Behçet’s syndrome



OVERVIEW

Definition.

Behcet’s syndrome is a chronic systemic vasculitic inflammatory disease characterized clinically by oral and vulvar ulcers, uveitis, and involvement of multiple systems.

It was first described in 1937 by Prof. Behcet in Turkey.

Epidemiology

Behcet’s syndrome has a high prevalence in East Asia, the Middle East and the Mediterranean coast.

According to statistics, the prevalence in the north of the country is 11 per 10,000 people.

The incidence is slightly higher in males than in females, and the age of prevalence is 16-40 years old.

Female patients have less vascular, neurological and ocular involvement than male patients and the disease is milder.

Types

Behçet’s syndrome is categorized into 3 types depending on the damage to the visceral system.

Vascular: there is involvement of large, medium and small arteries and/or veins.

Neurologic type: there is central or peripheral nerve involvement.

Gastrointestinal type: presence of gastrointestinal ulcers, bleeding, and perforation.

Etiology

Causes

The etiology is not clear; genetic, infectious, environmental, and immunologic factors may be associated with the disease.

Genetic factors

There is familial aggregation.

Human leukocyte antigen (HLA)- B5 and its subtype HLA-B51 are closely related to this disease.

Infections

Infections such as herpes simplex virus, hepatitis C virus, microvirus B19, cytomegalovirus, varicella-zoster virus, and streptococcus may predispose to Behçet’s syndrome.

Environmental factors

Use of pesticides and copper-containing insecticides may be associated with disease onset and disease activity.

Immune Factors

Current research has identified a variety of cytokines and chemokines associated with the inflammatory response in Behçet’s syndrome. These include T helper cells (Th)1, Th2, Th17, interleukin-2, interleukin-4, interleukin-6, and interleukin-10.

Pathogenesis

It is hypothesized that the above pathogenic causes cause immune dysfunction and neutrophil hyperfunction, which in turn leads to vascular endothelial cell damage and abnormal function, as well as related tissue damage.

Symptoms

Behçet’s syndrome is characterized by systemic involvement of the entire body. Typical symptoms include oral ulcers, genital ulcers, ophthalmia, and skin lesions. In some patients, it takes several years or even longer before clinical symptoms appear.

Typical symptoms

Oral ulcers

Recurrent episodes accompanied by pain.

The ulcers are round or oval, with clear margins, varying depths, and a yellowish-white covering at the bottom.

They usually subside on their own after 1 to 2 weeks without scarring.

Ulcers can occur in any part of the oral cavity, such as the buccal mucosa, the edge of the tongue, the lips, the soft palate and so on.

It is mostly the first symptom.

Genital ulcers

Often found on the labia majora and minora and the vagina in women, and on the scrotum and penis in men, but can also be found on the perineum or around the anus.

The ulcers are deep and large, painful and slow to heal.

The ulcers are less frequent and fewer in number.

Ophthalmia

All tissues of both eyes can be involved, with uveitis being the most common.

It manifests as blurred vision, decreased visual acuity, eye congestion, pain, photophobia and tearing, and foreign body sensation.

Repeated episodes of uveitis can lead to visual impairment or even blindness.

Skin lesions

There are various manifestations, including pustules, erythema nodosum, papules, acne-like rash, etc. One or more skin lesions may be present.

Erythema nodosum is the most common, most commonly found in the lower limbs below the knee, with red infiltrative subcutaneous nodules on the surface and tenderness, which usually subside on their own, leaving only hyperpigmentation on the skin surface, and seldom break out.

Systemic symptoms

Symptoms of neurological damage

Involvement of the central nervous system is more common, and headache, optic disk edema, hemiparesis, aphasia, mental abnormality and other manifestations may occur.

Peripheral nervous system involvement is less common, mainly manifested as numbness and weakness of the limbs, sensory disorders, etc.

