Behcet’s Disease (BD)

Behcet’s disease also known as Behcet’s Syndrome, is a rare, chronic, auto inflammatory disorder. It is characterized by ulcers affecting the mouth and genitals, various skin lesions and abnormalities affecting the eyes. Its occurrence are thought to be caused by vasculitis i.e. inflammation of blood vessels throughout the body.

The disease carries the name of a Turkish dermatologist Hulusi Behcet, who, in 1937, described a trial of oral ulcers, genital ulcers and ocular inflammation, became the first physician to describe the disease in modern times. Behcet’s disease tends to develop in young adults, generally in their 20’s and 30’s, although patients of all ages and both the sexes are affected with it. Studies suggest that there are approximately 16,000 – 20,000 cases of Behcet’s disease in the United States. This condition is considered to be rare in the United States, as it affects less than 200,000 people.

BD is a chronic disease with remissions and exacerbations that “burn out” after approximately 10 years of activity. Ocular involvement is common and visual prognosis is poor if the patient is not treated properly. Central Nervous System (CNS) and gastrointestinal involvement, which are less common, may lead to death. The diagnosis of the Behçet’s Disease is made on the basis of clinical criteria.

Subdivisions of BD.

• Neuro-Behcet
• Ocular-Behcet
• Vasculo-Behcet

Causes         

The exact cause of Behçet’s disease is unknown, although it is generally thought to occur as a result of a problem with the immune system but it has been suggested that both genes and environmental factors are likely to be involved.

• Genetic Factor

Studies suggest that some people are born with genes that make themmore vulnerable of developing BD. This is because Behçet’s disease tends to be much more common in certain ethnic groups where the genes that are linked to the condition may be more common.

Research has so far shown that many people who have developed Behçet’s disease have a gene called HLA B51, and this may increase the risk of developing the disease considerably. However, it must be emphasized that presence of the gene in and of itself is not enough to cause Behcet’s, as many people possess the gene, but relatively few develop Behcet’s. Despite the predisposition to Behcet’s conferred by HLA–B51, familial cases are not the rule, constituting only about 5% of cases. Thus, it is believed that other factors (perhaps more than one) play a role.

Other genes were found to have a role in the pathogenesis of the disease through defects in sensing and processing of signals that are related to regulation of innate and adaptive immunity. Different ethnicities showed association between IL10, IL23R, STAT4, CCR1, UBAC2, GIMAP2/GIMAP4, KLRC4 and rare variants in TLR4, NOD2, and MEFV genes in Behcet’s disease patients.

• Environmental Factor

Genetics are not solely responsible for BD, as there are many cases, where patients do not possess any of the genes associated with it. For example, a red apple and a green apple are both apples but they are slightly different. In the same way a single gene may have slightly different variations in different people but still be the same gene doing pretty much the same job. Ethnic groups known to be at risk of developing the condition can also reduce their risk by leaving their native country. For example, rates of Behçet’s disease are lower in Japanese people who live outside Japan. This suggests that an external environmental factor may also have a role in triggering the condition.

It is often suggested that a viral or bacterial infection may play a role, or that the range of bacteria (the microbiome) present in individuals with BD is somehow different. Investigations of the etiology of BD have focused on herpes simplex virus infection, streptococcal infection, Helicobacter pylori, and autoimmunity or cross-reactivity between microbial and oral mucosal antigens.

The theory is that when a person comes into contact with this virus or bacteria, something in their genes causes their body to react badly and attack their healthy tissue, leading to BD.

• Resultant abnormal inflammation

Inflammation is a necessary function of the body, being needed to fight infections. In people with BD, the inflammatory response becomes too enthusiastic, whereby a small insult to the body (e.g. a thorn prick) may result in a big inflammatory response, and inflammation may occur without an obvious cause.

• Immunological Abnormalities

Various immunological aberrations have been observed in patients with BD, ranging from auto antibodies to oral mucosa and a decrease in T4 cells, especially before exacerbation of the disease, to an increased level of soluble interleukin2 receptors.

Symptoms

Behcet’s Disease is not contagious, therefore, it does not spread from one person to another. Symptoms vary from person to person.

