Nonspecific ulcerative colitis. Crohn's disease in children

Granulomatous or regional enteritis and/or colitis, transmural ileitis, terminal ileitis, CD, Crohn Disease

RCHD (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical Protocols of the Ministry of Health of the Republic of Kazakhstan - 2014

Crohn's disease [regional enteritis] (K50), Ulcerative (CHRONIC), Ulcerative (CHRONIC), Ulcerative (CHRONIC), Ulcerative (CHRONIC), Ulcerative colitis, unspecified (K51.9)

Gastroenterology for children, Pediatrics, Surgery for children

general information

Short description

Approved by the Expert Commission

For Health Development

Ministry of Health of the Republic of Kazakhstan

Ulcerative colitis- chronic recurrent inflammatory lesion of the colon, spreading continuously in the proximal direction from the rectum.

Crohn's disease- non-specific primary chronic, granulomatous inflammatory disease involving all layers of the intestinal wall in the process, characterized by intermittent (segmental) lesions of various parts of the gastrointestinal tract. The consequence of transmural inflammation is the formation of fistulas and abscesses.

I. INTRODUCTION

Protocol name: Nonspecific ulcerative colitis. Crohn's disease in children.

Protocol code

ICD code(s) - 10:

K50.0 Crohn's disease of small intestine

K50 Crohn's disease (regional enteritis)

K50.1 Crohn's disease of colon

K50.8 Other types of disease

K50.9 Crohn's disease, unspecified

K51 Ulcerative colitis

K51.0 Ulcerative (chronic) enterocolitis

K51.1 Ulcerative (chronic) ileocolitis

K51.2 Ulcerative (chronic) proctitis

K51.3 Ulcerative (chronic) rectosigmoiditis

K51.9 Ulcerative colitis, unspecified

Abbreviations used in the protocol

ALT - alanine aminotransferase

AST - aspartate aminotransferase

APTT - activated partial thromboplastin time

CD - Crohn's disease

HIV - human immunodeficiency virus

GCS - glucocorticosteroids

ENT - otorhinolaryngologist

INR - international normalized ratio

KLA - complete blood count

OAM - general urinalysis

PT - prothrombin time

PTI - prothrombin index

PCR - half-merase chain reaction

RFMK - soluble fibrinomonomer complexes

CRP - C-reactive protein

ESR - erythrocyte sedimentation rate

TV - thrombin time

Ultrasound - ultrasonography

TNF - tumor necrosis factor

FEGDS - fibroesophagogastroduodenoscopy

ECG - electrocardiography

UC - ulcerative colitis

5-ASA - 5-aminosalicylic acid

ANCA - anti-neutrophil cytoplasmic antibodies

IgG - class G immunoglobulins

PUCAI - Pediatric Ulcerative Colitis Activity Index

РCDAI - Pediatrics Crohn's Disease Activity Index

Protocol development date: 2014

Protocol Users- pediatricians of hospitals and polyclinics, pediatric gastroenterologists, general practitioners, paramedics of emergency medical services.

Classification

Clinical classification

Ulcerative colitis:

According to the length of the inflammatory process:

proctitis,

Left-sided colitis (including proctosigmoiditis, up to the splenic flexure);

Total colitis (widespread colitis or pancolitis with or without retrograde ileitis).

By the nature of the flow:

Recurrent (often, rarely);

Continuous

Attack severity:

Easy,

Average,

Heavy)

In response to steroid therapy:

Steroid resistance - persistence of disease activity despite intravenous or oral administration of an adequate dose of corticosteroids for 7-14 days

Steroid dependence is the achievement of clinical remission during corticosteroid therapy and the resumption of symptoms when the dose is reduced or within 3 months after their complete withdrawal, as well as in cases where steroid therapy cannot be stopped within 14-16 weeks.

The degree of activity in children is determined by the pediatric activity index for ulcerative colitis (PUCAI) (Table 1)

Table 1 Pediatric Activity Index for Ulcerative Colitis (PUCAI)

Symptoms	Points
(1) Abdominal pain
No pain	0
moderate pain	5
severe pain	10
(2) Rectal bleeding
Absent	0
Small amount of blood found in less than 50% of stools	10
Small amount of blood in almost all stools	20
Significant volume (>50% of stool)	30
(3) Stool consistency
Formed	0
Practically formed	5
Not fully developed	10
(4) Number of stools per day
0-2	0
3-5	5
6-8	10
>8	15
(5) Night stool (any awakening occasion)
No	0
Yes	10
(6) Activity level
No Activity Limit	0
Rare activity restrictions	5
Severe activity restrictions	10
Sum of PUCAI scores (0-85)

Score interpretation:

High activity: 65 and above

Moderate activity: 35-64

Light activity: 10-34
. Remission (disease not active): below 10

Crohn's disease

To assess the clinical activity (severity) of CD, the CD activity index (Pediatrics Crohn’s Disease Activity Index (PCDAI), Best index) is used.

The calculation takes into account only clinical (not endoscopic) criteria. The maximum number of points is 600 (Table 2). РCDAI<150 баллов расценивается как ремиссия БК, индекс >150 points - as an active disease with a division into low (150-200 points), moderate (200-450) and high activity (more than 450 points).

Table 2. Pediatric Crohn's Disease Activity Index PCDAI

Criteria		Points
Stomach ache	No	0
	low intensity	5
	strong intensity	10
Stool, frequency, consistency	0-1r/d, liquid without blood impurities	0
	2-5r / d, with a small admixture of blood	5
	More than 6 r / d	10
well-being, activity	No Activity Limit	0
	Moderate activity restriction	5
	Significant activity limitation	10
Body mass	No weight loss	0
	Decrease in body weight by 1-9%	5
	Weight loss over 10%	10
Height	Below one cent	0
	From 1-2 cents	5
	Below two cents	10
Soreness in the abdomen	No soreness	0
	Soreness, there is a seal	5
	Severe soreness	10
Pararectal manifestations	No	0
	Active fistula, tenderness, abscess	10
Extraintestinal manifestations	No	0
	one	5
	More than two	10
Hematocrit in children under 10 years of age	>33	0
	28-32	2,5
	<28	5
Hematocrit (girls 11-19 years old)	>34	0
	29-34	2,5
	<29	5
Hematocrit (boys 11-14 years old)	>35	0
	30-34	2,5
	<30	5
Hematocrit (boys 15-19 years old)	>37	0
	32-36	2,5
	<32	5
ESR	<20	0
	20-50	2,5
	>50	5
Albumin (g/dl)	>3.5	0
	3.1-3.4	5
	<3.0	10

The minimum score is 0, the maximum is 100, the higher the score, the higher the activity of inflammation.

