Introduction to Crohn's disease

Introduction

Crohn's diseaseAlso known as "localized enteritis", "segmental enteritis", "chronic intestinal wall eutectic inflammation" and so on. Its characteristics are unclear, more common in young people, manifested as granulomatous inflammatory lesions, combined with fibrosis and ulcers. It can invade any part of the gastrointestinal tract, including the mouth and anus. The lesions are segmental or jumping, and can invade the outside of the intestines, especially the skin. The clinical manifestations vary according to the location, extent and extent of the lesion, which can be manifested as abdominal pain, diarrhea, abdominal mass, fistula formation and intestinal obstruction, accompanied by fever and anemia. The course of the disease is slow and easy to relapse.

Cause

(1) Causes of the disease

It has not been determined so far. Recent studies have tended to suggest that the disease may be the result of a combination of genetic susceptibility and a variety of exogenous factors.

Genetic susceptibility

(1) Genetic factors: A large amount of data indicates that Crohn's disease is related to genetic factors. The study found that the coincidence rate of Crohn's disease among twins with single egg development was significantly higher, at 67%, while the twins of twins had a coincidence ratio of only 8%. At the same time, it was found that patients with Crohn's disease showed inconsistency with their spouses and did not differ from the general population.

The above indicates that the disease has family aggregation. It has also been reported that the Jewish family has a high incidence of the disease in the Jewish family compared with non-Jewish people and finds mainly those of the Ash Kenazi race. The survey of Askenazi people scattered around the world has a higher incidence of Crohn's disease than those of non-Askens children living in the same area. Perhaps the Askenaz Jews represent humans. People with genetic susceptibility. It has also been reported that patients with Crohn's disease are more associated with HLA-DR4 type serum antigens. How genetic factors affect the occurrence of this disease is unclear. Some people think that genetics determine the body's immune response. The genetic factors of patients with inflammatory bowel disease determine that they have an excessive immune response to some antigenic substances in the intestinal lumen.

(2) Changes in susceptibility: At present, most scholars believe that the occurrence of Crohn's disease may be related to the abnormal immune response of the body to various antigens stimulated in the intestine. A growing body of evidence suggests increased T cell activation in the lamina propria of Crohn's disease, including increased expression of surface markers for T cell activation, increased production of T cell cytokines, and increased cytotoxic T cell function. This increase in T cell activation leads to aggregation of effector cells such as neutrophils. Subsequent synthesis of destructive substances (such as proteases and reactive oxygen metabolites) results in intestinal damage in Crohn's disease. The triggering mechanism of T cell activation is unclear.

In the past, there was some conviction that it was caused by chronic mycobacterial infection, but there is no reliable evidence. It is currently believed that it may not be singular and is more likely to be activated by a number of widely occurring triggering substances. The fundamental defect of Crohn's disease leads to the permanent activation of T cells, a defect that is currently being explored. It may be a foreign antigen, increased antigen delivery (increased intestinal permeability), and a genetically predisposed mucosal immune disorder. The result of a complex interaction.

Current research indicates that the view that this disease was once considered an autoimmune disorder is inaccurate. In fact, there is no credible evidence that there is an immune response directly associated with any autoantigen that can cause the inflammatory process observed in Crohn's disease.

2. Exogenous factors

(1) Infectious factors: In the early years, the pathological manifestations of Crohn's disease were similar to those of non-calcified tuberculosis. It was suspected that the disease was caused by Mycobacterium tuberculosis, but the pathogen was not isolated by various methods. In the late 1970s and early 1980s, there were reports of mycobacteria of Kansasii or mycobacteria similar to Mycobacterium tuberculosis in the intestinal segment and mesenteric lymph nodes excised from Crohn's disease.

Studies have found that these mycobacteria inoculated in the peritoneal cavity of mice can cause granuloma in the liver and spleen and develop acid-fast bacilli. These acid-fast bacilli are then administered orally to the dairy sheep, and non-caseal granuloma can occur at the end of the ileum of the sheep after several months. It is believed that mycobacteria may be the cause of Crohn's disease. However, some authors have observed that these mycobacteria are also present in some non-inflammatory bowel diseases or normal human intestinal tissues, and it has been reported that Streptococcus faecalis can cause local granuloma in the intestinal wall of rabbits, so these branches are not certain. Bacilli is the exact cause of the disease.

