MOST COMMON SYMPTOMS AND SIGNS
OF BEHCET’S DISEASE
Behcet’s may cause either anterior uveitis (inflammation in the front of the eye) or posterior uveitis (inflammation in the back of the eye), and sometimes causes both at the same time.
Anterior uveitis results in pain, blurry vision, light sensitivity, tearing, or redness of the eye.
Posterior uveitis may be more dangerous and vision–threatening because it often causes fewer symptoms while damaging a crucial part of the eye — the retina.
Painful sores in the mouth called “aphthous ulcers” (known as oral aphthosis [af-THO-sis] and aphthous stomatitis) affect almost all patients with Behçet’s disease. Individual sores or ulcers are usually identical to canker sores, which are common in many people. These sores are usually a result of minor trauma. They are often the first symptom that a person notices and may occur long before any other symptoms appear. However, the lesions are more numerous, more frequent, and often larger and more painful. Aphthous ulcers can be found on the lips, tongue, and inside of the cheek. Aphthous ulcers may occur singly or in clusters, but occur in virtually all patients with Behcet’s. The sores usually have a red border and several may appear at the same time. They may be painful and can make eating difficult. Mouth sores go away in 10 to 14 days but often come back. Small sores usually heal without scarring, but larger sores may scar.
Skin problems are a common symptom of Behçet’s disease. Skin sores often look red or resemble pus-filled bumps or a bruise. The sores are red and raised, and typically appear on the legs and on the upper torso. In some people, sores or lesions may appear when the skin is scratched or pricked. When doctors suspect that a person has Behçet’s disease, they may perform a pathergy test, in which they prick the skin with a small needle; 1 to 2 days after the test, people with Behçet’s disease may develop a red bump where the doctor pricked the skin. However, only half of the Behçet’s patients in Middle Eastern countries and Japan have this reaction. It is less commonly observed in patients from the United States, but if this reaction occurs, then Behçet’s disease is likely.
Pustular skin lesions that resemble acne, but can occur nearly anywhere on the body. This rash is sometimes called “folliculitis”.
Skin lesions called erythema nodosum: red, tender nodules that usually occur on the legs and ankles but also appear sometimes on the face, neck, or arms. Unlike erythema nodosum associated with other diseases (which heal without scars), the lesions of Behcet’s disease frequently ulcerate.
Aneurysms (outpouchings of blood vessel walls, caused by inflammation) of arteries in the lungs, rupture of which may lead to massive lung hemorrhage.
Arthritis or “arthralgias” which is inflammation of the joints, occurs in more than half of all patients with Behçet’s disease. Arthritis causes pain, swelling, and stiffness in the joints, especially in the knees, ankles, wrists, and elbows. Arthritis that results from Behçet’s disease usually lasts a few weeks and does not cause permanent damage to the joints.
Behçet’s disease affects the central nervous system in about 23 percent of all patients with the disease in the United States. The central nervous system includes the brain and spinal cord. Its function is to process information and coordinate thinking, behavior, sensation, and movement. Behçet’s disease can cause inflammation of the brain and the thin membrane that covers and protects the brain and spinal cord. This condition is called meningoencephalitis. People with meningoencephalitis may have fever, headache, stiff neck, and difficulty coordinating movement, and should report any of these symptoms to their doctor immediately. If this condition is left untreated, a stroke (blockage or rupture of blood vessels in the brain) can result.
Central nervous system involvement is one of the most dangerous manifestations of Behcet’s. The disease tends to involve the “white matter” portion of the brain and brainstem, and may lead to headaches, confusion, strokes, personality changes, and (rarely) dementia. Behcet’s may also involve the protective layers around the brain (the meninges), leading to meningitis. Because the meningitis of Behcet’s disease is not associated with any known infection, it is often referred to as “aseptic” meningitis.
Genital sores affect more than half of all people with Behçet’s disease. The sores look similar to the mouth sores and may be painful. After several outbreaks, they may cause scarring.
Male — painful genital lesions that form on the scrotum, similar to oral lesions, but deeper.
Female — painful genital ulcers that develop on the vulva.
Behçet’s disease causes inflammation and ulceration (sores) throughout the digestive tract that are identical to the aphthous lesions in the mouth and genital area.
