Leukodystrophy (BD) is a systemic, chronic, vascular inflammatory disease with the main clinical manifestations of recurrent oral ulcers, genital ulcers, ophthalmia, and skin lesions, and can also involve blood vessels, the nervous system, the gastrointestinal tract, the joints, the lungs, the kidneys, and the epididymis, etc. The majority of patients have a good prognosis, and those with ocular, central nervous, and large-vessel involvement have a poor prognosis. The disease has a high incidence in East Asia, the Middle East and the Mediterranean region, and is known as the Silk Road disease. There is no precise information about the incidence in China, and the disease can occur at any age, with a prevalence of 16-40 years old. The most common age is 16~40 years old. Most of the patients in China are females, and male patients have more vascular, nervous system and eye involvement than females, and their condition is more serious. Clinical manifestations All systems of the body can be involved in this disease, but it is seldom that multiple clinical manifestations occur at the same time. Sometimes it takes several years or even longer for various clinical signs and symptoms to appear one after another. 1, oral ulcers: almost all patients have recurrent, painful oral ulcers (Aphthous ulceration, Aphthous ulceration), most patients with this disease as the first symptom. Ulcers can occur in any part of the mouth, mostly located in the tongue edge, cheeks, lips, soft palate, pharynx, tonsils and other places. Can be single, can also appear in batches, was rice or soybean size, round or oval, clear edge, depth varies, the bottom of the yellow cover, surrounded by a clear edge of the red halo, about 1 ~ 2 weeks after the self-subsidence without leaving scars. In severe cases, the ulcers are deep and large, and the healing is slow, occasionally leaving scars. Recurrent oral ulcers are the most basic symptom necessary to diagnose this disease. 2, genital ulcers: about 75% of patients with genital ulcers, lesions and oral ulcers are basically similar. However, the number of occurrences is less. The ulcers are deep and large, with severe pain and slow healing. The affected areas are vulva, vagina, perianal, cervix, scrotum and penis. Vaginal ulcers may be painless with only increased discharge. Some patients can cause hemorrhage or scrotal vein wall necrosis rupture bleeding due to deep ulcers. 3, ophthalmia: about 50% of patients are involved, both eyes can be involved. Ocular lesions can appear months or even years after the onset of the disease, and its manifestations are blurred vision, vision loss, eye congestion, eye pain, photophobia and tearing, foreign body sensation, mosquitoes and headache. It usually presents with a chronic, recurrent, progressive course. Eye involvement causes blindness in up to 25% of cases and is the leading cause of disability in this disease. The most common and severe ocular lesion is uveitis. Anterior uveitis, i.e., iridocyclitis, may or may not be accompanied by pus in the anterior chamber, whereas posterior uveitis and uveitis are the main causes of visual impairment. All the rest of the tissues of the eye can be involved, with keratitis, herpetic conjunctivitis, scleritis, choroiditis, retinitis, optic nerve papillitis, necrotizing retinal vasculitis, and fundus hemorrhage. In addition there may be lens hemorrhage or atrophy, glaucoma, and retinal detachment. The edema of the optic disc alone suggests cerebral venous thrombosis, and intracranial vascular lesions caused by leukoaraiosis can lead to visual field defects. 4, skin lesions: high incidence of skin lesions, up to 80% ~ 98%, with a variety of manifestations, nodular erythema, herpes, papules, acne-like rash, erythema multiforme, annular erythema, necrotizing tuberculosis rash-like damage, herpetic necrotizing vasculitis, Sweet’s disease-like lesions, pyoderma, etc. A patient may have one or more of these lesions. A patient may have one or more of these lesions. The skin signs of special diagnostic value are nodular erythema-like lesions and inflammatory reaction to tiny trauma (pinprick). 5, joint damage: 25% to 60% of patients have joint symptoms. The manifestation is relatively mild limited, asymmetric arthritis. It mainly involves knee joints and other large joints. HLA-B27 positive patients may have sacroiliac joint involvement, which is similar to ankylosing spondylitis. 6. Nervous system damage: also known as neuroleukodystrophy, the incidence rate is about 5%~50%. It often appears several months to several years after the disease, and a few (5%) may be the first symptom. Clinical manifestations vary according to the site of involvement. Involvement of the central nervous system is more common, including headache, dizziness, Horner’s syndrome, pseudobulbar palsy, respiratory disorders, epilepsy, ataxia, aseptic meningitis, optic papilloedema, hemiplegia, aphasia, paraplegia of different degrees, urinary incontinence, bilateral lower limb weakness, sensory disorders, impaired consciousness, and psychiatric abnormalities, etc. The peripheral nerve involvement is less common. Peripheral nerve involvement is less common, manifesting as numbness and weakness of the limbs, peripheral-type sensory deficits, and so on. Neurological damage also has the tendency of alternating episodes and remission, and may have multiple site involvement at the same time. Most patients have a poor prognosis, especially brainstem and spinal cord damage is one of the main causes of disability and death in this disease. 