Behcet's disease
Introduction
Introduction to Behcet Behcet's disease (BD) is a systemic, chronic, vascular inflammatory disease. The main clinical manifestations are recurrent oral ulcers, genital ulcers, ophthalmia and skin damage. It can also involve blood vessels, nervous system, and digestion. Most of the patients with tract, joint, lung, kidney, epididymis and other organs have a good prognosis. The prognosis of the eyes, central nervous system and large blood vessels is poor, which is good for male young adults. The disease is divided into vascular type, neurological type, gastrointestinal type, etc. according to the systemic damage of its internal organs. Vascular type refers to large and medium-sized arteries, and those with venous involvement; neurological refers to those with central or peripheral nerve involvement; gastrointestinal type refers to gastrointestinal ulcers, hemorrhage, perforation, etc. Behcet disease (Behcet disease, Behcet disease), also known as Behcetsyndrome, or eye-mouth-genital, or Behce syndrome, is the same as Chinese medicine. It was reported in 1937 by the Turkish dermatologist Behcet. Behcet's disease not only invades the eyes, mouth and genitals, but also causes vascular inflammatory diseases involving multiple systems throughout the body, except that the time of occurrence of various system and organ lesions is different. Some patients have lesions of 1-2 kinds of organs first, and later there are lesions of other organs, which makes it difficult to diagnose. basic knowledge The proportion of sickness: 0.2% Susceptible people: good for men and young adults Mode of infection: non-infectious Complications: erythema, headache
Cause
Cause of Behcet's disease
Infection (30%):
1. Virus: Early detection of the virus as its cause, after epidemiology, tissue culture, serology, animal inoculation, immunofluorescence and electron microscopy, etc. have not been further confirmed, the dyeing report believes that the disease may be associated with lentivirus infection Caused by autoimmune abnormalities; some reports have found evidence of the relationship between HSV-1 and the disease, such as evidence of the relationship between anti-HSV-1 and the disease in the patient's blood, such as the patient's blood anti-HSV-1 antibody titer High HSV-1 affects CD4 lymphocytes and causes immune abnormalities, and HSV-1 has DNA homologous to peripheral blood lymphocytes of the disease.
2. Streptococcus: Because some patients often develop tonsillitis, pharyngitis and periodontitis, it is believed that the disease is related to the bacteria in these lesions. The study found that the anti-streptococcus antibody titer in the patient's serum increased; from the patient's mouth Among the isolated strains, streptococcus is the most closely related, and especially S. sanguinis, the intradermal test and macrophage migration inhibition test can obtain positive results; streptococcus 65 The -KDa heat shock protein test can cause skin hypersensitivity and systemic symptoms. These studies were mainly conducted by Japanese scholars. Although they are considered to have an important role in the pathogenesis, no consistent conclusions have been reached.
3. Tuberculosis: Since 1964, there have been reports of cases related to tuberculosis infection in China, that is, tuberculosis, such as tuberculosis, lymphatic tuberculosis, etc., can be old after the initial damage of Behct disease. Sexual lesions, but active lesions, most of the OT trials are strongly positive; anti-tuberculosis drug treatment, not only has a significant effect on the primary lesions to improve the damage caused by Behcet's disease, it is considered to be an allergic manifestation of tuberculosis, tuberculosis The 65-KDa heat shock protein of bacteria is also involved in the occurrence of this disease.
Trace elements (30%):
A few reports have found that patients with pathological tissues such as vascular endothelial cells, macrophages, sural nerves and aqueous humor, serum and neutrophils have increased levels of various trace elements, and more are organic chlorine, organic phosphorus and copper ions. The latter is the highest, which may be caused by occupational or environmental factors.