It has also been suspected that the cause of Crohn's disease is a virus. In 1970, Mitchell and Rees inoculated mesenteric lymph nodes and tissue homogenates from patients with Crohn's disease through a 220 nm filter screen and inoculated on the toes of rats. After 6-24 months, epithelioid cell granuloma and giant cell granuloma occurred on the toes of rats. In the same way, granuloma can occur in the ileum of rabbits. Immunosuppressive drugs have no effect on the pathogenesis, suggesting that there may be an infectious microorganism that may be a virus. However, the results of this experiment have not been repeated. It is also believed that Crohn's disease is associated with viral infections such as measles and influenza. However, the true virus particles have not been isolated from the intestinal tissue of Crohn's disease patients, so the cause of this disease cannot be confirmed as a virus.

(2) Environmental factors: The incidence of urban residents is higher than that of rural people. This difference also exists in Sweden, where rural health care is high, which may be related to social and economic status.

Some studies have shown that oral contraceptives increase the risk of inflammatory bowel disease. But other studies have failed to confirm.

Numerous studies have shown that smokers are at increased risk of Crohn's disease. And smoking can increase the likelihood of recurrence of Crohn's disease. The mechanism is still unclear.

Some potential environmental factors can trigger the development of Crohn's disease. The increase in edible refined sugar has been identified as a disadvantage. An ordinary period of birth can also be used as a stimulating factor to cause some pregnant women to develop Crohn's disease after childbirth.

(two) pathogenesis

1. Distribution of lesions The disease can be affected from any part of the gastrointestinal tract from the mouth to the anus. The lesions are leaping or segmental. Simultaneous involvement of the small intestine and colon is the most common, accounting for 40% to 60%; limited to 30% to 40% of the small intestine, mainly in the terminal ileum; lesions occurring in the anus or rectum alone are rare, accounting for 3%, mostly with the small intestine and Colonic lesions are present in combination; colons are less common, accounting for 5% to 20%. The stomach or duodenum, esophagus, and oral lesions account for about 10% or less.

2. The early pathological changes of the general pathology are small ulcers of the mouth ulcers, ranging in size. The smallest is the tip of the needle, accompanied by bleeding; the larger one is clearly shallow and the bottom is white. If a small lesion is missed during surgical resection, it can recur from there. Typical ulcers are longitudinal or limp, discontinuous, and vary in size.

Cobblestone-like changes are present in approximately 1/4 of the cases.

Thickening of the intestinal wall and intestinal stenosis are more common. About 95% of surgical cases have stenosis.

Some Crohn's disease can be seen with multiple inflammatory polyps.

3. Microscopically, the lesions under the microscope are found in the intestinal mucosa, submucosa and serosal layer, mainly the submucosa. Common lymphocyte aggregation can have a germinal center. The location of lymphocyte aggregation is closely related to blood vessels and dilated lymphatic vessels. Lymphocyte aggregation of the serosa layer can form a rosette-like pattern. Plasma cells, multinucleated cells, and eosinophils can also be seen. A mucosal layer can be seen in the sac abscess. Non-case granuloma is one of the important features of this disease. It consists of epithelioid cells and giant cells. There is no cheese necrosis in the center, which is uncommon. It is only found in about 50% of cases. It should be noted that granulomas can also be found in Yersinia infection or Chlamydia infection, which can be identified by an experienced pathologist.

Glassy and adenoid inclusions are seen in 5% of cases, as seen in sarcoidosis and tuberculosis. Granuloma is often very atypical and has a distinct boundary formed by lymphocytes. It can be seen in the whole layer of the intestinal wall, but the submucosa and serosal layer are most likely to appear. In addition to the intestinal wall, granulomas can also be found in local lymph nodes.

The fissure ulcer of the intestinal wall extends deep into the muscularis propria. Transmural penetration is the basis for the formation of internal fistulas and cutaneous fistulas and abscesses. The fracture under the naked eye is linear and may have branches, surrounded by edema and island-like mucosa. In the cross section, the fissure branches appear as intramural abscesses.