Symptoms of digestive tract damage

Mostly seen in the seizure stage, often manifested as right lower abdominal pain, accompanied by local pressure and rebound pain, may also appear nausea, vomiting, abdominal distension, lack of appetite, diarrhea, dysphagia and other symptoms.

The whole digestive tract from the mouth to the anus can be involved, and in severe cases, perforated ulcers, intestinal paralysis and peritonitis can occur.

Symptoms of heart and blood vessel damage

Large and middle arteritis: fever, headache, pain or pressure in the carotid artery area, arthralgia, etc. may occur.

Large and medium phlebitis: pain may be present in the area along the venous route, accompanied by nodules or localized erythema. Deep vein thrombosis is common and commonly presents with lower extremity edema and pain.

Heart: aortic valve insufficiency, mitral stenosis and insufficiency, atrioventricular block, myocardial infarction and pericardial effusion may occur.

Symptoms of lung damage

Cough, hemoptysis, chest pain, dyspnea and so on.

In severe cases, massive hemoptysis may be life-threatening.

Symptoms of joint damage

Pain, swelling, and even limited movement of a single joint or a few joints.

The knee joint is most commonly involved.

The pain is transient and can be recurrent and self-limiting.

Symptoms of epididymitis

Bilateral or unilateral epididymis may be involved.

The main manifestations are swelling, pain and pressure in the epididymis.

Other symptoms

The following systemic symptoms may also occur with disease activity or with new organ damage:

Fever.

Dizziness and weakness.

Myalgia.

Lack of appetite.

Seek medical attention

Conditions requiring medical attention

In case of recurrent mouth ulcers, genital ulcers, ophthalmia and skin damage, medical attention is required.

Suggested departments to consult

Rheumatology.

In case of eye, mouth and genital mucosal lesions, ophthalmology, stomatology, obstetrics and gynecology can be consulted.

Preparation for consultation

If there are no special circumstances, you need to register through the hospital’s official website, official app, 114 and other regular channels, prepare the social security card (medical insurance card) and other medical information, bring the previous medical information, and apply for the record for patients who have traveled to other places for medical treatment.

What questions the doctor may ask

What are the symptoms?

How long have these symptoms been present?

Do mouth ulcers occur frequently?

Where do the genital ulcers occur? How long have they lasted?

Is there a rash?

Has there been any loss of vision? Has there been any redness, itching, or foreign body sensation in the eyes?

Is there joint pain?

Has there been abdominal pain, diarrhea, or blood in the stool?

Is there any history of other systemic diseases?

Has anyone in the family suffered from similar diseases?

Have you had any related tests? What are the results?

Have you had any treatment? What kind of treatment? What is the effect?

Any history of drug allergy?

Are there any medications you are taking?

Diagnosis

Disease Diagnosis

Diagnosis basis

The diagnosis of Behçet’s syndrome is based on the history, clinical manifestations, examination findings, and exclusion of other diseases.

History of viral infections, autoimmune diseases, or systemic diseases.

Relatives who have patients with the disease.

Presence of recurrent oral ulcers, genital ulcers, ophthalmia and skin lesions.

Behçet’s syndrome may also be considered if accompanied by symptoms of macrovascular or neurologic damage, arthralgia, and central neuropathy.

These include routine blood tests, autoantibody tests, erythrocyte sedimentation rate, C-reactive protein, and genetic testing, which can help determine the cause of the disease.

Routine blood tests: Elevated blood white blood cell and platelet counts may be seen in the acute phase or during active disease.

Autoantibody test: positive anti-aortic endothelial cell antibodies may be present, and a few patients may be positive for antinuclear antibody spectrum, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies.

Erythrocyte sedimentation rate: often increased.

C-reactive protein: often elevated.

Chest X-ray/Chest CT: can detect lesions in the lungs and help the doctor determine the primary cause.

Magnetic Resonance Imaging (MRI): can detect lesions in the brainstem, paraventricular white matter and basal ganglia in the acute phase.

Gastroenteroscopy: it can clearly diagnose peptic ulcers, and ulcers in the ileocecal region are significant in the diagnosis of this disease.

