Crohn's disease

　　1. Etiology

　　The etiology of this disease is not yet clear, and there are theories such as virus, bacteria, allergic reaction, autoimmune, and social environmental factors. From the immunological perspective, patients with this disease show an enlarged thymus in mediastinal air contrast, and pathological histology finds that the percentage of thymic lymphoid follicles is as high as 71%. In peripheral blood, the wandering function of neutrophils is hyperactive, the activity of lysosomal enzymes in neutrophils is hyperactive, immune complexes appear, and there is a lack of suppressive T cells.

　　2. Pathogenesis

　　For inflammatory bowel diseases including Behcet's disease, using luminol to stimulate peripheral blood neutrophils with PMA, and studying the chemiluminescence of the photons emitted during the associated phagocytic action, the results show that the activity is significantly increased in Behcet's disease patients. At this time, due to the generation of reactive oxygen species, tissue damage occurs in tissues including vascular endothelial cells.

　　Pathologically, Behcet's disease intestinal ulcers are classified into necrotic type, granulomatous type, and mixed type. The necrotic type is an acute or subacute lesion, the granulomatous type is a chronic lesion, and the mixed type is between the two. Under the microscope, there is edema of the intestinal mucosa, dilatation of the intestinal lymphatics in the lamina propria and submucosal tissue. The vascular lesions of the intestine are accompanied by vascular inflammatory changes due to ulcers, mainly manifested as intimal thickening. The vascular lesions are particularly obvious in the submucosal tissue vessels, especially veins. These vascular lesions are unrelated to the size of the ulcers and are affected by the passage of time. The vascular lesions in the acute phase ulcers (necrotic type) are less severe than those in the chronic phase ulcers (granulomatous type). The deeper the ulcers, the more obvious the vascular lesions. The intestinal mucosa without ulcers often does not show significant vascular inflammatory changes. These vascular lesions are basically not much different from those in pulmonary tuberculosis, Crohn's disease, and ulcerative colitis.

　　Severe cases may present with intestinal bleeding, intestinal paralysis, intestinal perforation, and fistulas. The inflammation involves the muscular layer and intermuscular nerves, leading to reduced tension of the intestinal wall, weakened peristalsis, intestinal gas accumulation, content stasis, and marked expansion of the intestinal wall, thus causing peritonitis. The release of bacterial metabolites and toxins leads to systemic toxic symptoms, including massive gastrointestinal bleeding, colon perforation, colon stricture, perianal abscess, and others.

　　The main clinical symptoms include: recurrent ulcerative lesions on the oral mucosa; nodular erythema-like skin rash, subcutaneous thrombophlebitis, follicular dermatitis-like rash, positive needle test, and other skin symptoms; recurrent anterior chamber inflammation of the eye, retinitis, chorioretinitis; vulvar ulcers; in addition, it often complicates arthritis, epididymitis, and symptoms of the digestive tract, cardiovascular system, central nervous system, respiratory system, and urinary system as the secondary symptoms of the disease. The presence of all four main symptoms during the course of the disease indicates a complete type of the disease, while the presence of three main symptoms, or two main symptoms plus two secondary symptoms, or the presence of eye symptoms plus one other main symptom indicates an incomplete type of the disease. It is divided into vascular type, neural type, gastrointestinal type, etc., depending on the damage to the visceral system.

　　I. Main symptom manifestation

　　1. Recurrent aphthous ulcer:The disease attacks several times a year, during which multiple painful red nodules appear on the buccal mucosa, tongue edges, lips, soft palate, etc., followed by the formation of ulcers, with a diameter of generally 2-3mm. Some cases start with herpes, which spontaneously resolves within 7-14 days without leaving a trace. A few cases may last for several weeks without healing, leaving scars. The ulcers come and go, this symptom is almost seen in all patients and is the initial symptom of the disease, and it is considered an essential symptom for diagnosing the disease.

　　2. Skin lesions:The incidence of skin lesions is high, ranging from 80% to 98%, with diverse manifestations, including nodular erythema, vesicles, papules, acneiform eruptions, erythema multiforme, annular erythema, necrotic tuberculosis-like lesions, bullous necrotizing vasculitis, and impetigo. Patients may have one or more types of skin lesions, and particularly valuable skin signs for diagnosis are nodular erythema-like lesions and inflammatory reactions after minor trauma (such as needle sticks).

　　3. Ophthalmopathy:The most common ocular lesions are uveitis or chorioretinitis, and retinitis caused by vasculitis can also occur. The recurrence of these conditions can lead to severe visual impairment or even blindness, with more male patients having ocular inflammation than female patients.