Due to edema and lymphatic vessel expansion and an increase in the number of collagen fibers, the submucosa is widened and the intestinal wall is thickened.

symptom

Clinical manifestation

Crohn's disease is insidious onset, often asymptomatic in the early stage, or mild in symptoms and easily overlooked. From symptomatic to confirmed diagnosis, it usually averages 1 to 3 years. The course of the disease is often chronic and recurrent. More common in young people, women are slightly more than men.

Common symptoms

(1) systemic performance: weight loss, increasing weight loss is the most common symptom. About one-third of patients have low or moderate fever, without chills. At this time, there are often active lesions or complications.

(2) Abdominal pain: the most common symptom, intermittent attack. Lighter only has bowel and abdominal discomfort, and severe cases can be severe colic. Eating foods containing more cellulose often causes episodes of abdominal pain. Colonic lesions often have diarrhea and abdominal pain, and abdominal pain can be relieved after defecation or deflation. Sudden abdominal pain can occur at the end of the ileum due to lesions, which is caused by lesions in the visceral or peritoneal nerve endings. When the lesion invades the stomach and duodenum, abdominal pain is similar to peptic ulcer, and often accompanied by pyloric and duodenal obstruction.

When the lesion invades the ileocecal area. Pain often occurs in the umbilical cord and is later confined to the lower right abdomen. Some cases have no obvious symptoms and sudden abdominal pain. Similar to acute appendicitis or intestinal perforation, it is the first symptom of this disease. Therefore, it is often misdiagnosed as acute appendicitis or intestinal perforation. Crohn's disease is only found when open. The lesion invades the jejunum and can be manifested as upper abdominal pain. When it develops into a granulomatous abscess and extensive mesenteric damage, it is often misdiagnosed as a bone or kidney lesion with back pain.

(3) Defecation changes: Most patients have diarrhea, mostly intermittent seizures, and the number of stools is related to the extent of the lesion. 2 to 3 times a day to 10 times, or even dozens of times. For soft stools or loose stools, no pus or mucus. A wide range of diffuse small bowel lesions can have watery stools or fat stools. The onset of diarrhea is often associated with eating foods rich in cellulose. Emotional or nervous can also induce diarrhea, but unlike mental diarrhea, nighttime can be awakened by a sense of defecation. Patients with distal colon involvement may have symptoms such as urgency, urgency, or constipation, and difficulty in defecation.

(4) Nausea and vomiting: When the lesion invades the stomach and the duodenum, jejunum, ileum, or forms part of intestinal obstruction caused by intestinal stenosis, symptoms such as nausea, vomiting, and abdominal pain occur.

(5) Nutritional deficiency: A wide range of intestinal lesions can cause a decrease in the absorption area, dysbacteriosis, resulting in diarrhea, anorexia, and reduced food intake, resulting in varying degrees of malnutrition. The extent of malnutrition is closely related to the extent and location of the lesion. It is characterized by anemia, hypoproteinemia, vitamin deficiency, electrolyte imbalance and so on. Due to calcium deficiency, osteoporosis is seen and the trunk is painful. Young and pre-pubertal patients may experience growth retardation due to malnutrition and delayed maturity. It can be improved after surgery.

(6) Relationship with pregnancy in women: Pregnancy can make the condition worse or worse. If the disease occurs during pregnancy, it will pose a threat to the fetus and mother, prone to stillbirth, miscarriage, premature delivery, fetal malformation.

(7) Extra-gastrointestinal manifestations: This disease may be associated with multiple arthritis. When the lesion is relieved or surgically removed, the joint symptoms disappear. The skin may have urticaria, erythema multiforme, nodular erythema, and the like. In addition, conjunctivitis, iridocyclitis, corneal ulcer, keratitis can occur. Fatty liver, amyloidosis, cirrhosis, primary sclerosing cholangitis, etc. can also occur.

