bubble_chart Overview

Behcet's syndrome is a vasculitic disease. The initial description of this syndrome primarily referred to the triad of recurrent oral ulcers, genital ulcers, and uveitis. Later, it was recognized as a systemic disease that can affect multiple systems and organs. Cases that are typical or meet diagnostic criteria can be referred to as Behcet's disease. However, many patients present atypically or do not yet meet the diagnostic criteria, especially in conditions such as ulcerative colitis, granulomatous enteritis, segmental ileitis, etc., which can also cause similar triad manifestations. Therefore, it is preferable to collectively refer to them as Behcet's syndrome.

This disease was first reported by the Turkish dermatologist Behcet, and cases have since been identified worldwide. The incidence of this disease is significantly higher in Japan, Korea, China, the Middle East (Turkey, Iran), and the eastern Mediterranean region compared to Western European and American countries. Due to this geographical distribution, some scholars refer to this syndrome as the "Silk Road disease."

bubble_chart Pathogenesis

This disease is essentially a vasculitis lesion. Lymphocytes and mononuclear cells can be observed infiltrating the vascular walls, perivascular areas, and surrounding tissues. There may be necrosis of the vascular walls and vascular thrombosis. The affected vessels can be arteries or veins, ranging from capillaries and small vessels (such as subcutaneous nodules) to medium and large vessels such as renal arteries, pulmonary arteries, the aorta, lower limb arteries and veins, pulmonary veins, and the inferior vena cava. Epithelial cell destruction can lead to ulcers in the mouth and genital areas, and even gastrointestinal ulcers, resulting in massive gastrointestinal bleeding.

bubble_chart Pathological Changes

The cause of the disease remains unclear. American scholars believe it is related to herpes simplex virus infection; Japanese scholars suggest a connection with streptococcal infection; Chinese scholars propose a possible close relationship with subcutaneous nodule disease; others consider it an autoimmune disorder.

bubble_chart Clinical Manifestations

It mainly manifests as oral ulcers, genital ulcers, and uveitis (triad), and may also involve skin lesions (tetrad), as well as other systemic organs.

1. Oral Ulcers

The ulcers are typically well-defined, painful, and located on the lips, gums, tongue, or buccal mucosa. They are round or oval in shape, with a white or yellow pseudomembrane covering the surface. They are often multiple and usually heal within 1–2 weeks but recur frequently. Some patients may have persistent ulcers that affect appetite. Almost all patients experience oral ulcers.

2. Genital Ulcers

These commonly occur on the scrotum, glans penis, female labia, vaginal wall, or even the cervix and urethra. The morphology of these ulcers is similar to oral ulcers, though recurrence is less frequent. Physical examination may reveal external genital ulcers or scars from healed ulcers.

3. Ocular Inflammation

Early-stage manifestations include conjunctivitis and iridocyclitis, while late-stage (third-stage) symptoms may involve hypopyon, uveitis, and hemorrhages in the conjunctiva, cornea, and retina. Ocular symptoms are rarely the initial presentation of the disease. They usually appear several years after the first occurrence of oral ulcers. Symptoms include eye and periorbital pain, photophobia, pupillary deformation, and impaired vision in one or both eyes. This condition is a leading cause of blindness in Japan. Fundus examination may reveal hemorrhages, arteriovenous occlusion, and optic nerve atrophy.

4. Skin Symptoms

Common manifestations include erythema nodosum, polymorphic erythema, folliculitis, acne-like rashes, and skin hypersensitivity. The pathergy test involves inserting a 20-gauge or smaller needle into the skin under sterile conditions at a slant. A positive result is indicated by the formation of pustules or folliculitis with surrounding erythema at the puncture site within 24–48 hours. The positivity rate is 90% in Japanese and Turkish patients and 62.2% in Chinese patients. This test is highly specific and rarely positive in other diseases or normal individuals.

5. Joint Manifestations

50–60% of patients report arthralgia, with possible acute or chronic synovitis, though joint swelling and bone destruction are rare. Large joints, especially the knees, are most commonly affected.

6. Central Nervous System Manifestations

Central nervous system involvement occurs in 10–18% of patients. Symptoms may include headache, neck stiffness, meningitis, epilepsy, flaccid paralysis, sensory and motor disturbances, cerebellar ataxia, cranial nerve damage, and various psychiatric symptoms. CNS involvement often indicates severe disease with a poor prognosis.

7. Venous and Arterial Vasculitis

Vasculitis can affect veins and arteries of all sizes in nearly any location, though venous thrombosis in the lower limbs and varicose veins are most common. Obstruction of the superior or inferior vena cava may occur. Arterial involvement mainly includes arterial occlusion and aneurysms, leading to digital necrosis, pulselessness, or aneurysm rupture and hemorrhage. Pulmonary artery involvement can cause pulmonary hypertension.

8. Gastrointestinal Manifestations

Intestinal ulcers are often found in the ileocecal region but may occur elsewhere, presenting with abdominal pain, diarrhea, bleeding, perforation, fistulas, or intestinal strictures.