　　4. Recurrent vulvar ulcers:The characteristics of oral ulcers are similar, but they occur less frequently and in fewer numbers. Common sites in female patients include the large and small labia, followed by the vagina. In male patients, the scrotum and penis can also be affected, as well as the perineum or around the anus. Approximately 75% of patients have this symptom, with deep and large ulcers, severe pain, and slow healing.

　　Characteristics of gastrointestinal lesions

　　Patients with Behcet's disease presenting with digestive system symptoms account for 21.5% to 60%, and patients with gastrointestinal lesions commonly develop symptoms between the ages of 20 to 50, with a male-to-female ratio of 1.4:1. More than half of the cases are incomplete, with the main symptoms being right lower quadrant pain, abdominal mass, abdominal distension, belching, vomiting, diarrhea, hematochezia, and other symptoms. Severe cases may present with intestinal hemorrhage, intestinal paralysis, intestinal perforation, fistula formation, and other complications. Ulcers in this disease can be found in the entire gastrointestinal tract from the esophagus to the large intestine. Pu Shan's analysis of 719 patients with Behcet's disease showed that 13 cases (1.8%) had gastric and duodenal ulcers, 18 cases (2.5%) had multiple ulcers at the distal ileum, 5 cases (0.7%) had hematochezia, totaling 36 cases (5%). Wang Hongjin analyzed 89 cases of Behcet's disease, with 28 cases (31.5%) affected by the digestive system, including 28 cases (31.5%) with oral ulcers, 3 cases (3.4%) with esophageal ulcers, 1 case (1.1%) with gastric ulcers, 1 case (1.1%) with duodenal ulcers, 4 cases (4.5%) with ileocecal ulcers, 2 cases (2.2%) with transverse colon ulcers, 3 cases (3.4%) with rectal ulcers, and 7 cases (7.9%) with anal ulcers. Ma et al. analyzed 131 cases of Behcet's disease with surgical intestinal lesions, with 105 cases (80.2%) having lesions at the distal ileum and cecum, proposing that this site is a common site of occurrence. Takano reported on 66 patients with surgical Behcet's disease, with 36.4% having lesions in the small intestine, 45.6% in the small and large intestine, 16.6% in the colon, 1.5% in the stomach and duodenum. The majority of these surgical cases were due to massive hematochezia or presented as acute abdomen, perforation, intestinal obstruction, or emergency surgery performed as appendicitis. Forty percent of the surgical cases had intestinal ulcer perforation, recurrence after surgery, fistula formation at the anastomosis, and wound dehiscence requiring reoperation, accounting for 33.9% of the cases. The course of the disease often alternates between remission and recurrence, with a persistent course.

　　3. Other

　　Systemic symptoms such as arthritis are common, with a few cases showing joint swelling, mainly involving the knees. Some patients may experience fever during the active phase of the disease, usually low-grade fever, occasionally high fever, and symptoms such as fatigue, myalgia, dizziness, etc. Some patients may develop visceral lesions due to local vasculitis. When large arteries are involved, they may appear stenosis or aneurysm formation. Pulmonary involvement may manifest as hemoptysis, shortness of breath, pulmonary embolism, and other symptoms. The nervous system may present with meningitis, brainstem damage, benign intracranial hypertension, spinal cord damage, and peripheral nerve lesions.

　　Since the incidence of oral mucosal ulcers in Behcet's disease is the highest (over 95%), people have long speculated that gastrointestinal mucosa may also show ulcers. The earliest literature reports on the complications of Behcet's disease with digestive system lesions were in 1940, and in 1958, Behcet proposed the gastrointestinal Behcet's syndrome through systematic observation and research on the digestive tract of Behcet's disease.

　　Behcet's disease does not have a specific serological examination, and there may be a slight increase in globulin levels, mild erythrocyte sedimentation rate (ESR) acceleration, about 40% increase in anti-PPD antibodies, and a positive HLA-B51 antigen.

　　1. The needle reaction is the only test with relatively strong specificity for the disease at present. After 24 to 48 hours of intravenous puncture, intramuscular injection, or intradermal injection, the patient will show pustules or folliculitis at the needle puncture site, with a surrounding erythema, known as a positive needle reaction.

　　2. The intestinal ulcers of Behcet's disease are most commonly found in the ileocecal region, and colonoscopy is the most meaningful examination. Ulcers usually occur on the opposite side of the mesentery, appearing as small, deep, circular ulcers with a tendency for multiple occurrences and perforation. Careful observation shows that enteroscopy is helpful in detecting small intestinal ulcers. The appearance and morphology of small intestinal ulcers and large intestinal ulcers are different. Small intestinal ulcers are small and deep, often multiple, with mucosa concentrating around the ulcers. The peripheral elevation of the ulcers is not prominent, and the ulcers are acute, clearly outlined circular excised ulcers without a white coating at the base. Most of them are less than 2 cm in diameter, and some can be as large as 2 to 3 cm in diameter; endoscopy can see the mucosa concentrating around the center of the opposite ulcers, with a marked elevation around the ulcer margin, forming a collar-like shape. The ulcers appear irregularly sunken, resembling the morphology of Borrmann 2 or Borrmann 3 cancer. It is difficult to distinguish from simple ileocecal ulcers solely based on the morphology of the ulcers.