(8) Anal and rectal lesions: abscess around the anus or around the rectum. Sinus and fistula are the more common manifestations of Crohn's disease. Crohn et al reported that the incidence of fistula was 14.2%, and it was reported that the incidence rate was 81%. Infections around the rectum and anus can develop into rectal abscesses, rectal vaginal fistulas. Extensive ulcers and granulomatous lesions can be found around the anus and on the buttocks. Individual patients with anal fistula are the first sign of the disease.

(9) Common signs: The parts of the lesions are different, and their signs are also different. The mass can be touched at the site of the lesion, and there is local tenderness. The lower right abdominal mass is more common, the shape is sausage-like, the boundary is unclear, and it is relatively fixed. Intestinal obstruction often has bloating, and the intestinal type and the dilated bowel can be seen. Ulcers, sinus or fistulas can be seen around the anus. In some cases, clubbing, liver palm, and nodular erythema (mostly occurring in front of the sputum). Occasionally hepatosplenomegaly.

2. Classification of disease activity Due to the large difference in the condition of the disease, the disease activity index is currently graded internationally using the disease activity index. The following two methods for calculating points are commonly used:

(1) The Crohn's disease activity index (CDAI), based on the eight variables of the disease, proposed by Best and Singbton, the Crohn's disease collaboration group, is calculated as:

1 number of loose stools (total number in 7 days) × 2.

2 abdominal pain (0 = no, 1 = light, 2 = medium, 3 = heavy), (total number of 7 days) × 5.

3 general health (0 = good, 1 = poor, 2 = poor, 3 = very poor, 4 = very poor), (total in 7 days) × 7.

4 The following conditions (1 point each): A. joint pain / arthritis; B. iritis / uveal (follicular) inflammation; C. nodular erythema / gangrenous pyoderma / aphthous ulcer; D Anal fissure / anal fistula / abscess; E. other fistula; F. body temperature > 38 ° C in the past 1 week. (sum of total points) × 20.

5 diarrhea to take fenofol (phenethyl piperidine) / opioids (0 = no, 1 = yes) × 30.

6 abdominal mass (0 = no, 2 = suspicious, 5 = positive) × 10.

7 hematocrit, male: (47-pressure) × 6 or female: (42-pressure) × 6.

8 body weight: a percentage below the standard body weight × 1. A CDAI of less than 150 is a stationary phase, a greater than 150 is an active phase, and a greater than 450 is extremely severe. This calculation is complicated.

(2) Watkinson and Truelove further explored the activity of inflammatory bowel disease in the name of the International Society of Gastroenterology, and proposed another method for calculating integration, according to their International Organization for the Study of IBD. The abbreviation is called the IIOBD method. The calculation method takes the sum of 10 variables, and each number is 1 point to calculate the activity index of the disease. 0 or less is the stationary period, and 1 or more is the active period. The 10 variables are as follows:

1 abdominal pain; 2 diarrhea ≥ 6 times / d or mucus stool; 3 perianal complications; 4 fistula; 5 other complications; 6 abdominal mass; 7 weight loss or weight loss; 8 body temperature > 38 ° C; 9 abdominal tenderness; Hemoglobin <100g / L. There is a statistically positive correlation between IOIBD and CDAI, the correlation coefficient is good, and the method is simple.

diagnosis

The clinical diagnosis of Crohn's disease is difficult, and the previous diagnosis is often after surgery.

1. Postoperative pathological diagnosis criteria must have 4 of the 5 characteristics under the microscope to confirm the diagnosis:

(1) Segmental all-wall inflammation.

(2) A fissure ulcer.

(3) The submucosal height is widened (caused by edema, lymphatic vessels, vasodilation, etc.).

(4) Lymphocyte aggregation.

(5) Sarcoidic granuloma (non-caseous epithelioid granuloma), and no intestinal necrosis of the intestinal wall and mesenteric lymph nodes.

2. Clinical diagnostic criteria are not yet uniform. Has a typical clinical manifestations, the following conditions should be considered in the small intestine Crohn disease: small intestine segmental chronic inflammation, X-ray barium angiography with typical Crohn's disease signs or pathological tissue (including biopsy or surgical materials) have granulomas, No cheese necrosis in the center.

Colonic Crohn's disease should be considered in the following cases: colonic segmental chronic inflammation, with Crohn's disease in the small intestine, typical Crohn's disease manifested by X-ray or colonoscopy, histopathology with granuloma, and no cheese necrosis at the center.