7, digestive tract damage: also known as intestinal leukosis. The incidence rate is 10%~50%. From the mouth to the anus of the whole digestive tract can be involved, ulcers can be single or multiple, varying in depth, can be seen in the lower esophagus, stomach, ileum, distal ileum, ileocaecum, ascending colon, but the ileocaecum is more common. Clinical manifestations may include epigastric fullness, belching, dysphagia, middle and lower abdominal distension, vague pain, paroxysmal colic, diarrhea, black stools, constipation and so on. In severe cases, there may be perforated ulcers and even death due to complications such as hemorrhage. Intestinal leukoaraiosis should be noted with inflammatory bowel disease and non-steroidal anti-inflammatory drugs caused by mucosal lesions to distinguish, right lower abdominal pain should be noted with appendicitis to distinguish, often clinical cases of postoperative wound non-healing. 8, vascular damage: the basic lesion of this disease is vasculitis, the whole body large and small blood vessels can be involved, about 10% to 20% of patients with large and medium-sized vasculitis, is the main cause of death and disability. When the arterial system is involved, the elastic fiber of the arterial wall is destroyed and the endothelial fiber of the arterial wall is proliferated, resulting in arterial stenosis, dilatation or aneurysm, and the corresponding clinical manifestations appear, such as dizziness, headache, syncope and pulselessness. Aneurysms on the aortic arch and its branches are at risk of rupture. Involvement of the venous system is more common than that of the arterial system. superficial or deep migratory thrombophlebitis and venous thrombosis, resulting in stenosis and embolization, occur in about 25% of patients. Involvement of the inferior vena cava and lower extremity veins is more common, and Budd-Chiari syndrome, ascites, and swelling of the lower extremities may occur. Upper vena cava obstruction can have maxillofacial and neck swelling and elevated venous pressure in the upper limbs. 9, lung damage: the incidence of lung damage is low, about 5%~10%, but most of the disease is serious. Pulmonary vascular involvement can have pulmonary aneurysm formation, rupture of the aneurysm can form pulmonary vascular – bronchial fistula, resulting in intrapulmonary hemorrhage; pulmonary vein thrombosis can cause pulmonary infarction; alveolar peripapillary inflammation can make the endothelial hyperplasia and fibrosis affecting the function of air exchange. When the lungs are involved, patients have cough, hemoptysis, chest pain, dyspnea and so on. Massive hemoptysis can lead to death. 10, other: kidney damage is rare, there may be intermittent or persistent proteinuria or hematuria, renal hypertension, renal pathology may have IgA glomerular proliferative lesions or amyloidosis. Cardiac involvement is less common and may include myocardial infarction, valvular lesions, conduction system involvement, and pericarditis. There may be ependymal thrombosis in the cardiac chambers, and in a few patients, the heart shows dilatation-like changes, constrictive pericarditis-like manifestations, and cardiac lesions are associated with local vasculitis. The incidence of epididymitis is about 4%~10%, which is more specific. Acute onset, manifested as single or bilateral epididymis swelling pain and pressure, 1~2 weeks can be relieved, easy to recur. Pregnancy may aggravate the disease in most patients, and remission of uveitis has also been reported. There can be intrauterine fetal growth retardation, and most of the disease worsens after delivery. Nearly 10% of patients with fibromyalgia syndrome-like manifestations, more common in women. Diagnostic points 1, clinical manifestations: the course of the disease in the doctor observed and recorded recurrent oral ulcers, ophthalmia, genital ulcers and characteristic skin damage, in addition to the appearance of macrovascular or neurological damage is highly suggestive of the diagnosis of leukoaraiosis. 2.Laboratory examination: there is no specific laboratory abnormality in this disease. In the active stage, there may be rapid blood sedimentation, elevated C-reactive protein; some patients are positive for cryoglobulin and platelet agglutination; HLA-B51 positive rate is 57%~88%, which is related to eye and digestive tract lesions. 3.Pathergy test: use a 20-gauge sterile needle to stab obliquely into the middle of the flexure surface of the forearm for about 0.5cm along the longitudinal direction with a slight twist and then withdraw, after 24~48 hours, the local appearance of folliculitis-like red spots with a diameter of >2mm or pustular herpes-like changes are positive. This test has high specificity and correlates with disease activity, with a positive rate of about 60%~78%. Similar lesions appearing after venipuncture or skin trauma are of equal value. 4.Special examination: Neuroleukodystrophy is often characterized by increased cerebrospinal fluid pressure and mildly elevated white blood cell count. Brain CT and magnetic resonance (MRI) examination of the brain, brainstem and spinal cord lesions can be helpful. The sensitivity of MRI examination in the acute stage is as high as 96.5%, and it can find increased signals in the brainstem, paraventricular white matter and basal ganglia. MRI in the chronic stage should be noted to distinguish from multiple sclerosis.MRI can be used for the diagnosis of neuroleukodystrophy and the follow-up observation of the treatment effect. Barium gastrointestinal imaging and endoscopy, angiography, color Doppler can help to diagnose the site and scope of the lesion. Lung radiographs may show diffuse exudate or round nodular shadows of varying sizes unilaterally or bilaterally, and blurred shadows of increased density around the pulmonary hilum in the case of pulmonary infarction. High-resolution CT or pulmonary angiography, isotope lung ventilation/perfusion scanning are helpful in the diagnosis of lung lesions. 