(1) treatment
1. mesalazine (5-aminosalicylic acid salt): mesalazine (5-aminosalicylic acid salt) combined with diazosulfapyridine, that is, sulfasalazine salicylate, has been used as the main drug for treating Crohn's disease and ulcerative colitis for more than 30 years. After oral administration of the drug, the activated 5-aminosalicylic acid salt and sulfapyridine were released through the action of bacterial azo reductase. This operation is usually performed when all sulfasalazine is sent to the colon containing a large number of bacteria. The mechanism of mesalazine (5-aminosalicylic acid) includes inhibiting the synthesis of leukotriene B4 (an effective chemotactic component), inhibiting the production of interleukin-1 and scavenging oxygen free radicals. Oral sulfasalazine 4g/d is suitable for the treatment of Crohn's disease of mild and moderate colon type and ileum type. Because the drug is rarely released in the small intestine, there is no doubt that its effect on Crohn's disease in the small intestine is limited. The side effects of this drug limit its use in most patients (about 25%). Common side effects include nausea, vomiting, headache, rash and fever. When the dose is gradually increased to 1g, the therapeutic dose is maintained for 4 times /d for 1 week, which can alleviate some side effects. Rare side effects are anemia, hemolysis, epidermolysis, pancreatitis, pulmonary fibrosis and sperm motility disorder. Patients receiving sulfasalazine for a long time should take folic acid to avoid folic acid deficiency.
Almost all the side effects of sulfasalazine are caused by sulfasalazine. Therefore, people choose and constantly develop other compounds containing 5-aminosalicylic acid or pure 5-aminosalicylic acid preparations. 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, but it will not work at the distal end of the digestive tract. Sustained-release 5-aminosalicylic acid is coated with pH-sensitive methacrylate, and the release level of the drug in the digestive tract changes with the pH value of the solution. Such as Rowasa(Eudragit-L 100), when pH >; Released at 5 o'clock; Salofalk or Claversal(Eudragit-L), when pH >: released at 6 o'clock; Asacol(Eudragit-S), when pH >; It was released at seven o'clock. Another preparation, Pentasa, is to wrap 5-aminosalicylic acid in small particles of ethyl cellulose and release it continuously over time. Two new compounds containing 5-aminosalicylic acid are Oshara zine and balsalazide. Oshara zine is a dimer of 5-aminosalicylic acid salt, while balsalazine is a compound that binds 5-aminosalicylic acid to an inactive carrier by diazo chain. These two new 5-aminosalicylic acid compounds are diazo chains, so they are similar to sulfasalazine, and also need to be degraded by bacterial azo reductase to release 5-aminosalicylic acid. At present, Oshara zine has been applied in the United States, and balsalazide is being developed in the United States. It is reported that these sulfasalazine analogues have less side effects and are easily tolerated by patients. Rare side effects include pancreatitis, alopecia, pericarditis and nephrotoxicity.
Mesalazine (5-aminosalicylic acid) can also be used as enema and suppository. The enema can be used to treat Crohn's disease of terminal colon, and the suppository is suitable for patients whose lesions are confined to rectum and its surroundings.
How to choose various preparations of mesalazine (5-aminosalicylic acid) depends on the distribution of patients' lesions and the release characteristics of the drug. See figure 1.
2. Corticosteroids: Corticosteroids are the main drugs to treat moderate and severe Crohn's disease. Its mechanism of action is mainly to restore the function of T cells and repair chemotaxis and phagocytosis. And can reduce cytokinesis. Most patients with moderate Crohn's disease can be relieved fairly quickly by taking 40 ~ 60 mg/d prednisone orally. Severe patients should be given intravenous methylprednisolone at a dose of 60 ~ 100 mg/d, and gradually reduced after remission. Finally, the minimum maintenance dose is given. However, due to the potentially destructive side effects of corticosteroids, long-term use should be avoided as much as possible. These destructive side effects include (but are not limited to) diabetes, osteoporosis, hypertension, typical Cushing's disease, psychosis, aseptic necrosis of bone, neuropathy and fibroma. Patients with Crohn's disease should try to increase the dose of mesalazine (5-aminosalicylic acid) to reduce the effect of corticosteroids. It has been suggested that the following indicators are indications for the use of hormones:
(1) When other drugs are ineffective, but there is no surgical indication.
(2) when the condition is serious and in a dangerous state, but there is no indication for surgery.
(3) There are systemic complications, such as arthritis, erythema nodosum and uveitis.
(4) The condition is complicated and deteriorated after repeated operations, and it is no longer suitable for further operations.
At present, some countries have developed a corticosteroid with strong local activity and little systemic effect. These drugs are used as enemas in Europe. The oral sustained-release preparation being developed is expected to be used in clinic. It has been reported that oral administration of a new type of sustained-release corticosteroid is as effective as prednisone in the treatment of active Crohn's disease, but it has little toxicity and low recurrence rate.
