Ulcerative colitis is a chronic inflammatory disease of the colon of unknown etiology characterized gemorragicescom-purulent inflammation of the colon with the development of local and systemic complications.
Accurate data on the prevalence of ulcerative colitis are difficult to obtain, often go unreported mild cases, especially in the initial period of the disease. These patients typically seen in outpatient non-specialized institutions and it is difficult to quantify. Ulcerative colitis most commonly in urbanized countries, particularly in Europe and North America. In these regions the incidence of ulcerative colitis (primary morbidity), ranging from 4 to 20 cases per 100 000 population, with an average of 8-10 cases per 100 000 inhabitants per year. The prevalence of ulcerative colitis (number of patients) is 40-117 patients per 100 000 inhabitants. The greatest number of cases occur in the age 20-40 years. A second peak in incidence observed in older age group after 55 years. The highest mortality rates are seen within 1 year of the disease due to cases of extremely severe fulminant course of the disease and 10 years after it began because of the development in some patients of colorectal cancer.
It remains unclear the role of environmental factors, in particular Smoking. Numerous epidemiologic studies have shown that ulcerative colitis is more common in non-smokers. It is even allowed to offer nicotine as a therapeutic agent. People who have had an appendectomy have a lower risk of developing ulcerative colitis, as well as persons exposed to excessive physical stress. The role of dietary factors in ulcerative colitis is much less than in Crohn’s disease. Compared to healthy individuals the diet of patients with ulcerative colitis, contains less dietary fiber and more carbs. In anamnesis of patients with ulcerative colitis more frequently than in the General population, there are cases in pediatric infectious diseases.
The exact etiology of ulcerative colitis to date, unknown. Discusses three basic concepts:
- The disease is caused by the direct effects of some exogenous environmental factors that are not yet installed. The main reason is considered infection.
- Ulcerative colitis is an autoimmune disease. If there is a genetic predisposition of the organism to the influence of one or several of the starting factors triggers a cascade of mechanisms directed against self-antigens. The same pattern holds for other autoimmune diseases.
- This disease is caused by an imbalance of the immune system of the gastrointestinal tract. Against this background, the influence of various adverse factors leads to excessive inflammatory response that occurs due to hereditary or acquired defects in mechanisms of regulation of the immune system.
In the development of inflammation in ulcerative colitis involves numerous mechanisms of tissue and cellular damage. Bacterial and tissue antigens cause stimulation of T – and b-lymphocytes. During exacerbation of ulcerative colitis reveals a deficit of immunoglobulins, which contributes to the penetration of microbes, a compensatory stimulation of b-cells with the formation of immunoglobulins M and G. the Deficit of T-suppressors leads to increased autoimmune reactions. Enhanced synthesis of immunoglobulins M and G accompanied by the formation of immune complexes and activation of the complement system, which have a cytotoxic effect, stimulates the chemotaxis of neutrophils and phagocytes with the subsequent release of inflammatory mediators, which cause destruction of epithelial cells.
An important role in the pathogenesis of ulcerative colitis is given to the violation of the barrier function of the intestinal mucosa and its ability to recover. It is believed that through defects of the mucous membrane in the deeper tissues of the intestine may penetrate a variety of food and bacterial agents, which then trigger a cascade of inflammatory and immune responses.
Of great importance in the pathogenesis of ulcerative colitis and provocations of disease recurrence are characteristics of a patient and psychogenic influences. Individual response to stress with abnormal neurohumoral response may be the trigger of the disease. In the neuro-psychological status of the patient with ulcerative colitis are marked peculiarities, which are expressed in emotional instability.
In the acute stage of ulcerative colitis are marked pericardial edema and hyperemia of mucosa with thickening and flattening of the folds. With the development of the process or its transition to chronic increases destruction of the mucosa and produce ulceration, penetrating only up to the submucosa or, more rarely, to the muscle layer. Chronic ulcerative colitis is characterized by the presence of pseudopolyps (inflammatory polyps). They represent the islets of mucosa left by its destruction, or conglomerate, formed as a result of excessive regeneration of the glandular epithelium.
In severe chronic diseases of the gut shortened, narrowed its lumen, absent haustra. Muscularis is usually not involved in the inflammatory process. For strictures of ulcerative colitis are uncommon. Ulcerative colitis can affect any parts of the colon, but the rectum is always involved in the pathological process, which has a diffuse continuous. The intensity of inflammation in different segments can be different; changes are moving in the normal mucosa, with no clear boundaries.
Histological examination in the acute phase of ulcerative colitis in the mucous membrane of the capillaries and hemorrhages, formation of ulcers as a result of necrosis of the epithelium and formation of crypts abscesses. A decrease in the number of goblet cells, infiltration of lamina propria by lymphocytes, plasma cells, neutrophils and eosinophils. In the submucosal layer changes are negligible, except in the cases of penetration of the ulcer into the submucosal basis.
For the length of the process are distinguished:
- distal colitis (proctitis or proctosigmoiditis);
- left sided colitis (lesion, colon to the right of the bend);
- total colitis (lesion of the entire colon with involvement in the pathological process in some cases the terminal segment of the ileum).