The symptoms of Behcet’s disease are outlined below:

• Eyes – BD causes anterior uveitis – inflammation in the front of the eye, or posterior uveitis – inflammation in the back of the eye and at times can cause both at a same time. This results in pain, blurry vision, light sensitivity, tearing, or redness of the eye. Eye inflammation usually comes on in unpredictable, repetitive attacks. Help should be sought quickly if any symptoms develop, as treatment may be required to avoid damage to sight.
• Mouth – Almost everyone with BD will develop painful sores in the mouth called “aphthous ulcers”. These are very similar in appearance to ulcers that frequently occur in the general population, usually as a result of minor trauma. 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.
• Skin – Many people with BD will also develop skin lesions. A lesion is any type of unusual growth or abnormality that develops on your skin, such as a bump or a discoloured area of skin. 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.
• Lungs – Aneurysms (outpouchings of blood vessel walls, caused by inflammation) of arteries in the lung, rupture of which may lead to massive lung hemorrhage. This may include –
  • pain in a limb
  • a sudden agonizing headache
  • dizziness
  • breathlessness
  • coughing up blood
  • confusion
  • loss of consciousness
• Joints – Behcet’s disease affects the joints in up to two in every three people with the condition, causing arthritis-like symptoms such as pain, stiffness, swelling, warmth and tenderness. Unlike some conditions affecting the joints, permanent joint damage is rare in BD and symptoms can usually be controlled successfully.
• Brain – 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. BD may also involve the protective layers around the brain (the meninges), leading to meningitis. Because the meningitis of BD is not associated with any known infection, it is often referred to as “aseptic” meningitis.
• Genitals –
  • Male — painful genital lesions that forms on the scrotum, similar to oral lesions, but deeper. Men may also experience inflammation (swelling) of the testicles.
  • Female — painful genital ulcers that develop on the vulva.

Genital ulcers caused by Behçet’s disease are not contagious and cannot be spread through sexual intercourse.

• Gastrointestinal – Ulcerations may occur anywhere in the gastrointestinal tract from the mouth to the anus. The terminal ileum and cecum are common sites. Involvement of the GI tract by Behcet’s may be difficult to distinguish from inflammatory bowel disease.
• Blood clots and blood vessels – The blood vessels predominantly affected are veins. Veins of any size or position may be involved, but particularly the deep veins of the legs, causing Deep Vein Thrombosis (DVT). Arteries are less commonly affected. Aneurysms (expansion of arteries) can occasionally occur.There is no good evidence that Behçet’s syndrome predisposes to ordinary heart disease.
• Tiredness – Most patients with BD report feeling fatigued and this may well impact on quality of life. The reasons for fatigue are often complex, often including inflammation, loss of physical fitness, pain, and low mood and/or poor sleep.

Treatment

As BD can affect many different parts of the body, the specialists involved in the treatment may include:

• Dermatologist – a doctor who specializes in treating skin conditions
• Rheumatologist – a doctor who specializes in treating joint conditions
• Ophthalmologist – a doctor who specializes in treating eye conditions
• Neurologist – a doctor who specializes in treating conditions that affect the nervous system and brain

A variety of medications can treat Behcet’s Disease and alleviate pain and other symptoms.

• Medications & Drugs

This type of treatment focuses on relieving the symptoms and depends on which parts of the body the disease affects.

1. Rashes and sores in the mouth and genital area:

• For mild disease — Corticosteroids (ointments, creams, rinses) applied to the skin (topical). Side effects of corticosteroids include weight gain, persistent heartburn, high blood pressure and bone thinning (osteoporosis).
• For more significant disease or if topical treatment is not successful —colchicine, dapsone (DDS) orthalidomide (Thalomid)
• For more severe disease — Immune suppressants, including a pill form of corticosteroid,azathioprine(Imuran) or methotrexate (Methotrexate LPF, Rheumatrex). Since these medications suppress the actions of your immune system, they may increase your risk of infection. Other possible side effects include liver and kidney problems, low blood counts, and high blood pressure.
• For mouth pain — Novocaine-type agents a mixture of of Kaopectate, diphenhydramine (Benadryl) and lidocaine as a mouth rinse can provide temporary relief

2. Arthritis — The most commonly prescribed medications are colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine) and methotrexate.

3. Eye disease — Corticosteroids (drops, injections or pills), colchicine, and immunosuppressants (including cyclosporine drops or pills, cyclophosphamide, and azathioprine).

Studies suggest that interferon (Betaseron and others), adalimumab (Humira), etanercept (Enbrel), infliximab (Remicade) or rituximab (Rituxan) may improve severe disease that has not responded to other treatment. For severe disease that affects many parts of the body, combinations of medications may be prescribed. 

• Surgical Treatment

Although various treatment modalities appear, surgical intervention often is indicated for arterial aneurysms. In patients with recurrent or massive hemoptysis, surgery may be necessary. Endovascular treatment for pseudoaneurysms due to BD seems to be an effective choice when the disease activity is strictly controlled with immunosuppressive therapy. In other serious consequences, such as gastrointestinal bowel perforation, enterocutaneous fistula formation, thrombotic obstruction in large-caliber vessels, cardiac involvement, and complications of eye involvement such as glaucoma, vitreous opacities, surgery may also be the only possible remedy.