What is Behcet Disease?
Behcet disease was first recognized in 1937 by Hulusi Behçet, a doctor from Istanbul. He documented the cases of three patients who had sores in their mouth and genital area, uveitis (a type of eye inflammation), and inflamed skin. Other symptoms were discovered later and were included in the range of symptoms of this disease. Behcet disease has unknown origins and is recognized as an auto-inflammatory disease – a condition where the body’s own immune system triggers inflammation. It affects the blood vessels in the body in a condition known as systemic vasculitis.
This disease is marked by symptoms that affect the skin and mucous membranes, including repeating mouth and genital sores, and eye troubles, particularly persistent uveitis that comes and goes. It can affect arteries and veins of all sizes. Sometimes, Behcet disease is also referred to as Behcet syndrome or malignant aphthosis.
What Causes Behcet Disease?
The exact cause of Behcet disease is unclear but it seems that both genetics and factors from the environment contribute to it.
The disease is more common along the “Silk Route,” a historical trade path, and often occurs within families, which indicates there might be a genetic influence. However, the disease does not follow traditional patterns of inheritance. The highest risk factor is with people who carry HLA-B51/B5, a genetic trait found more often in Japanese, Middle Eastern, and Turkish populations. These individuals have a higher chance of developing Behcet disease than those who do not carry this trait. There are other related genes, but it’s uncertain how much they contribute to the development of the disease.
Some evidence suggests that exposure to certain infectious agents, particularly hypersensitivity to Streptococcus sanguinis antigens, might play a role in causing Behcet disease. Although other infectious agents like Staphylococcus aureus, Herpes simplex virus type 1, and Prevotella species have been suggested as possible triggers, their direct links to Behcet disease have not been confirmed. Currently, it’s believed that exposing genetically susceptible individuals to an infection or other external agent may trigger an auto-inflammatory response leading to Behcet disease.
Risk Factors and Frequency for Behcet Disease
Behcet’s disease is typically seen in young adults between the ages of 20 and 40, but it can also occur in children, albeit less frequently. It’s important to note that this disease affects both males and females equally. However, in Arab communities, it appears to be more common in males, whereas in countries like Korea, China, the United States, and some parts of northern Europe, more females have the disease. Interestingly, the disease tends to be more serious in males and younger people. While most people with the disease don’t have any family members with it, there are some cases where it does run in families. There are even cases where the disease starts earlier in each new generation, a phenomenon known as genetic anticipation.
When looking at where this disease is most common, it seems to follow the path of the ancient Silk Route, with the highest numbers seen in the Middle and Far East. Turkey has the highest number of people with the disease, affecting 420 out of every 100,000 people. In comparison, in the United States, about 5.2 out of every 100,000 people have the disease.
- Behcet’s disease usually appears in young adults aged 20-40 but can also be seen in children.
- Both males and females are affected equally by the disease, but it can be more common in males in Arab populations and more common in females in Korea, China, the US, and some northern European countries.
- The disease tends to be more severe in males and younger populations.
- Most cases occur in individuals with no family history of the disease, but some familial clusters have been reported.
- Evidence of genetic anticipation, or the onset of disease occurring earlier in successive generations, has been seen.
- The disease is most prevalent along the ancient Silk Route, particularly in the Middle and Far East.
- Turkey has the highest occurrence of the disease, affecting 420 people per 100,000 population.
- In the US, the prevalence of Behcet’s disease is about 5.2 people per 100,000 population.
Signs and Symptoms of Behcet Disease
Behcet’s disease is an illness that often first appears as skin spots or mouth sores. However, it’s also associated with more serious problems including inflammation in certain areas of the eye, major vessels, and brain.
The most common symptom of Behcet’s disease is mouth sores, which occur in 97% to 99% of people with the condition. These sores can be painful, happen multiple times, and appear in multiple spots inside the mouth. Unlike mouth sores, about 90% of these ulcerations heal without leaving scars.
More than 80% of Behcet’s patients experience genital sores. These sores, contrary to the mouth sores, do cause scars in more than 70% of cases. Genital ulcers appear on the scrotum in men and the vagina in women.
Behcet’s disease can also cause a variety of skin issues. Common ones include red, swollen skin bumps on the lower limbs and shallow blood-filled formations related to deep vein thrombosis. Other skin manifestations can include acne-like lesions often indistinguishable from regular acne, sores that resemble pyoderma gangrenosum, pustular vasculitic lesions, signs of small-vessel vasculitis and Sweet syndrome.