5.Diagnostic criteria: This disease has no specific serologic and pathologic features, diagnosis is mainly based on clinical symptoms, so attention should be paid to detailed history taking and typical clinical manifestations. At present, the diagnostic criteria formulated by the International Study Group on Leukosis in 1989 are more often used [treatment plan and principle] There is no recognized effective cure for this disease. A variety of drugs are effective, but most of them are prone to relapse after stopping the drugs. The purpose of treatment is to control the existing symptoms, prevent and control the damage of important organs and slow down the progress of the disease. 1, general treatment: acute active period, should be bed rest. During the interictal period, attention should be paid to the prevention of recurrence. Such as controlling mouth and pharyngeal infections, avoid eating irritating food. The accompanying infected person can be treated accordingly. 2, local treatment: oral ulcers can be localized with glucocorticoid cream, ice boron powder, tin-like powder, etc., genital ulcers with 1:5000 potassium permanganate cleaning with antibiotic ointment; ocular conjunctivitis, keratitis can be applied glucocorticoid ointment or eye drops, uveitis must be applied to dilate the pupil to prevent post-inflammatory adhesions, severe ophthalmitis can be injected with adrenal corticotropic hormone in the subglobe-conjunctivitis. (1) Non-steroidal anti-inflammatory drugs: anti-inflammatory and analgesic effects. For the relief of fever, skin nodules erythema, genital ulcer pain and arthritis symptoms have a certain efficacy, commonly used drugs are ibuprofen 0.4 ~ 0.6g 3 times a day; naproxen, 0.2 ~ 0.4g 2 times a day; diclofenac sodium, 25mg 3 times a day, etc., or other non-steroidal drugs and COX-2 selective inhibitors (see rheumatoid arthritis treatment). (2) Colchicine: it can inhibit neutrophil chemotaxis, and has a certain therapeutic effect on arthropathy, erythema nodosum, oral and genital ulcers, and uveitis, with a commonly used dosage of 0.5mg 2~3 times daily. Adverse effects such as hepatic and renal damage and granulocytopenia should be noted. (3) Thalidomide: It is used for the treatment of severe oral and genital ulcers. It is recommended to start with a small dose and gradually increase to 50mg three times a day. It is contraindicated in pregnant women to avoid causing fetal malformations (see Ankylosing Spondylitis Medications), and has the side effect of causing neuraxial degeneration. (4) Glucocorticoids: effective in controlling acute symptoms, commonly used for prednisone 40~60mg/d. Serious patients, such as severe ophthalmitis, central nervous system lesions, severe vasculitis patients can be considered to use intravenous application of high-dose methylprednisolone shock, 1000mg/d, 3~5 days for a course of treatment, and immunosuppressants with the combination of the effect is better. Regular application of glucocorticoids has adverse effects (see Systemic lupus erythematosus medication). (5) Immunosuppressive drugs: these drugs should be used when there is damage to important organs. They are often used in combination with adrenocorticotropic hormone. The side effects of these drugs are large and should be closely monitored during use. (6) other ① α interferon: the treatment of oral damage, skin disease and joint symptoms have a certain effect, can also be used for acute treatment of eye lesions. ② TNF-α monoclonal antibody (infliximab) for the treatment of recurrent uveitis has been reported, still need further clinical observation. (iii) Tretinoin preparations have shown positive efficacy in oral ulcers, subcutaneous nodules, arthropathy, and ophthalmia. It is less effective for intestinal symptoms. ④ Antiplatelet drugs (aspirin, Pansentin) and antifibrin therapy (urokinase, streptokinase) can also be used to treat thrombotic disorders, but they should not be stopped abruptly to avoid rebound. ⑤ If the patient has tuberculosis or a history of tuberculosis, and the PPD skin test is strongly positive (5IU with blisters), anti-tuberculosis treatment (triple) can be tried for at least three months, and the efficacy can be observed. 4, Surgery: Surgery is feasible when severe intestinal leukoencephalopathy is complicated by intestinal perforation, but the recurrence rate of intestinal leukoencephalopathy after surgery can be as high as 50%. Recurrence has nothing to do with the surgical method and primary site, so the choice of surgery should be careful. After surgery for vascular lesions, aneurysms can also form again at the postoperative anastomosis, so surgery is generally not recommended, and interventional therapy can reduce the complications of surgery. Eye blindness with persistent pain can be removed surgically. After surgery, immunosuppressive therapy should be continued to reduce recurrence. The disease is generally chronic and easy to treat. Remissions and relapses can last for weeks or years, or even decades. Blindness, vena cava obstruction and paralysis can occur during the course of the disease. The disease is occasionally fatal due to involvement of the central nervous system, cardiovascular system, and gastrointestinal tract.