Behcet’s Syndrome

Behcet’s syndrome is a rare condition that causes inflammation of blood vessels throughout the body, leading to painful mouth sores, genital ulcers, eye problems, and many other symptoms that can come and go unpredictably.

Table of contents

• What is Behcet’s Syndrome?
• Who Gets Behcet’s Syndrome?
• Signs and Symptoms
• What Causes Behcet’s Syndrome?
• How is it Diagnosed?
• Treatment Approaches
• Living with Behcet’s Syndrome

What is Behcet’s Syndrome?

Behcet’s syndrome, also called Behcet’s disease, is a rare condition that causes inflammation (swelling and irritation) of blood vessels throughout the body^[1][2]. This inflammation can affect blood vessels of all sizes, from the smallest to the largest, including both arteries and veins^[2].

The disease was first described in modern times in 1937 by Hulusi Behçet, a Turkish dermatologist who identified three patients with oral and genital ulcers, eye inflammation, and skin problems^[4]. It is sometimes known as Silk Road disease because it is most common along the ancient Silk Route^[2][7].

Behcet’s syndrome is not contagious and cannot be spread from person to person^[15]. It is a chronic condition, which means it lasts a long time, but symptoms can come and go in a pattern of flare-ups and remission periods^[3].

Behcet disease, Behcet’s disease, Silk Road disease, Behcet syndrome, malignant aphthosis

Who Gets Behcet’s Syndrome?

Behcet’s syndrome is seen all over the world, but it is much more common in certain regions^[2]. The disease is most common in Northern Turkey, where up to 420 cases occur per 100,000 people^[2]. It is also frequently found in the Mediterranean basin, Middle East (up to 300 cases per 100,000 people), and the Far East, including Japan and China (about 15 cases per 100,000 people)^[2][6].

In the United States, Behcet’s syndrome is much less common, affecting about 7 cases per 100,000 people^[2]. People from the Middle East, East Asia, Turkey, and Iran are more likely to develop this condition^[6].

Anyone can develop Behcet’s syndrome at any age, though symptoms usually begin to appear between the ages of 20 and 30^[2][6]. Men and women are affected equally, although men tend to have more severe disease^[2][10].

Signs and Symptoms

Behcet’s syndrome affects everyone differently. Symptoms can vary greatly from person to person and may come and go over time^[1]. The condition typically follows a pattern of periods when symptoms get worse (called flare-ups or relapses) followed by times when symptoms disappear or lessen (called remission)^[3].

Mouth Sores

Painful mouth sores are the most common sign of Behcet’s syndrome, occurring in virtually all patients at some point^[1][2]. These sores look like canker sores but are typically more numerous, more frequent, and more painful^[2]. They begin as raised, round sores in the mouth and quickly turn into painful ulcers^[1]. The sores can appear on the lips, tongue, and inside the cheeks, and usually heal within one to three weeks, though they often come back^[1][2].

Genital Sores

Open sores can develop on the scrotum in men or on the vulva in women^[1][2]. These sores look similar to mouth ulcers and are often painful. They can leave scars when they heal^[1]. Genital sores are not as common as mouth sores^[2].

Eye Problems

Eye inflammation, called uveitis, can affect both the front and back parts of the eye^[1][7]. This causes redness, pain, blurred vision, sensitivity to light, and tearing^[1][2]. Uveitis most often affects both eyes and can lead to vision loss if not treated properly^[1]. Severe eye disease that can cause blindness is more common in the Middle East and Japan than in the United States^[2].

Skin Problems

Several types of skin problems can occur with Behcet’s syndrome^[1][2]. Some people develop sores that look like acne on their bodies. Others get raised, tender growths called nodules on their skin, especially on the lower legs (known as erythema nodosum)^[1][7]. A distinctive feature is that a red bump or sore may develop if the skin is scratched or pricked with a needle—doctors call this a positive pathergy test^[2][3].

Joint Pain

Joint swelling and pain commonly affect the knees, ankles, elbows, wrists, and hips^[1][2]. Joint inflammation causes swelling, redness, and tenderness. These symptoms can last one to three weeks and go away on their own, and they usually don’t cause permanent damage to the joints^[1][2].