Genetic factors (20%):
The disease has a regional morbidity, such as more common in the Mediterranean coastal countries; there are bloody familial cases, can be seen in 2, 3 or 4 generations, and the incidence is more male, HLA-B5 (+) is immune hereditary The positive rate of the marker is 67%-88%, indicating that the pathogenesis is related to HLA-B5, but also related to HLA-D, especially HLA-DR. The susceptibility gene of Behcet disease is located on the 6-arm of chromosome, in HLA. Between -B and TNF-beta sites, this may provide direction for future research on gene therapy. Behcet's disease has no genetic pattern and may be recessively inherited by the system.
Immune abnormality (10%):
Anti-oral mucosal antibodies and anti-arterial wall antibodies are present in the serum of the patients; in addition, there are complexes in the serum, which are up to 60% positive and are related to the disease activity; in addition to IgG, IgT and IgM are slightly elevated, sometimes IgE Elevation; DIF examination revealed IgG, IgA, CIC and C3 in the vessel wall, especially in the venule wall. In vitro, the lymphocyte transformation test values of these patients were generally low, and the DNCB skin test was mostly negative, T-cell and TH cell values are reduced; infiltrating cells in nodular erythema-like lesions are mainly T cells, especially TH and NK cells, while infiltrating cells in the eye tissue are mainly CD4 lymphocytes and macrophages, few B cells and NK cells, these CD4 lymphocytes and macrophages are HLA-DR (+), the above facts indicate that the disease has humoral immunity and cellular immunity often, but generally tend to believe that cellular immune abnormalities are more closely related to the disease.
Sex hormones (5%):
Sex hormones such as testosterone, progesterone, estradiol, luteinizing hormone, follicle stimulating hormone and pituitary prolactin were measured in 21 male and preovulatory females. Statistical analysis of male testosterone and female progesterone values compared with the control group Low, the p value was <0.01 and 0.05, the rest were in the normal range; 14 cases of preovulatory women with PGF-2d were measured, the average value was about 2 times lower than the control group (p<0.001).
Other (5%):
Although the etiology of this disease is not clear, the pathogenesis is related to immune abnormalities. During the process of immune regulation and inflammation, changes in cellular components and various active substances produced, such as plasmin inhibitors, can dissolve plasmin. Fibrin activity is reduced, and fibrinogen content is increased; and neutrophil chemotaxis is enhanced; tumor necrosis factor (TNF-beta), IL-2 and IL-6 are produced, which are in the development of lesions. May also have a role.
Prevention
Behcet prevention
Pay attention to the combination of work and rest, maintain good mood; pay attention to cleanliness, prevent various infections; strengthen nutrition, improve the body's ability to resist disease, can alleviate the disease and reduce recurrence.
Diet should be light and nutritious and easy to digest, eat less greasy frying and spicy food. Quit smoking, drink less and drink coffee. Smoking is the most vulnerable to damage to the respiratory surface barrier and induces disease onset. Tobacco, alcohol and coffee all stimulate nervous excitement. Some people want to eliminate tension and fatigue, but actually weaken the body's disease resistance and easily lead to disease. Therefore, strengthening physical fitness and maintaining hygiene are the key.
Complication
Behcet's disease complications Complications
Common complications of this disease:
1. Skin complications, almost all patients have skin nodular erythema, folliculitis, rash or pustular rash, but also non-specific allergic reactions of the skin: if sterile needles are used to penetrate the sterile skin, 24 to 28 hours The internal manifestations are nodules, induration, papules or small pustules.
2. Allergic small vasculitis of the cardiovascular system, superior vena cava syndrome, endarteritis, aortic regurgitation, peripheral aneurysm, etc.
3. Brain stem syndrome of the nervous system, recurrent paroxysmal headache, etc.
4. Gastrointestinal mucosal ulcer, perforation, proliferation, etc. of the gastrointestinal system; hyperthermia-like manifestations.