Diagnostics

II. METHODS, APPROACHES AND PROCEDURES FOR DIAGNOSIS AND TREATMENT

List of basic and additional diagnostic measures

The main (mandatory) diagnostic examinations carried out at the outpatient level:

UAC (6 parameters);

Determination of total protein and protein fractions;

Coagulogram (plasma tolerance to heparin, APTT, recalcification time, PV-PTI-INR, RFMK, TV, fibrinogen);

Coprogram;

Bacteriological examination of feces for dysbacteriosis;

Ultrasound of the abdominal organs;

Additional diagnostic examinations performed at the outpatient level:

Biochemical blood test (determination of ALT, AST, thymol test, bilirubin, total cholesterol, glucose, CRP);

Examination of feces for helminth eggs;

Determination of p24 HIV antigen in blood serum by ELISA method;

X-ray examination of the stomach with contrasting (double contrasting);

The minimum list of examinations that must be carried out when referring to planned hospitalization:

UAC (6 parameters);

Biochemical blood test (total protein and fractions, CRP, AST, ALT, bilirubin, thymol test, alkaline phosphatase, electrolytes)

Examination of feces (coprogram);

Fibrorectosigmoidoscopy with examination of a histological preparation

Basic (mandatory) diagnostic examinations carried out at the hospital level(in case of emergency hospitalization, diagnostic examinations not performed at the outpatient level are carried out):

UAC (6 parameters);

Biochemical blood test (determination of total protein, protein fractions, serum iron);

Coagulogram (determination of plasma tolerance to heparin, APTT, recalcification time, PV-PTI-INR, RFMK, TV, fibrinogen);

Determination of blood electrolytes;

Analysis of feces for occult blood;

Fibrorectosigmoidoscopy with the study of a histological preparation;

Total fibrocolonoscopy;

Irrigoscopy / irrigography (double contrasting);

Histological examination of biopsy specimens

Additional diagnostic examinations carried out at the hospital level(in case of emergency hospitalization, diagnostic examinations are performed that are not performed at the outpatient level):

Determination of antineutrophil cytoplasmic Ig G (ANCA combi) in blood serum by ELISA method;

Total video colonoscopy;

CT scan of the large intestine (virtual colonoscopy);

Diagnostic criteria for CD and UC:

Complaints and anamnesis:

Crohn's disease:

Pain in the right iliac region

Perianal complications (paraproctitis, anal fissures, anorectal fistulas)

Fever

Extraintestinal manifestations (Bechterew's disease, arthritis, skin lesions)

Internal fistulas

Weight loss

Ulcerative colitis:

Bleeding from the rectum;

Increased bowel movements;

Constant urge to defecate;

Stool predominantly at night;

Pain in the abdomen mainly in the left iliac region;

Tenesmus.

Physical examination:

Deficiency in body weight;

Symptoms of intoxication;

Symptoms of polyhypovitaminosis,

Pain on palpation of the abdomen mainly in the right and left iliac regions.

Pediatric ulcerative colitis activity index (PUCAI).

Laboratory research:

UAC: accelerated ESR, leukocytosis, thrombocytosis, anemia, reticulocytosis.

Blood chemistry: hypoproteinemia, hypoalbuminemia, CRP, increase in alpha-2 globulins

ELISA: detection of antineutrophil cytoplasmic Ig G (ANCA) confirms the diagnosis of autoimmune diseases (ulcerative colitis).

Instrumental research:

Colonoscopy, sigmoidoscopy: the presence of transverse ulcers, aphthae, limited areas of hyperemia, edema in the form of a "geographic map", fistulas with localization in any part of the gastrointestinal tract.

Barium contrast radiography- rigidity of the intestinal wall and its fringed outlines, strictures, abscesses, tumor-like conglomerates, fistulous passages, uneven narrowing of the intestinal lumen up to the "lace" symptom. With UC: granulation (granularity) of the mucosa, erosion and ulcers, jagged contours, wrinkling.

Histological examination- edema and infiltration of lymphoid and plasma cells of the submucosal layer, hyperplasia of lymphoid follicles and Peyer's patches, granulomas. With the progression of the disease, suppuration, ulceration of lymphoid follicles, the spread of infiltration to all layers of the intestinal wall, hyaline degeneration of granulomas.

Ultrasound: wall thickening, decrease in echogenicity, anechoic thickening of the intestinal wall, narrowing of the lumen, weakening of peristalsis, segmental disappearance of haustra, abscesses.

Indications for expert advice:

Optometrist - to exclude damage to the organ of vision);

Rheumatologist - with involvement in the autoimmune process of the joints);

Surgeon - if acute toxic dilatation of the colon is suspected; in the absence of positive dynamics from conservative therapy);

Oncologist (if signs of dysplasia, cancer appear).

Phthisiatrician - to resolve the issue of biological therapy

Differential Diagnosis

Differential diagnosis of UC and CD

Table 3 Differential diagnosis of UC and CD

Indicators	Ulcerative colitis	Crohn's disease
Age of onset	any	up to 7-10 years - very rarely
The nature of the onset of the disease	Acute in 5-7% of patients, in the rest gradual (3-6 months)	Acute - extremely rare, gradual over several years
Bleeding	During the period of exacerbation - permanent	Rarely, more often - with involvement of the distal colon in the process
Diarrhea	Frequent, loose stools, often with nocturnal bowel movements	Stool is rarely observed, more often than 4-6 times, mushy mainly in the daytime
Constipation	Rarely	More typical
Stomach ache	Only during the period of exacerbation, intense before defecation, subside after defecation	Typical, often mild
Palpation of the abdomen	Spasmodic, painful colon	Infiltrates and conglomerates of intestinal loops, more often in the right iliac zone
Perforations	With toxic dilatation into the free abdominal cavity, there are few symptoms	More typical covered
Remission	Characteristic, perhaps a long absence of exacerbations with the reverse development of structural changes in the intestine	There are improvements, there is no absolute remission, the structure of the intestine is not restored
Malignization	With a disease duration of more than 10 years	Rarely
Exacerbations	The symptoms of the disease are pronounced, but are less treatable	Symptoms of the disease gradually increase without much difference from the period of well-being
Perianal lesions	In 20% of patients, maceration, cracks	In 75% of patients, perianal fistulas, abscesses, ulcers are sometimes the only manifestations of the disease.
The prevalence of the process	Large intestine only: distal, left-sided, total	Any part of the digestive tract
Strictures	not typical	Meet often
haustration	Low, flattened or absent	Thickened or normal
mucosal surface	grainy	Smooth
microabscesses	Eat	No
Ulcerative defects	Irregular shape without clear boundaries	Aphtha-like ulceration with a halo of hyperemia or fissure-like longitudinal defects
contact bleeding	Eat	No
Barium evacuation	Normal or accelerated	Slowed down
Colon shortening	Often, the lumen is tubular	Not typical
Small bowel injury	Often absent, with retrograde ileitis - uniform as a continuation of colitis	Intermittent, uneven, with wall rigidity, often on a significant throughout