Ulcerations may occur anywhere in the gastrointestinal tract from the mouth to the anus. This leads to abdominal pain, diarrhea, and/or bleeding. Because these symptoms are very similar to symptoms of other diseases of the digestive tract, such as ulcerative colitis and Crohn’s disease, careful evaluation is essential to rule out these other diseases.
- Above is a colonoscopy of a Behcet’s Disease Patient – showing ulcers.
Diagnosing Behçet’s disease is very difficult because no specific test confirms it. When a patient reports symptoms, the doctor must examine the patient and rule out other conditions with similar symptoms. Because it may take several months or even years for all the common symptoms to appear, the diagnosis may not be made for a long time and is often a retrospective diagnosis. A patient may even visit several different kinds of doctors before the diagnosis is made.
Criteria for Behçet’s disease:
- Mouth sores (oral ulcers) at least three times in 12 months
- Any two of the following:
- Recurring genital sores/ulcers
- Eye inflammation with loss of vision
- Characteristic skin lesions
- Positive pathergy (skin prick test)
Besides finding these signs, the doctor must rule out other conditions with similar symptoms, such as Lupus, Crohn’s disease, and Rheumatoid Arthritis. The doctor also may recommend that the patient see an ophthalmologist to identify possible complications related to eye inflammation. A dermatologist may perform a biopsy of mouth, genital, or skin lesions to help distinguish Behçet’s from other disorders.
There is no specific “Behçet’s’test”. Consequently, the diagnosis is based on the occurrence of symptoms and signs that are compatible with the disease, the presence of certain features that are particularly characteristic (e.g., oral or genital ulcerations), elimination of other possible causes of the patient’s presentation, and – whenever possible – proof of vasculitis by biopsy of an involved organ.
International Study Group for Behçet’s Disease
An international group of physicians has established a set of guidelines to aid in the classification of Behçet’s patients. This study group created the criteria for the purpose of conducting research on the disease. The criteria put forth by the study group include:
recurrent oral ulcerations (apthous or herpetiform) at least three times in one year
In addition, a patient must also meet two of the following:
recurrent genital ulcerations
eye lesions (uveitis or retinal vasculitis) observed by an opthalmologist
skin lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions, acneiform nodules) adult patients not on corticosteroids
positive “pathergy test” read by a physician within 24-48 hours of testing
* It is important to note that the criteria set forth by the International Study Group of Physicians was intended for classification of patients for research only, not for a Behçet’s diagnosis.
The pathergy test is a simple test in which the forearm is pricked with a small, sterile needle. Occurrence of a small red bump or pustule at the site of needle insertion, 1 to 2 days after the test, constitutes a positive test. Although a positive pathergy test is helpful in the diagnosis of Behçet’s disease, only a minority of Behçet’s patients demonstrate the pathergy phenomenon (i.e., have positive tests). Patients from the Mediterranean region are more likely to demonstrate a positive response to a pathergy test. However, only 50% of patients in Middle Eastern countries and Japan have this reaction. This reaction is even less common in the United States. In addition, other conditions can occasionally result in positive pathergy tests, so the test is not 100% specific.
Pictured below is an example of the pathergy test: 1) taken at the time when the patient was “stuck” with the sterile needle; 2) the area immediately after the stick; 3) & 4) show the area one day and two days after the needle stick, respectively.
After the Diagnosis
Most people with Behçet’s disease can lead productive lives and control symptoms with proper medication, rest, and exercise. There are many medicines available to doctors to use to relieve pain, treat symptoms, and prevent complications. When treatment is effective, flares usually become less frequent. Many patients eventually enter a period of remission (a disappearance of symptoms). Sometimes, treatment does not relieve symptoms, and gradually more serious symptoms such as eye disease may occur. Serious symptoms may appear months or years after the first signs of Behçet’s disease occur.
Researchers are exploring possible genetic, bacterial, and viral causes of Behçet’s disease as well as improved drug treatment. Researchers are also investigating factors in the environment, such as bacterial or viral factors, that may trigger Behçet’s disease. In addition, researchers are identifying other medicines to better treat Behçet’s disease.
