Scheme of drug therapy for nonspecific ulcerative colitis in children. Ulcerative colitis (Nonspecific ulcerative colitis). Crohn's disease

Treatment of nonspecific ulcerative colitis depends on the localization of the pathological process in the intestine, its extent, the severity of the attacks, and the presence of local and systemic complications.

The main goals of conservative therapy:

• pain relief,
• prevention of relapse of the disease,
• preventing the progression of the pathological process.

Ulcerative colitis of the distal intestine: proctitis and proctosigmoiditis are treated on an outpatient basis, as they have a milder course. Patients with total and left-sided lesions of the colon are treated in a hospital setting, since they have more pronounced clinical manifestations and there are great organic changes.

Nutrition of the sick

The diet for ulcerative colitis should spare the intestines, help increase its regenerative abilities, eliminate fermentation and putrefactive processes, and also regulate metabolism.

Sample menu for ulcerative colitis:

• Breakfast - rice or any other porridge with butter, steamed cutlet, tea;
• Second breakfast - approximately forty grams boiled meat and berry jelly;
• Lunch - soup with meatballs, meat casserole, dried fruit compote;
• Dinner - mashed potatoes with fish cutlet, tea;
• Snack - baked apples.

Drug treatment

Treatment of ulcerative colitis of the intestine is carried out in three main directions:

• preventing or stopping internal bleeding;
• restoration of water-salt balance in the body;
• cessation of pathogenic effects on the intestinal mucosa.

Phytotherapy

Infusions from medicinal herbs have a mild restorative effect: they envelop the damaged intestinal mucosa, heal wounds, and stop bleeding. Herbal infusions and decoctions can replenish fluid loss in the body and restore water and electrolyte balance.

The main components of medicinal herbal mixtures are:

1. The leaves and fruits of currants, raspberries and strawberries help the liver fight any acute inflammatory process in the body.
2. Dried blueberries cleanse the intestines of putrefactive microorganisms and help in the fight against cancer cells.
3. Nettle improves blood clotting, relieves inflammation, and cleanses the intestines of decay and putrefaction products.
4. Peppermint fights emotional lability, diarrhea, relieves inflammation and spasms, and has a pronounced antimicrobial effect.
5. Chamomile is a powerful herbal antibiotic that can also relieve spasms.
6. Yarrow stops diarrhea, has bactericidal properties and cleanses the intestines of pathogenic microorganisms.
7. St. John's wort stimulates intestinal motility and has an anti-inflammatory effect.

These herbs are used to treat ulcerative colitis in the form of infusions and decoctions. They are combined into collections or brewed separately.

• Dry raspberry leaves and branches are poured with boiling water and left for half an hour. Take one hundred milliliters four times a day before meals.
• A collection of medicinal herbs is prepared as follows: mix a teaspoon of centaury grass, sage leaves and flowers pharmaceutical chamomile. Then pour a glass of boiling water and leave for thirty minutes. Drink one tablespoon every two hours. After three months, the intervals between doses of the infusion are lengthened. This treatment is harmless and can last for a long time.
• Peppermint leaves are poured with boiling water and left for twenty minutes. Take a glass twenty minutes before meals. An equally effective remedy for colitis is an infusion of strawberry leaves, which is prepared in a similar way.
• Fifty grams of fresh pomegranate seeds are boiled over low heat for half an hour, poured with a glass of water. Take two tablespoons twice a day. Pomegranate decoction is a fairly effective remedy for allergic colitis.
• One hundred grams of yarrow herb is poured with a liter of boiling water and left for a day in a closed container. After straining, the infusion is boiled. Then add one tablespoon of alcohol and glycerin and stir well. Take thirty drops half an hour before meals for a month.
• Mix in equal quantities medicinal sage, peppermint, chamomile, St. John's wort and cumin. This mixture is placed in a thermos, poured with boiling water and left overnight. Since next day, take the infusion regularly, half a glass three times a day for a month.

Folk remedies

• One hundred grams of dried watermelon rinds are poured into two glasses of boiling water and taken one hundred milliliters six times a day.
• Eight grams of propolis should be eaten daily to reduce the symptoms of colitis. It must be chewed for a long time on an empty stomach.
• Squeeze the juice from onions and take one teaspoon three times a day. This folk remedy is very effective in the treatment of ulcerative colitis.
• The whey obtained by squeezing feta cheese is recommended to be taken twice a day.
• Cores walnuts eaten regularly for three months. Positive results will become noticeable within a month from the start of treatment.
• How to cure ulcerative colitis using microenemas? For this, starch microenemas are shown, prepared by diluting five grams of starch in one hundred milliliters of cool water.
• Microenemas made from honey and chamomile, which are pre-brewed with boiling water, are considered effective. One enema requires fifty milliliters of solution. The duration of treatment is eight procedures.
• Viburnum berries are poured with boiling water and viburnum tea is drunk immediately before eating.

Crohn's disease and ulcerative colitis (UC) are considered together in many sources due to the commonality of symptoms. That's two autoimmune diseases, they are not fully studied, their etiology (cause), mechanism of occurrence is not clear, and there is no uniform approach to therapy. But these are still two different ailments, which requires considering UC, treatment of nonspecific ulcerative colitis, new methods of treating UC separately from Crohn's disease.

Modern approach to the treatment of ulcerative colitis

The treatment tactics for nonspecific ulcerative colitis depend on the severity of the attack, the localization of the process itself in the large intestine and its extent, and the presence of complications (local and/or systemic). Depending on this, they apply various methods treatments and their combinations. There are conservative and surgical treatment methods.

Principles of conservative treatment of ulcerative colitis

The “gold standard” for the treatment of UC is basic therapy, based on the prescription of drugs acting on the very link of the pathological process and is aimed at:

Achieving stable clinical remission (reducing the manifestations of the disease).
Improving quality of life.
Reduced number of local and systemic complications.
Reducing the number of indications for surgical treatment.
Minimizing side effects from treatment with basic drugs.

Basic therapy includes the prescription of three lines of drugs.

First line– preparations of 5-aminosalicylic acid (5-ASA), they selectively act on the intestinal mucosa, accumulating in it, providing an antimicrobial and anti-inflammatory effect.

Sulfasalozin is the first representative of this line, it was created in 1942 as antibacterial drug. Only later was it noticed that patients with UC feel better with it, and the manifestations of the disease decrease. But he has a very a large number of side effects.