There are various suggestions for specific diagnostic criteria at home and abroad. The following two are recommended for reference.

(1) Peking Union Medical College Hospital proposes the following standards:

1 typical clinical symptoms.

2X line showed gastrointestinal fissure ulcer, pebbles, pseudopolyps, multiple stenosis, fistula formation and so on. The lesions are distributed in segments. CT can show thickened intestinal fistula, pelvic or abdominal abscess.

3 Longitudinal or sacral ulcers with a leaping pattern were seen under endoscopy. The surrounding mucosa was normal or hyperplasia with pebbles or lesion biopsy with non-caseous necrotizing granulomas or massive lymphocyte aggregation.

If both 1 and 2 or 3 are clinically diagnosed as Crohn's disease. When the differential diagnosis is difficult, surgical exploration should be performed to obtain a pathological diagnosis.

(2) Standards recommended by the Japanese Society of Digestive Diseases:

1 discontinuous regional lesions.

2 paving stone samples or longitudinal ulcers.

3 total wall inflammation.

4 non-caseous epithelioid granuloma.

5 cracked ulcers.

6 anal lesions.

Those with 123 are suspected, plus 4 or 5 or 6 can be diagnosed. Or have 4, plus any two of 123 for diagnosis.

Identification

Differential diagnosis of Crohn's disease.

1. Small bowel and ileocecal diseases

(1) Acute appendicitis: general diarrhea is rare, right lower quadrant pain is more serious, tenderness and muscle tension are more obvious. The onset is acute, the course of disease is short, there is fever, and white blood cells are increased. However, some cases are still difficult to identify accurately. When suspicious acute appendicitis is severe and persistent, a laparotomy should be performed to avoid more serious consequences of necrosis or perforation of the appendix. Abdominal CT scans help to distinguish between the two.

(2) Intestinal tuberculosis: It is not easy to identify with this disease, and the X-ray performance is also very similar. In other areas such as the lungs or reproductive system, there are tuberculosis lesions, mostly intestinal tuberculosis. Colonoscopy and biopsy can help identify, if you still can not identify, you can try anti-tuberculosis treatment. If the effect is not significant, it is often necessary to open the laparotomy and diagnose it by pathological examination. In pathological examination, caseous granuloma can be found in tuberculosis, while non-case granuloma is found in Crohn's disease.

(3) small intestinal lymphoma: diarrhea, abdominal pain, fever, weight loss, fatigue is more obvious, more likely to occur intestinal obstruction. Symptoms are mostly persistent and worse. Abdominal mass and Crohn's disease are clearer than the boundary, harder, and generally no tenderness. There may be superficial lymph nodes and hilar lymphadenopathy as well as obvious swelling of the liver and spleen. X-ray and enteroscopy can detect masses and ulcers in the intestine. Small bowel biopsy is helpful for diagnosis.

(4) Duodenal ampullary ulcer: Duodenal Crohn's disease is often similar to the symptoms and X-ray findings of peptic ulcer. However, the pain of Crohn's disease is not as regular as that of duodenal ulcer. Fiber endoscopy and biopsy are helpful for diagnosis. Antacid treatment is effective for peptic ulcers but not for Crohn's disease.

(5) Non-granulomatous ulcerative jejunal ileitis: abdominal pain and diarrhea are prominent manifestations of this disease. Weight loss, malabsorption and hypoproteinemia are more pronounced. The small bowel biopsy lesions were diffuse, the villi flattened and thickened, the basement membrane was infiltrated, and the mucosal ulcers.

2. Colon disease

(1) Ulcerative colitis

(2) ischemic colitis: caused by blood vessel blood supply disorders. More common in the elderly. The onset is more acute, with more abdominal pain first, followed by diarrhea and blood in the stool. The course of the disease is an acute process. Colonoscopy and barium enema are helpful for diagnosis.

(3) Nodules and rectal tuberculosis: rarer than ileocecal. Its characteristics are seen in the ileum and small intestine tuberculosis.