A particular reaction known as a pathergy reaction is also common in Behcet’s disease. This reaction creates red bumps or blisters on the skin 24 to 48 hours after a needle has been inserted. It’s seen as a strong indicator of Behcet’s disease. This reaction, however, is more commonly observed in patients from Turkey and Japan than those from Northern Europe or the United States.
More than half of people with Behcet’s disease experience eye problems, though these issues more frequently impact men and younger patients. These eye issues usually arise within a few years of diagnosis and are rarely late symptoms if they didn’t occur earlier. Common eye issues include uveitis, which can lead to redness and light sensitivity, while posterior uveitis can lead to vision loss.
About 50% of people with Behcet’s disease experience a form of arthritis which doesn’t cause damaging erosion or deformity and occurs predominantly in those who experience acne-like spots. The most commonly affected joints are knees, ankles, wrists, and elbows.
Vascular involvement is important in Behcet’s disease and is seen in 25% of patients. Symptoms can include minor and deep vein inflammations, predominantly in the lower limbs. Rarely, obstructions in major veins or the vena cava can occur.
Only between 5% and 10% of people with Behcet’s disease experience brain involvement. When it does occur, it may lead to varied signs and symptoms depending on the areas of the brain affected. brain involvement can cause chronic headaches and visual problems.
Behcet’s can also involve the digestive system, usually creating sores in areas like the esophagus, colon, or end of the small intestine. They can also cause perforations in these areas. Also, features resembling inflammatory bowel disease can present in Behcet’s disease.
Behcet’s may also affect the heart, causing pericarditis, myocarditis, endocarditis, and inflammation of coronary arteries. Kidney involvement is rare yet can still occur.
Testing for Behcet Disease
Diagnosing Behcet’s disease can be a challenge since there aren’t any specific lab tests that can confirm it. Usual lab reports might show non-specific signs such as chronic anemia, increased white blood cell count, and raised inflammation markers.
Diagnosis might include imaging tests that are targeted based on the affected organ. This could involve X-rays or needle joint fluid removal for arthritis, CT scans for internal bleeding, clotting, or poor blood flow, angiograms to check for bulging blood vessels, and spinal taps to check for meningitis. The point of these tests is to rule out any other conditions that might be causing the symptoms.
Thorough eye exams are also necessary to check for any eye involvement when someone first shows symptoms. Skin lesions might also be examined under a microscope to confirm the diagnosis.
Several guidelines for diagnosing Behcet’s disease do exist but should be used carefully in a clinical setting. The International Team in charge of revising the standards for this disease updated them in 2008. The updated guidelines use a point system, assigning one point for mouth sores, skin symptoms, and certain vascular and pathergy test results. Genital sores and eye symptoms are assigned two points each. A total of three or more points is required to diagnose Behcet’s disease.
It should be noted, though, that this criteria isn’t without issues. Other conditions like inflammatory bowel disease, lupus, reactive arthritis, and herpes infections can all cause similar symptoms to Behcet’s disease, so it’s important to rule these out first.
Treatment Options for Behcet Disease
The following are treatment methods for different manifestations of certain medical conditions:
To treat oral and genital sores:
– Apply triamcinolone acetonide cream 3 to 4 times a day until it doesn’t hurt anymore.
– Topical sucralfate 1g/5mL four times daily can also be used with or instead of topical corticosteroids.
– Topical anesthetics may be used for temporary relief, although they are usually not as effective as steroids or sucralfate.
To prevent sores from recurring:
– Daily intake of colchicine 1 to 2 mg in divided doses. This treatment is often more effective in genital ulcers.
– Apremilast is gradually increased at a rate of 10 mg daily over six days to reach a maintenance dose of 30 mg twice daily. This treatment is generally more effective in oral ulcers.
If multiple sores or isolated oral or genital ulcers do not respond to the treatments mentioned above:
– Prednisone 15 mg/day may be used. The dose should be reduced to 10 mg/day after one week and typically ends after a two- to three-week period.
If all the above treatments fail:
– Azathioprine therapy can be started. The initial dosage is 50 mg daily, increasing by 50 mg every four weeks as tolerated, up to a maximum dose of 2.5 mg/kg/day.