Mesalazine 5-Amino-2-hydroxybenzoic acid is the second representative of 5-ASA drugs. Its derivatives are:

Salofalk, it starts, is released in the final section ileum.

Pentas, it begins its action in the duodenum and is not replaceable in case of high intestinal lesions.

Second line– glucocorticoid drugs.

Systemic - (prednisolone, methylprednisolone, hydrocortisone. They have a lot of side effects, with prolonged use or an incorrectly prescribed dosage, numerous complications develop, the most dangerous of which is inhibition of the function of the adrenal cortex.

Topical steroids (budenofalk fluticasone, budesonide) are drugs that act locally on the intestinal mucosa, with minimal systemic manifestations.

Third line– cytostatics, they suppress the work immune system and are reserve drugs. They are prescribed if the disease cannot be treated with drugs of the first two groups. The peculiarity of their action is that the therapeutic effect is achieved 1-2 months after the start of treatment.

Non-selective (non-selective) - metatrexate, 6-mercaptopurine, azathioprine, azafalk.
Selective (selective) – sandimum, cyclosporine A.

Therapy biological drugs– a new direction in the treatment of UC. Recombinant cytokines, recombinant α-interferon and TNF antibody inhibitors (Remicade, adalimumab) are used.

Auxiliary therapy: enzymes, antibiotics, detoxification therapy, parenteral nutrition (proteins, fats, carbohydrates), probiotics (lactobacteria, bifidobacteria), extracorporeal hemocorrection.

Indications for surgical treatment of UC

Absolute:

All acute conditions: peritonitis, acute dilatation of the large intestine, abscesses and infiltrates in the abdominal cavity, intestinal perforation, intestinal bleeding.
Acute and continuous recurrent course of UC, lack of effect from conservative treatment for more than 4 weeks.
Tumor degeneration.

In all other cases, the issue of surgical treatment of UC is decided individually.

Treatment of UC is a complex and lengthy process, requiring close contact between the patient and the doctor; without this condition it is not possible to achieve stable remission.

Article prepared by:

The disease UC (nonspecific ulcerative colitis) is chronic and immune in nature. The exact reasons for its development have not yet been established by science. The risk group for the development of pathology includes all people, regardless of gender and age. However, in the interval from 20 to 40 years and from 60 to 70, more patients are diagnosed with Ulcerative Colitis. The disease occurs in 50-80 people out of 100, the female population predominates. From 3 to 15 new cases are registered per year.

In this article you will learn:

The concept of pathology and its causes

Nonspecific ulcerative colitis (K51.9 in ICD-10) is a chronic inflammatory process in the large intestine, caused by the aggressive influence of cells of the rectum and colon on each other and accompanied by ulcerative lesions of the intestinal mucosa.

The pathology has no established etiology, which makes diagnosis and, accordingly, treatment difficult.

However, with a competent approach and correct therapy, UC is curable. You can achieve stable remission and significantly improve your quality of life. In 4% of cases, remission lasts 15 years.

TO possible reasons occurrence of UC include immune disorders and genetic predisposition. Any viruses or bacteria, infections or congenital pathologies. If we follow the gene theory, then specific genes can provoke UC (they have so far been tentatively identified and not definitively confirmed).

Additionally, among the possible negative factors, the researchers identified smoking and non-compliance with nutritional rules, taking non-steroidal drugs, removal of appendicitis at an early age, and nervous strain.

The likelihood of a combination of external and internal factors(for example, the scheme “stress – activation of bacteria against the background of a decrease in the body’s regulatory forces”).

Forms of pathology

Atypical ulcerative colitis has several medical classifications. The forms of the disease and their description are presented in the table.

The total type is more susceptible to a severe course. The left-sided type is the most common (80 out of 100). The continuous type occurs in 10 cases out of 100.

Necrotizing ulcerative colitis is a separate type of pathology diagnosed in newborns (usually premature infants) who have been exposed to oxygen and nerve starvation in the womb. But it can also occur as a complication in severe colitis in adults. Characterized by cell death (the last advanced stage).

Signs of pathology

Symptoms of UC in adults include:

• bloody diarrhea with mucus and/or pus;
• discharge of blood from the anus outside of bowel movements;
• abdominal pain similar to contractions, intensifying after eating food;
• false urge to go to the toilet;
• swelling of the legs;
• despite frequent bowel movements, a feeling of incomplete emptying;
• bloating.

Signs of ulcerative colitis intensify as the pathology develops. Tachycardia and fever are added. Over time, noticeable weight loss occurs and signs of nutritional deficiencies are observed.

Symptoms on advanced stages often accompanied by extraintestinal signs, which complicates the diagnosis and treatment of ulcerative colitis in adults.

Detection methods

Diagnosis of UC includes medical history, palpation and examination, and instrumental techniques:

Symptoms of ulcerative colitis of the intestine in women can be confused with gynecological pathologies, which requires additional consultation with a specialist. Treatment is carried out with hormonal drugs, which also requires consultation with a gynecologist.

Possible consequences

Disability from ulcerative colitis and death are the worst complications. You can maintain your ability to work by mild stage diseases. Disability group 3 allows for some work.

Inflammation tends to spread and affect other organs (eyes, mouth, bones and joints, skin). For the intestines, the progression of the disease is dangerous due to oncology. There is a risk of fistulas and abscesses.

The most common complications are narrowing, obstruction, persistent bleeding, perforation and dilatation of the intestine. The latter is dangerous due to rupture. Any of these complications require immediate hospitalization.

The first thing to do in the event of an exacerbation of UC is to go to the hospital for qualified help, the purpose of which is to relieve the attack.

Traditional treatment

Treatment of ulcerative colitis with drugs involves taking corticosteroids (Prednisolone, Budesonide), 5-ASA (Mesalazine, Colazal), antidepressants (Methotrexate) and cytostatic drugs (Infliximab). In severe cases with severe fever and strong signs of inflammation, antibiotics (Metronidazole) are used.

To eliminate symptoms, medications that relieve pain and stop diarrhea (Loperamide) are prescribed. If necessary, rehydration is carried out, the body is saturated with iron.

5-ASA is usually prescribed as an anti-inflammatory agent. The use of corticosteroids is indicated only during periods of severe exacerbation of the second and third degrees of severity of the disease and for only a few months.