(4) Amoebic enteritis: Finding amoeba protozoa is helpful for diagnosis, but chronic amoebic enteritis is difficult to find amoeba. The hemagglutination test is reported to be a useful method for diagnosing amoebic enteritis.

(5) Colonic lymphoma: see small intestinal lymphoma. Diagnosis can generally be confirmed by colonoscopy and biopsy.

(6) Radiation colitis: consistent with the radiation site, the extent of the lesion is related to the amount of radiation.

complication

1. Intestinal obstruction is a relatively common complication of Crohn's disease, accounting for 66% of a group of cases in Beijing. The cause of intestinal obstruction is more common in the formation of fibrous stenosis, but also due to acute inflammatory edema. A few are caused by oppression of abscess or adhesion mass. Intestinal obstruction begins with incomplete obstruction and can be quickly relieved by conservative treatment. Can appear repeatedly, eventually complete intestinal obstruction.

2. The fistula forms a lesion that invades the muscular layer and the serosal layer. If further developed, adhesion to another small intestine, colon or adjacent visceral adhesion forms an internal hemorrhoid. If the fistula leads to the bladder or vagina, the contents of the intestine are discharged from the urethra and vagina. The fistula can be asymptomatic or massively diarrhea (depending on the amount of fluid in the digestive tract). The fistula can extend outward to the skin, called the external malleolus. It often occurs after the postoperative anastomosis, and may also occur in patients without surgery, often around the anus, occasionally in the groin or waist. The external hemorrhoids indicate extensive peri-intestinal inflammation and are often considered to be indications for surgical treatment. The incidence of fistula was reported to be around 40% in foreign countries, and the incidence of fistula in a group of cases in Beijing was 11.7%.

3. Abdominal abscess Abdominal fistula, such as secondary infection of the sinus, forms an abdominal abscess. The most common site is in the right lower abdomen corresponding to the terminal ileum, followed by the liver and spleen. The clinical manifestations are fever and abdominal pain, and there may be a mass with tenderness. With increased white blood cells. CT and B-ultrasound are helpful for diagnosis, and the pus culture is mostly Gram-negative bacteria.

4. Gastrointestinal bleeding Both upper and lower digestive tract can be bleeding. Blood in the stool caused by colonic lesions is more common. Occult chronic bleeding is more than visible bleeding. It has been reported that visible bleeding accounts for 17% to 25%, and severe blood loss can occur in a few cases. Often caused by iron deficiency anemia.

5. Intestinal perforation Intestinal perforation in Crohn's disease is less common because the serosal surface of the affected bowel often adheres to adjacent structures. In the case of group 1 in Beijing, intestinal perforation accounted for 10%.

6. The incidence of cancerous Crohn's disease is higher than that of normal people, and it is reported in Western countries as 1% to 3%. In patients with long-term activity, the risk of canceration in the intestinal segment of the lesion is high. The risk of small bowel cancer in patients with Crohn's disease is 100 times higher than that in the normal population. However, because small bowel cancer is rare in the normal population, the absolute risk of Crohn's disease in small bowel cancer is still quite low. The risk of colon cancer in patients with colonic Crohn's disease remains controversial. There is evidence that when the extent of the lesion is large, the risk of canceration is higher.

treatment

Western medicine treatment

Mesalazine5-aminosalicylic acidSalt) Mesalazine (5-aminosalicylate), which is a combination of diazonium and sulfapyridine, is sulfasalazine (salicylide sulphate) as the main drug for the treatment of Crohn's disease and ulcerative colitis. It has been more than 30 years old. This drug is released by oral action of the azo-reductase of the bacteria after oral administration of the activated 5-aminosalicylate and the carried sulfapyridine.

This effect is usually carried out by the complete sulfasalazine being administered to the colon containing a large amount of bacteria. The mechanism of action of mesalazine (5-aminosalicylic acid) includes inhibition of leukotriene B4 (an effective chemotactic component) synthesis, inhibition of interleukin-1 production, and oxygen free radical scavenging. Oral sulfasalazine 4g/d is indicated for the treatment of mild and moderate colonic and ileal Crohn's disease. Because of the low release of this drug in the small intestine, its role in small bowel type Crohn's disease is undoubtedly limited. The side effects of the drug limit its use in most patients (about 25%). Common side effects are nausea, vomiting, headache, rash and fever.