According to the severity of the clinical manifestations are mild disease, moderate and severe. The nature of the disease:
- lightning form;
- acute form (first attack);
- chronic recurrent form (with repeated exacerbations, not more often 1 time in 6 to 8 months.);
- continuous form (prolonged exacerbation of more than 6 months. with adequate treatment).
It is noted the correlation between length of lesion and severity of symptoms, which in turn determines the volume and nature of the treatment.
The diagnosis of ulcerative colitis is formulated taking into account the nature of the flow (recurrence) of the disease, the prevalence of (distal, left-sided and total colitis), severity of disease (mild, moderate, severe), phase of the disease (exacerbation, remission), indicating local and systemic complications. For example: ulcerative colitis, total lesions, chronic relapsing course, of moderate severity.
By the time of diagnosis, approximately 20% of patients revealed a total colitis, in 30-40% left lose and at 40-50 % — proctitis or proctosigmoiditis.
For the clinical picture of ulcerative colitis is characterized by local symptoms (intestinal bleeding, diarrhea, constipation, abdominal pain, tenesmus) and General manifestations of toxemia (fever, weight loss, nausea, vomiting, weakness, etc.). The intensity of symptoms in ulcerative colitis correlated with the extent of the pathological process in the intestine and the severity of inflammatory changes.
For hard total defeat of the colon characteristic profuse diarrhea with an admixture of significant amounts of blood in the stool, sometimes bleeding with clots, cramping abdominal pain before defecation, anemia, symptoms of intoxication (fever, decrease in body weight, expressed General weakness). Under this option, ulcerative colitis, may develop complications, life-threatening, toxic megacolon, colon perforation and massive intestinal bleeding. Especially unfavorable course is observed in patients with fulminant ulcerative colitis.
During exacerbation of moderate severity observed rapid stool up to 5-6 times a day with a constant admixture of blood, cramping abdominal pain, subfebrile body temperature, fatigue. Some patients have extraintestinal symptoms — arthritis, erythema nodosum, uveitis, etc. Moderate attack of ulcerative colitis in most cases is amenable to conservative therapy with modern anti-inflammatory drugs, primarily corticosteroids.
Severe and moderate acute ulcerative colitis characteristic of the total and, in some cases, left-sided lesions of the colon. Light attack of the disease in total defeat appear insignificant frequent stools and a small admixture of blood in the stool.
The clinical picture of patients with proctitis and proctosigmoiditis very often manifests no diarrhoea and constipation and a false urge to have a bowel movement with the release of fresh blood, mucus and pus, tenesmus. If in the inflamed distal colon transit of intestinal contents is accelerated in the proximal segments of the observed stasis. This pathophysiological mechanism associated constipation with distal colitis. Patients can long time not see blood in the stool, General condition suffers a little, employability is preserved. This latent period after the occurrence of the ulcerative colitis before the diagnosis can be very long — sometimes it is several years old.
Ulcerative colitis observed a variety of complications that can be divided into local and systemic.
Local complications include colon perforation, acute toxic dilatation of the colon (or toxic megacolon), massive intestinal bleeding, colon cancer.
Acute toxic dilatation of the colon is one of the most dangerous complications of ulcerative colitis. It develops as a result of severe ulcerative-necrotic process and its associated toxicity. Toxic dilatation is characterized by the extension segment or the entire affected intestine during severe attacks of ulcerative colitis. Patients with toxic dilatation of the colon in the initial stages need intensive conservative therapy. When its ineffectiveness is performed surgery.
Perforation of the colon is the most common cause of death in fulminant form of ulcerative colitis, especially with the development of acute toxic dilatation. Due to extensive ulcerous-necrotic process, the wall of the colon becomes thinner, loses its barrier function and becomes permeable to various toxic products in the gut. In addition to stretching of the intestinal wall a crucial role in the occurrence of perforation plays bacterial flora, especially E. coli with pathogenic properties. In the chronic stage of the disease, this complication is rare and occurs mainly in the form of periodicheskogo abscess. Treatment of perforation of the surgery only.
Massive intestinal bleeding are relatively rare and as a complication represent a less complex problem than acute toxic dilatation of the colon and perforation. Most patients with adequate bleeding anti-inflammatory and hemostatic therapy allows to avoid surgery. With the continuing massive intestinal bleeding in patients with ulcerative colitis, surgery is indicated.
The risk of developing colon cancer in ulcerative colitis increases dramatically with duration of disease more than 10 years, if the colitis began at the age of 18 and especially 10 years.