The goal of treatment at present is to eliminate symptoms, reduce inflammation, and prevent relapses. However, new treatments for ulcerative colitis are being developed regularly. Research is being conducted on the effectiveness of innovative topical drugs based on bioprocesses and gene structures. In Israel, Remicade, an anti-TNF drug (tumor necrosis factor), is actively used in practice.

If a combination of medications, diet and physiotherapy is ineffective, surgical treatment is indicated: resection with anastomosis or segmental resection.

Traditional therapy

Non-traditional methods of treatment include suppositories and a solution of mumiyo, infusions of herbs and plants (chamomile, mint, blueberries, nettle, St. John's wort, celandine), propolis, honey, sea buckthorn.

Drug treatment of ulcerative colitis

Doctor of Medical Sciences, Prof. V.G. Rumyantsev, Head of the Department of Colon Pathology, Central Research Institute of Gastroenterology, Moscow Department of Health

Ulcerative colitis is a disease of unknown etiology with a chronic, undulating course. Its morphological basis is superficial, diffuse inflammation of the mucous membrane, initiated in the rectum and spreading in the proximal direction. The process does not extend beyond the colon and therefore the patient can be relieved of painful sensations by radical surgery. Drug therapy allows you to control the course of the disease with an acceptable level of quality of life. It is encouraging that the course of even total colitis is becoming more favorable. The severity of attacks and the frequency of exacerbations are reduced, and the process often regresses, limited to the rectum and sigmoid colon. Thus, non-surgical treatment remains the leading option in the treatment of ulcerative colitis. The superficial nature of the inflammation and the obligatory involvement of the rectum determines three essential features of the treatment of the disease: the first is the effectiveness of “locally” acting anti-inflammatory drugs, in particular sulfasalazine and its analogues; the second is the need to use rectal dosage forms and, finally, the third is the less successful effect of immunomodulatory agents than in Crohn's disease. The choice of treatment is based on the location and extent of the lesion, the severity of the attack, sensitivity and refractoriness to certain medications, and the fundamental possibility of achieving remission in a given patient.

Goal of therapy
It is extremely important for the clinician to clearly understand the goal of treating the disease, taking into account the real possibilities drug treatment. The question remains debatable regarding the possibility of achieving “biological” remission. Thus, with ulcerative colitis, asymptomatic patients in 35-60% of cases retain endoscopic activity, and 90% of patients, even with endoscopic remission, show histological signs of inflammation, a third of which are acute.

Endoscopic and histological remission lag in time. When should therapy be stopped? The answer to this question is provided by a retrospective analysis of the frequency of exacerbations. If with endoscopic remission 4% of exacerbations of ulcerative colitis are observed during the year, then with continued endoscopic activity - already 30%. Availability histological features acute inflammation increases the risk of exacerbations by another 2-3 times. Therefore, in all cases of recurrent ulcerative colitis, one should strive for histological remission, which is the basis for discontinuation of therapy. This rule does not apply to chronically continuous or active types of the disease, severe acute forms, and patients with frequent exacerbations. In these cases, long-term maintenance therapy and a change in guidelines may be required - to achieve a minimum level of activity at which the patient is relieved of painful symptoms and maintains a normal quality of life, to avoid surgery or frequent re-exacerbations. From a practical point of view, it is important that induction of clinical endoscopic remission should be the goal of treatment of any newly diagnosed ulcerative colitis, chronically recurrent forms of the disease and those chronically active cases where therapy is considered inadequate. If endoscopic control is not possible, you should use the following rule: therapy is carried out until stool normalization and then for at least 3 weeks, which should be sufficient to achieve an endoscopic effect.

Mild to moderate attack of distal colitis
Distal ulcerative colitis is a concept that includes three main forms of the disease: proctitis - an inflammatory process extending up to 20 cm from the edge of the anus, proctosigmoiditis (from 20 to 40 cm) and left-sided colitis (40-80 cm). They account for a total of 60-70% of all cases of ulcerative colitis and have important features of pathogenesis, clinical presentation and treatment that distinguish them from total damage to the colon. These differences are due to the unequal functional activity of the right and left half of the colon, the characteristics of motility, absorption and metabolism in the intestinal wall. Distal colitis occurs without systemic complications. As a result of retention of intestinal contents above the zone of active inflammation, the clinical picture False urges often come out with mucus and blood, with constant “traumatization” of the mucous membrane with dense, formed feces. Urgency may be accompanied by anal incontinence. The accessibility of the inflammatory zone for rectally administered drugs, the high concentration they create in the intestinal wall and the low concentration in the systemic circulation serve as a prerequisite for predominantly local therapy of distal ulcerative colitis. The clinical effect with the rectal route of drug administration is almost always higher than with oral administration. By manipulating the volume and rate of administration, using various dosage forms, it is possible to ensure delivery of the drug to the desired segment of the colon. The liquid enema reaches the splenic flexure, and with a volume of over 100 ml it moves further in the proximal direction. The foam is distributed in the rectum and sigmoid colon, and suppositories are limited only to the rectum.

