disease²⁰.
Treatment and Management
Multidisciplinary Treatment Team
Optimal management and follow-up of patients with Behçet’s disease should be coordinated by a physician with specific expertise in the condition, in either pediatric or adult practice. Treatment is most often led by a specialist in internal medicine, dermatology or rheumatology²¹. The general practitioner or pediatrician also plays an important role in coordinating care and ensuring follow-up of the proposed treatment plan.
Depending on the manifestations present, the following specialists may also be involved:
Ophthalmologists
Neurologists
Vascular surgeons
Gastroenterologists
Pulmonologists²¹
Other healthcare professionals, including therapeutic-education staff, clinical dietitians, specialist nurses, physiotherapists, occupational therapists, psychologists and social workers, may also be involved when needed²¹.
Medical Treatment
For thrombosis associated with Behçet’s disease, immunosuppressive treatment is generally preferred over anticoagulant therapy²². This is because thrombosis in BD is primarily driven by inflammation.
Some newer treatment options include:
Apremilast, which is approved in the United States for treatment of oral ulcers in patients with Behçet syndrome. Its effects on other manifestations of the disease are still being investigated²³.
Tumor necrosis factor (TNF) inhibitors have been shown to be safe and effective for treating ocular manifestations of BD, including with long-term use²³.
Other medications such as ustekinumab, secukinumab and tocilizumab have shown promising results in early studies, but further research is needed to define their role in the treatment of Behçet’s disease²³.
Physiotherapy
To help prevent corticosteroid-induced myopathy, patients should be encouraged to remain physically active. One recommendation is brisk walking for 30–45 minutes daily²¹. If muscle atrophy develops, targeted physiotherapy with strengthening exercises may be required to restore muscle strength. Physical activity is also important for reducing the risk of corticosteroid-induced osteoporosis²¹.
Differential Diagnoses
Behçet’s disease can mimic several other conditions depending on the organ systems involved. Important differential diagnoses include:
System involvement | Differential diagnoses |
Mucocutaneous involvement | Herpes simplex, neutropenia, pemphigus, chronic inflammatory bowel disease, medication adverse effects, vitamin deficiencies²¹ |
Musculoskeletal system | Systemic lupus erythematosus, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, sarcoidosis, inflammatory bowel disease⁹ |
Vascular system | Mycotic aneurysms, relapsing polychondritis, Takayasu arteritis²¹ |
Gastrointestinal system | Crohn’s disease, ulcerative colitis, peptic ulcer disease, Reiter syndrome, infectious colitis, NSAID toxicity, chronic inflammatory bowel disease⁹,²¹ |
Neurological system | Multiple sclerosis, sarcoidosis, brain tumors, lymphomas, infectious meningoencephalitis²¹ |
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