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Treatment

Treatment goals:

Ensuring remission

Prevention of complications

Operation Warning

Treatment tactics

Non-drug treatment

Mode:

Mode 1 - bed;

Mode 2 - semi-bed;

Mode 3 - general.

diet therapy- Boiled and steamed pureed foods are recommended, with a restriction of fiber, fat and individually intolerant foods (usually milk). Diet number 4 (b, c). Milk and dairy products, fats (medium and short chain), fried, spicy and salty foods, foods containing coarse vegetable fiber (mushrooms, bran, plums, dried apricots, kiwi, white cabbage, radishes, etc.) are excluded from nutrition, limit products containing gluten (wheat, rye, oats, etc.). Patients with dehydration are shown additional fluid administration. In case of total intestinal damage, in order to ensure functional rest, it is possible to transfer to full parenteral nutrition with the transition to tube or enteral nutrition using polymer and elemental diets.

Medical treatment

5-ACK

Oral 5-ASA is recommended as first-line therapy for the induction and maintenance of remission in children with mild to moderate active ulcerative colitis. Combination therapy with oral 5-ASA and topical 5-ASA is more effective.

Mesalazine: orally 30-50 mg/kg/day (max. 4 g/day) in 2 divided doses; rectally 25 mg / kg (up to 1 g once); (children from 6 years old) for 8-12 weeks with a gradual dose reduction.

Sulfasalazine: oral 40-60 mg / kg / day. in 2 doses (max. 4 g / day) (children from 6 years old).

Oral corticosteroids in UC in children are effective in inducing remission, but not in maintaining remission. Oral corticosteroids are recommended for use in moderate to severe attacks with systemic manifestations and in selected patients with severe attacks without systemic manifestations or in patients who have not achieved remission on therapy with the optimal dose of 5-ASA. In a severe attack, intravenous steroid therapy is performed.

Prednisolone at the rate of 1-2 mg/kg of body weight per day (4-8 weeks) with a gradual dose reduction and withdrawal within 3-4 months. .

When prescribing hormone therapy, the following should be considered:

Mandatory is the concomitant intake of calcium, vitamin D supplements
. During the period of treatment, regular monitoring of blood glucose levels is necessary.

Thiopurines

Recommended to maintain remission in children with 5-ASA intolerance or in patients with a frequently relapsing course (2-3 exacerbations per year) or the development of a hormone-dependent form of the disease during 5-ASA therapy at maximum doses; thiopurines are ineffective in inducing remission. Thiopurines are recommended for maintenance therapy in acute severe colitis after induction of remission with steroids because these patients are more likely to have an aggressive course of the disease. However, in children with acute severe colitis who have not previously received 5-ASA, maintenance 5-ASA monotherapy may be considered if there is a rapid response to steroids. The therapeutic effect of thiopurines is achieved within 10-14 weeks from the start of treatment.

Azathioprine 1-2.5 mg/kg;

Mercaptopurine - 1-1.5 mg / kg in 2 doses.

Thiopurine therapy should be discontinued in the event of clinically significant myelosuppression or pancreatitis.

Methotrexate can only be used in a limited subset of patients with UC who are unresponsive or intolerant to thiopurines.

biological therapy

In patients with chronic continuous or hormone-dependent UC, not controlled by 5-ASA or thiopurines, fistulous forms of CD, as well as in the treatment of children and adolescents 6-17 years old, infliximab should be considered. Infliximab should be prescribed for the hormone-resistant form of the disease (resistance to both oral and intravenous drugs). If infliximab was given for an acute attack in a thiopurine-naive patient, biologic therapy may be used as an adjunct to thiopurine therapy. In this case, infliximab therapy can be discontinued after approximately 4-8 months. Infliximab is the first-line biological therapy for children with UC at a dose of 5 mg/kg (3 induction doses over 6 weeks followed by 5 mg/kg every 8 weeks as maintenance therapy). Individual dose adjustment may be required. Adalimumab should only be used in patients who have lost their response to infliximab or are intolerant to infliximab. The optimal initial dose is 160 mg followed by 80 mg after 2 weeks. Maintenance infusions subcutaneously (40 mg every 2 weeks) in patients in whom the first administration of the drug was effective, increase the duration of remission

Infliximab 5 mg/kg (3 induction doses for 6 weeks followed by 5 mg/kg every 8 weeks as maintenance therapy).

Adalimumab 160 mg followed by 80 mg 2 weeks later, then maintenance infusions subcutaneously (40 mg every 2 weeks)

Before starting biological therapy, consultation with a phthisiatrician - screening for tuberculosis (X-ray of the chest organs, quantiferon test, if it is impossible to carry out - Mantoux test, Diaskin test)

Medical treatment provided on an outpatient basis

Mesalazine 250 mg, 500 mg tab.;

Sulfasalazine 500mg tab.;

Prednisolone 0.05 tab.

List of additional medicines(less than 100% chance of application):

Metronidazole 250 mg tab.;

Thiamine bromide 5% 1.0;

Pyridoxine hydrochloride 5% 1.0;

Retinol palmitate capsules 100,000 IU;

Alpha-tocopherol acetate capsules 100 mg;

Lactulose 250 ml, 500 ml oral solution.

Medical treatment provided at the inpatient level

List of Essential Medicines(having a 100% cast chance):

Mesalazine 250 mg, 500 mg tab.

Sulfasalazine 500mg tab.

Prednisolone 0.05 tab.

Ulcerative colitis is a chronic inflammatory bowel disease characterized by superficial mucosal inflammation, rectal bleeding, diarrhea, and abdominal pain. Unlike Crohn's disease, ulcerative colitis is usually limited to the colon and the inflammation itself is limited to the mucosa. The disease affects any age group from infants to the elderly, with a peak incidence between the ages of 15 and 30 and between 50 and 70 years of age.

The mechanism of occurrence and development of nonspecific ulcerative colitis

Although the exact mechanism of the onset and development of the disease (etiopathogenesis) of ulcerative colitis has not yet been clearly established, several immunological, genetic and environmental factors have been identified that contribute to the disease. In recent years, the main focus of research has shifted to the interaction between the gut microbiota and the defense mechanisms of the gut barrier, the mucosal layer, and the mucosal immune system. Ulcerative colitis can be thought of as an immune-mediated disorder that develops in genetically predisposed individuals due to dysregulated immune responses against intraluminal antigens in the gut.