5. Rheumatoid-like pain in the joints of the extremities.
6. Large hemoptysis of the respiratory system, pulmonary vasculitis, etc.
Symptom
Symptoms of Behcet's disease Common symptoms Acne-like rash conduction block congestion hyperthermia joint pain traumatic intestinal paralysis
The whole system is involved, and the more common ones are the oral cavity, the skin, the genitals and the eyes, the central nervous system, the blood vessels and the digestive tract are all serious, and the male incidence is high. Japanese scholars report the incidence of various organ system damage. They were: oral ulcer 100%, rash 90%, external genital ulcer 97%, eye damage 79%, eye damage more men than women, the incidence rate was 90% and 40%, respectively, other system damage is the central nervous system 28%, digestive system 20%, cardiovascular system 15%, joint 15%, Huang Zhengji and other analysis of the incidence of clinical manifestations of Behcet's disease in China: 99% of oral ulcers, 43.2% of ocular lesions, 73.6 of external genital lesions %, skin lesions 96.8%, nervous system 26%, large blood vessels 8.7%, digestive tract 8.4%, arthritis 60.9%.
A small number of patients are acutely ill, and can be damaged at the same time in two or more parts within 5 days to 3 months. The condition is severe, often accompanied by high fever. After a certain period of remission, chronic recurrent episodes can occur. The time is 1 to 2 months, most of which are chronic diseases. The damage occurs in one part. After repeated episodes and remissions in different periods, the disease occurs in other parts. The latter is mainly local damage, and the systemic symptoms are less, but It can be acutely aggravated during the course of the disease.
Whether it is acute or acute exacerbation in a chronic course, the main systemic symptoms are high fever, headache, fatigue, loss of appetite, joint pain or swelling, etc., heat type is uncertain, a few cases can continue to be hot, excessive fatigue, poor sleep Menstruation, seasonal climate changes, etc., can make the damage of different parts worse, a small number of patients have a family history, no contact infection cases.
1. Basic symptoms: refers to the most common and often the first symptoms in this disease. They can appear in succession or at the same time for several years. Most of the onset is hidden, and a few onset are accompanied by fever. , fatigue and other systemic symptoms.
(1) recurrent oral ulceration (recurrent oral ulceration): at least 3 episodes per year, more than one painful red nodules appear in the buccal mucosa, lips, lips, soft palate, etc., followed by ulceration, the diameter of the ulcer is generally 2 ~ 3mm, some with herpes onset, about 7 to 14 days after the self subsided, leaving no scars, there are several weeks of unhealed scars, ulcers one after another, this symptom is seen in 98% of patients, and this is The first symptom of a disease, which is considered to be the most basic and necessary symptom for the diagnosis of this disease.
(2) recurrent genital ulceration (recurrent genital ulceration): basically similar to the symptoms of oral ulcers, but the number of occurrences is small, the number is also small, the common site is the female patient's large, labia minora, followed by the vagina; male scrotum And the penis can also appear around the perineum or anus, about 80% of this symptom.
(3) Skin lesions: Skin mucosal damage is a major symptom of this disease, accounting for 95.7%, and the following four types of skin damage:
1 nodular erythema: it is the most common type of skin damage, mainly in the lower limbs, especially the lower leg, sometimes in the upper limbs and trunk, more common in the extension of the side, the subcutaneous nodules are generally broad beans to walnuts, shallow Different, there are pain and tenderness, the skin color is reddish, dark red or purple, the texture is hard, ranging from a few to dozens, irregular distribution, about 1 month can be self-resolving, but easy to relapse, or For one side to fade, one side is new, most of which are heavier in summer, rarely ruptured, and some of the nodular red range can exceed the nodule area. The more outward the color, the lighter it seems to have a blush.
2 thrombophlebitis: mainly occurs in the lower limbs, sometimes also in the upper limbs, for the hard subcutaneous ropes of the touch, there is local tenderness, if it occurs in the deep subcutaneous, the physical examination only has subcutaneous sling; if it occurs in Subcutaneous superficial veins may have different degrees of redness on the skin surface and high skin wounds. Superficial thrombophlebitis may also be secondary to intravenous drug injection.