TREATMENTS FOR BEHÇET’S DISEASE
There is no cure for Behçet’s disease. Treatment typically focuses on reducing discomfort and preventing serious complications. Corticosteroids and other medications that suppress the immune system may be prescribed to treat inflammation. Behçet’s is a chronic disease that recurs. However, patients may have periods of time when symptoms go away temporarily (remission). The severity of the disease varies from patient to patient. Some patients may live somewhat normal lives, but others may become blind or severely disabled.
Behçet’s disease affects different parts of the body, therefore, a patient probably will see several different doctors. It may be helpful to both the doctors and the patient for one doctor to manage the complete treatment plan. This doctor can coordinate the treatments and monitor any side effects from the various medications that the patient takes.
A rheumatologist (a doctor specializing in arthritis and other inflammatory disorders) often manages a patient’s treatment and treats joint disease. The following specialists also treat other symptoms that affect the different body systems:
- Gynecologist-treats genital sores in women
- Urologist-treats genital sores in men
- Dermatologist-treats genital sores in men and women, and skin and mucous membrane problems
- Ophthalmologist-treats eye inflammation
- Gastroenterologist-treats digestive tract symptoms
- Hematologist-treats disorders of the blood
- Neurologist-treats central nervous system symptoms
Although there is no cure for Behçet’s disease, people usually can control symptoms with proper medication, rest, exercise, and a healthy lifestyle. The goal of treatment is to reduce discomfort and prevent serious complications such as disability from arthritis or blindness. The type of medicine and the length of treatment depend on the person’s symptoms and their severity.It is likely that a combination of treatments will be needed to relieve specific symptoms. Patients should tell each of their doctors about all of the medicines they are taking so that the doctors can coordinate treatment.
Topical medicine is applied directly on the sores to relieve pain and discomfort. For example, doctors prescribe rinses, gels, or ointments. Creams are used to treat skin and genital sores. The medicine usually contains corticosteroids (which reduce inflammation), other anti-inflammatory drugs, or an anesthetic, which relieves pain.
Doctors also prescribe medicines taken by mouth to reduce inflammation throughout the body, suppress the overactive immune system, and relieve symptoms. Doctors may prescribe one or more of the medicines described below to treat the various symptoms of Behçet’s disease. The treatment of Behçet’s syndrome depends on the severity and the location of its manifestations in an individual patient.
Steroid (cortisone) gels, pastes (such as Kenalog in Orabase) and creams can be helpful for the mouth and genital ulcers. Colchicine can also minimize recurrent ulcerations. Mouth and genital ulcers healed and were reported at a national meeting of the American College of Rheumatology as less frequent in 9 or 12 patients who were treated with Trental (pentoxifylline). Trental also seemed to maintain the healed ulcers for up to the 29 months of the study. The effectiveness of Trental, the researchers said, seemed to be enhanced by the combination with colchicine in some patients.
Joint inflammation can require non-steroidal anti-inflammatory drugs (such as ibuprofen and others) or oral steroids. Colchicine and oral and injectable cortisone are used for inflammation involving the joints, eyes, skin, and brain. Sulfasalazine has been effective in some patients for arthritis.
- Corticosteroids – Prednisone is a corticosteroid prescribed to reduce pain and inflammation throughout the body for people with severe joint pain, skin sores, eye disease, or central nervous system symptoms. Patients must carefully follow the doctor’s instructions about when to take prednisone and how much to take. It also is important not to stop taking the medicine suddenly, because the medicine alters the body’s production of the natural corticosteroid hormones. Long-term use of prednisone can have side effects such as osteoporosis (a disease that leads to bone fragility), weight gain, delayed wound healing, persistent heartburn, and elevated blood pressure. However, these side effects are rare when prednisone is taken at low doses for a short time. It is important that patients see their doctor regularly to monitor possible side effects. Corticosteroids are useful in early stages of disease and for acute severe flares. They are of limited use for long-term management of central nervous system and serious eye complications.
- Immunosuppressive drugs - These medicines (in addition to corticosteriods) help control an overactive immune system, which occurs in Behçet’s disease, and reduce inflammation throughout the body, and can lessen the number of disease flares. Doctors may use immunosuppressive drugs when a person has eye disease or central nervous system involvement. These medicines are very strong and can have serious side effects. Patients must see their doctor regularly for blood tests to detect and monitor side effects.