Systemic complications of ulcerative colitis are also called extraintestinal manifestations. Patients can meet liver, mucosa of the oral cavity, skin, joints. The exact origins of extraintestinal manifestations is not fully understood. In their formation involved the alien, including toxic agents entering the body from the lumen of the intestine, and immune mechanisms. Erythema nodosum occurs not only as a reaction to the reception sulfasalazine (linked sulfapyridine), but occurs in 2-4% of patients with ulcerative colitis or Crohn’s disease regardless of treatment. Gangrenous pyoderma is a very rare complication, observed in 1-2% of patients. Episcleritis occurs in 5-8% of patients with exacerbation of ulcerative colitis, acute arthropathy — 10-15%. Arthropathy is manifested by the asymmetric involvement of large joints. Ankylosing spondylitis is diagnosed in 1-2% of patients. Liver lesions observed in 33.3% of patients with ulcerative colitis and Crohn’s disease, appearing most or transient increase in transaminaz in blood, or hepatomegalia. Most common serious hepatobiliary disease with ulcerative colitis is primary sclerosing cholangitis, which is a chronic constrictive inflammation of intra – and extrahepatic bile ducts. It is found in approximately 3% of patients with ulcerative colitis.
The diagnosis of ulcerative colitis established on the basis of assessment of the clinical picture of the disease, data sigmoidoscopy, endoscopic and radiological investigations.
In the endoscopic picture there are four degrees of inflammatory activity in the gut: minimal, moderate, severe and pronounced.
- Grade I (minimal) is characterized by mucosal edema, hyperemia, lack of vascular pattern, easy contact bleeding, punctate hemorrhage.
- Grade II (moderate) is defined by oedema, hyperemia, granularity, contact bleeding, erosions, confluent hemorrhages, fibrinous coating on the walls.
- Grade III (severe) is characterized by the appearance of multiple coalescing erosions and ulcers on the background of the above-described changes in the mucosa. In the lumen of the intestine the pus and blood.
- Grade IV (pronounced) in addition to these changes, is determined by the formation of pseudopolyps and bleeding of granulation tissue.
Severe form of ulcerative colitis of the rectum
In remission mucosa is thickened, vascular pattern is restored, but not completely renovated. There may be granularity of the mucosa, thickened folds.
In a number of countries to evaluate endoscopic activity of ulcerative colitis use endoscopic index proposed by Rakhmilevich, which takes into account the same characteristics, estimated in points.
Often with high activity, the surface of the intestinal mucosa completely covered with fibrinous-purulent bloom, after the removal of which revealed a diffuse granular bleeding surface with multiple ulcers of various depths and shapes with no signs of epithelialization. For ulcerative colitis characterized by rounded and star-shaped ulcers, ulcer-prints, usually not penetrating deeper than the lamina propria mucosa, and rarely the submucosa. In the presence of multiple microisv or erosion the mucous membrane looks moth-eaten.
For ulcerative colitis in the active stage of the process under study with a barium enema x-ray is characterized by the following signs: the absence of Austr, smoothed contours, ulcerations, edema, serration, double loop, pseudopolyps, restructuring type longitudinal folds of the mucous membrane, the presence of free mucus. In the long-term current ulcerative colitis due to swelling may develop thickening of the mucosa and submucosa. This increases the distance between the rear wall of the rectum and the anterior surface of the sacrum.
After emptying of the colon from the barium revealed the absence of Austr, mainly longitudinal and coarse transverse folds, ulcers and inflammatory polyps.
X-ray examination is of great importance not only to diagnose the disease, but its severe complications, in particular acute toxic dilatation of the colon. This is done by plain radiography of the abdomen. When I degree of dilation increases the diameter of the intestine at its widest point is 8-10 cm, at II — 10 to 14 cm and at III — more than 14cm.
In the treatment of attacks of ulcerative colitis, there is a positive dynamics of all main radiological manifestations of the disease — reduce the length, size and tone the colon. This is because during the barium enema these changes are manifested by spasm and not organic contraction, characteristic of granulomatous colitis and intestinal tuberculosis.
The clinical picture of ulcerative colitis requires differential diagnosis of diseases of the colon infectious and noninfectious etiologies. The first attack of ulcerative colitis can occur under the guise of acute dysentery. Correct diagnosis help data sigmoidoscopy, and bacteriological tests. Salmonellosis frequently simulates the picture of ulcerative colitis, as occurs with diarrhea and fever, but unlike him, bloody diarrhoea appears only on the 2nd week of illness. From other forms of colitis of infectious origin that require differentiation from ulcer, it should be noted gonorrheal proctitis, pseudomembranous enterocolitis, viral diseases.
The most difficult differential diagnosis between ulcerative colitis, Crohn’s disease, and ischemic colitis.
Tactics of treatment of ulcerative colitis is determined by the localization of the pathological process in the colon, length, severity of attacks, presence of local and/or systemic complications. Conservative therapy aimed at the most rapid relief of the attack, preventing relapse and disease progression. Distal forms of ulcerative colitis-proctitis or proctosigmoiditis — characterized by a slight current, so it is often treated on an outpatient basis. Patients with left-sided and total defeat, as a rule, being treated in hospital, as the course of the disease characterized by greater severity of clinical symptoms and large organic changes.
Food patients should be nutritious and include foods rich in proteins, vitamins, with restriction of animal fats and with the exception of coarse vegetable fiber. Recommended of lean fish, meats (beef, chicken, Turkey, rabbit), cooked, boiled or steamed, pureed porridge, potatoes, eggs, dried bread, walnuts. Excluded from the diet of raw vegetables and fruits, since they contribute to the development of diarrhea. Often, patients with marked lactose intolerant, so dairy products are added only when they are well tolerated. These recommendations are consistent with diets 4, 4B, 4B of the Institute of nutrition.