For the local treatment of ulcerative colitis, many drugs have been proposed, but only corticosteroids, which act on the “proximal” mediators of the immune-inflammatory cascade, and aminosalicylates, which also act on multiple, but “distal” links in the pathogenesis, are considered basic. The use of liquid glucocorticoid enemas was first proposed back in the 50s, and their proven ability to reduce the inflammatory response upon contact with mucous membranes made this therapy popular. Rectally administered steroids are poorly absorbed and are therefore safer than orally administered steroids. Short courses of rectally administered corticosteroids (prednisolone at a dose of 20-40 mg/day, hydrocortisone - 100-250 mg/day, etc.) are effective in the treatment of distal ulcerative colitis of any severity, but they are not recommended for continuous use to maintain remission due to side effects phenomena. And this small risk is enough to strive to use “systemic” glucocorticoids according to strict indications. An alternative in the treatment of distal colitis is the use of 5-aminosalicylic acid (5-ASA) or topical steroids. 5-ASA preparations are as effective in treating active inflammation as glucocorticoids, and even superior to them. They also help those patients in whom hydrocortisone therapy was unsuccessful. It should be noted that the effective dose of rectally administered 5-ASA preparations can vary widely - from 1 to 4 g per day. In a double-blind, controlled study, the effect of placebo and 5-ASA at doses of 1, 2 and 4 g was compared in 287 patients /10/. Clinical improvement with placebo was obtained in 27% of patients, with 5-ASA - in 67, 65 and 75%, respectively. The drug was safe not only in traditional quantities, but also when administered intraintestinal at a dose of 8 g/day. Aminosalicylates in Europe and the USA are considered first-line drugs for the treatment of ulcerative colitis, while glucocorticoids are used in the absence of effect or allergy to 5-ASA. Before prescribing systemic steroids, budesonide 2 mg/day is used in enemas. The drug has a high affinity for hormonal receptors and 90% of it is converted into metabolites that lack biological activity already during the first passage through the liver. Budesonide enemas were comparable in inducing remission to systemic hormones, but weaker than 5-ASA at a dose of 4 g. The drug did not inhibit the pituitary-adrenal axis, and in combination with mesalazine provided an effect exceeding the effect of each drug separately. The possibility of inducing remission of distal colitis using monotherapy with sulfasalazine and its analogues is excluded, although such attempts are still often made. This is due to the fact that oral drugs do not create therapeutic concentrations in the mucous membrane of the rectum and sigmoid colon. 5-ASA is released in the right colon, and only a small amount reaches the rectum. A study of the concentration of the drug in the intestinal mucosa shows that only rectal administration allows you to count on the effect. Both systemic steroids and 5-ASA can be used to induce remission of distal colitis. All other things being equal, you need to use the drug to which the patient is more sensitive and change it when resistance is detected. Usually the effect appears
after 1-2 weeks, but treatment of active distal colitis is continued for the period necessary to achieve complete clinical and endoscopic remission - 6-8 weeks. Justified in case of prolonged attack long-term treatment with a transition to intermittent administration of drugs 2-3 times a week. If treatment with rectal 5-ASA does not produce the desired result, therapy can be intensified by combination with topical steroids or additional oral 5-ASA. Oral medications are always prescribed for left-sided colitis and can be used for more limited lesions in order to prevent progression of the process in the proximal direction.

Mild to moderate widespread ulcerative colitis
In the treatment of mild to moderate widespread colitis, sulfasalazine and its analogues are used orally in combination with local therapy. Which 5-ASA preparations should you prefer? If sulfasalazine is well tolerated, there is no need to use “pure” 5-ASA preparations. Side effects of sulfasalazine (headache, nausea, vomiting, dizziness) are caused by toxic concentrations of sulfapyridine due to its slow or weak acetylation in the liver.
Slow acetylators suffer earlier and more severely. Special studies have found that in the USA up to 60% of people in the general population are slow acetylators, while in Japan up to 90% are fast acetylators. As for Russia, there is no information about this. It can be assumed that the genetically determined “slow” type of acetylation is less common than in the USA and Europe. Sulfasalazine is used in the active phase of the disease at a dose of 4-6 g per day. In case of toxic reactions, the search for a tolerable dosage begins with 0.5 g, gradually increasing over several weeks to 2 g / day (the “titration” method). For those patients who develop an allergy in the form of a rash and fever, you can start taking sulfasalazine with a dose of 1 mg, slowly increasing it over 2-3 months. In recent years, these techniques have been rarely used due to a certain degree of risk and the existence of safe alternative treatments. These include preparations of “pure” 5-ASA (Mesacol, Salofalk, Pentasa). They lack sulfapyridine and the release of 5-ASA is based on pH and time-dependent mechanisms. Mesacol releases 5-ASA in the colon at pH-7, Salofalk - in the terminal ileum at pH-6, Pentasa - throughout small intestine. They are equally useful in the treatment of generalized ulcerative colitis, although drugs with more distal release appear to be preferable. Unlike local application 5-ASA, where the dose-dependent effect of the drug has not been established, oral aminosalicylates are more effective the higher the dose. Sutherland et al. /32/ conducted a meta-analysis of 8 trials, including 1000 patients, which compared 5-ASA and placebo in inducing remission of ulcerative colitis. A dose-dependent effect was confirmed: a) less than 2.0 g per day, OR - 1.5; 95%; CI - 0.89-2.6; b) from 2.0 to 2.9 g/day, OR - 1.9; 95%; CI - 1.3-2.8; c) more than 3.0 g per day, OR - 2.7; 95%; CI - 1.8-3.9. At least 80% of patients with moderately active ulcerative colitis can respond to 5-ASA therapy at a dose of 2.0-4.8 g/day. Studies are being conducted to establish safe upper dose limits for 5-ASA.
As already indicated, in the treatment of widespread ulcerative colitis it is necessary to combine oral and rectal dosage forms. The therapeutic strategy for using aminosalicylates for widespread colitis can be quite flexible. Therapy is usually started with sulfasalazine. There are two reasons for transferring a patient to “pure” 5-ASA drugs: serious side effects and the need to use high doses. If sulfasalazine is ineffective, 5-ASA preparations with pH-dependent release are used. If the capsules are excreted unchanged in feces, this serves as a signal for the use of 5-ASA with a time-dependent coating.

Treatment of severe ulcerative colitis
There is no alternative to corticosteroids in the treatment of a severe attack of ulcerative colitis. Usually preference is given parenteral use hydrocortisone 400 mg/day or prednisolone 120 mg/day for 5-7 days, after which the patient is transferred to oral administration at the rate of 1.0-1.5 mg/kg body weight. Treatment is continued for 3 or more months, gradually reducing the dose. Remission rates approach 80%. In case of a moderate attack of ulcerative colitis, therapy is immediately started with prednisolone tablets. The initial dose differs between centers. There are at least three approaches to dose selection: the first is the minimum dose with a gradual increase to the optimal dose, the second is the average dose, sufficient for the vast majority of patients, and, finally, the obviously excessive dose, which is corrected after achieving clinical effect given the speed of its advance. However, in our opinion, the first dose is unacceptable in cases of severe colitis, since it requires significant time to find an effective dose, and this is fraught with the development of complications and unjustified surgical intervention. Reducing the “overestimated” dose may be slow or
fast. Starting with a dose of 30 mg/day, aminosalicylates are added, which are left as maintenance treatment after discontinuation of corticosteroids. In order to prevent osteoporosis, patients are prescribed calcium and vitamin D supplements. If necessary, the patient is transferred to parenteral or enteral nutrition, correction of water and electrolyte disturbances, and antibacterial therapy with metronidazole, cephalosporins or ciprofloxacin are carried out.
The use of oral aminosalicylates concomitantly with steroids in severe ulcerative colitis is not supported for the following reasons:
1) they are weaker than glucocorticoids in their anti-inflammatory effect;
2) aminosalicylates reduce the response to steroids;
3) side effects that occur when taking aminosalicylates can worsen the course of colitis, and therefore simulate resistance.
Regarding pulse therapy and short courses hormonal treatment, there is no consensus. It is possible to successfully use pulse therapy with methylprednisolone at a dose of 1 g/day or dexamethasone at a dose of 100 mg/day in the form of 3-day infusions. However, short courses of hormonal therapy to interrupt the attack are effective only during the period when the first signs of exacerbation appear in severely ill patients with inflammatory bowel diseases. In this case, therapy with high doses of steroids is continued for no more than 10-14 days with a transition to intermittent use of hormones or aminosalicylates. This is the period during which hormonal treatment can be discontinued without “withdrawal syndrome.” Of course, this is only possible in young patients in the absence of serious concomitant diseases and previous long-term hormonal therapy.