3 folliculitis-like and sputum-like lesions: more men than women, folliculitis-like damage more than sputum-like damage, the lesion can occur in any part of the body surface, more common in the head, face, chest and genitals, how much skin lesions Different, it can be repeated, with summer as the weight, the basal infiltration of these lesions is more significant, the top pustules are less, the surrounding redness is larger, accompanied by different degrees of induration, bacterial culture is negative, antibiotic treatment is invalid.
4 acupuncture reaction: injection (muscle, vein), acupuncture and other stab wound skin dermis, after 24 to 48 hours, can produce reddish papules in the acupuncture site, the center has pustules, and later gradually scarred, this reaction is called For the acupuncture reaction, it subsided in about 1 week, and the disease activity period was mostly positive. It has specific diagnostic significance, and sometimes the acupuncture reaction is negative. At this time, it is injected with normal saline, and pustules can be present in the acupuncture site after 24 hours. It must be emphasized that Behcet's disease cannot be ruled out even if the acupuncture reaction is negative.
Examine
Behcet's examination
[Laboratory Inspection]
1. Skin irritation test: 0.1ml of normal saline was injected into the forearm and the red induration or small pustules with diameter greater than 2mm appeared in 48h. The small papules were positive, suggesting that the chemotaxis of neutrophils was enhanced, and the positive rate was about 40%.
2. C-reactive protein (CRP) determination: CRP increased before and after the onset of ocular inflammation, especially before the onset of the attack; CRP increased with neutrophil count increased, 1 week of eye disease The positive rate is 86.1%, so it is considered that the determination of CRP has a certain value for predicting the onset of ocular inflammation.
3. Erythrocyte sedimentation rate and white blood cell classification: When the disease occurs, the erythrocyte sedimentation rate is significantly accelerated, and the neutrophil ratio is also significantly increased.
4. Pathological examination: The basic pathological changes of all affected organs are vasculitis, most of which are exudative, a few are proliferative, or both. Acute exudative lesions manifest as luminal congestion and thrombosis. Fibrin-like degeneration of the wall and its surrounding tissue, and neutrophil infiltration and red blood cell spillover, neutrophil nucleus often breaks into nuclear dust, obvious edema, cellulose exudation, abscess formation, proliferative pathology There are no exceptions.
5. Serum fibrinolysis system and immunogenetics (small arm of chromosome 6) can be examined if necessary or necessary.
[Other inspections]
1. X-ray examination: digestive tract barium meal examination, patients with a course of less than 7 years, often with stomach, duodenal bulb and small intestine ulcer, ulcer perforation may occur in some cases, the small intestine may have different degrees of functional changes, It can be seen that the intestinal lumen is widened, the small intestine mucosa is thickened, and there is a segmentation phenomenon. Sometimes the jejunal intestinal wall is straight and sausage-like.
Patients with advanced disease over 10 years may have a wide polypoid filling defect in the stomach, small intestine and colon, which is obvious in the small intestine and colon, and may have proliferative unequal knots in the ileocecal and ascending colon. Nodular filling defects, mucosal folds disorder, pathological diagnosis of ulcerative gyrus, colitis.
Pulmonary manifestations are less common. If pulmonary vascular infarction or hemorrhage, it is often seen in the lung field or the hilar area with similar pneumonia. The density of lung metastases is increased by round or elliptical shadows, and the heart shadow can be enlarged. There is mild ventricular enlargement, and arachnoid adhesions can be found in myelography.
Angiography can detect segmental stenosis changes in different parts of the renal artery, mesenteric artery, and cerebral arteries.
2. Electrocardiogram: Some patients may have ST segment and T wave changes, most of which have sinus tachycardia.
3. EEG: When the nervous system is involved, most of them show diffuse slow waves, but there are also many waveform changes without characteristic waveforms. Those with brainstem symptoms may have diffuse slow waves and no brainstem symptoms. Mild to moderate slow waves can occur.