In a recent meta-analysis of genome association studies for Crohn's disease and ulcerative colitis, more than 160 loci associated with inflammatory bowel disease were identified. Many of them are associated with both ulcerative colitis and Crohn's disease. The lower heritability in monozygotic twins of 15% in ulcerative colitis and 30% in Crohn's disease indicates that the genetic contribution in colitis is much weaker than in Crohn's disease, and environmental factors have an extremely strong influence on the disease, both in increase in the incidence of ulcerative colitis and its spread throughout the world.

Interestingly, children who emigrated with their parents from areas with a low prevalence of ulcerative colitis to areas with high rates developed ulcerative colitis more often than their parents. This suggests that environmental factors during infancy and early childhood influence the developing immune system and gut microbiota, and are critical in the development of ulcerative colitis. Eating a diet high in saturated fat, common in today's daily diet, changes the composition of the intestinal microflora, leading to an increase in colitis.

Diagnostic criteria for non-specific ulcerative colitis

The diagnosis of ulcerative colitis is based on the history and clinical evaluation, and then confirmed by laboratory, radiological, endoscopic, histological, and serological findings.

The most important diagnostic criteria

1. Clinical symptoms that must be present for at least 4 weeks:
- Diarrhea
- Explicit or occult (hidden) rectal bleeding. Occult bleeding is only recognized by fecal occult blood testing.
- Abdominal pain before, after or during a bowel movement
- The following intestinal infections must be excluded: Salmonella, Shigella, Yersinia, Campylobacter, E coli 0157: H7, Clostridium difficile.

2. Laboratory indicators of the disease
- Iron-deficiency anemia
- Thrombocytosis
- Hypoalbuminemia
- Autoantibodies: perinuclear antineutrophil cytoplasmic antibodies ANCA, antibodies to intestinal goblet cells GAB
- Increased fecal calprotectin

3. Endoscopic features and histological criteria

Patients with ulcerative colitis are classified according to the prevalence and severity of the disease, age, presentation characteristics, and genetic markers. Infectious, ischemic, and other causes of colitis should be ruled out before making a diagnosis.

However, there is no generally accepted catalog of well-defined criteria or scoring for the classification of ulcerative colitis. In this connection, in 5-10% of patients with inflammatory bowel diseases, it is not possible to make an accurate diagnosis of ulcerative colitis or Crohn's disease.

Medical history and clinical manifestations of UC

The patient's history should include the above clinical symptoms consistent with inflammatory bowel disease and a possible family history, as first-degree relatives of patients with UC have a 10- to 15-fold increased risk of developing the disease. Clinically, UC is characterized by bloody diarrhea and chronic abdominal pain; nonspecific inflammation of the mucosa in the terminal ileum occurs in 10-20% of patients with ulcerative colitis. Involvement of the upper gastrointestinal tract is a controversial issue, especially in children.

The overall clinical picture mainly depends on the degree of intestinal damage, disease activity, as well as non-universal manifestations and complications. Inflammatory arthropathies and primary sclerosing cholangitis are the most common and important non-universal manifestations in ulcerative colitis and are diagnosed in approximately 2-10% of patients. Other extraintestinal manifestations include: skin (erythema nodosum, pyoderma gangrenosum), eyes (episcleritis, uveitis), and bones (osteoporosis).

Endoscopic diagnosis of UC

At diagnosis, patients should undergo endoscopic evaluation, ileocolonoscopy, and gastroduodenoscopy. According to the degree of the disease, patients are classified as having proctitis, left-sided colitis, or pancolitis. Unlike adults, UC in children is more likely to involve the entire colon (pancolitis) and is therefore more commonly associated with acute colitis.

Laboratory and serological markers

Laboratory features are not specific markers for ulcerative colitis. They detect the very fact of an inflammatory process or absorption problems: iron deficiency, anemia, and can help assess the activity of the disease, as well as possible complications. The most commonly studied serological markers in inflammatory bowel disease are antineutrophil cytoplasmic antibodies (ANCA) and antibodies to Saccharomyces cerevisiae (ASCA). Perinuclear or atypical ANCA can be found in 50-70% of patients with ulcerative colitis and less than 10% of patients with Crohn's disease. An ANCA positivity and a negative test for Crohn's disease-specific antibodies to Saccharomyces cerevisiae indicate that UC is more likely than Crohn's disease.

In patients with unclassified inflammatory bowel disease, the determination of ANCA and ASCA may help in establishing a definitive diagnosis. Another serological marker specific for UC is antibodies to intestinal goblet cells GAB, which occur in 15-28% of patients with ulcerative colitis. If the autoantigenic targets used for testing are properly selected and prepared, GABs are highly specific for UC.

Activity indices of ulcerative colitis

To classify and predict the treatment of UC, there are several activity indices, although for clinical practice it is enough to describe the activity of the disease as mild - stools with blood up to four times a day, moderate - stools from four to six times a day and severe - stools more than six times a day. temperature, tachycardia. In fulminant colitis (rapidly progressive, acute), as the most severe form, stools with blood more than 10 times a day, with anemia and signs of toxic megacolon.

Original article: Conrad K, et al, Diagnosis and classification of ulcerative colitis, Autoimmun Rev (2014),

These recommendations were developed by the expert commission of the Russian Gastroenterological Association, Association of Coloproctologists of Russia LLC and the Society for the Study of Inflammatory Bowel Diseases at the Association of Coloproctologists of Russia, consisting of:

Ivashkin Vladimir Trofimovich
Shelygin Yury Anatolievich
Abdulganieva Diana Ildarovna
Abdulkhakov Rustem Abbasovich
Alekseeva Olga Polikarpovna	Nizhny Novgorod
Baranovsky Andrey Yurievich	Saint Petersburg
Belousova Elena Alexandrovna
Golovenko Oleg Vladimirovich
Grigoriev Evgeny Georgievich
Kostenko Nikolay Vladimirovich	Astrakhan
Nizov Alexey Alexandrovich
Nikolaeva Nonna Nikolaevna	Krasnoyarsk
Osipenko Marina Fedorovna	Novosibirsk
Pavlenko Vladimir Vasilievich	Stavropol
Parfenov Asfold Ivanovich
Poluektova Elena Alexandrovna
Rumyantsev Vitaly Grigorievich
Timerbulatov Vil Mamilovich
Tkachev Alexander Vasilievich	Rostov-on-Don
Caliph Igor Lvovich
Khubezov Dmitry Anatolievich
Chashkova Elena Yurievna
Shifrin Oleg Samuilovich
Schukina Oksana Borisovna	Saint Petersburg