Continuous course of ulcerative colitis and hormonal dependence
There is a category of patients who, even with adequate treatment, cannot achieve lasting improvement or remission and require constant maintenance therapy. These may be patients with distal or widespread colitis with varying degrees of activity. Among them are patients with hormonal dependence. Hormonal dependence is generally considered to be the inability to reduce the dose of prednisolone below 10 mg/day without exacerbation of the disease or an outbreak of the process within 3 months after stopping hormonal treatment /7/. In this case, there are four options: the use of gentle intermittent use of hormones, transfer to topical steroids, the use of azathioprine/methotrexate or infliximab. Intermittent use of hormones was borrowed from pediatric practice.
The optimal dose has been shown to be 40 mg of prednisolone every other day. The best results and minimal side effects were observed at this dose. Suppression of the pituitary-adrenal axis was not observed, which made it possible to stop treatment at once, without fear of “withdrawal syndrome.” This regimen was successful in patients with frequent exacerbations and chronic continuous course of the disease. Two methods have been developed for transition from basic course hormonal therapy: by transferring 1 tablet (5 mg) of prednisolone from one day to another every 10 days or by reducing the dose by 5 mg every second day with an interval of 6-10 days. The first method was more reliable and less likely to cause reactivation.
Transferring the patient to topical steroids (budesonide) can also avoid dangerous side effects. Literature data indicate that in 2/3 of hormonally dependent patients, systemic steroids can be reduced or discontinued. It must be remembered that budesonide at the recommended dose (9 mg/day) corresponds to 30 mg of prednisolone. They are prescribed simultaneously and only then the systemic steroids are gradually reduced until complete withdrawal.
Much more often in the treatment of hormonally dependent forms inflammatory diseases intestines, immunosuppressants are used, in particular azathioprine. An analysis of more than 20 years of experience in its use in hormonal-dependent ulcerative colitis has shown that induction of remission with simultaneous withdrawal of steroids becomes possible in 40-80% of patients. Azathioprine therapy is continued for 4 years or more. However, it should be taken into account that the effect of the drug is delayed and appears no earlier than 3 months. Therefore, it is important to use an adequate dose of azathioprine (2.0-2.5 mg/kg) and duration (at least 6 months). The drug is relatively safe, but in individuals with genetically low activity of thiopurine methyltransferase, the development of leukopenia and sepsis may occur. Treatment with azathioprine is contraindicated in them. Fortunately, monozygotic low thiopurine methyltransferase activity is rare, occurring in only 0.3% of cases. Another 11.1% have heterozygous or intermediate activity, requiring a dose reduction of 50%.
If the effect is insufficient, they resort to prescribing methotrexate. It is an analogue of dehydrofolic acid, which low doses exhibits immunomodulatory properties.
Methotrexate 25 mg weekly IM or SC has been shown to be effective in inducing and maintaining remission of Crohn's disease. However, it can be successfully used in some cases of ulcerative colitis. Side effects relatively small. The use of methotrexate is limited by the teratogenic effect, hepatotoxicity and the possibility of developing liver fibrosis with long-term use. The drug can also be used orally in the form of 5 mg tablets every other day, but the bioavailability of oral methotrexate varies significantly. This method of administration is suitable only during the period of maintaining remission.
When treatment fails, intolerance to these immunosuppressive drugs or the need for a rapid response, infliximab has been used in recent years. A single intravenous administration of infliximab at a dose of 5 mg/kg can stop active manifestations of the disease, and repeated infusions every 8 weeks can maintain remission. Infliximab has a sparring effect with respect to glucocorticoids. It is recommended to use it for a year as monotherapy or in combination with azathioprine.