4. Acupuncture reaction: This is the only specific test with strong specificity in this disease. It is practiced by using a sterile intradermal needle to penetrate the skin in the middle of the flexion of the forearm and then withdrawing. After 48 hours, observe the needle penetration. The skin reaction, if there is red papules or red papules with white herpes, it is regarded as a positive result. At the same time, some cases of positive acupuncture test, but some are negative, the patient is receiving vein When the puncture is checked or the intramuscular injection is treated, acupuncture positive reaction often occurs, and the positive rate of venipuncture is higher than that of intradermal puncture. The positive reaction of acupuncture has no obvious relationship with the site of disease involvement, but it is positively correlated with the activity of the disease. The positive result of acupuncture test appears in more than 60% of BD patients in China, while the positive rate in the Mediterranean coastal countries is 80%. In Europe and the United States, the positive rate of this test is low, and the false positive of this test is less, and its specificity is 90%.
5. Other related examinations: relevant examinations of the affected system according to the clinical manifestations of the patients, including imaging such as magnetic resonance, angiography, ultrasound cardiovascular examination, endoscopy, cerebrospinal fluid, etc.
Diagnosis
Diabetes diagnosis and identification
diagnosis
1, clinical manifestations
During the course of the disease, recurrent oral ulcers, ophthalmia, genital ulcers, and characteristic skin lesions observed and recorded by doctors, and large blood vessel or nervous system damage are highly suggestive for the diagnosis of Behcet's disease.
2, laboratory inspection
There is no specific laboratory abnormality in this disease. The active phase may have increased erythrocyte sedimentation rate and C-reactive protein. Some patients have positive cold globulin and platelet aggregation function. The positive rate of HLA-B51 is 57%~88%, with eye and digestion. Pathological changes.
3. Acupuncture reaction test (Pathergy test)
Using a 20-gauge sterile needle in the middle of the forearm flexion, slanting about 0.5cm and slightly twirling in the longitudinal direction and exiting. After 24 to 48 hours, a small folliculitis-like red dot or pustule-like lesion with a diameter of >2 mm appeared locally. Positive, this test is highly specific and related to disease activity, the positive rate is about 60% to 78%, and similar lesions appear after venipuncture or skin trauma are of equal value.
4, special inspection
Neurobehavioral disease often has increased cerebrospinal fluid pressure and a slight increase in white blood cell count. Brain CT and magnetic resonance imaging (MRI) have certain help on brain, brain stem and spinal cord lesions. The sensitivity of acute MRI examination is as high as 96.5%. Found in the brain stem, paraventricular white matter and basal ganglia increased signal, chronic phase MRI should be distinguished from multiple sclerosis, MRI can be used for the diagnosis and treatment of neurobehide disease follow-up observation.
Gastrointestinal barium angiography and endoscopy, angiography, color Doppler can help diagnose the location and extent of the lesion.
Pulmonary X-ray films can be characterized by diffuse exudation or round nodular shadows of different sizes on one or both sides. In pulmonary infarction, there can be a blurred image of increased density around the hilum, high-resolution CT or pulmonary vessels. Contrast, isotope lung ventilation / perfusion scan, etc. are helpful for the diagnosis of lung lesions.
5, diagnostic criteria
The disease has no specific serological and pathological features. The diagnosis is mainly based on clinical symptoms. Therefore, detailed medical history collection and typical clinical manifestations should be paid attention to. At present, the diagnostic criteria established by the International Behcet's disease research group in 1989 are used.
Behcet's International Diagnostic Standard
1. Repeated oral ulcers have been observed by doctors or patients complained of aphthous ulcers or scars, repeated attacks within 3 years 3 times.
2. Repeated genital ulcers have been observed by doctors or patients complained of genital aphthous ulcers, especially men.
3. Before and/or after uveitis of the eye lesion, there is cell infiltration or retinal vasculitis in the vitreous when the slit lamp is examined.
4. Skin lesions nodules erythematous lesions, pseudo folliculitis, purulent papules, acne-like rash (not taking glucocorticoids).
5. The acupuncture reaction was positive with a 20-gauge sterile needle, obliquely inserted into the skin, and the result was determined by a doctor 24 to 48 hours.