3. Immunosuppressants: 6- mercaptopurine and azathioprine have certain effects on the treatment of Crohn's disease. For those patients who depend on or tolerate corticosteroids, these drugs can be used for treatment. Generally, the dosage of 6-MP is 50mg/d, and the average effective time is 3 months. Some patients can be completely effective in 6 ~ 9 months. For those who are ineffective after 3 months of treatment, the dosage can be increased to1.5 mg/(kg d) until satisfactory curative effect is achieved. About 75% patients taking 6-MP can gradually reduce or significantly reduce the dosage of corticosteroids. 1/3 fistula can be cured after more than 2 years of treatment. Because these drugs take effect slowly and are clinically used for intractable patients, it is reported that they are mainly used for long-term treatment of not less than 4 to 5 years, otherwise the recurrence rate is very high. However, these drugs have obvious side effects. Include myelosuppression, pancreatitis, hepatitis and infection. Therefore, the whole blood cell count is monitored once a week 1 month after taking the medicine. For the next two months, monitor 1 time every two weeks. Monthly monitoring 1 time during long-term treatment. It is reported that pancreatitis occurs in 3% ~ 5% of patients, and most of them occur in 1 month. 5% ~ 10% patients can be infected, but the incidence of serious infection is less than 2%. It is reported that taking purine analogues may cause cancer. It is reported that renal transplant patients developed lymphoma after taking azathioprine. However, there is no convincing evidence that the risk of malignant tumor in patients with inflammatory bowel disease increases significantly after taking such drugs. Pregnant women try to avoid using such drugs.
Other immunosuppressive drugs used to treat Crohn's disease, such as cyclosporine and methotrexate, are rarely used. It is reported that their curative effect is limited and their side effects are greater than 6-MP, so they are only suitable for those who are ineffective in 6-MP and have better curative effect through clinical comparison. Preliminary report shows that cyclosporine can be used to treat fistula.
4. Antibiotics: Metronidazole is widely used in the anti-infection treatment of Crohn's disease, especially for Crohn's disease with perianal colon. There are some other antibacterial treatments, but there are not enough reliable data.
5. Nutritional support: Active nutritional supplement is an important adjuvant therapy for Crohn's disease. It is reported that elemental diet has the same effect as prednisone (especially for small intestinal diseases). Severe patients with large fistula or obstruction should be given total parenteral nutrition when they cannot be nourished by small intestine.
6. Psychotherapy: Education In recent years, many reports have emphasized the belief of educating patients and psychotherapy to eliminate their nervousness and fear and improve their health. This is very beneficial to the recovery of chronic diseases.
7. Diet: Eat less dregs, non-irritating and nutritious food. Alcohol, tea, coffee, cold food and spices are not edible. Restricting lactose may benefit some patients. If it's serious, hurry.
8. Symptomatic treatment: electrolyte disorders should be corrected, and anemia should be properly transfused.
(2) Prognosis
The mortality of Crohn's disease is 5% ~10%; The operative mortality was 4%. The main causes of death are abdominal infection, abscess, peritonitis, intestinal fistula and other complications, chronic consumption failure and cancer.
It is possible for the disease to relieve itself, especially for patients with mild to moderate symptoms. It is reported that placebo-controlled studies show that after 4 months of follow-up, the spontaneous remission rate is 30%. 20% and 65,438+00% are stable in 65,438+0 years and 2 years respectively. Among the patients in remission, 70% and 50% were still stable after 1 year and 2 years respectively. Therefore, when evaluating the efficacy of drugs, we should consider the factors of self-remission of diseases. However, it should be emphasized that in order to better control and stabilize the disease, the role of drug treatment can never be ignored.
After internal and surgical treatment of Crohn's disease, although most patients can be relieved and stable, and have a good quality of life and health, the recurrence rate in the resection group (after long-term follow-up, the clinical recovery and symptom improvement accounted for 73.2%) is high (the total recurrence rate is over 50%). The annual recurrence rate after operation was 8% ~ 10%. However, it should be pointed out that there are many factors affecting the recurrence of lesions, which still need further discussion. In the statistics of recurrence rate, the examination methods and diagnostic criteria adopted also have obvious influence. For example:
① According to endoscopic examination, the recurrence rate after operation 1 year and 3 years was 70% and 85% respectively.
② According to clinical symptoms, X-ray examination, endoscopy or pathological examination, the recurrence rates at 2, 3 and 4 years after operation were 20%, 30% and 40% ~ 50% respectively.
③ According to the need of reoperation, the recurrence rate is 25% ~ 30% in 5 years after operation and 40% ~ 50% in 20 years after operation.
This disease is a chronic disease, and the lesions can develop progressively or have repeated acute attacks. It may take several operations to deal with it. According to reports, after 1 operation, 45% of patients need a second operation; 25% patients need a third operation after the second operation. The lesion is located at the end of ileum. During the follow-up of 10 years, about 30% patients need to undergo more than one enterotomy. About 5% need more than 3 bowel resection. After many operations, especially after many intestinal resections, about 1.5% patients developed short bowel syndrome, which is quite difficult to deal with and still needs to be studied and solved.