All drugs used in the treatment of ulcerative colitis can be divided into two large groups. The first includes basic anti-inflammatory drugs and includes aminosalicylates, i.e., drugs containing 5-aminosalicylic acid (5-ASA, mesalazine), corticosteroids and immunosuppressants. All other drugs play a supportive role in the treatment of ulcerative colitis or are under clinical study.
At high concentrations of mesalazine may inhibit specific functions of neutrophils in humans (e.g., migration, degranulation, phagocytosis and the formation of free toxic oxygen radicals). In addition, mesalazine inhibits the synthesis of factors that activates platelets. Thanks to its antioxidant properties, mesalazine is able to catch free oxygen radicals.
Mesalazine effectively inhibits the formation of cytokines — interleukin-1 and interleukin-6 (IL-1, IL-6) in the intestinal mucosa and also inhibits the formation of receptors for IL-2. Thus, the mesalazine directly interfere in the course of immune processes.
It was shown that “ballast” component sulfapiridin is mainly responsible for the incidence of side effects sulfasalazine. Literature data about the frequency of side-effects caused by sulfasalazine, ranging from 5 to 55 %, averaging 21 %. In addition to nausea, headache, male infertility occur anorexia, diarrhoea disorders, hematological reactions (leukopenia and hemolytic anemia) and hypersensitivity reaction with multi-organ lesions.
In order to preserve the anti-inflammatory activity inherent sulfasalazine, and avoid the side effects associated with sulfapyridine component, in recent years, have developed drugs that contain “pure” 5-ASA. As an example of the new generation aminosalicylates can cause drug salofalk worth us, developed by the German pharmaceutical company “Dr. Falk Farma”. The drug comes in three dosage forms: tablets, suppositories, microclysters and. Tablets mesalazine protected from contact with gastric contents using a special acid resistant polymer shell, which dissolves at a pH more than 6.5. Such pH values, usually recorded in the lumen of the ileum. After dissolution of the shell in the iliac intestine creates a high concentration of active anti-inflammatory component (mesalazine). The choice of a particular dosage form of salofalk is determined by the length of the zone of inflammation in the colon. For proctitis it is advisable to use the suppositories, while left lesions — mikroklizm, and with total colitis pills.
Recently appeared in Russia, pentas, being equally effective, has a number of features. It differs from other drugs mesalazine microgranulated structure and nature of the coating. Pills pentasa consist of microgranules in ethylcellulose shell dissolution which does not depend on pH in the gastrointestinal tract. It provides a slow, gradual and uniform release 5-ASA throughout the intestinal tube, starting from the duodenum. The uniformity of the release contributes to a constant concentration of the drug in different sections of the intestine, which not depends not only on pH but also on the speed of transit, so the pentas can be successfully used in inflammatory diseases of the bowel with diarrhea unscathed. These features allow the use of the drug not only for ulcerative colitis and Crohn’s disease with lesions of the colon and ileum, but especially in patients with vysokotekhnologichnoi localization of Crohn’s disease.
Daily dose aminosalicylates is determined by the severity of an attack of ulcerative colitis and the nature of the clinical response to the drug. For the relief of acute and moderate attack administered 4-6 g sulfasalazine or 3-3. 5 g mesalazine per day, divided into 3-4 reception. In the absence of good clinical response the daily dose of mesalazine may be increased to 4.0—4.5 g, but to increase the daily dose sulfasalazine usually fails due to development of significant side effects.
Sulfasalazine inhibits the conjugation of folic acid in the brush border of the jejunum inhibits the transport of this vitamin inhibits the activity of related enzyme systems in the liver. Therefore, the complex treatment of patients with ulcerative colitis receiving treatment with sulfasalazine, you must include folic acid at a dose of 0.002 g 3 times a day.
For cupping attacks of ulcerative colitis usually requires 3 to 6 weeks. This is followed by anti-relapse treatment with sulfasalazine (3 g/day) or mesalazine (2 g/day).
Modern drugs for the treatment of proctosigmoiditis and left-sided colitis is most often used suspension salofalk worth us. Disposable tank contains, respectively, 4 g mesalazine 60 ml suspension or 2 g mesalazine in 30 ml suspension. The drug is administered into the rectum 1-2 times a day. Daily dose is 2-4 g depending on the severity of the process in the gut. If the length of the inflammatory process in the rectum not more than 12 cm from the edge of the anus, it is advisable to use candles salofalk worth us. The usual daily dose in these cases is 1.5—2 g.
When using aminosalicylates fails to achieve remission in 75-80% of cases of ulcerative colitis.
The most effective anti-inflammatory drugs in the treatment of ulcerative colitis remain steroid hormones, which in severe forms of the disease are superior to the activity of the aminosalicylates. Corticosteroids accumulate in inflammatory tissue and block the liberation of arachidonic acid, preventing the formation of prostaglandins and leukotrienes that cause inflammation. Inhibiting chemotaxis, steroid hormones indirectly exhibit immunomodulatory effects. The effect on tissue fibrinolysis reduces bleeding.
