Behçet’s Disease Treatment in Ankara, Turkey

Behçet’s disease is a chronic and recurrent systemic vasculitis, that is, widespread vascular inflammation, that can affect vessels of every size in our body. This autoinflammatory condition, which entered the medical literature through the definition of our Turkish physician Prof. Dr. Hulusi Behçet, arises as a result of a complex reaction developed by the immune system against healthy tissues. It is a multisystemic syndrome that is not limited only to symptoms in the skin and mucosa, but can also involve the eyes, joints, nervous system, and digestive system. This process, which can be controlled with early diagnosis and correct treatment protocols, is an important clinical condition followed under the leadership of dermatology specialists.

In Which Geographies and in Whom Is Behçet’s Disease More Common?

When we look at the geographical distribution of the disease, the map that appears before us takes us to the dusty pages of history, to the Silk Road. This disease does not show a homogeneous distribution in the world epidemiologically; on the contrary, it follows a very specific route. This historical trade route, extending from the Far East through Central Asia to Anatolia and from there to the Mediterranean basin, is also the homeland of Behçet’s disease.

Since Turkey is located right at the heart of this belt, it is the country in the world where the disease is seen most frequently. This has made us Turkish physicians the most experienced experts in the world on this subject because we frequently manage in our daily practice cases that our western colleagues may perhaps see once in their professional lives. Studies conducted in our country show that the prevalence of the disease in our society is quite high. For this reason, Behçet’s disease is definitely one of the first possibilities that comes to mind in every patient who presents to our outpatient clinic with a complaint of recurrent oral sores.

The disease generally tends to occur during young adulthood, the most active period of life, that is, in one’s 20s and 30s. Of course, we also have cases that begin in childhood or after the age of 40, but these are rarer. When we look at the gender distribution, the frequency of occurrence in women and men is close to each other. However, an important parenthesis must be opened here; the course of the disease differs according to gender. While the disease generally follows a louder and harsher course in young male patients, it tends to be somewhat milder in female patients. Serious conditions such as eye and vascular involvement may create a riskier picture especially in the young male population.

What Are the Genetic and Environmental Factors in the Development of the Disease?

One of the questions my patients ask me most frequently and with concern is why this disease found them. The exact cause of Behçet’s disease is like a puzzle that has not been solved even today, but the data we have gives us very strong clues. This disease is an immune system confusion that begins when environmental factors pull the trigger in genetically predisposed individuals.

Here, the concept of “genetic predisposition” must be understood correctly. Behçet’s disease is not a classical hereditary disease that passes directly from mother and father like hair color or eye color. However, the risk of the disease occurring is higher in individuals carrying HLA-B51, one of the tissue group antigens, compared to the rest of the society. Carrying this gene is not a guarantee that you will get the disease; it only shows that the ground is suitable for this disease.

Even if the ground is suitable, a spark is required for the disease to emerge. This is where environmental factors come into play. When the immune system, which is the body’s defense mechanism, encounters some external factors, it becomes confused, and the soldiers (white blood cells) that should normally attack microbes begin to attack their own vessel walls.

Possible factors thought to trigger this process are:

• Oral flora disorders
• Some viral infections
• Some bacterial infections
• Intense stress and emotional trauma
• Irregular living conditions

Can Sores (Aphthae) in the Mouth Be a Symptom of Behçet’s Disease?

Almost an indispensable feature of Behçet’s disease, the symptom that sounds the starting whistle of the disease in the vast majority of patients is oral sores. For us physicians, these sores are like the disease’s “business card.” However, what we are talking about here is a much different, stubborn, and painful picture than the simple mouth sores that everyone experiences once or twice in life due to fatigue or vitamin deficiency.

Behçet’s aphthae seriously reduce our patients’ quality of life. I never forget one of my patients saying, “Doctor, because of the pain in my mouth, even drinking water turns into torture, and words grow in my mouth while I speak.” These sores generally appear inside the lips, on the cheek mucosa, tongue, gums, or soft palate. In appearance, they are ulcers resembling volcanic craters, covered in the middle with a yellow or gray layer and surrounded by a red halo.

What is important for us diagnostically is that these sores have a recurrent character. Aphthous attacks recurring at least three times a year generally prompt us to investigate Behçet’s disease.

The types of aphthae we encounter in clinical practice are:

• Minor aphthae
• Major aphthae
• Herpetiform aphthae

Minor aphthae are the most common type, small in diameter, and generally heal without leaving scars. Major aphthae are rarer, but their diameter is larger than 1 centimeter, they are very deep, their healing may take weeks, and when they heal, they may leave a scar behind.