Cardiac ultrasound, peripheral vascular ultrasound, vascular MRI: it can clarify the presence of arterial and venous thrombosis, arterial occlusion, aneurysm, arterial and venous inflammation.

Needle reaction test

Fundoscopy: to clearly diagnose uveitis and/or retinal vasculitis.

Diagnostic criteria

The classification criteria developed by the International Behçet’s Disease Study Group are commonly applied and include the following aspects

Recurrent oral ulcers: recurrent episodes at least 3 times in 1 year.

Recurrent vulvar ulcers: ulcers or scarring on the vulva.

Ocular lesions: including anterior uveitis, posterior uveitis, retinal vasculitis, and the presence of cells within the vitreous on slit lamp microscopy.

Skin lesions: including erythema nodosum, pseudofolliculitis, papulopustular eruption, acne-like nodules that have not been treated with glucocorticoids and are not present at puberty.

Needle prick test: positive result.

The presence of recurrent oral ulcers with 2 or more of the other 4 items can be considered as the disease.

Other diseases need to be excluded for the above manifestations.

Not all cases of Behçet’s syndrome fulfill the above criteria, and the clinical diagnosis cannot be based solely on the above criteria.

Differential diagnosis

Recurrent Aphthous ulcer

Similarity: Recurrent aphthous ulcers.

Differences: Recurrent aphthous ulcers usually have no obvious systemic symptoms. In addition to recurrent oral ulcers, Behçet’s syndrome is accompanied by other systemic symptoms such as rash, genital ulcers, and ophthalmia.

Rheumatoid arthritis

Similarities: Both have joint pain.

Differences: Rheumatoid arthritis is characterized by symmetrical polyarticular swelling and pain, morning stiffness, and joint deformity. Behçet’s syndrome has milder joint symptoms and rarely has joint destruction, deformity and functional limitation.

Systemic lupus erythematosus

Similarities: Both are characterized by recurrent oral ulcers, joint pain, and skin rash.

Differences: Systemic lupus erythematosus is characterized by butterfly-shaped erythema on the face, photosensitive alopecia, and foamy urine.

AIDS

Similarity: Rash, arthralgia and neurological symptoms may occur.

Difference: AIDS has a long incubation period, and in the early stage, there may be mild fever, rash, headache, nausea, muscle and joint pains, and mild enlargement of lymph nodes throughout the body, which usually lasts for about 1 to 3 weeks and then relieves on its own, and is easy to be ignored. Human immunodeficiency virus (HIV) antibody and needle reaction test can identify the disease.

Treatment

Aims of treatment: to control the existing symptoms, prevent damage to important organs, and stop the progression of the disease.

Treatment methods: general treatment, local treatment, systemic medication, surgery, traditional Chinese medicine and so on.

General treatment

The disease should be properly recognized and viewed, and more communication can be made with family members in order to maintain a good psychological state and establish optimism.

During the acute active period, bed rest should be provided, pay attention to turning over regularly, and avoid dragging, pulling, pushing and other movements.

In daily life, pay attention to personal hygiene, take baths, change clothes and pants, and keep the skin and perineum clean.

Remove eye secretions regularly, at least twice a day, to prevent infection.

Eat a light diet, avoid spicy and stimulating foods, and eat small and frequent meals.

Pay attention to the changes of your condition and go to the hospital once the symptoms worsen or recur.

Localized treatment

Mouth ulcer treatment

Local application of glucocorticoid cream, ice boron powder, tin-like powder, etc. can be applied under doctor’s guidance to facilitate ulcer healing and reduce pain.

Apply gargle in the morning and evening and after eating to keep the mouth clean.

Usually should not eat too hard or high temperature food, so as not to damage the oral mucosa.

Vulvar ulcer treatment

Localized vulvar ulcers can be treated with wet compresses with benzalkonium chloride solution to reduce exudation and control inflammation.

Women should avoid sexual intercourse if there is aggravation of vulvar and vaginal wall ulcers.