Hormonal resistance
Hormonal resistance is the most serious problem that clinicians have to face. The interpretation of the concept of “resistance” is especially difficult in ulcerative colitis. Thus, in a severe attack, resistance is established after the first 5 days of intensive hormonal therapy, and in distal forms - after 6-8 weeks of treatment - 5-ASA orally and locally - steroids. There is much that is unclear about the emergence of hormonal resistance. Some describe a reduced level of receptors only in resistant patients, while others describe a reduced level of receptors in all patients without exception compared to controls. Corticosteroid receptors express either the active alpha chain or its opposite, the beta chain. The latter is determined precisely by hormonal stability /1/. Patients with ulcerative colitis with high levels of antineutrophil cytoplasmic antibodies are refractory. In addition, increased expression of the multidrug resistance gene, identified in peripheral lymphocytes of patients with inflammatory diseases of the colon who require surgery /8/, may be important in this process.
For nonspecific ulcerative colitis, after 5 days of unsuccessful IV corticosteroid therapy, cyclosporine is prescribed. It is a powerful immunosuppressant with selective action to a T-lymphocyte immune response that inhibits the transcription and production of IL-2 and interferon-gamma. The increasing use of cyclosporine in clinical practice confirms the usefulness of such treatment. Colectomy can usually be avoided in 40-69% of patients. The protocol for the use of cyclosporine involves starting treatment with an intravenous infusion at a dose of 2-4 mg/kg and maintaining a blood concentration of no more than 500 ng/ml for 7-10 days. Next, the patient is transferred to taking the drug orally at a dose of 5-8 mg/kg and the concentration is monitored at a level of about 300 ng/ml. Later it was shown that a similar effect can be obtained using oral microemulsion cyclosporine at a dose of 5 mg/kg with high bioavailability. Treatment is continued for 3 months, combining it with the prescription of azathioprine, which is left as maintenance therapy. Usually, the well-established side effects of cyclosporine (impaired renal function, hypertension) are feared and blood pressure, renal and liver function are monitored, and blood concentrations are monitored. Our experience with Neoral confirms the ability of cyclosporine to overcome hormonal resistance with a good long-term effect in 64% of patients. The concentration of cyclosporine in the blood varied from 80 to 170 ng/ml and in no case was treatment interrupted due to dangerous side effects. In our opinion, oral cyclosporine is quite safe and effective drug in the treatment of severe forms of ulcerative colitis, which can be used in wide clinical practice as an alternative to surgery.
A new agent, infliximab, is being used for resistant forms of Crohn's disease. These are chimeric monoclonal antibodies to tumor necrosis factor. Its main mechanism of action is related to the neutralization of this proinflammatory cytokine on cell membranes and induction of apoptosis of activated T cells. The first experience of using infliximab in patients with ulcerative colitis did not allow us to draw a final conclusion about the effectiveness of the drug in achieving remission of the disease, overcoming hormonal dependence and resistance. However, two published large randomized trials tipped the balance in favor of infliximab (24, 29). In these studies, 364 patients who did not respond to at least one of the standard treatments (including oral 5-ASA) received infliximab at doses of 5 mg/kg, 10 mg/kg, or placebo. After a triple induction regimen at 0, 2, and 6 weeks, they received repeat infusions every 8 weeks. Not only clinical, but also endoscopic remission was achieved in 60-62% of patients when taking infliximab at a dose of 5 mg/kg after 8 weeks. compared to 31-34% when taking placebo (P0.001). Moreover, remission remained at 54 weeks (46 vs. 18%). Taken together, the results of these two studies provide clear evidence for the effectiveness of treatment for active refractory ulcerative colitis.
Although these data relate to outpatients, it can be assumed that the drug is also effective in cases of unsuccessful treatment with IV steroids /12/. Treatment with chimeric antibodies inevitably leads to the formation of antibodies to the drug itself, which is accompanied by an increased risk of infusion reactions and a reduction in the duration of response to Therapy due to a decrease in therapeutic concentration. The risk of antibody formation can be reduced by combination with other immunosuppressants, pre-administration of glucocorticoids and regular maintenance treatment. The risk of opportunistic infections and tuberculosis must be taken into account. A positive Mantoux test, even in the absence of radiological changes in the lungs, serves as a basis for anti-tuberculosis therapy for at least a month, ahead of infliximab infusion during this period.
Therapy should be carried out under supervision and control in a specialized setting medical institution, equipped necessary equipment for intensive care of possible severe infusion reactions. The drug should not be used as preliminary therapy for refractory disease subject to surgical treatment. Although most experts believe that infliximab does not increase the risk of surgical complications, half of them prefer to delay surgical intervention for 1 month after attempting treatment with the drug.
Treatment with infliximab is safe during pregnancy and breastfeeding. It is contraindicated in active tuberculosis and other infections, in patients with heart failure, in demyelinating diseases, optic neuritis, in patients with a history of malignant neoplasms and lymphoma.

Maintaining remission
Ultimately, it is important not only to achieve remission, but also to maintain it for as long as possible. For this purpose I use, first of all, aminosalicylates. The optimal dose for maintenance treatment is 2 g/day, with which “addiction” does not develop and the protective effect lasts for many years. A meta-analysis comparing sulfasalazine and “newer” aminosalicylates showed a slight advantage of sulfasalazine in maintaining remission of ulcerative colitis (OR - 1.29; 95%; CI - 1.06-1.57) /33/. A dose-dependent effect in maintaining remission is not observed according to the meta-analysis, although a number of researchers believe that the maintenance dose should be equal to the remission induction dose /11/. Apparently, in order to prevent exacerbation, both continuous and intermittent administration of 5#ASA can be used. Mesalazine at a dose of 2.4 g/day for a week of each month was as effective as continuous use at a dose of 1.6 g/day, and the use of 3 g of sulfasalazine at the first symptoms of an outbreak led to the same result as regular use. intake 2 g/day. In order to maintain remission of distal colitis, both oral and rectal medications in the form of suppositories and enemas can be used indefinitely /4/. With equal dosage, single administration has advantages over multiple administration. The unpopularity of rectal forms in patients can also be mitigated by intermittent administration. It must be remembered that rectal treatment with 5-ASA for left-sided
colitis better than placebo and oral mesalazine (OR - 2.41; 95%; CI -1.05-5.54) /19/, better than glucocorticoids (OR - 2.03; 95%; CI - 1.28-3 ,20) /20/, but is inferior to combined treatment (oral + local) /6, 25/. After suffering a severe attack of ulcerative colitis, maintenance treatment should be carried out for a long time - up to two years. If exacerbations are seasonal, then preventive therapy for only months is usually sufficient. increased risk. If treatment with 5-ASA is ineffective, they resort to taking azathioprine for 2-4 years. In recent years, interest in the use of probiotics as a means of preventing exacerbations of ulcerative colitis has increased significantly. As shown in two controlled studies where patients with ulcerative colitis received 5-ASA or E. coli Nissle 1917 capsules as maintenance treatment, the effectiveness of probiotics and 5-ASA was similar /15, 23/.