How Are Genital Area Ulcers and Skin Findings Distinguished?

After oral sores, the second most specific and diagnostic finding of the disease is ulcers occurring in the genital area. Our patients may sometimes have difficulty expressing these complaints because of cultural reasons or hesitation. However, as a dermatologist, it is my duty to reassure my patient and explain how vital this information is for diagnosis. Genital ulcers are very similar in appearance to the aphthae in the mouth, but structurally they are deeper.

The most typical feature of these ulcers is the scar they leave behind while healing. In the medical literature, we call this a “punch-out” scar, that is, a scar as if pierced with a punch. Even if the patient does not have an active sore when they come to me, seeing these scars during the examination allows me to understand that they had an attack in the past and strengthens my hand on the road to diagnosis. They are generally located on the scrotum in men and in the external genital area in women.

Not only ulcers, but we can also see the signatures of the disease in different areas of the skin. The body reflects this fire in the vessels onto the skin in various ways. For example, on the front surface of the legs, over the shinbone, painful, red, and warm swellings may occur. These give a feeling as if you hit your leg somewhere and it swelled up. In addition, inflamed bumps resembling adolescent acne but appearing in unexpected areas of the body (on the legs, arms) are also among the skin findings of Behçet’s disease.

The main findings we observe on the skin are:

• Genital ulcers
• Erythema nodosum
• Papulopustular lesions
• Superficial thrombophlebitis
• Acneiform eruptions

What Are the Risk and Symptoms of Eye Involvement?

The organ that worries us the most and on which we focus most meticulously while managing Behçet’s disease is the eye. Because skin or mucosal sores somehow heal and even if they leave scars, they do not lead to loss of vital function; however, eye involvement is a very serious process that can progress silently and deeply and cause permanent vision loss. Inflammation of the eye’s vascular layer, the uvea, namely “uveitis,” is one of the most important systemic involvements of Behçet’s disease.

Eye involvement generally occurs within the first few years of the disease. We know that this risk is higher especially in young male patients. The disease progresses in attacks, and each attack may leave some damage, however small, in that delicate and complex structure of the eye. These damages may accumulate over time and lead to decreased visual acuity. For this reason, I definitely refer every patient I diagnose with Behçet’s disease to an ophthalmologist specialized in this field, even if they currently have no eye complaints at all. Thanks to early diagnosis and strong treatment protocols, the risk of blindness can nowadays be prevented to a very large extent.

The eye symptoms patients should pay attention to are:

• Severe redness in the eye
• Eye pain
• Blurred vision
• Sensitivity to light
• Floating black spots
• Loss in the visual field

What Is the Pathergy Test and Why Is It Important in the Diagnostic Process?

Unfortunately, there is no single “gold standard” blood test or imaging method that allows us to diagnose Behçet’s disease. Diagnosis is made entirely by combining clues like a detective, bringing together the patient’s complaints, clinical findings, and examination results. Here, while collecting these clues, we have a very interesting test specific to Behçet’s disease that we use: the Pathergy Test.

This test actually serves to measure the excessive and exaggerated response of the patient’s skin to trauma. Compared to healthy individuals, the skin of Behçet’s patients is “more sensitive” and “more reactive.” To perform the test, with the tip of a sterile needle, we enter and exit the inner surface of the patient’s forearm at an oblique angle into the skin. We do not inject any medicine, substance, or virus; what we do is only a mechanical needle prick.

We re-evaluate our patient 24 to 48 hours after the procedure. If a pimple-like, inflamed, red bump has formed at that tiny point where the needle was inserted, we consider the test positive. This indicates that the immune system has given an excessive inflammatory response to even a simple needle hole as if there had been a major injury. A positive test strongly reinforces the diagnosis. However, a negative test, that is, the absence of a reaction, does not mean that the patient does not have Behçet’s disease. Although the sensitivity of the test has decreased today, it still occupies an important place among the diagnostic criteria.

What Other Systems in the Body Can the Disease Affect?

The reason we call Behçet’s disease “multisystemic” is that it is not limited only to the externally visible skin and eyes, but also has the potential to affect vital organs deep within the body. Since it is a disease based on vascular inflammation, everywhere there is a vessel is a potential target area.

Especially vascular involvement has critical importance in terms of the course of the disease. The disease can affect both arteries and veins. The most common vascular problem we encounter is clot formation in the leg veins, namely deep vein thrombosis. Clots related to Behçet’s disease have an interesting feature; since these clots are tightly attached to the vessel wall because of inflammation, their risk of breaking off and going to the lungs (embolism) is lower compared to other clotting disorders, but they still require serious treatment. Arterial involvements are rarer, but they may carry a life-threatening risk because they can cause ballooning in the vessel wall (aneurysm).