The indication for steroid therapy are:
- acute severe and moderate forms of the disease and the presence of extraintestinal complications;
- left and total forms of ulcerative colitis with severe and moderate course in the presence of III degree of activity of inflammatory changes in the colon (on endoscopic findings);
- the lack of effect from other methods of treatment for chronic forms of ulcerative colitis.
In acute severe ulcerative colitis or severe attacks of chronic forms of the disease treatment should begin with the intravenous administration of prednisolone is not less than 120mg/day, uniformly distributed on 4-6 injections with simultaneous correction of water and electrolyte imbalance, administration of blood and blood substitutes and (if possible) conduct hemosorption in order to quickly eliminate endotoxemia. Suspension hydrocortisone should be administered intramuscularly, however, the duration of such administration is limited to 5-7 days due to the probable development of abscesses at the injection site and possible fluid retention. 5-7 days should go to oral prednisone. It is a gastroscopy to exclude gastric ulcer and duodenal ulcer. In moderate form and the absence of clinical signs and anamnestic indications of gastro-duodenal ulcers treatment should begin with oral administration of prednisolone. Usually the prednisolone is administered in the dose of 1.5—2 mg/kg of body weight per day. A dose of 100 mg should be considered maximum.
If tolerated hormonal preparations prescribed dose are advised to take to obtain a consistent positive result within 10-14 days. This is followed by a decrease in the so-called speed scheme — 10mg every 10 days. Starting with 30-40 mg recommended single dose of prednisone in the morning that practically does not cause serious complications. At the same time in a treatment scheme include mesalazine or sulfasalazine that should be taken to the full withdrawal of hormones. Starting with 30mg, the abolition of prednisolone more slowly — at 5mg a week. Thus, a full course of hormonal therapy lasts from 8 to 12 weeks. depending on the form of ulcerative colitis.
In the distal forms of destruction, and I—II degree of activity of the process according sigmoidoscopy should be prescribed hydrocortisone rectal drip or mikroklizmah. Moreover, if patients do not hold large volumes, then begin the introduction of hydrocortisone (65—125мг) should be 50 ml of isotonic solution of sodium chloride and with the subsiding of the inflammation, reduce the frequency of false desires gradually increase to 200-250 ml for a therapeutic enema. The drug is usually administered after stool in the morning or before bedtime.
Ulcerative proctitis and sphincteritis good enough effect have candles prednisolone (5 mg) administered 3-4 times a day. In more severe for distal forms, accompanied by fever, General weakness, anemia, and III — IV degree of activity according rectoscopy, in the case of absence of effect from sulphasalazine or mesalazine shown treatment with prednisolone orally at a dose of 30-50 mg/day.
Patients of middle and elderly age, the dose of prednisolone should not exceed 60 mg, as they are characterized by the presence of concomitant diseases: atherosclerosis, hypertension, diabetes, etc. In cases where ulcerative colitis background ateroskleroticescoe lesions of the mesenteric arteries, in the medical complex should be administered cardiovascular medications: trental, protectin.
For hormonal therapy associated with the development of side effects: delay in the tissue fluid, chlorides and sodium (swelling), hypertension, hypokalaemia, loss of calcium, osteoporosis, various autonomic disorders, impaired carbohydrate metabolism, adrenal insufficiency, gastric ulcer, gastro-intestinal bleeding. In these cases, the appointment of adequate symptomatic therapy of antihypertensive drugs, diuretics, calcium supplements, antacids. In case of violation of carbohydrate metabolism necessary diet with restriction of carbohydrates, according to testimony — fractional insulin (glycemia, respectively) or oral antidiabetic drugs. To prevent the development of thrombosis in patients with severe ulcerative colitis receiving treatment, there should be constant monitoring of the blood coagulation system and at the same time to appoint disaggregants: chimes, prodektina, etc.
ACTH-zinc phosphate is effective only in the acute form of ulcerative colitis, because its impact is mediated by the preserved function of the adrenal glands. The drug is administered intramuscularly at a dose of 20-40 mg depending on the severity of the attack.
In recent years in the treatment of inflammatory bowel diseases, especially Crohn’s disease, and the use of preparations containing as the active component of the glucocorticosteroid budesonide. Unlike conventional corticosteroids, budesonide has a very high degree of affinity to receptors and high (about 90 %) metabolism in the liver in the first pass. Due to this, he has a very powerful local anti-inflammatory action with minimal systemic side effects. As an alternative to prednisone and hydrocortisone to recommend the drug budenofalk. In designing the structure of budenofalk were taken into account physiological features of the gastrointestinal tract. Each capsule of budenofalk is about 350 microspheres consisting of budesonide coated with a polymer shell that is resistant to gastric juice. The release of budesonide from the microspheres occurs in the ileum and colon the intestines at pH values in excess of 6.4. Budenofalk is used for treating mild and moderate exacerbations of ulcerative colitis. The recommended daily dose is 1 capsule budenofalk containing 3 mg of budesonide, 4-6 times a day.