Unconventional treatment of ulcerative colitis
Many drugs have been proposed for general and local treatment of ulcerative colitis, although not in all cases their effectiveness has been adequately tested by multicenter controlled trials. clinical trials. As a rule, we are talking about auxiliary or “adjuvant” therapy. This includes leukotriene B4 inhibitors, anesthetics, stabilizers mast cells, immunoglobulins, reparants, protectors, antioxidants and nicotine. Omega-3 polyunsaturated fatty acids (Eikanol) have synergism with the action of 5-ASA and corticosteroids, inhibiting leukotriene B4. Use of Eikanol or other drugs fish oil may be useful in controlling active ulcerative colitis or preventing exacerbations /17/. For non-smokers, nicotine is effective when applied in the form of applications to the skin in a dose of 5-22 mg or enemas in a dose of 6 mg.
The effect is moderate, exceeding placebo by 25-30% /28/. Topical sodium cromoglycate may be prescribed as a trial treatment, especially if high levels of eosinophils are detected in the biopsy specimens. Of considerable interest was the use of a mixture of short-chain fatty acids (butyric, acetic, propionic), which are necessary elements for the nutrition and regeneration of the colon epithelium. In a large controlled trial of short-chain fatty acids in enemas in 91 patients with left-sided ulcerative colitis positive effect was obtained in 65% of observations /3/. However, to date it has not been possible to obtain pharmacologically stable drugs, and therefore a technique in which prebiotics are administered that enhance the endogenous synthesis of these acids is more often used. Thus, in 105 patients with ulcerative colitis, 5-ASA or the drug Plantago ovata (Mukofalk) were used to maintain remission. The effect was the same, but after taking Mucofalk, a significant increase in the content of butyric acid in feces was noted /9/.
Other sources can also be used to increase butyrate synthesis dietary fiber, for example, sprouted barley. In a controlled study in active phase ulcerative colitis and in the period of remission it was shown that barley food product significantly reduced the activity of the inflammatory process, allowed to reduce the use of steroids and the frequency of exacerbations /13/. In the case when it is necessary to improve the continence function during active distal colitis, anesthetics are used - lidocaine or ropivacaine in gel. It is curious that these drugs significantly reduce the activity of inflammation, affecting its neurogenic component /26/. The mediator of neurogenic inflammation in the colon is known to be substance P, which acts on neurokinin receptors. In a pilot study of a neurokinin-1 receptor antagonist in ulcerative colitis, a more rapid disappearance of pain and bleeding was noted; by the end of 4 weeks, 5 of 9 patients achieved remission /35/. In uncontrolled trials, an effect was also observed from intravenous transfusions of immunoglobulins (2 g/kg for 2-5 days, then 200-700 mg/kg every 2 weeks for 3-6 months) /16/. For some reason, arsenic preparations are rarely mentioned in the list of treatments for ulcerative colitis, although there were quite encouraging results. Clinical experience shows that Osarbon vaginal suppositories can be successfully used for minimal activity ulcerative colitis instead of traditional therapy. Sometimes used as a topical enema treatment of sucralfate and bismuth subsalicylate. A number of studies have confirmed their effectiveness /36/.
If azathioprine is intolerant, it is recommended to replace it with mycophenolate mofetil, an immunosuppressive drug used in transplantation and for autoimmune disorders, where it has proven to be more effective than azathioprine /31/. It has already been tested for Crohn's disease, but has been used relatively rarely for ulcerative colitis. There is only one cohort study comparing mycophenolate mofetil 20 mg/kg/day with azathioprine for active ulcerative colitis. After 12 months, 88% of patients were in remission on this drug and 100% on azathioprine /21/.
The same replacement exists for cyclosporine - tacrolimus (FK-506) - a macrolide immunosuppressant. There is positive experience in treating inflammatory bowel diseases. A number of researchers include low molecular weight heparin in the treatment of ulcerative colitis, although the treatment results are quite contradictory /2,
14, 18/.
Much effort is being made to find optimal therapy for severe refractory colitis. These are anti-cytokine strategy and sorption methods. The use of leukocytopheresis in severe hormonally dependent ulcerative colitis is very successful. Compared with placebo, the effect was 80% versus 33% /30/, while the rate of clinical improvement increased in proportion to the frequency of apheresis. Thus, when it was performed once a week, remission was achieved in 22.5 days, and when apheresis was performed 2-3 times a week, in 7.5 days /27/. Pegylated interferon-alpha at a dose of 0.5 mcg/kg can also be used in the treatment of ulcerative colitis. Using weekly injections for 12 weeks. Clinical and endoscopic remission is achieved in 60% of patients /34/. The first trials of human monoclonal antibodies to CD3 lymphocytes /22/ and IL-2 receptor antagonists /5/ look promising. Blocking chimeric monoclonal antibodies to CD25 have been shown to increase sensitivity to glucocorticoids, and therefore overcome hormonal resistance.
Thus, the arsenal of drugs suitable for use in the treatment of ulcerative colitis is constantly growing. Skillful use of unconventional techniques can increase efficiency basic therapy, but infatuation with them to the detriment of proven and included in the standards medicines would be a serious mistake, fraught with negative consequences for the patient. Knowledge of standards is necessary because facilitates the doctor’s choice of medications and their administration regimens, guarantees safety and high quality of care medical care to these patients.