In addition, the disease can also involve the nervous system. In this picture, which we call “Neuro-Behçet,” inflammation may be seen in the brain tissue or cerebral vessels. In addition, arthritis attacks with swelling and pain in the joints or digestive system involvement progressing with ulcers in the intestines may also be seen.

The other systems that the disease may affect are:

• Venous vascular system
• Arterial vascular system
• Central nervous system
• Musculoskeletal system
• Gastrointestinal system

According to What Are the Treatment Methods and Medication Selection Determined?

Behçet’s disease is chronic, that is, a long-term disease. Just like diabetes or hypertension, we need to learn to live with this disease and keep it under control. For now, there is no definitive curative treatment that would pull the disease out by the root and allow us to say, “it is over now, it will never come back again.” However, thanks to the possibilities of modern medicine, it is possible to completely silence the disease, that is, to achieve “remission.”

Our main goals in treatment are to prevent the patient’s flare-ups, relieve pain and complaints, and most importantly, prevent permanent damage from occurring in the organs. The treatment plan is entirely individualized; it is tailored to the patient’s condition with almost a tailor’s meticulousness. The treatment of a patient who only has sores in the mouth and that of a patient with inflammation in the eye or involvement in the brain are completely opposite.

The agents we use in treatment are generally aimed at regulating or suppressing the immune system. While local treatments and milder systemic drugs are preferred in simple skin and mucosal findings, in cases with organ involvement we bring our much stronger weapons into play.

The drug groups we frequently use in treatment are:

• Topical corticosteroids
• Colchicine
• Systemic corticosteroids
• Azathioprine
• Cyclosporine
• Biological agents
• Apremilast

Especially the drug called “Colchicine” is one of the cornerstones, that is, anchors, of Behçet’s disease treatment. By slowing the excessive mobility of the cells we call neutrophils, it provides us with great support in controlling both aphthae and joint pain. In more resistant or serious cases, biological agents (injection or serum treatments), which are the latest wonders of technology, offer our patients a very comfortable life.

What Should Patients Pay Attention to in Their Daily Lives?

Drug treatment is only one dimension of the matter; the other half of the treatment is the arrangements the patient will make in their own lifestyle. When speaking with my patients in my outpatient clinic, I always add a “life prescription” alongside the medication prescription. Because our body is a whole, and improvement in our general health directly has a positive effect on the course of the disease.

One of the greatest enemies for Behçet’s patients is stress. Stress is the strongest fuel that fans the imbalance in the immune system. I always tell my patients this: “I know it is easy to say do not be sad, it will pass, but learning to manage your stress is at least as effective as the medicine you take.”

As for nutrition, we do not have strict prohibitions, but a dietary pattern that will reduce the general fire (inflammation) in the body is very beneficial. A Mediterranean-type diet, that is, a diet rich in fresh vegetables, fruit, olive oil, and fish, supports the immune system. In addition, oral hygiene is very critical; poor tooth and gum health may cause oral aphthae to occur more frequently.

The lifestyle recommendations that patients should pay attention to are:

• Regular and quality sleep
• Effective stress management
• Oral and dental hygiene
• Balanced nutrition
• Staying away from smoking
• Avoiding unnecessary fatigue

Why Is Multi-Branch (Multidisciplinary) Follow-Up Necessary?

Behçet’s disease is such a dynamic and variable process that it cannot be managed by a single doctor alone. Dermatology is generally the first stop and the captain’s bridge of this process because patients see the first signs on their skin. However, in order to keep the ship safely afloat, we must be in close cooperation with other specialties.

As dermatologists, we evaluate the patient as a whole. When we feel there is a problem in the eyes, we refer our patient to an eye diseases specialist (ophthalmologist); when there is persistent pain in the joints, to a rheumatology specialist; and in vascular problems, to a cardiovascular surgeon. This is not the patient “going from doctor to doctor,” but on the contrary, being placed under a “holistic protective shield.”

Especially Behçet outpatient clinics in centers accepted as worldwide references in this field, such as Istanbul University-Cerrahpaşa, are the best examples of this multidisciplinary approach. Patients are evaluated together with professors from different branches in certain councils, and the most accurate treatment decision is made with a common mind. This coordination prevents the patient from receiving incomplete treatment and ensures that possible complications are noticed early.

The branches in which patients should be kept under regular follow-up are:

• Dermatology
• Eye diseases
• Rheumatology
• Neurology