The most serious problem in the treatment of ulcerative colitis is a hormonal dependence and resistance. This category of patients the worst results of conservative therapy and the highest hirurgicheskie activity. According to GNCC, hormonal dependence is formed from 20-35% of patients with severe ulcerative colitis. Often the signs of addiction and resistance occur simultaneously, forcing you to resort to unsafe and aggressive methods of influence.
Hormonal dependence is a response to therapy with glucocorticoids, in which a positive therapeutic effect is replaced by a reactivation of the inflammatory process against the background of dose reduction or withdrawal of corticosteroids. This is a special case of a refractory colitis. We believe that there are at least 4 different etiopathogenetic variant of hormone-dependence: true dependence hormonal, combined with steroiddependent, about from inadequate treatment actually chronic adrenal insufficiency and mixed or combined form.
Currently unknown until the end of the causes and mechanisms of formation of hormone-dependence. Nevertheless, we believe that a number of etiological factors will undoubtedly find its place defects itself hormone therapy, persistent inflammation, transient or persistent decrease in the function of the pituitary-adrenal system. Probably, in some cases, the hormonal dependence of the resistance and hereditary, in others-represent an acquired defect of hormone receptors and imbalance between proliferation and cell death, i.e. the deregulation of apoptosis. The hypothesis of low density of hormone receptors in patients with inflammatory diseases of the colon, especially in refractory period, has recently received a convincing confirmation.
It belongs immunodepressantom responsible role in the treatment of patients with inflammatory diseases of the colon hormonal dependence and resistance. However, this role for various drugs is considered ambiguous. Among the drugs of the 1st line and long term use include 6-mercaptopurine and azathioprine. They are the perfect sparring partners for glucocorticoids. Purine analogues reduce and cancel the hormones in 60-70% of patients with hormone-dependent under certain rules, namely: they should be administered simultaneously with the hormones to their action managed to appear. Daily dose of azathioprine should not exceed 150 mg. Effect can be expected only by the end of the 3rd month of continuous reception. Purine analogs provide relatively few side effects and should be used in patients with hormone-dependent as long as possible — 2-3 years or more.
The drug is 2nd line for long-term therapy is methotrexate, which is used in case of intolerance to azathioprine or the need to accelerate the effect. It is administered orally or intramuscularly in a dose of 30 mg/week. The result can be obtained within 2-4 weeks. Side effects are rare. Unfortunately, like azathioprine, it does not provide a lasting effect. If you cancel arise exacerbation. Flash lighter than before, sometimes arise during therapy after 6 months. from the beginning of reception.
Cyclosporine can be used inside, intravenously in a dose of 4-6 mg/kg of body weight with good and quick effect, coming in 5-7 days. Short-term action. It is often used to interrupt attacks with subsequent transition to immunosuppressants, suitable for prolonged intake.
Violation of the barrier function of the colon in ulcerative colitis may be the cause of the development of the syndrome of toxemia. Its correction is necessary the appointment of an appropriate complex recovery eubioz, antibacterial therapy, hemosorption, ultraviolet irradiation of autologous blood.
As a result, expressed metabolic disorders and catabolite-tion of the action of steroid hormones appropriate parenteral administration of protein drugs: serum albumin, plasma protein, essential amino acids.
To improve the microcirculation and transcapillary exchange shows the introduction of reopoliglukine, gemodeza (in normal dosages).
With anemia (hemoglobin 90 g/l and below), which is a marker of severe attack of ulcerative colitis, it is recommended to conduct the transfusion of 250 ml single-group of blood with an interval 3— 4 days. While reducing the level of iron in blood serum must be included in the medical complex iron preparations.
Given the immunological disorders ulcerative colitis therapy disease used immunomodulators, levamisole timalin etc. However, their role is still unclear, the therapeutic effect of their use is short, so the activity of these drugs as a basic means questionable.
It is advisable to recommend the use of immunomodulators in combination with basic anti-inflammatory treatment.
Appointed b vitamins, C, A, D, K, which also contribute to the recovery eubioz in the intestine.
Complex treatment includes psychotropic drugs in normal dosages, focusing on individual tolerability.
Exacerbation of ulcerative colitis in some cases is accompanied by irritable bowel syndrome, often manifested by constipation. In this case justified the appointment of a wheat bran or brand name drugs containing ballast substances (mucofalk, etc.), which contribute to normalization of stool and also function as chelators.
Inpatient treatment ends with the clinical and endoscopic remission after which the patient is subject to dispensary observation in the clinic at a General practitioner, a gastroenterologist or proctologist.