ABBREVIATIONS 4

1. INTRODUCTION 4

2. DEFINITION AND CLASSIFICATION OF ULCERATIVE COLITIS 5

3. DIAGNOSTICS OF ULCERATIVE COLITIS 7

4. CONSERVATIVE TREATMENT OF ULCERATIVE COLITIS 10

5. SURGICAL TREATMENT OF ULCERATIVE COLITIS 13

6. FORECAST 18

ABBREVIATIONS

C-rP - C-reactive protein

5-ASA - 5-aminosalicylic acid

6-MP - 6-mercaptopurine

AB - antibiotics

AZA - azathioprine

CD - Crohn's disease

IBD - inflammatory bowel disease

GCS - glucocorticosteroids

CI - confidence interval

IARA - ileoanal reservoir anastomosis

IFM - infliximab

NSAIDs - non-steroidal anti-inflammatory drugs

PSC - primary sclerosing cholangitis

RCT - randomized controlled trial

RRR - irritable reservoir syndrome

LE - level of evidence

UC - ulcerative colitis

1. 1. Introduction

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), has been and remains one of the most serious problems in modern gastroenterology. Despite the fact that in terms of the incidence of IBD, they are significantly inferior to other gastroenterological diseases, but in terms of the severity of the course, the frequency of complications and mortality, they occupy one of the leading places in the structure of diseases of the gastrointestinal tract all over the world. The constant interest in IBD is primarily due to the fact that, despite a long history of study, their etiology remains unknown, and the pathogenesis has not been sufficiently elucidated 1 2 .

Ulcerative colitis (UC) is a chronic disease that only affects the large intestine and never spreads to the small intestine. The exception is the condition designated by the term "retrograde ileitis", however, this inflammation is temporary and is not a true manifestation of UC.

The prevalence of UC ranges from 21 to 268 cases per 100,000 population. The annual increase in morbidity is 5-20 cases per 100 thousand of the population, and this figure continues to increase (approximately 6 times over the past 40 years) 3 .

The social significance of UC is determined by the predominance of the disease among people of young working age - the peak incidence of UC occurs at 20-30 years old, as well as the deterioration in the quality of life due to the chronicity of the process, and, consequently, frequent inpatient treatment 4 .

These recommendations for the diagnosis and treatment of patients with UC are a guide for practitioners who manage and treat such patients. The recommendations are subject to regular revision in accordance with new research data in this area. These recommendations are based on literature data and the European Evidence-Based Consensus for the diagnosis and treatment of ulcerative colitis, which is the leading guideline for the treatment of UC in the countries of the European Union.

These recommendations include the following sections: definition and classification of ulcerative colitis, diagnosis, conservative and surgical treatment. For certain provisions of the recommendations, the levels of evidence are given according to the generally accepted classification of the Oxford Center for Evidence-Based Medicine (Table 1).

Table 1. Evidence levels and grades of recommendation based on Oxford Center for Evidence-Based Medicine guidelines 5

Level	Diagnostic study	Therapeutic research
	Systematic Review of Level 1 Homogeneous Diagnostic Tests	Systematic review of homogeneous RCTs
	Qualitative gold standard validating cohort study	Single RCT (Narrow CI)
	Specificity or sensitivity is so high that a positive or negative result rules out/diagnoses	All or Nothing Study
	Systematic review of homogeneous diagnostic studies >2 levels	Systematic review of (homogeneous) cohort studies
	Exploratory cohort study with a qualitative gold standard	Single cohort study (including low quality RCTs; i.e. with<80% пациентов, прошедших контрольное наблюдение)
		Study of "outcomes"; environmental studies
	Systematic review of level 3b and higher homogenous studies	Systematic Review of Homogeneous Case-Control Studies
	Study with inconsistent recruitment or no gold standard study in all subjects	Separate case-control study
	Case-control or low-quality or non-independent gold standard study	Case series (and low quality cohort or case-control studies)
	Expert opinion without rigorous critical appraisal or based on physiology, laboratory animal studies, or development of "first principles"	Expert opinion without rigorous critical appraisal, laboratory animal studies, or development of "first principles"
A Level 1 Concordant Studies IN Consistent Tier 2 or Tier 3 studies or extrapolation from Tier 1 studies WITH Tier 4 studies or extrapolation from Tier 2 or 3 D Level 4 evidence or difficult to generalize or low-quality research at any level

Inflammatory bowel diseases, which include ulcerative colitis and Crohn's disease, have been and remain one of the most serious problems in modern gastroenterology. Despite the fact that in terms of the incidence of inflammatory bowel diseases they are significantly inferior to other gastroenterological diseases, they occupy one of the leading places in the structure of diseases of the gastrointestinal tract in terms of the severity of the course, the frequency of complications and mortality throughout the world. The constant interest in inflammatory bowel diseases is primarily due to the fact that, despite a long history of study, their etiology remains unknown, and the pathogenesis has not been sufficiently disclosed.

Ulcerative colitis is a chronic disease that only affects the large intestine and never spreads to the small intestine. The exception is the condition referred to as "retrograde ileitis", but this inflammation is temporary and is not a true manifestation of ulcerative colitis.

The prevalence of ulcerative colitis is 21 to 268 cases per 100,000 population.

population. The annual increase in the incidence is 5-20 cases per 100 thousand of the population, and this figure continues to increase (approximately 6 times over the past 40 years).

The social significance of ulcerative colitis is determined by the predominance of the disease among people of young working age - the peak incidence of ulcerative colitis occurs at 20-30 years, as well as the deterioration in the quality of life due to the chronicity of the process, and therefore frequent inpatient treatment.

SCOPE OF RECOMMENDATIONS
These clinical recommendations are applicable in the implementation of medical activities within the framework of the Procedure for the provision of medical care to the adult population with diseases of the colon, anal canal and perineum of the coloproctological profile, as well as within the framework of the Procedure for the provision of medical care to the population with diseases of the gastroenterological profile.

Definitions
Ulcerative colitis is a chronic disease of the colon characterized by immune inflammation of its mucosa.

In ulcerative colitis, only the large intestine is affected (with the exception of retrograde ileitis), the rectum is necessarily involved in the process, inflammation is most often limited to the mucous membrane (with the exception of fulminant colitis) and is diffuse.

An exacerbation (relapse, attack) of ulcerative colitis is understood as the appearance of typical symptoms of the disease in patients with ulcerative colitis in the stage of clinical remission, spontaneous or drug-supported.

An early relapse is defined as a relapse occurring less than 3 months after medically achieved remission. In practice, signs of clinical exacerbation are an increase in the frequency of defecation with blood and / or characteristic changes found during endoscopic examination of the colon. Remission of ulcerative colitis is considered the disappearance of the main clinical symptoms of the disease and the healing of the colon mucosa.

Allocate:
- clinical remission - the absence of blood in the stool, the absence of imperative / false urges with a frequency of bowel movements no more than 3 times a day;
- endoscopic remission - the absence of visible macroscopic signs of inflammation during endoscopic examination of the colon;
- histological remission - the absence of microscopic signs of inflammation.