Doctors may use one or more of the following drugs depending on the person’s specific symptoms.
- Azathioprine (Imuran) - classified as an immunosuppressant medication. Azathioprine is used to suppress the immune system in patients who have had kidney transplants. Although its exact mechanism of action in rheumatoid arthritis is not known, its effect in suppressing the immune system appears to decrease the activity of this illness. Most commonly prescribed for people with organ transplants because it suppresses the immune system, azathioprine is now used for people with Behçet’s disease to treat uveitis and other uncontrolled disease manifestations. This medicine can upset the stomach and may reduce production of new blood cells by the bone marrow.
- Chlorambucil - Doctors may use these drugs to treat uveitis and meningoencephalitis. People taking either agent must see their doctor frequently because either can have serious side effects, such as permanent sterility and cancers of the blood. Patients have regular blood tests to monitor blood counts of white cells and platelets.
- Colchicine - Commonly used to treat gout, which is a form of arthritis, colchicine reduces inflammation throughout the body. The medicine sometimes is used to treat arthritis, mucous membrane, and skin symptoms in patients with Behçet’s disease. A research study in Turkey suggested that the medication works best for males with the disorder. Common side effects of colchicine include nausea, vomiting, and diarrhea. The doctor can decrease the dose to relieve these side effects.
- Cyclophosphamide - drug that is used primarily for treating several types of cancer. In order to work, cyclophosphamide first is converted by the liver into two chemicals, acrolein and phosphoramide. Acrolein and phosphoramide are the active compounds, and they slow the growth of cancer cells by interfering with the actions of deoxyribonucleic acid (DNA) within the cancerous cells. It is, therefore, referred to as a cytotoxic drug. Unfortunately, normal cells also are affected, and this results in serious side effects. Cytoxan also suppresses the immune system and is also referred to as immunosuppressive.
- Cyclosporine - Like azathioprine, doctors prescribe this medicine for people with organ transplants. When used by patients with Behçet’s disease, cyclosporine reduces uveitis and uncontrolled disease in other organs. To reduce the risk of side effects, such as kidney and liver disease, the doctor can adjust the dose. Patients must tell their doctor if they take any other medicines, because some medicines affect the way the body uses cyclosporine.
- Enbrel (Etanetcept) - Etanercept is an injectable drug that blocks tumor necrosis factor alpha (TNF alpha) and is used for treating rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. TNF alpha is a protein that the body produces during the inflammatory response, the body’s reaction to injury. TNF alpha promotes the inflammation and its associated fever and signs (pain, tenderness, and swelling) in several inflammatory conditions including rheumatoid arthritis and ankylosing spondylitis. Etanercept is a synthetic (man-made) protein that binds to TNF alpha. It thereby acts like a sponge to remove most of the TNF alpha molecules from the joints and blood. This prevents TNF alpha from promoting inflammation and the fever, pain, tenderness and swelling of joints in patients with rheumatoid or psoriatic arthritis and ankylosing spondylitis. Etanercept reduces the signs and symptoms of rheumatoid arthritis, the arthritis of psoriasis, and ankylosing spondylitis. It prevents the progressive destruction of the joints in patients with rheumatoid arthritis and the arthritis of psoriasis.
- Interferon - are multiple substances naturally produced by cells in the body to help fight infections and tumors. They may also be synthetic (man-made) versions of these substances. Alpha interferons, such as Roferon-A, Intron-A, and Alferon-N, are used to treat hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi’s sarcoma. They are also used to treat laryngeal papillomatosis (growths in the respiratory tract) in children, genital warts, and some kinds of hepatitis. Gamma interferon, like Actimmune, is a synthetic (man-made) version of a substance naturally produced by cells in the body to help fight infections and tumors. Gamma interferon is used to treat chronic granulomatous disease and osteopetrosis. Interferon beta-1a, like Avonex and Rebif, is used to treat the relapsing forms of multiple sclerosis (MS) and genital warts. This medicine will not cure MS, but it may slow some disabling effects and decrease the number of relapses of the disease. Interferon beta-1b, such as Betaseron, is also used to treat the relapsing-remitting form of multiple sclerosis (MS). Again, this medicine will not cure MS, but may decrease the number of relapses of the disease. There are no generic forms of Interferon available.