The question of the nature and duration of relapse prevention in ulcerative colitis remains unresolved. According to one of the points of view of anti-relapse treatment is recommended for life. However, given the high cost of drugs and the risk of side effects in their long-term use in the gastroenterological Department GNCC adhere to the following tactics: after arresting an attack of ulcerative colitis the maintenance dose recommended aminosalicylates (3.0 g sulfasalazine or 2.0 g mesalazine per day) for a period of 6 months. If during this period, there were clinical signs of acute disease, and when the control endoscopy after 6 months. States remission relapse treatment can be canceled. If during the course of anti-relapse therapy the patient’s condition was unstable, sometimes needed to increase the dose aminosalicylates to eliminate the symptoms of an exacerbation, and when the control endoscopy revealed signs of active inflammation, anti-relapse treatment should be extended for another 6 months. Patients with a chronic continuous course of ulcerative colitis require long-term continuous treatment is usually high doses aminosalicylates, however, this therapy is not in the full sense of the word-relapse. It is, rather, a deterrent to anti-inflammatory treatment. In these patients are also widely used cytotoxic agents (azathioprine or 6-mercaptopurine) and intermittent regimens of corticosteroids.
Surgery for ulcerative colitis is necessary in 10-20% of patients. The surgical method may be radical, but this should be completely remove the colon as a substrate for a possible relapse. However, this severe traumatic operation results in the majority of cases to loss of the anal bowel movement and the formation of a permanent ileostomy in the abdominal wall. In fact, the operated patients become disabled, and this significantly limits the use of surgical treatment. Indications for surgery currently divided into three main groups:
- The ineffectiveness of conservative therapy;
- The complications of ulcerative colitis (intestinal bleeding, toxic dilatation of the colon, perforation of the colon);
- The occurrence of colorectal cancer on a background of ulcerative colitis.
GNCC has experience of surgical treatment of more than 500 patients with ulcerative colitis. In recent years, developed and implemented a comprehensive approach for the treatment of patients, including the intensive therapy in the preoperative period, the timely identification of indications for surgery, effective rehabilitation in the postoperative period. Used new technology surgery, including bloodless sparing operation (laparoscopically assisted operations, Ultracision, Ligasure). The goals of surgical rehabilitation is a differentiated approach using different variants ileorectostomy to restore anal defecation. All of these approaches have helped to reduce the frequency of postoperative complications from 55% to 12%, and mortality from 26 to almost 0 %. Primary and delayed reconstructive surgery became possible in 53% of the operated patients.
Indications for surgery
The ineffectiveness of conservative therapy. The fate of patients the progression of inflammatory changes cannot prevent drugs, including hormonal (hormoneresistant form). The continuing attack of ulcerative colitis, severe intoxication and blood loss lead to the depletion of the patient, with severe metabolic disorders, anemia, carry a risk of developing septic complications. In these cases, taking the decision of having the surgery. Preoperative preparation includes intensive conservative treatment, correction of anemia, hypoproteinemia and electrolyte disturbances. Interim criterion (duration) expectations of effect of conservative therapy is 2-3 weeks. after the start of the complex of intensive therapy with adequate doses of glucocorticoids (prednisolone 2 mg/kg/day).
In certain group of patients (20-25% in severe forms), there is the so-called hormone-dependent ulcerative colitis. Maintenance of remission of inflammatory process in the colon only occurs in the face of constant supporting hormonal therapy (15-30 mg of prednisone orally per day. Long-term treatment with hormones for 6 months. and more leads to the development of severe adverse events: steroid diabetes, osteoporosis with pathological fractures, hypertension, etc. This fact also necessitates the use of operation, which allows not only to cancel corticosteroids, but also to eliminate the inflammation.
Intestinal bleeding. Blood loss through the rectum in ulcerative colitis is rarely threatening. However, sometimes the hemorrhage not amenable to conservative correction, takes a life-threatening nature. In such cases, you should make the decision about surgery without waiting for the effect from the ongoing anti-inflammatory therapy, including steroids, hemostatic, transfusion of blood products, combat hypovolemia. It is important to objectively assess the amount of blood, patients allocated with faeces, as visual assessment not only to the patient but the physician is usually inadequate. The most accurate method of determining blood loss is radioisotope study that allows after pre-label the patient’s red blood cells isotope of chromium or technetium daily to determine the number of red blood cells in the stool. Blood loss of 100 ml per day or more is a special operation. Such an objective assessment of blood loss is possible not always and not everywhere. Indirect criteria of severity of blood loss are diarrhea over 10 times per day with heavy admixture of blood in the stool bulk more than 1000 ml a day, the preservation of baseline red blood on the background of blood transfusion.
Toxic dilatation of the colon occurs as a result of the cessation of peristaltic contractions of the colon wall, which leads to accumulation in the lumen of the intestinal contents, including large amounts of gas. The colon in these conditions is greatly expanded, until a critical level is 9-15 cm in diameter. The terrible symptoms of dilatation are sudden slowing of the stool on the background of the source of the diarrhea, bloating and increased pain and increase in symptoms of intoxication. Simple and valuable diagnostic technique is dynamic radiographic examination of the abdominal cavity, in which is noted the growth of pneumatosis of the colon and enhancing its clearance. Upon detection of dilatation of 6-9 cm (grade I dilatation) carry out an attempt of endoscopic decompression (evacuation of the colon through the colonoscope). The preservation of the dilatation and growth (9-11 cm — II degree, 11-15 cm — grade III) is an indication for emergency surgery.