Classification
Proper classification of ulcerative colitis according to the extent of the lesion, the nature of the course, the severity of the attack, and the presence of complications determines the type and form of drug administration, as well as the frequency of screening for colorectal cancer.

To describe the extent of the lesion, the Montreal classification is used, which assesses the extent of macroscopic changes during endoscopic examination of the colon.

According to the nature of the flow, there are:
- acute (less than 6 months from the onset of the disease):
- with a fulminant onset;
- with a gradual onset;
- chronic continuous (lack of more than 6-month periods of remission against the background of adequate therapy);
- chronic relapsing (the presence of more than 6-month periods of remission):
- rarely recurrent (once a year or less);
- often recurrent (2 times or more per year). The severity of the disease is generally determined by the severity of the current attack, the presence of extraintestinal manifestations and complications, refractoriness to treatment, in particular the development of hormonal dependence and resistance. However, to formulate the diagnosis and determine the tactics of treatment, the severity of the current exacerbation (attack) should be determined, for which the simple Truelove-Witts criteria, usually used in everyday clinical practice, and the ulcerative colitis activity index, usually used in clinical trials, are used. There are mild, moderate and severe attacks of ulcerative colitis.

The classification of ulcerative colitis depending on the response to hormonal therapy facilitates the choice of rational treatment tactics, since the goal of conservative treatment is to achieve stable remission with the cessation of glucocorticosteroid therapy. For these purposes, the following are distinguished.
1. Hormonal resistance
- In the case of a severe attack, persistence of disease activity despite intravenous administration of glucocorticosteroids at a dose equivalent to 2 mg/kg per day of prednisone for more than 7 days, or
- in the case of a moderate attack, the persistence of disease activity with oral administration of glucocorticosteroids at a dose equivalent to 1 mg / kg per day of prednisolone for 4 weeks.

2. Hormonal addiction
- An increase in disease activity with a decrease in the dose of glucocorticosteroids below a dose equivalent to 10-15 mg of prednisolone per day for 3 months from the start of treatment.
- the occurrence of a relapse of the disease within 3 months after the end of treatment with glucocorticosteroids.

Formulation of the diagnosis
When formulating a diagnosis, one should reflect the nature of the course of the disease, the extent of the lesion, the severity of the current attack or the presence of remission, the presence of hormonal dependence or resistance, as well as the presence of extraintestinal or intestinal complications of ulcerative colitis. The following are examples of the wording of the diagnosis.
- Ulcerative colitis, chronic relapsing course, proctitis, moderate attack.
- Ulcerative colitis, chronic continuous course, left-sided lesion, moderate attack. Hormonal addiction. Extraintestinal manifestations (peripheral arthropathy).
- Ulcerative colitis, chronic relapsing course, total defeat, severe attack. Hormonal resistance. Toxic megacolon.

Diagnostics
CLINICAL DIAGNOSTIC CRITERIA

The main clinical symptoms of ulcerative colitis include diarrhea and/or false urges with blood, tenesmus and urge to defecate, and nocturnal defecation. With a severe attack of ulcerative colitis, general symptoms may appear, such as weight loss, general weakness, anorexia, and fever. Intestinal complications of ulcerative colitis include intestinal bleeding, toxic dilatation and perforation of the colon, and colorectal cancer.

If differential diagnosis is necessary, the following additional studies are carried out:
- magnetic resonance imaging;
- computed tomography;
- transabdominal ultrasound scanning of the small intestine and colon;
- transrectal ultrasound of the rectum and anal canal;
- X-ray contrast study of the small intestine with barium suspension;
- fibrogastroduodenoscopy;
- capsule endoscopy;
- single or double balloon enteroscopy.

For the purpose of differential diagnosis and selection of therapy for extraintestinal manifestations of ulcerative colitis and concomitant diseases, consultations may be required:
- psychotherapist, psychologist (neurosis, planned operation with stoma, etc.);
- endocrinologist (steroid diabetes mellitus, adrenal insufficiency in patients on long-term hormonal therapy);
- dermatologist (differential diagnosis of erythema nodosum, pyoderma, etc.);
- rheumatologist (arthropathies, sacroiliitis, etc.);
- obstetrician-gynecologist (pregnancy).

Endoscopic examination of the colon is the main method for diagnosing ulcerative colitis, but there are no specific endoscopic signs. The most characteristic are continuous inflammation, limited to the mucous membrane, starting in the rectum and spreading proximal, with a clear border of inflammation. The endoscopic activity of ulcerative colitis is best reflected by contact fragility (bleeding on contact with the endoscope), the absence of a vascular pattern, and the presence or absence of erosions and ulcerations. The detection of persistent narrowing of the intestine against the background of ulcerative colitis requires the obligatory exclusion of colorectal cancer.

Microscopic signs of ulcerative colitis include deformity of the crypts (branching, multidirectionality, the appearance of crypts of different diameters, a decrease in the density of crypts, "shortening of the crypts", the crypts do not reach the underlying layer of the muscularis mucosa), an "uneven" surface in the biopsy of the mucosa, a decrease in the number of goblet cells, basal plasmacytosis, infiltration of the lamina propria, the presence of crypt abscesses and basal lymphoid accumulations. The degree of inflammatory infiltration usually decreases with distance from the rectum.

DIFFERENTIAL DIAGNOSIS
Inflammatory bowel disease is a group of chronic inflammatory bowel diseases with unknown etiology. Ulcerative colitis is included in the group of these diseases.

If ulcerative colitis is suspected, differential diagnosis begins with the exclusion of inflammatory diseases of the colon, which do not belong to the group of inflammatory bowel diseases. These are infectious, vascular, drug-induced, toxic and radiation injuries, as well as diverticulitis, etc. At the next stage of differential diagnosis, the clinical diagnoses of ulcerative colitis and Crohn's disease, which belong to the group of inflammatory bowel diseases, are verified.

Treatment
CONSERVATIVE TREATMENT
Principles of therapy
Treatment options for ulcerative colitis include medication, surgery, psychosocial support, and dietary advice.

The choice of the type of conservative or surgical treatment is determined by the severity of the attack, the extent of the colon lesion, the presence of extraintestinal manifestations, the duration of the anamnesis, the efficacy and safety of previous therapy, as well as the risk of complications of ulcerative colitis.

The goal of therapy is to achieve and maintain a steroid-free remission (cessation of glucocorticosteroids within 12 weeks after the start of therapy), prevention of complications of ulcerative colitis, prevention of surgery, and with the progression of the process, as well as the development of life-threatening complications, the timely appointment of surgical treatment. Since the complete cure of patients with ulcerative colitis is achieved only by removing the substrate of the disease (coloproctectomy), when remission is achieved, the non-operated patient should remain on constant maintenance (anti-relapse) therapy. It should be especially noted that glucocorticosteroids cannot be used as maintenance therapy. Below are recommendations on the choice of drugs for induction and maintenance of remission, depending on the extent of the lesion and the severity of the attack.