Male patients should frequently turn over the foreskin to prevent adhesion of the ulcerated surface.

Ophthalmia treatment

Glucocorticoid eye ointment or eye drops can be applied for conjunctivitis and keratitis.

Uveitis must be applied to dilate the pupil to prevent post-inflammatory adhesions.

Glucocorticoids may be injected under the bulbar conjunctiva in severe cases of uveitis.

Systemic medication

During the drug treatment, it should be insisted that the treatment should be in strict accordance with the doctor’s instruction, and should not change the drug dosage without authorization or stop the drug suddenly, so as to ensure that the treatment plan is implemented. You should know the name, dosage, time and method of administration of the drugs used.

Non-steroidal anti-inflammatory drugs

They have anti-inflammatory and analgesic effects and are effective in relieving fever, skin nodules and erythema, painful vulvar ulcers and arthritic symptoms.

Available ibuprofen, indomethacin, loxoprofen, celecoxib, naproxen, meloxicam, diclofenac and so on.

Be aware of the risk of gastrointestinal ulcers, bleeding, and perforation.

Avoid taking two or more NSAIDs at the same time.

Only relieves symptoms of pain, redness and swelling, does not control or stop the condition from worsening.

Colchicine

Inhibits neutrophil chemotaxis and is useful for arthropathy, erythema nodosum, oral and genital ulcers, and uveitis.

May have adverse reactions such as nausea, vomiting, diarrhea, and abdominal pain.

Thalidomide

Used to treat oral and genital ulcers and skin lesions.

Strict contraception while taking the drug.

May cause adverse reactions such as neuraxial degeneration.

Glucocorticoids

May stop the progression of early ulcers or reduce ulcer inflammation.

Prednisone and methylprednisolone can be used.

Serious patients such as severe ophthalmia, central nervous system lesions, patients with severe vasculitis can be applied intravenously high-dose methylprednisolone shock, and the combination of immunosuppressive drugs is more effective.

Long-term application of glucocorticoids should pay attention to infection, osteoporosis, hypokalemia and other adverse reactions.

Immunosuppressant

Mostly used in combination with glucocorticoids, can reduce the cumulative use of glucocorticoids and adverse effects.

May inhibit oral ulcers, ocular lesions, arthritis and deep vein thrombosis, and improve the prognosis of the disease.

It can be used in combination with other immunosuppressants, but should not be used in combination with interferon-alpha to avoid myelosuppression.

Blood routine and liver function should be rechecked regularly during the use of the drug.

It is used for the treatment of lesions of the nervous system, skin and mucous membranes.

It can be taken in small doses for a long period of time. Adverse reactions such as bone marrow suppression, liver damage and gastrointestinal symptoms should be noted during use.

It is usually used in combination with prednisone in acute central nervous system damage or pulmonary vasculitis or ophthalmia.

It is used to treat patients with digestive system involvement or arthritis.

Blood routine, urine routine and liver function should be rechecked regularly during the use of the drug.

For persistent ophthalmia.

Generally not used for people with combined central nervous system damage.

Monitor blood pressure when applying, renal function impairment is its main adverse reaction.

Biological agents

Under doctor’s supervision, tumor necrosis factor-α inhibitor, anti-CD20 monoclonal antibody, interleukin-6 receptor inhibitor and low-dose interleukin-2 can be used for treatment.

Other drugs

Tretinoin: It can be used in the treatment of oral ulcers, subcutaneous nodules, arthritis, and ophthalmia. It is less effective for intestinal symptoms.

Thrombolytic anticoagulant drugs: If the presence of newly formed thrombus is clearly diagnosed, thrombolytic anticoagulant therapy can be carried out. Streptokinase, urokinase, low molecular heparin, warfarin, etc. can be chosen.

Surgical treatment

Those with aneurysms should be treated with interventional therapy or surgical resection in conjunction with the clinic.