　　3. X-ray examination often reveals mucosal ulceration shadows concentrated at the ileocecal junction, the mucosa of the affected intestinal tract may appear stenosis, and there may be increased tension in the small and large intestines.

　　Prognosis:This disease is a systemic disease, with remission and recurrence occurring repeatedly. It is important to well master the systemic inflammatory status such as peripheral blood leukocytes, erythrocyte sedimentation rate, C-reactive protein, and needle reaction. Most patients have a good prognosis. Recurrent intestinal ulcer bleeding, perforation, postoperative recurrence of intestinal ulcers, malabsorption, and concurrent infection have poor prognosis, with a mortality rate of about 10%.

      Western medical treatment for intestinal Behcet's disease

　　一、Drug therapy:

　　1. Aminosalicylic acid preparations:Sulfasalazine (SASP) is a commonly used drug for the treatment of this disease. Literature reports indicate that most patients can control symptoms with sulfasalazine (SASP). After oral administration, most of the drug reaches the colon and is decomposed by intestinal bacteria into mesalazine (5-aminosalicylic acid) and sulfapyridine. The former is the main active ingredient, which remains in the colon and contacts with the intestinal epithelium to exert anti-inflammatory effects. The mechanism of action may be to inhibit prostaglandin synthesis by affecting one or more steps of arachidonic acid metabolism, clearing oxygen free radicals to reduce inflammation, and inhibiting the immune response of immune cells. The dosage is 4g/d, taken in four divided doses; after symptoms are relieved for 3-4 weeks, the dosage can be gradually reduced, and then maintained at 2g/d in divided doses, for 3 months to 1 year. Side effects are of two types: one is dose-related side effects, such as nausea, vomiting, decreased appetite, headache, reversible male infertility, etc., taking the drug after meals can reduce gastrointestinal side effects. The other type of side effect is allergic, including rash, granulocytopenia, autoimmune hemolytic anemia, aplastic anemia, etc. Therefore, regular blood tests must be performed during medication, and other drugs should be used if such side effects occur. In recent years, special preparations of 5-ASA have been developed, such as sustained-release or controlled-release tablets made by encapsulating 5-ASA microparticles with high molecular material membranes, which can reach the distal ileum and colon to exert pharmacological effects. Such preparations are collectively referred to as mesalazine. These preparations release 5-ASA after being broken down by bacteria in the colon. The efficacy of the new 5-ASA preparations is similar to that of sulfasalazine, with significantly reduced side effects, but the high price is a drawback. They are suitable for those who cannot tolerate sulfasalazine.

　　2. Glucocorticoids:Corticosteroids are generally used when inflammation is obvious or when the efficacy of salicylate preparations is poor. The basic mechanism of action is non-specific anti-inflammatory and inhibits immune reactions. Generally, prednisolone (Prednisolone) is taken orally at a dose of 40-60mg/d during the acute phase, and the dose is gradually reduced to 10-15mg/d after the inflammation is controlled, and attention should be paid to not reducing the dose too quickly to prevent rebound. During the reduction period, salicylate preparations should be gradually substituted for hormone therapy. Long-term use can promote the deterioration of ocular symptoms in patients with ocular symptoms.

　　3. Immunosuppressants:Immunosuppressants are tried for chronic active cases with poor response to glucocorticoid therapy or dependence on glucocorticoids. After adding these drugs, the dose of glucocorticoids can be gradually reduced or even discontinued, and one of the following immunosuppressants can be chosen: cyclophosphamide (CTX) 50-100mg per day, azathioprine (AZP) 50-100mg, or mercaptopurine (6-MP) 30-50mg, and attention should be paid to their side effects when used.

　　4. Other drugs:When ocular symptoms appear, colchicine (colchicine) can be used at a dose of 0.5-1.0mg per day, and oral ulcers can be treated with hormone ointment. In addition, levamisole, transfer factor, and others can be tried, and the clinical evaluation is different.

　　2. Surgical treatment

　　In cases of intestinal perforation during surgical treatment, emergency surgery should be performed. Abdominal pain is obvious, palpable mass in the abdomen, and deep ulcers, as well as those who are ineffective with conservative medical treatment, also advocate for surgical resection. Due to the high recurrence rate after surgery, the criteria for indications should be handled with caution. The surgery is generally resection of the ileocecal region or right hemicolonic resection, and recurrence after surgery is mostly on the ileal side, so some people propose that the resection of the ileum should be sufficient.