Perforation of the colon usually occurs on the background of increasing toxic dilatation in case of unreasonable refusal of timely surgery. The reason for the perforations also serve deep ulcers with necrotic changes in all layers of the intestinal wall. It is important to keep in mind that during intensive hormonal treatment, antibiotics, antispasmodics and analgesics in patients with perforation on a background of ulcerative colitis is not the classic picture of acute abdomen, so the correct diagnosis can be very difficult. Again helps x-ray examination, when we celebrate the appearance of free gas in the abdominal cavity. The success of the operation depends on the timing of diagnosis and prescription of the development of peritonitis.
Cancer on a background of ulcerative colitis. In a population of patients with ulcerative colitis colon cancer occurs significantly more often, especially at prescription of disease more than 10 years. Adverse features are malignant undifferentiated forms, multiple and rapid metastasis, the extensive destruction of the colon tumor. When ulcerative colitis occurs the so-called total form of colon cancer, when vnutrismennyh tumor growth, the histological examination in all departments, while visually, the intestine may remain characteristic of chronic inflammatory process. The main methods of secondary prevention of cancer when ulcerative colitis is the annual dispensarization of patients, especially with total forms and the disease duration over 10 years, and multiple mucosal biopsy even in the absence of visual changes. Detection of dysplasia in biopsy specimens of the mucosa should be treated as a precancer, and the more in-depth and frequent examination.
Ulcerative colitis radical surgery is total removal of the colon with the formation of a permanent single-barrel ileostomy for brook. However, surgeons are looking for ways of rehabilitation of this severe category of patients, to develop the reconstructive surgery with restoration of bowel movements anal. In addition, simultaneous traumatic coloproctectomy associated with increased rates of morbidity and mortality in patients with very severe initial state.
The operation of choice in surgical treatment of severe ulcerative colitis is Subtotal resection of the colon with formation of an ileostomy and salmostoma. In this case, conduct intensive treatment of the stored segment of the colon in the postoperative period — the hormones in microclyster and candles, locally mesalazine, metronidazole, sanitation intestine antiseptic and astringent solutions. Option of resection can be colectomy the type of operation Hartmann, for example, if perforation has occurred in distalnom the sigmoid colon or the sigmoid colon was the source of the bleeding.
In the late postoperative period within 6 months. up to 2 years to decide on the second stage of surgical treatment. In the absence of relapses of ulcerative colitis in the rectum is disabled, perform the formation of ileorectal reconstructive anastomosis (with preventive ileostomy or not). With the development of stricture of the rectum requiring its removal — abdominal-anal resection of the saved departments the sigmoid and rectum. Reconstructive phase in this case can be the development of a reservoir from the small intestine (AutoProtect ampoules of the rectum), the imposition ileoanal anastomosis with preventive ileostomy. Preventive ileostomy in both cases close after healing of the anastomosis after 1 — 2 months. Be aware that even the formation of anastomosis between the small intestine and the anorectal line can’t guarantee a cure from ulcerative colitis, since 25-30 % of patients 3-5 years after such an operation is marked regeneration of the mucous membrane of the rectum small bowel in the tank even with a possible malignancy.
One-stage colectomy with abdominal-anal resection of the rectum is used during massive intestinal bleeding, when the source of bleeding is the rectum.
For moderate ulcerative colitis in the background of the satisfactory condition of the patient can also be the reason for the surgery, if the disease is hormone-dependent form. In this case, it is possible to perform one-stage surgery with the reconstructive stage — colectomy with formation of ileorectal anastomosis or colectomy with abdominal-anal resection of the rectum, formation of oleoresinous and overlay ileoanal anastomosis with preventive ileostomy.
With the development of colon cancer on a background of ulcerative colitis colectomy is used, combined with the abdominal-anal resection of the rectum. When the tumor in the rectum perform a colectomy and abdominoperineal extirpation of the rectum. Surgery for cancer is usually completes the formation of a permanent single-barrel ileostomy for brook.
Heavy initial state, most of the patients before surgery, influences the postoperative period, the development of postoperative complications and mortality. Complications are often associated with poor tissue regeneration in immunocompromised patients (eventrate, an inconsistency of seams intestinal Stom), there are also serous peritonitis, pleural effusion as a manifestation of polyserositis, and abscesses of the abdominal cavity, ileostomy dysfunction, pneumonia. Especially important active tactics of surgeon in case of complications on the background of reducing the resistance of the patient.
When operations for intestinal bleeding, toxic dilatation and perforation of the colon postoperative complications reach 60-80 %, and mortality ranges from 12 to 50%. In cases of timely surgical intervention in a specialized hospital complications and mortality do not exceed the level in other abdominal operations, accounting for 8-12% of postoperative complications and 0.5% and 1.5% postoperative mortality.
Prognosis after surgical treatment
With timely operation and dynamic monitoring of patients life expectancy is favorable. The required annual monitoring in case of preservation of the rectum with multiple biopsies and monitoring of malignancy. Most patients are long-term disabled (need of applying for disability).