Blood Vessel Problems

Inflammation in veins and arteries can cause redness, pain, and blood clots^[1][2]. This can lead to swelling in the arms or legs. Inflammation in large arteries can lead to serious complications including aneurysms (bulges in the artery wall that can burst) and narrowed or blocked blood vessels^[1][7].

Brain and Nervous System

The brain and its covering (the meninges) can be affected by Behcet’s syndrome^[2][7]. This can cause fever, headache, stiff neck, and difficulty coordinating movement. In rare cases, a stroke can occur when blood vessels in the brain are blocked or ruptured^[2].

Digestive System

The gastrointestinal tract can develop lesions similar to those in the mouth and genital areas^[2][7]. This can cause abdominal pain or blood in the stool. These lesions are more dangerous because they can cause the intestine to bleed or rupture^[2].

Other Organs

In rare cases, the lungs or kidneys can be affected^[2]. Aneurysms of arteries in the lung can rupture, leading to massive lung bleeding^[7].

What Causes Behcet’s Syndrome?

The exact cause of Behcet’s syndrome remains unknown, although scientists believe genetics and environmental factors both play a role^[3][4].

Most experts believe Behcet’s syndrome is an autoinflammatory condition, which means the immune system becomes overactive and attacks the body’s own blood vessels, causing repeated episodes of inflammation^[3]. It is not clear what triggers this problem with the immune system.

Genetic Factors

The increased occurrence of Behcet’s syndrome along the “Silk Route” and within families suggests a genetic component^[4]. The most frequent genetic association is with a gene called HLA-B51 (also known as HLA-B5)^[4][6]. People who carry this gene marker are at higher risk for developing Behcet’s syndrome compared to non-carriers. However, having this gene does not mean someone will definitely develop the disease, and the condition does not follow a simple pattern of inheritance^[4].

Environmental Factors

Although no specific environmental factor has been definitively identified, scientists believe exposure to certain infectious agents may trigger the disease in people who are genetically predisposed^[4]. Some research has suggested a connection to bacteria such as Streptococcus sanguinis and Staphylococcus aureus, as well as viruses like herpes simplex virus, but their direct role in causing Behcet’s syndrome has not been confirmed^[4].

The current belief is that exposure to an infectious or external agent somehow initiates an autoinflammatory response in genetically susceptible individuals^[4].

How is it Diagnosed?

Diagnosing Behcet’s syndrome can be difficult because there is no single definitive test for the condition^[3][6]. Instead, healthcare professionals make the diagnosis based mainly on a person’s medical history, physical examination, and symptoms^[6][8].

Nearly everyone with Behcet’s syndrome gets mouth sores, so mouth sores that come back at least three times in 12 months are often needed for a diagnosis^[8]. In addition to recurrent mouth ulcers, a diagnosis typically requires at least two of the following symptoms^[3][8]:

• Genital sores that keep coming back
• Eye inflammation
• Skin lesions (any unusual growths or abnormalities on the skin)
• Pathergy (hypersensitive skin)

Tests Used in Diagnosis

Several tests may be performed to check for signs of the condition or to rule out other diseases^[3][8]:

Blood tests can help rule out other conditions that may cause similar symptoms. Sometimes doctors check for the HLA-B*51 gene marker, but finding this gene does not confirm the diagnosis on its own^[6].

Pathergy test: A healthcare professional pricks the skin with a sterile needle and examines the area one to two days later^[3][8]. If the test is positive, a small red bump forms under the skin where the needle was inserted. This shows that the immune system reacts too strongly to a minor injury.

Other tests such as urine tests, imaging scans (X-rays, CT scans, or MRI scans), and skin biopsies may be needed to check for signs of the disease or to help rule out other causes^[3].

Other potential causes must be ruled out before the diagnosis is made^[3].

Treatment Approaches

There is currently no cure for Behcet’s syndrome, but various treatments can help control symptoms and prevent serious complications^[3][8]. Treatment varies depending on which organs are involved and how severe the symptoms are^[10].

Because Behcet’s syndrome can affect different parts of the body, patients often work with a team of specialists including rheumatologists (doctors who specialize in inflammatory conditions), dermatologists (skin specialists), ophthalmologists (eye specialists), and others^[3][6]. The rheumatologist typically oversees the treatment plan^[6].