9. Other Manifestations

Epididymitis may occur. Pulmonary involvement can present as parenchymal lung shadows, while renal involvement may lead to focal nephritis. Several cases in China have progressed to leukemia, with two cases also showing malignant histiocytosis. Whether this represents malignant progression of the disease, a paraneoplastic syndrome, or coincidental comorbidity requires further investigation.

bubble_chart Auxiliary Examination

1. Blood routine: anemia, normal or low white blood cells, which may increase during acute episodes.

2. Increased erythrocyte sedimentation rate, elevated α₂ and γ globulins.

3. Elevated C-reactive protein, polyclonal hypergammaglobulinemia is common, and blood IgM and IgG levels are significantly increased in patients with arthritis or ocular involvement. Anti-oral mucosal antibodies can be detected in the serum of over 40% of patients.

4. Serum copper and plasma ceruloplasmin levels are significantly increased, especially during active disease.

5. X-rays may reveal abnormalities in the lungs, cardiovascular system, or digestive tract.

bubble_chart Diagnosis

There is no specific serological or pathological diagnostic method, and the diagnosis is primarily clinical. A definitive diagnosis can be made for those with oral, ocular, and genital lesions (triple symptom) or with the addition of skin lesions (quadruple symptom). A positive skin prick test can aid in diagnosis. For incomplete or atypical cases, a comprehensive analysis should be conducted in conjunction with systemic manifestations. The diagnosis of Behcet's syndrome can refer to the criteria established by the Japanese Ministry of Health and Welfare (see appendix) and the international classification standards.

Appendix: Diagnostic Criteria for Behcet's Syndrome

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Diagnostic Conditions

Major Symptoms:

1. Recurrent aphthous ulcers of the oral mucosa
2. Skin Symptoms
   1. Erythema nodosum-like rash
   2. Subcutaneous thrombophlebitis
   3. Follicular acne-like rash
   4. Positive skin prick test
3. Ocular Symptoms
   1. Iridocyclitis
   2. Retinochoroiditis
   3. Secondary lesions of the above two
4. Genital Lesions
   1. Aphthous ulcers on the male scrotum
   2. Painful ulcers on the female labia majora, labia minora, or vaginal wall

Minor Conditions:

1. Rheumatoid arthritis
2. Gastrointestinal symptoms, such as multiple ulcers in the ileocecal region
3. Epididymitis
4. Vascular symptoms, such as occlusive thrombophlebitis, arterial occlusion, or aneurysms
5. Neurological symptoms

Diagnostic Standards

• Complete Type: Simultaneous or sequential appearance of all four major symptoms during the clinical course
• Incomplete Type: Presence of three major symptoms or typical ocular symptoms plus one major symptom
• Suspected Type: Appearance of two major symptoms during the clinical course
• Possible Type: Recurrent appearance of one major symptom

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Appendix: International Classification Criteria for Behcet's Disease

1. Recurrent oral ulcers observed by a physician or confirmed by the patient as aphthous or herpetic ulcers, recurring at least three times within a year.
2. Recurrent genital ulcers observed by a physician or confirmed by the patient as aphthous ulcers or scars, especially in males.
3. Eye disease: Uveitis (anterior and/or posterior), cells visible in the vitreous upon slit-lamp examination, or retinal vasculitis.
4. Skin lesions: Erythema nodosum-like lesions, pseudofolliculitis, pustular papules, or acne-like rashes (occurring without the use of corticosteroid drugs).
5. Positive prick test: A sterile 20-gauge needle is inserted obliquely into the skin, and the result is assessed by a physician after 24–48 hours.

The diagnosis can be made if recurrent oral ulcers are present along with two or more of the remaining four criteria.

Other symptoms closely related to the disease and supportive of its diagnosis include arthralgia (arthritis), subcutaneous thrombophlebitis, deep vein thrombosis, arterial thrombosis and/or aneurysms, central nervous system involvement, gastrointestinal ulcers, epididymitis, and family history.

bubble_chart Treatment Measures

There is currently no effective cure. The goal of treatment is to alleviate symptoms and reduce organ damage. For patients without significant organ involvement, colchicine is the first-line drug. For those with visceral involvement, especially eye disease affecting vision, combination therapy is often required.

1. Colchicine: This drug has anti-chemotactic effects and is used to prevent ulcers, iritis, synovitis, and phlebitis. The dosage is 0.5mg, 2–3 times daily. Toxic reactions include bone marrow suppression, nausea, vomiting, loss of appetite, diarrhea, and constipation.

2. Corticosteroids: Prednisone is typically used at 30–40mg once daily. For severe cases, intravenous hydrocortisone or dexamethasone may be administered, switching to oral administration after symptom relief. Although corticosteroids can alleviate oral ulcers and joint inflammation, symptoms often recur upon dose reduction or discontinuation. Central nervous system damage is usually difficult to treat.

3. Immunosuppressants: For severe uveitis, immunosuppressants such as 50mg three times daily or 200mg intravenous injection once daily or every other day may be used. Side effects to monitor include leukopenia, gastrointestinal reactions, and alopecia areata. Cyclosporine A (Cycosporin A) has shown some efficacy for ocular manifestations but limited effects on other systemic damage. The dosage is 125–300mg once daily for a 3-month course. Root, Leaf, or Flower of Common Threewingnut Glycoside, 30mg three times daily, may cause leukopenia, thrombocytopenia, loss of appetite, amenorrhea, and reduced sperm count. Other immunosuppressants like chlorambucil and methotrexate may also be used.

4. Other Therapies: For subcutaneous nodule disease, anti-subcutaneous nodule medications should be administered.

bubble_chart Prognosis

The disease recurs and progresses progressively, with some cases lasting up to 40 years. Patients who develop pulmonary vasculitis leading to hemoptysis or central nervous system lesions have a poor prognosis.