Proctitis
Light and medium attack
Therapy consists in prescribing mesalazine suppositories (1-2 g/day) or mesalazine rectal foam (1-2 g/day). The therapeutic response is assessed within 2 weeks. When responding, therapy at the indicated doses is prolonged up to 6-8 weeks.

With treatment failure, it is effective to connect rectal forms of clueocorticosteroids (suppositories with prednisolone 10 mg x 1-2 times a day). When remission is achieved, maintenance therapy is carried out - local administration of mesalazine (candles or rectal foam) 1-2 g x 3 times a week as monotherapy (at least 2 years). If treatment is ineffective, oral forms of mesalazine should be added at a dose of 3-4 g / day. If there is no effect, the appointment of systemic corticosteroids (prednisolone 0.75 mg/kg) in combination with azathioprine 2 mg/kg or 6-mercaptopurine (6-MP) 1.5 mg/kg is indicated. Local therapy (suppositories with prednisolone 10 mg x 1-2 times a day) can be continued. When glucocorticosteroid-induced remission is achieved, maintenance therapy is carried out with azathioprine 2 mg/kg or 6-MP 1.5 mg/kg for at least 2 years.

Heavy attack (evolves extremely rarely)
Treatment of an attack consists in the appointment of systemic corticosteroids at a dose equivalent to 1 mg / kg of prednisolone in combination with local therapy with mesalazine or prednisolone (suppositories, rectal foam). When remission is achieved, maintenance therapy is carried out with local mesalazine preparations (suppositories, rectal foam) 1-2 g x 3 times a week as monotherapy or in combination with oral mesalazine 1.5-2 g for at least 2 years. In case of relapse requiring repeated administration of glucocorticosteroids, azathioprine 2 mg/kg (or 6-MP 1.5 mg/kg) is additionally prescribed, and further maintenance therapy is carried out with immunosuppressants (azathioprine or 6-MP) for at least 2 years.

Left-sided and total colitis
Light attack
The first attack or relapse requires the appointment of oral mesalazine 3 g/day in combination with mesalazine enemas 2-4 g/day (depending on endoscopic activity). The therapeutic response is assessed within 2 weeks. With a response, therapy continues for up to 6-8 weeks. In the absence of the effect of local and oral preparations of 5-aminosalicylic acid, it is advisable to connect rectal forms of glucocorticosteroids (enemas with hydrocortisone suspension 125 mg x 1-2 times a day). Lack of response to oral 5-ASA therapy in combination with topical treatment is usually an indication for systemic glucocorticosteroids.

When remission is achieved, maintenance therapy is carried out using oral mesalazine 1.5 g / day. Additional administration of mesalazine in enemas 2 g 2 times a week (so-called weekend therapy) increases the likelihood of long-term remission. It is acceptable to prescribe sulfasalazine (3 g) instead of mesalazine.

Medium attack
At the first attack or relapse, it is necessary to prescribe mesalazine tablets 4-5 g / day in combination with mesalazine enemas 2-4 g / day (depending on endoscopic activity). The therapeutic response is assessed within 2 weeks. With a response, therapy is prolonged up to 6-8 weeks. When remission is achieved, maintenance therapy with mesalazine 1.5-2 g / day orally + mesalazine in enemas 2 g 2 times a week is carried out. It is acceptable to prescribe sulfasalazine 3 g / day instead of mesalazine.

In the absence of effect from 5-ASA, the administration of systemic steroids at a dose equivalent to 1 mg/kg of prednisolone in combination with aza-thioprine 2 mg/kg or 6-MP 1.5 mg/kg is indicated. When remission is achieved, further maintenance therapy is carried out with azathioprine 2 mg/kg per day or 6-MP 1.5 mg/kg for at least 2 years. If there is no effect from systemic steroids for 4 weeks, biological therapy is indicated (infliximab 5 mg / kg for 0, 2, 6 weeks, or golimumab 200 mg at week 0, 100 mg at week 2, and then 50 or 100 mg per day). depending on body weight monthly) in combination with azathioprine 2 mg/kg or 6-MP 1.5 mg/kg. Maintenance therapy is with azathioprine (or 6-MP) plus infliximab every 8 weeks or golimumab every month for at least 1 year. If prolonged use of infliximab/golimumab is not possible, maintenance therapy is carried out only with thiopurines, in case of intolerance to thiopurines - infliximab/golimumab as monotherapy.

heavy attack
In case of severe exacerbation of the disease, accompanied by diarrhea more than 5 times a day, tachycardia over 90 per minute, fever over 37.8 ° C, anemia less than 105 g / l, a patient with ulcerative colitis should be hospitalized in a multidisciplinary hospital with subsequent obligatory observation by a specialist - gastroenterologist and coloproctologist. With a severe attack of ulcerative colitis, the following measures are necessary:
- Intravenous administration of glucocorticosteroids: prednisolone 2 mg/kg per day.
- Local therapy with enemas with mesalazine 2-4 g / day or hydrocortisone 125 mg / day.
- Infusion therapy: correction of protein and electrolyte disorders, detoxification (hypokalemia and hypomagnesemia increase the risk of toxic dilatation of the colon).
- Correction of anemia (blood transfusion for anemia below 80 g / l, then iron therapy, preferably parenterally).
- Endoscopic examination of the colon on admission should be performed without preparation, as it increases the risk of toxic dilatation.
- Connection of additional enteral nutrition in malnourished patients. Fully parenteral nutrition and / or temporary restriction of food intake by mouth is not advisable.
- In the presence of fever or suspected intestinal infection - the appointment of antibiotics.
- 1st line - metronidazole 1.5 g/day + fluoroquinolones (ciprofloxacin, ofloxacin) IV for 10-14 days;
- 2nd line - intravenous cephalosporins for 7-10 days.

Continuation of hormonal therapy for more than 7 days in the absence of effect is impractical. With a clinical response after 7 days, the patient is shown to receive oral glucocorticosteroids: prednisolone 1 mg / kg or methylprednisolone 0.8 mg / kg, followed by a decrease to complete withdrawal of 5-10 mg of pre-nisolone or 4-8 mg of methylprednisolone per week ( during the first 5-7 days, combine with additional intravenous administration of prednisolone 50 mg / day). It should be remembered that the total duration of the course of glucocorticosteroids should not exceed 12 weeks. When the dose of steroids is reduced to 30-40 mg, mesalazine at a dose of 3 g should be connected as maintenance therapy. When remission is achieved, maintenance therapy is carried out with 1.5-2 g of oral mesalazine for 2 years. It is acceptable to prescribe sulfasalazine 3 g instead of mesalazine.