Some side effects can be alleviated when the dose is gradually increased to 1 g and the treatment volume of 4 times/d is maintained for 1 week. Rare side effects are anemia, hemolysis, epidermal release, pancreatitis, pulmonary fibrosis, and sperm motility disorders. Patients who have been treated with long-term sulfasalazine should take folate to avoid folate deficiency.

Almost all of the side effects of sulfasalazine are caused by sulfapyridine. Thus, other compounds containing 5-aminosalicylic acid or pure 5-aminosalicylic acid formulations have been selected and continuously developed. However, when the patient directly uses the natural structure of 5-aminosalicylic acid, it can be completely absorbed at the proximal end of the digestive tract without functioning at the distal end of the digestive tract.

The sustained release 5-aminosalicylic acid is encapsulated by pH-sensitive eumethacrylate (Eudragit), and the level of release of the drug in the digestive tract changes as the pH of the solution changes. For example, Rowasa (Eudragit-L100), released when pH>5; Salofalk or Claversal (Eudragit-L), released when pH>6; Asacol (Eudragit-S), released when pH>7. Another formulation, Pentasa, encapsulates 5-aminosalicylic acid in small particles of ethylcellulose and is continuously released over time.

Two new compounds containing 5-aminosalicylic acid are olsalazine and balsalazine. Olsalazine is a 5-aminosalicylate dimer, and balsalazine is a compound that attaches 5-aminosalicylic acid to a non-functional carrier on a diazo chain. Both of these new 5-aminosalicylic acid compounds are diazo-based chains, so they have a similar operation to sulfasalazine, which also requires degradation by bacterial azo reductase to release 5-amino water. Salicylic acid. Currently olsalazine has been applied in the United States, and balsalazine is being developed in the United States. These sulfasalazine analogs are reported to have fewer side effects and are easily tolerated by patients. Rare side effects are pancreatitis, hair loss, pericarditis, and nephrotoxicity.

Mesalazine (5-aminosalicylic acid) can also be used as an enema and suppository. The enema can be used for the treatment of terminal colonic Crohn's disease. The suppository is suitable for patients whose lesion is limited to the rectum and its surroundings.

How to choose various preparations of mesalazine (5-aminosalicylic acid) depends on the distribution of lesions in the patient and the release characteristics of the drug.

2. Corticosteroid corticosteroids are the main drugs for the treatment of moderate to severe Crohn's disease. Its mechanism of action is mainly to restore T cell function, and to repair both chemotaxis and phagocytosis. And can reduce cytokinesis. Most patients with moderate Crohn's disease, oral administration of 40 ~ 60mg / d prednisone, can make the disease relieved quite quickly.

Severe patients should be treated with intravenous prednisolone at a dose of 60-100 mg/d. After the condition is relieved, the amount is gradually reduced. Finally, a minimum maintenance dose is given. However, due to the potentially damaging side effects of corticosteroids, long-term use should be avoided. These devastating side effects include (and are not limited to) diabetes, osteoporosis, hypertension, typical Cushing's disease, psychosis, aseptic necrosis of the bones, neuropathy, and fibroids. Patients with Crohn's disease should try to increase the amount of mesalazine (5-aminosalicylic acid) in order to reduce the effects of corticosteroids. Some of the following indicators have been suggested for the use of hormones:

(1) Other drugs are not effective, but there are no indications for surgery.

(2) The condition is seriously at risk, but there is no indication for surgery.

(3) There are systemic complications such as arthritis, nodular erythema, uveal (follicular) inflammation.

(4) Multiple operations, the condition is complicated and deteriorated, and it is no longer necessary to perform surgery again.

At present, some countries have developed a corticosteroid with strong local activity and small systemic effect. These drugs are used in Europe as an enema. Oral sustained release agents under development are already in use in the clinic. It has been reported that oral sustained-release corticosteroids have the same efficacy as prednisone in the treatment of active Crohn's disease, but with low toxicity and low recurrence rate.