Medicines for Skin and Mouth Symptoms

Topical corticosteroids are medicines applied directly to affected areas as creams, gels, ointments, mouthwashes, or eye drops^[8][11]. These can help reduce inflammation and pain from mouth sores, genital ulcers, and skin lesions. Special mouthwashes containing corticosteroids can reduce pain from mouth sores^[8].

Colchicine is a medicine often used to treat gout that can help prevent mucocutaneous symptoms from coming back^[6][11].

Apremilast (Otezla) is the first and only medicine approved by the U.S. Food and Drug Administration specifically for oral ulcers associated with Behcet’s syndrome^[6][9]. This oral medication can help treat oral and genital ulcers.

Medicines for More Serious Symptoms

For more severe symptoms affecting the whole body, several types of medicines may be used:

Oral corticosteroids (taken as pills or capsules) work throughout the body to reduce inflammation^[8][11]. While effective, long-term use can cause side effects such as weight gain, stomach ulcers, mood swings, increased risk of infections, high blood pressure, weak bones, cataracts, and diabetes^[11].

Immunosuppressants are medicines that reduce the activity of the immune system, interrupting the inflammation process^[8][11]. Examples include azathioprine, cyclosporine, cyclophosphamide, and methotrexate. These medicines can cause side effects including increased risk of infections, nausea, diarrhea, hair loss, and effects on blood cells and liver function^[11]. Regular blood tests are needed to monitor for these effects.

Biological therapies are newer medicines that target specific parts of the inflammation process more selectively^[8][11]. For example, TNF inhibitors (tumor necrosis factor inhibitors) such as infliximab (Remicade) and adalimumab (Humira) work by blocking a protein that causes inflammation. These are used for severe cases, particularly for eye involvement^[6][11].

Treatment Based on Symptoms

The treatment approach depends on which parts of the body are affected:

For eye disease, azathioprine is widely used as the initial treatment^[14]. For severe eye disease involving vision loss or damage to the retina, cyclosporine or infliximab may be combined with azathioprine and corticosteroids^[14].

For gastrointestinal symptoms, treatment options include medications like sulfasalazine or mesalamine, systemic corticosteroids, azathioprine, TNF inhibitors, or thalidomide^[14].

Some patients with mild symptoms may only need medicines during flare-ups, while others with more severe disease need to take medicines continuously^[8].

Living with Behcet’s Syndrome

Living with Behcet’s syndrome can be challenging, but with proper treatment and self-care, many people are able to lead fulfilling lives^[6][18].

Following Your Treatment Plan

It is important to take medications exactly as prescribed and follow your healthcare provider’s recommendations^[6][18]. During flare-ups, it is helpful to rest and reduce stress. If symptoms worsen or new symptoms develop, contact your rheumatology provider promptly to discuss whether medication changes are needed^[6][18].

Lifestyle Measures

Several lifestyle approaches may help manage symptoms:

Rest and exercise: While rest is important during flare-ups, regular moderate exercise like walking or swimming can help reduce symptoms, decrease stress, and improve mood^[6][18]. Exercise can also help increase joint flexibility and lower joint pain over time.

Healthy diet: Eating a balanced diet with plenty of vegetables and fruits provides your body with important nutrients and can help you maintain a healthy weight^[19][20]. Reducing sugars and processed foods while increasing fiber-rich whole foods can help reduce inflammation. Maintaining a healthy weight is particularly important because excess weight puts more strain on joints.

Stress management: Stress can trigger flare-ups in some people. Activities that combine physical movement with relaxation, such as yoga, tai chi, or Pilates, may help reduce stress levels^[19].

Finding Support

Because Behcet’s syndrome is rare, it can cause feelings of isolation^[6][18]. Joining local support groups or online communities can help connect with others who understand the challenges of living with the disease and reduce feelings of being alone.

Long-Term Outlook

For most people living with Behcet’s syndrome, symptoms can be controlled with treatment, allowing them to conduct normal lives^[15]. While the disease is chronic, symptoms often decrease and can even disappear for several years at a time. The severity of the disease is often more pronounced in the first years after diagnosis but tends to decrease in most patients after they reach their forties^[10]. The better patients are able to control initial symptoms with treatment, the less likely they are to develop more serious complications^[15].