- Kenalog (Triamcinolone) – a topical steroid. It reduces or inhibits the actions of chemicals in the body that cause inflammation, redness, and swelling. It is used to treat the inflammation caused by a number of conditions such as allergic reactions, eczema, and psoriasis.
- Methotrexate - Methotrexate is classified as an antimetabolite drug, which means it is capable of blocking the metabolism of cells. It has been found very helpful in treating rheumatoid arthritis. It seems to work, in part by altering aspects of immune function which may play a role in causing rheumatoid arthritis.
- Prednisone - is an oral, synthetic (man-made) corticosteroid used for suppressing the immune system and inflammation. It has effects similar to other corticosteroids such as triamcinolone (Kenacort), methylprednisolone (Medrol), prednisolone (Prelone) and dexamethasone (Decadron). These synthetic corticosteroids mimic the action of cortisol (hydrocortisone), the naturally-occurring corticosteroid produced in the body by the adrenal glands. Corticosteroids have many effects on the body, but they most often are used for their potent anti-inflammatory effects, particularly in those conditions in which the immune system plays an important role. Such conditions include arthritis, colitis, asthma, bronchitis, certain skin rashes, and allergic or inflammatory conditions of the nose and eyes. Prednisone is inactive in the body and, in order to be effective, first must be converted to prednisolone by enzymes in the liver. Therefore, prednisone may not work as effectively in people with liver disease whose ability to convert prednisone to prednisolone is impaired.
- Remicade (Infliximab) - Infliximab is an injectable antibody that blocks the effects of tumor necrosis factor alpha (TNF-alpha). By blocking the action of TNF-alpha, infliximab reduces the signs and symptoms of inflammation. This medication is administered via an IV-infusion.
- Sulfasalazine – a prodrug, that is, it is not active in its ingested form. It is broken down by bacteria in the colon into two products: 5-aminosalicylic acid (5ASA), and sulfapyridine. There is some controversy as to which of these two products are responsible for the activity of azulfidine. Whereas it is known that 5ASA has therapeutic benefit, it is not clear whether sulfapyridine adds any further benefit. In the colon, the products created by the breakdown of sulfasalazine work as anti-inflammatory agents for treating inflammation of the colon. The beneficial effect of sulfasalazine is believed to be due to a local effect on the bowel, although there may also be a beneficial systemic immune-suppressant effect as well. Following oral administration, 33% of the sulfasalazine is absorbed, all of the sulfapyridine is absorbed, and about 33% of the 5ASA is absorbed. Sulfasalazine was approved by the FDA in 1950.
- CellCept – contains the active ingredient mycophenolate mofetil. Cellcept belongs to a group of medicines called immunosuppressants. Immunosuppressants are used to prevent rejection of transplanted organs, and work by stopping your immune system from reacting to the transplanted organ. Cellcept may be used together with other medicines known as cyclosporin and corticosteroids.
- Thalidomide – Thalidomide is an oral medication used for treating the skin conditions of leprosy, a disease caused by a parasite, Mycobacterium leprae. The mechanism of action of thalidomide is not well understood. The immune system reaction to Mycobacterium leprae plays an important role in producing the skin manifestations of leprosy. Scientists believe that thalidomide modifies the reaction of the immune system to Mycobacterium leprae and thereby suppresses the skin reaction. Thalidomide also is being evaluated as a treatment for HIV. Thalidomide was approved by the FDA in July, 1998.
- Trental (Pentoxifylline) - decreases the “stickiness” (viscosity) of blood and thereby improves its flow. This increase blood flow helps patients with peripheral arterial disease to obtain better circulation and oxygen delivery to vital tissues. Pentoxifylline is used in patients to treat a condition of painful legs that develop with exercise because of inadequate circulation to the legs and feet.
- Combination Treatment – Cyclosporine is sometimes used together with azathioprine when one medication fails to work by itself. A common combination is prednisone along with an immunosuppressive drug.
Rest and Exercise
Although rest is important during flares, doctors usually recommend moderate exercise, such as swimming or walking, when the symptoms have improved or disappeared. Exercise can help people with Behçet’s disease keep their joints strong and flexible.