Behcet’s disease is a rare, chronic, and systemic inflammatory disorder that causes inflammation of blood vessels throughout the body. This condition is a form of vasculitis, meaning the body’s immune system mistakenly attacks its own arteries and veins. Characterized by episodes of relapse and remission, symptoms flare up and then subside over time. Because blood vessels supply every organ, Behcet’s can potentially affect any part of the body, leading to a wide range of complications.
Defining Behcet’s Disease
Behcet’s disease is classified as a multisystem, chronic vasculitic disorder involving inflammation of the blood vessel walls. This inflammation damages both arteries and veins, which can restrict blood flow and lead to the formation of blood clots or aneurysms. The disease is often considered to be at the crossroad between an autoimmune disorder (adaptive immune response) and an autoinflammatory disorder (innate immune system dysfunction).
Behcet’s disease exhibits features of both, including recurrent inflammatory attacks and enhanced activity of immune cells like neutrophils. The condition is named after the Turkish dermatologist Dr. Hulusi Behçet, who first described the triad of symptoms in 1937. The disease has a varied global prevalence but is most common along the historical “Silk Road,” spanning from the Mediterranean to East Asia, with Turkey reporting the highest rates.
Primary Clinical Manifestations
The presentation of Behcet’s disease is highly variable, defined by a recurrent pattern of symptoms affecting multiple organ systems. Manifestations can appear sequentially, making the initial diagnosis challenging. The disease is often first recognized by painful sores in the mouth and genital regions.
Oral and Genital Ulcers
Painful, recurrent oral ulcers affect nearly all patients and are often the first symptom to appear. These sores resemble common canker sores but are frequently more numerous, larger, and more painful, making eating and swallowing difficult. They typically appear on the lips, tongue, cheeks, and palate, healing within one to three weeks but sometimes leaving scar tissue.
Recurrent genital ulcers are another hallmark, presenting as painful sores on the scrotum or penis in men and the vulva or vagina in women. These lesions can be deeper than oral ulcers and frequently result in scarring. The presence of these two types of ulcers is a major factor in clinical diagnosis.
Ocular Involvement
Eye inflammation is a serious complication, occurring in over half of all patients and posing the greatest risk of long-term disability. It commonly presents as uveitis (inflammation of the middle layer of the eye), causing pain, redness, and blurred vision. Retinal vasculitis (inflammation of blood vessels in the retina) is particularly concerning as it can lead to permanent vision loss if not aggressively treated.
Skin Lesions
A variety of skin lesions are characteristic of Behcet’s disease and often fluctuate with disease activity. Erythema nodosum appears as tender, red, and raised nodules, typically found on the lower legs, arms, or face. Other common findings include acne-like lesions, folliculitis, and painful papules and pustules.
A unique sign is the pathergy phenomenon, an exaggerated skin reaction to minor trauma, such as a needle prick. A sterile papule or pustule forms at the site of trauma within 24 to 48 hours. This reaction reflects the underlying hypersensitivity of the immune system and is highly suggestive of Behcet’s disease.
Systemic Involvement
Inflammation can affect the joints, causing a non-destructive form of arthritis that leads to pain, swelling, and stiffness, most often in the knees, ankles, wrists, and elbows. Unlike other forms of arthritis, the joint damage is usually temporary and does not cause permanent deformity.
Gastrointestinal involvement can manifest as ulcers and inflammation anywhere from the esophagus to the anus, leading to abdominal pain, diarrhea, and bleeding. When the central nervous system is affected (Neuro-Behcet’s disease), symptoms range from headaches and poor balance to serious complications like stroke or aseptic meningitis. Vascular involvement can cause deep vein blood clots (deep vein thrombosis) or the formation of aneurysms in arteries, which are life-threatening events.
Underlying Causes and Risk Factors
The exact cause of Behcet’s disease remains unknown, but it is a multifactorial disorder resulting from genetic and environmental influences. The immune system overreacts to a trigger in genetically susceptible individuals, leading to chronic inflammation.
A strong genetic predisposition is evidenced by the association with the human leukocyte antigen (HLA) system, specifically the HLA-B51 gene. This gene is found more often in people with Behcet’s disease, particularly those of Middle Eastern and East Asian descent. However, having the HLA-B51 gene is not a guarantee of developing the disease.
Environmental triggers, such as exposure to certain bacteria or viruses, may initiate the immune response. This mechanism, known as molecular mimicry, suggests that an infectious agent’s proteins resemble self-proteins, causing the immune system to mistakenly attack the body’s own tissues. The disease typically begins between the ages of 20 and 40.
Diagnostic Criteria and Process
No single laboratory test definitively confirms Behcet’s disease, making diagnosis challenging and often delayed. Diagnosis relies heavily on a thorough clinical assessment by a physician, observing a specific pattern of recurrent symptoms and ruling out other diseases. This requires careful documentation of the disease’s history.
To standardize diagnosis, physicians use frameworks like the International Criteria for Behcet’s Disease (ICBD). This framework requires recurrent oral ulcers plus at least two other specific manifestations: recurrent genital ulcers, defined eye lesions, specific skin lesions, or a positive pathergy test. Oral ulcers must have occurred at least three times over a 12-month period.
The pathergy test involves inserting a sterile needle into the forearm skin and observing the site for a small, red bump or pustule after 24 to 48 hours. Blood tests measure general inflammation markers, such as C-reactive protein and erythrocyte sedimentation rate, and help exclude other conditions like lupus or inflammatory bowel disease.
Managing the Disease and Long-Term Outlook
Treatment focuses on controlling inflammation, reducing the frequency and severity of flares, and preventing irreversible organ damage. Since the disease affects multiple systems, a multidisciplinary approach involving rheumatologists, ophthalmologists, and dermatologists is necessary.
For mild disease, topical corticosteroids manage localized inflammation and pain in mouth and genital ulcers. Systemic treatment is required for severe symptoms or organ involvement, often beginning with corticosteroids like prednisone for acute flares. Long-term management involves immunosuppressive drugs to prevent relapse.
Immunosuppressants, such as Azathioprine, Methotrexate, and Cyclophosphamide, broadly suppress immune cell function. For resistant cases, biologic agents are utilized. Targeted therapies, such as TNF-alpha inhibitors like Adalimumab or Infliximab, block specific inflammatory pathways and effectively manage ocular and systemic disease.
The long-term outlook is variable, but most patients manage symptoms effectively with consistent treatment. While chronic, modern therapies have significantly improved quality of life and reduced severe complications. Prognosis is primarily influenced by the severity of vascular and neurological involvement, and eye inflammation, which remains the leading cause of major disability.