Anyone with repeated oral ulcers accompanied by 2 of the remaining 4 items can be diagnosed as this disease.
Other symptoms that are closely related to the disease and are conducive to the diagnosis of this disease are: joint pain (arthritis), subcutaneous embolic phlebitis, deep vein thrombosis, arterial embolism and/or aneurysm, central neuropathy, digestive ulcer, Epididymitis and family history (Table 3).
Although oral ulcers are not specific in nature, they occur in 98% of BD, and when it is combined with vulvar ulcers, eye lesions, and skin lesions, the specificity is greatly improved, so it is considered to be one of the basic symptoms of BD. When two symptoms are present in the three main symptoms of oral ulcer, external genital ulcer and eye damage, Behcet's disease can be diagnosed on the premise of excluding other related diseases.
Differential diagnosis
In the clinic, the disease should be differentiated from simple oral ulcers, reiter syndrome, ankylosing spondylitis, and inflammatory bowel disease.
1. Simple recurrent oral ulcer is the most common type of ulcerative damage of the oral mucosa with recurrent characteristics. It occurs mostly in young adults, and the mucous membranes of the lips, cheeks, tongue, and tongue are prone to occur. Initially, the oral mucosa is congested. (redness), edema (slightly bulging), the red spot of the size of the millet grain, quickly ruptured into a round or oval ulcer, the center is slightly concave, the surface is grayish yellow, surrounded by a narrow blush, spontaneous Severe burning pain, intensified pain, affecting patients' speech and eating, generally no obvious systemic symptoms, and Behcet's disease is a systemic disease, not only oral ulcers, but also eye lesions, perineal ulcers and acupuncture reactions Wait.
2. Although Rett syndrome may have oral ulcers, balanitis and conjunctivitis, it is easy to be confused with Behcet's disease, but the former has no acupuncture reaction and phlebitis.
3. The basic lesion of ankylosing spondylitis is adhesion point inflammation, often HLA-B27 positive, severe or advanced spine rigidity, the spine joints are bamboo-like changes, can be distinguished from Behcet's disease.
4. Crohn's disease may have oral ulcers, mainly manifested as segmental ulcers or hyperplasia of the digestive tract, paving pebbles-like changes in the intestines; ulcerative colitis is characterized by lower gastrointestinal ulcers, mainly sigmoid colon lesions, From the bottom up to the ileum, some people call it "reverse ileitis", patients with inflammatory bowel disease have more severe diarrhea, stool is pus blood, and X-ray or fiber colonoscopy can assist diagnosis, and with Identification of Behcet's disease.
5. Systemic lupus erythematosus can have ocular lesions, oral ulcers and nerves, cardiovascular system lesions, but its condition is progressively aggravated, not periodic episodes, and LE cells, anti-nuclear antibodies are positive, these abnormal findings are never seen Behcet's disease.
6. Wegener's granuloma has ocular lesions and multiple systemic damage, but its condition is progressively deteriorated. X-ray examination of the lungs shows a variety of infiltrates, sometimes with cavities, and histopathological features are granulomatous. Vasculitis, and severe renal damage, no genital ulcers, negative acupuncture test, easy to distinguish with Behcet's disease.
7. Tuberculous arthritis is sometimes accompanied by nodular erythema, but no eye damage and genital ulcers, generally no cardiovascular and nervous system damage, anti-tuberculosis treatment is effective, although tuberculosis infection can cause Behcet's disease, anti-spasm treatment Effective, but the Behcet's disease caused by Mycobacterium tuberculosis not only has nodular erythema and arthritis, but also vascular system, nervous system and mucosal changes, the identification of the two is not difficult.
8. Multiple arteritis When Behcet's disease is characterized by vascular lesions, it should be distinguished from multiple arteritis. The latter is mainly characterized by no pulse in the upper or lower limbs, no oral cavity, genital ulcer, and histopathological changes. Giant cell arteritis, no venous changes, negative acupuncture reactions, few skin lesions.