Treatment for skin lesions and arthritis, and gastrointestinal, renal, and eye diseases, as well as vascular and neurological conditions, also follow specific medical protocols involving medications such as colchicine, prednisolone, azathioprine, and TNF-alpha inhibitors.
Exact doses, routines, and combinations must be tailored to each patient’s condition. All these therapies should be started and monitored under a doctor’s supervision.
What else can Behcet Disease be?
Behcet’s disease is diagnosed based on the symptoms a patient is experiencing. However, it can be confusing because other conditions have similar symptoms. Before a doctor confirms that a patient has Behcet’s disease, they’ll first need to rule out these other diseases:
1. Inflammatory Bowel Disease (IBD): IBD and Behcet’s disease have several symptoms in common, including mouth sores, eye inflammation, joint inflammation, certain rashes, and a skin condition called pyoderma gangrenosum. Colon biopsy might not be enough to tell these two diseases apart. However, conditions such as sacroiliitis (inflammation of the joints between the spine and the pelvis) and axial inflammatory arthritis (a type of arthritis affecting the spine) can occur in IBD but not Behcet’s disease. Other signs like vascular inflammation, brain involvement, and a positive pathergy test (a skin prick test) could point towards IBD rather than Behcet’s disease.
2. Reactive Arthritis: This type of arthritis can also cause similar symptoms to Behcet’s disease, including joint inflammation, eye inflammation and skin disorders. But conditions like sacroiliitis and inflammation of the spine are common in reactive arthritis, not Behcet’s disease. Additionally, symptoms like urinary tract inflammation, lesions on the head of the penis, and eye redness, commonly found in reactive arthritis, are usually not seen in Behcet’s disease.
3. Systemic Lupus Erythematosus (SLE): SLE can have very similar symptoms to Behcet’s disease and can affect the same organs. However, inflammatory blood clots are usually not common in SLE. Furthermore, there are specific autoantibodies (proteins produced by the immune system that mistakenly target the body’s own tissues) that can help distinguish SLE from Behcet’s disease.
4. Herpetic Infections: These types of infections can also cause oral and genital sores like Behcet’s disease. It might be helpful to get a culture from the sore to rule out herpes before considering Behcet’s disease.
Other diseases that should be considered, based on which organs are affected, include sarcoidosis (inflammation that produces small lumps of cells in various organs), other types of inflammation of the blood vessels (vasculitides), relapsing polychondritis (a condition that causes inflammation and deterioration of cartilage) and multiple sclerosis (a disease affecting the nervous system).
What to expect with Behcet Disease
Behcet’s disease is an incurable condition that can potentially have serious health impacts and even lead to death. Men and younger people who develop the disease often face the worst outcomes. This disease can be lethal due to severe lung and blood vessel complications, as well as issues with the nervous system, gastrointestinal tract, and kidneys – particularly a condition called amyloidosis.
Still, there’s some good news. Over 60% of patients see their disease subside after the initial years, which are usually the most severe. Also, the frequency of disease flare-ups, overall health impacts, and mortality rate tends to improve for most patients over time.
Possible Complications When Diagnosed with Behcet Disease
Behcet disease is associated with several potential life-long complications beyond its increased mortality rate. This disease affects different parts of the body, including the eyes and the nervous system.
Complications are:
- Hypopyon-related uveitis and retinal involvement could lead to a high risk of blindness.
- Coronary or pulmonary arterial aneurysmal rupture, which carries a high mortality risk, is associated with Behcet disease.
- The disease can interfere with the central nervous system, causing significant health problems and potentially permanent disabilities or even death.
- Patients affected with ocular involvement such as anterior and posterior uveitis can become permanently blind.
- Behcet disease also increases the risk of miscarriages due to causing inflammation of the blood vessels in the placenta.
Preventing Behcet Disease
It’s important for patients to understand that there currently isn’t a cure for Behçet syndrome. However, the condition’s symptoms can be effectively managed with the right medications. Some of these medications can be harmful to a pregnancy, so it’s vital for patients to talk to their doctors about any plans for a pregnancy before they begin treatment. Patients should be made aware of the various symptoms they might experience and be urged to seek immediate medical attention if these symptoms arise. This allows doctors to potentially adjust their medications as necessary.