Gastrointestinal perforation, hemorrhage and obstruction should be treated with surgery urgently, and the application of immunosuppressant can reduce the risk of postoperative complications and recurrence.

Traditional Chinese Medicine (TCM)

It is recommended to go to regular hospitals for traditional Chinese medicine treatment under the guidance of doctors, and do not believe in local remedies, secret prescriptions, biased prescriptions and other unidentified treatments.

Prognosis

Cure

There is no effective cure for this disease, and remission and relapse can last for weeks or years, but most patients have a good prognosis.

In severe cases, there is central nervous system, cardiovascular system, gastrointestinal involvement, and occasionally life-threatening conditions.

Blindness is reduced by early and standardized treatment of uveitis to prevent involvement of the healthy eye, but some patients are still left with severe visual impairment.

Hazards

The disease is chronic, long-lasting and prone to recurrent episodes, which can affect normal work and life.

People with vulvar ulcers are often afraid to have sex, worrying that their partners will mistake them for sexually transmitted diseases, resulting in marital discord and negative emotions such as low mood and low self-esteem.

If glucocorticosteroids are taken for a long period of time, they are prone to infections, osteoporosis, hypokalemia, hypertension, hyperglycemia, hyperlipidemia and other adverse effects, which further affect the health and quality of life.

Daily life

Daily life

Diet

Eat more fresh vegetables, fruits, lean meat and other high-protein, high-vitamin and easy-to-digest foods.

Avoid spicy and stimulating foods, such as wine, strong tea, coffee, raw garlic, ginger, chili peppers and curry.

Avoid high-sugar diets to avoid blood sugar fluctuations and inflammation exacerbation, such as beverages, candies, snacks and so on.

Those with severe mouth ulcers should choose a liquid diet (lotus root powder, rice soup, etc.) or a semi-liquid diet (congee with minced meat, congee with minced vegetables, congee with egg, etc.). It is not advisable to eat food that is too hard or too hot to avoid damaging the oral mucosa.

If peptic ulcer exists, give soft, high-calorie, high-protein, high-vitamin, easy-to-digest and nutritious food with small amount and multiple meals.

Living Habits

Pay attention to a neat and clean environment, and open windows regularly for ventilation every day.

Pay attention to keep the skin and perineum clean.

Clothes are recommended to choose pure cotton fabrics and avoid chemical fibers to protect the skin.

Bed rest should be provided during the acute stage, and appropriate activities can be carried out during the recovery stage to enhance physical fitness.

Do not watch TV or use computer for a long time to avoid increasing eye fatigue.

Pay attention to eye hygiene, avoid rubbing the eyes with hands to prevent bacterial invasion.

Avoid going to places where people gather.

Observe the weather changes and increase the clothing appropriately in cold weather.

Strictly quit smoking and avoid exposure to “second-hand smoke”.

Psychological care

Face the disease with a positive and optimistic attitude, and build up confidence to overcome the disease.

Talk to your family, partner and friends about your inner feelings.

For people with genital damage, it is very important to get support from your partner. The partner should give sufficient care and comfort, and say more positive and encouraging words.

Strive to live on your own or take part in work that you can do to enrich your life.

In case of severe anxiety, depression, insomnia, etc., it is recommended to go to the hospital in time for formal psychological treatment.

Regular follow-up

Follow the doctor’s prescribed time for follow-up consultation.

Seek timely medical treatment for any changes in your condition

If symptoms worsen or new symptoms appear, consult a doctor promptly.

Prevention

The cause of Behçet’s syndrome is not fully understood and it is difficult to prevent it effectively. However, the following measures can reduce the risk of developing the disease and enable early detection, diagnosis and treatment.

If any of your relatives have Behçet’s syndrome, you should have regular medical checkups and consult a doctor if you feel unwell.

Actively treat autoimmune diseases or other systemic diseases.

Eat a balanced diet with a variety of food types.

Avoid going to closed, airless public places and crowded places during the epidemic season.

Ensure good mood and sufficient sleep, and have a regular work schedule.