3. Immunosuppressive drug 6 (6-mercaptopurine) andAzathioprineIt has a certain role in the treatment of Crohn's disease. For those who are dependent or tolerant to corticosteroids, these medications are available. general巯嘌呤(6-MP)The dosage is 50 mg/d, and the effective time is 3 months on average. Some patients have a fully effective treatment time of 6 to 9 months.

For those who have been ineffective for 3 months, the dose can be increased to 1.5 mg/(kg·d) until a satisfactory effect is obtained. Approximately 75% of patients taking sputum (6-MP) can gradually reduce or significantly reduce the amount of corticosteroids. One-third of the fistulas can heal after more than 2 years of treatment. Due to the slow onset of these drugs and their clinical use in stubborn patients, it has been reported to be mainly used for long-term treatment for not less than 4 to 5 years, otherwise the recurrence rate is very high. However, such drugs have significant side effects. These include myelosuppression, pancreatitis, hepatitis and infection. Therefore, the whole blood count was monitored weekly in the first month of taking the drug. It was monitored every 2 weeks for the next two months. Monitored once a month for long-term treatment.

It has been reported that pancreatitis occurs in 3% to 5% of patients, mostly in the first month. Infections can occur in 5% to 10% of patients, but the incidence of severe infections is less than 2%. It has been reported that the use of guanidine analogues poses a risk of cancer. Lymphoma has been reported in kidney transplant patients taking azathioprine. However, there is no convincing evidence that patients with inflammatory bowel disease have a significant increase in the risk of developing malignant tumors after taking these drugs. Pregnant women try to avoid using these drugs.

Other immunosuppressive drugs for the treatment of Crohn's disease, such as cyclosporine,Methotrexate, less application. It is reported that their efficacy is limited, the side effects are larger than sputum (6-MP), so it is only suitable for sputum (6-MP) ineffective and clinically better than those with better efficacy. Preliminary reports indicate that cyclosporin can be used for the treatment of fistulas.

4. Antibiotics MetronidazoleIt is widely used in anti-infective treatment of Crohn's disease, especially for colonic perianal Crohn's disease. There are also other antibacterial treatments, but there is no sufficient credible data.

5. Nutritional support Proactive nutritional supplements are an important adjunct to Crohn's disease. It has been reported that dietary diets have the same effects as prednisone (especially small bowel disease). Patients with severe sputum or obstruction with large displacement should undergo total parenteral nutrition when they are unable to pass the small intestine.

6. Psychotherapy and Education In recent years, many reports have emphasized the mission and psychological treatment of patients, eliminating the patient's nervousness, fear, and improving the health of patients. This is very beneficial for the recovery of chronic diseases.

7. Diet should be less slag, non-irritating, nutritious food. Wine tea, coffee, cold food and flavoring are not suitable for consumption. Some patients may be beneficial in limiting lactose. Severe people are fasting.

8. Symptomatic treatment of patients with electrolyte disorders to correct, anemia in the right amount of blood transfusion.

The above content is for reference only, please consult the relevant physician or relevant medical institution if necessary.

prevention

First, the prevention before the disease

Traditional Chinese medicine believes that the disease is caused by factors such as spleen and kidney weakness, feeling exogenous evils, emotional internal injuries, and eating and drinking. Modern medicine believes that the cause of Crohn's disease is not clear, and may be closely related to viral infection, immunity, and genetic factors. Combining the Chinese and Western perspectives, we can prevent it from the aspects of daily life, diet, mental health, and physical fitness.

1. There must be regular life;

2. Fasting cold and unclean food;

3. Spiritual care;

4. Proper physical exercise;

Second, the prevention of illness

The disease is a chronic recurrent disease. Because the cause is unknown, there is no fundamental cure. Many patients have more than one complication in their course of disease requiring surgery, and the recurrence rate of surgical treatment is very high, as reported by up to 90%. The recurrence rate of this disease is related to factors such as the extent of the disease and the intensity of the disease. Fortunately, the mortality rate is not high. In addition, as the disease progresses and the age increases, the recurrence rate gradually decreases and the ratio of healthy people increases. In recent years, the use of various treatments is effective for most patients, which can help patients to overcome the difficult period of the disease.