Literature
1. Ayabe T., Imai S., Ashida T. et al. Glucocorticoid receptor beta expression as a novel predictor for therapeutic efficacy of corticosteroid in patients with ulcerative colitis.// Gastroenterology.1998.114. A 924.
2. Bloom S., Kiilerich S., Lassen M.R. et al. Randomized trial of Tinzaperin, a low molecular weight heparin (LMWH) versus placebo in the treatment of mild to moderately active ulcerative colitis.// Gastroenterology. 2003. 124.4. Suppl. 1. P. 540.
3. Breuer R.I., Soergel K.H., Lashner B.A. et al. Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: A randomized, placebo controlled trial.// Gut.1997.40.4. P. 485-491.
4. Casellas F., Vaquero E., Armengol J.R., Malagelada J.R. Practically of 5-aminosalicylic suppositories for long-term treatment of inactive distal ulcerative colitis.// Hepato-Gastroenterology.- 1999. 46. 28. P. 2343-2346.
5. Creed T., Hearing S., Probert Ch. et al. Basiliximab (IL-2 Receptor antagonist) as a steroid sensitizing agent in steroid resistant ulcerative colitis.// Gastroenterology.- 2003. 124. 4. Suppl. 1. P. 65.
6. D'Albasio G., Pacini F., Camarri E. et al. Combined therapy with 5#aminosalicylic acid tablets and enemas for maintaining remission in ulcerative proctitis: a randomized doubleblind study.// Am. J. Gastroenterol. - 1997. 92. P. 1143-1147.
7. ECCO Consensus on the Management of Crohn’s disease.// Gut.- 2006.- 55 (Suppl.1).
8. Farrel R.J., Murphy A., Long A. et al. High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy.// Gastroenterology. 2000. 118. P. 279-288.
9. Fernandez-Banares F., Hinojosa J., Sanches-Lombrana J.L. et al. Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis.// Am. J. Gastroenterol. 1999. 94. P. 427-433.
10. Hanauer S.B. Dose-ranging study of mesalamine (pentasa) enemas in the treatment of acute ulcerative proctosygmoiditis: Results of a multicentered placebo-controlled trial // Inflam. Bowel Dis. 1998. 4. P.79-83.
11. Hanauer S.B., Meyers S., Sachar D.B. The pharmacology of anti-inflammatory drugs in inflammatory bowel disease. In: Kirsner J.B., Shorter R.G., ed. Inflammatory bowel disease. 4 th ed. Baltimore. Williams and Wilkins.1995. P. 643-663.
12. Jarnerot G., Hertervig E., Friis Liby I. et al. Inflixomab as therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study // Gastroenterology rescue. 2005. 128. P. 1805-1811.
13. Kanauchi O., Mitsnyama K., Andoh A. et al. Beneficial effects of prebiotics, germinated barley foodstuff, in the long term treatment of ulcerative colitis: a multicenter open control study // Gastroenterology. - 2003. 124. 4. Suppl. 1. P. 1749.
14. Korzenik J., Miner P., Stanton D. et al. Multicenter, randomized, double-blind, lacebo-controlled trial of Deligoparin (ultra low molecular weight heparin) for active ulcerative colitis// Gastroenterology.- 2003.- 124.- 4. Suppl. 1. P. 539.
15. Kruis W., Schutz E., Fric P. et al. Double-blind comparison of an oral Echerichia coli reparation and mesalazine in maintaining remission of ulcerative colitis.// Aliment. Pharmacol. Ther. 1997. 15. P. 853-858.
16. Levine D.S., Fischer S.H., Christie G.L. et al. Intravenous immunoglobulin therapy for active, extensive, and medically refractory idiopathic ulcerative colitis and Crohn’s disease.// Am. J. Gastroenterol. 1992. 87. P. 91-100.
17. Loeschke K., Ucberschaer B., Pietsch A. et al. N#3 fatty acids retard early relapse in ulcerative colitis.// Abstract. Book A.G.A. 1996.A 781.
18. Marc A., De Bievre, Anton A. et al. A randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis.// Gastroenterology. 2003. 124. 4. Suppl. 1. P. 543.
19. Marshall J.K., Irvine E.J. Rectal aminosalicylate therapy for distal ulcerative colitis: a meta-analysis.// Aliment. Pharmacol. Ther. 1995. 9. 293-300.
20. Marshall J.K., Irvine E.J. Rectal corticosteroids vs. alternative treatment in ulcerative colitis: a meta-analysis.//Gut. 1997. 40. P. 775-781.
21. Orth T., Reters M., Schlaak J.F. et al. Mycophenolate mofetil versus azathioprine in patients with chronic active ulcerative colitis: a 12#month pilot study// Am. J. Gastroenterol. 2000. 95. P. 1201-1207.
22. Plevy S.E., Salzberg B.A., Regueiro M. et al. A humanized anti-CD3 monoclonal antibody, Visilizumab, for the treatment of severe steroid-refractory ulcerative colitis: Preliminary results of a phase 1 study // Gastroenterology.2003. 124. 4. Suppl. 1. P. 62.
23. Rembacken B.J., Snelling A.M., Hawkey P.M. et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomized trial. // Lancet. 1999. 21. P. 635-639.
24. Rutgeerts P., Feagan B., Olson A. et al. A randomized placebo-controlled trial of infliximab therapy for ulcerative colitis: Act 1 trial.// Gastroenterology. 2005. 128. A 689.
25. Safdi M., DeMicco M., Sninsky C. et al. A double blind comparison of oral vs. rectal mesalamine vs. combination therapy in the treatment of distal ulcerative colitis // Am. J. Gastroenterol. 1997. 92. P. 1867-1871.
26. Saibil F.G. Lidocaine enemas for intractable distal ulcerative colitis: efficacy and safety.// Gastroenterology.1998. 114. Pt 2. P. 4395.
27. Sakuraba A., Naganuma M., Hibi T., Ishii H. Intensive therapy of granulocyte and monocyte absorption apheresis induces rapid remission in patients with ulcerative colitis. // Gastroenterology. 2003. 124. 4. Suppl 1. T. 1379.
28. Sandborn Q., Tremaine W., Offord K. et al. Transdermal nicotine for mildly to moderately active ulcerative colitis.// Ann. Intern. Med. 1997. 126. P. 364-371.
29. Sandborn W., Rachmilewitz D., Hanauer S. et al. Infliximab induction and maintenance therapy for ulcerative colitis: the Act 2 trial // Gastroenterology. 2005. 128 (suppl.2). A 688.
30. Sawada K., Kusugam K., Suzuki Y. et al. Multicenter randomized double blind controlled trial for ulcerative colitistherapy with leukocytapheresis// Gastroenterology. 2003. 124. 4. Suppl. 1. P.542.
31. Skelly M.M., Curtis H., Jenkins D. et al. Toxicity of mycophenolate mofetil (MMF) in patients with inflammatory bowel disease (IBD)// Gastroenterology. 2000. 14. P. 171-176.
32. Sutherland L.R., May G.R., Shaffer E.A. Sulphasalazine revisited: a meta-analysis of 5-minosalicylic acid in the treatment of ulcerative colitis.// Ann. Intern. Med. 1993. 118. P. 540-549.
33. Sutherland L., Roth D., Beck P. et al. Alternative to sulphasalazine: a meta-nalysis of 5-SA in the treatment of ulcerative colitis.// Inflam. Bowel Dis. 1997. 3. P. 665-678.
34. Tilg H., Vogelsang H., Ludwiczek O. et al. A randomized placebo-controlled trial of pegylated interferon alpha in active ulcerative colitis // Gastroenterology. 2003. 124. 4. Suppl.1. P. 472.
35. Van Assche G., Noman M., Asnong K., Rutgeerts P. The use of the neurokinin-1 receptor Antagonist, SR-140333B, Nolpitantium Besilate, in mild to moderate active ulcerative colitis. // Gastroenterology. 2003. 124. 4. Suppl. 1. T 1377.
36. Wright J.P., Winter T.A., Candy S., Marks I. Sucralfate and methylprednisolone enemas in active ulcerative colitis—a prospective, single-blind study. // Dig. Dis. Sci. 1999. 44. 9. P. 1899-1901.