In the absence of the effect of steroid therapy after 7 days, 2nd line therapy is indicated, which includes the following treatment options:
- biological therapy with infliximab 5 mg/kg (administration as part of the induction course at 0, 2 and 6 weeks) or golimumab at a dose of 200 mg at week 0, then 100 mg at week 2, and then one month after the second injection (at a dose of 100 mg with a body weight of more than 80 kg or 50 mg with a body weight of less than 80 kg);
- the introduction of cyclosporine A in / in or orally 2-4 mg / kg for 7 days with monitoring of kidney function and determining the concentration of the drug in the blood.

When responding to the induction course of infliximab, further maintenance therapy is carried out with infusions every 8 weeks for at least 1 year in combination with azathioprine 2 mg/kg (or 6-MP 1.5 mg/kg). When responding to the induction course of golimumab, further maintenance therapy is carried out with monthly injections of 100 mg in patients weighing more than 80 mg and 50 mg in patients weighing less than 80 mg. With the effect of cyclosporine A therapy, after 7 days, it is necessary to switch to taking azathioprine 2 mg / kg in combination with oral cyclosporine (against a therapeutic dose of steroids) with a gradual withdrawal of steroids over 12 weeks. Maintenance therapy is carried out with oral cyclosporine for 3 months until the therapeutic concentration of azathioprine is reached. Further maintenance therapy is carried out with azathioprine 2 mg/kg for at least 2 years. If there is no response to the 2nd infliximab infusion, the 2nd golimumab injection or 7-day cyclosporine A therapy, surgical options should be considered.

Predicting the effectiveness of conservative therapy in a severe attack of ulcerative colitis
The joint observation of the patient by an experienced gastroenterologist and coloproctologist remains key to the safe management of a severe attack of ulcerative colitis. Although drug therapy is effective in many cases, there is evidence that delaying the necessary surgical treatment is detrimental to the patient's outcome, in particular by increasing the risk of surgical complications. Most of the studies on predictors of colectomy were conducted before the widespread use of biological therapy and cyclosporine and predict the ineffectiveness of glucocorticosteroids, rather than infliximab and immunosuppressants.
- Stool frequency >12 times a day on the 2nd day of IV hormonal therapy increases the risk of colectomy up to 55%.
- If on the 3rd day of hormonal therapy the frequency of stools exceeds 8 times a day or is from 3 to 8 times a day, and the level of C-reactive protein exceeds 45 mg / l, the probability of colectomy is 85% (the so-called Oxford index) .
- On day 3, you can also determine the Swedish index by the formula: stool frequency x 0.14 x C-reactive protein level. Its value of 8 or more increases the likelihood of colectomy up to 75%.
- The risk of colectomy is also increased by 5-9 times in the presence of hypoalbuminemia and fever on admission, and in the absence of more than 40% reduction in stool frequency after 5 days of IV hormonal therapy.
- The presence of deep ulceration of the colon (against which the residual mucosa is determined only in the form of "islands") increases the risk of colectomy to 86-93%.

The effectiveness of infliximab in hormonal resistance, according to various sources, ranges from 25 to 80%, which may be due to differences in the effectiveness of the drug in individual patients. Research on predicting the effectiveness of biological therapy remains limited, but it has been found:
- the effectiveness of infliximab in hormone-resistant severe attacks of ulcerative colitis decreases with age, in the presence of total damage to the colon, as well as in severe hypoalbuminemia, hemoglobin level less than 95 g/l and C-reactive protein level more than 10 mg/l at the time of the first administration of infliximab;
- the effectiveness of infliximab is significantly lower in patients in whom indications for anticytokine therapy arose already during the first attack of ulcerative colitis;
- the presence of extensive ulcerative defects of the colon mucosa during colonoscopy before infliximab therapy predicts its further ineffectiveness with 78% accuracy.

In patients at high risk of colectomy, a decision should be made on an individual basis whether to proceed with 2nd-line therapy with cyclosporine or infliximab or surgical treatment immediately after an ineffective course of IV glucocorticosteroids.

Prevention of complications of therapy
When prescribing hormone therapy, the following should be considered:
- a gradual reduction in the dose of steroids until complete abolition is strictly necessary;
- the total duration of hormone therapy should not exceed 12 weeks;
- concomitant intake of calcium, vitamin D, proton pump inhibitors is mandatory;
- during the period of treatment, regular monitoring of blood glucose levels is necessary.

When prescribing immunosuppressants and biological therapy, the following is necessary:
- before the start of biological therapy, consultation with a phthisiatrician - screening for tuberculosis (radiography of the chest organs, quantiferon test, if it is impossible to conduct it - Mantoux test, Diaskin test);
- biological therapy requires strict adherence to doses and administration schedule (irregular administration increases the risk of infusion reactions and inefficiency);
- against the background of immunosuppressive therapy, it is mandatory to control the level of leukocytes (general blood count monthly).

Prevention of opportunistic infections
Risk factors for developing opportunistic infections include:
- medications: azathioprine, intravenous hormonal therapy 2 mg/kg or orally more than 20 mg per day for more than 2 weeks, biological therapy;
- age over 50 years;
- concomitant diseases: chronic lung diseases, alcoholism, organic brain diseases, diabetes mellitus. In accordance with the European consensus on the prevention, diagnosis and treatment of opportunistic infections in inflammatory bowel diseases, such patients are subject to mandatory vaccination.

Required minimum vaccination:
- recombinant HBV vaccine;
- polyvalent inactivated pneumococcal vaccine;
- trivalent inactivated vaccine against influenza virus. For women under 26 years of age, in the absence of the virus at the time of screening, vaccination against the human papillomavirus is recommended.

SURGERY
Indications for surgical treatment
Indications for surgical treatment of ulcerative colitis are the ineffectiveness of conservative therapy (hormonal resistance, ineffectiveness of biological therapy) or the impossibility of its continuation (hormonal dependence), intestinal complications of ulcerative colitis (toxic dilatation, intestinal perforation, intestinal bleeding), as well as colon cancer or high risk its occurrence.

The ineffectiveness of conservative therapy is evidenced by:
- hormonal resistance;
- hormonal dependence.

Hormonal dependence can be effectively overcome with the help of biological drugs and / or immunosuppressants in 40-55% of cases, and with hormonal resistance, the appointment of cyclosporine A or biological therapy can induce remission in 43-80% of cases. However, in some patients with a high risk of complications and ineffectiveness of conservative therapy with the development of hormonal resistance or dependence, it is possible to perform surgical treatment without attempting the use of biological drugs or immunosuppressants. This issue is described in detail in the section “Predicting the effectiveness of conservative therapy in a severe attack of ulcerative colitis.” Intestinal complications

Intestinal complications of ulcerative colitis requiring surgical treatment include:
- intestinal bleeding, the presence of which is ascertained with a loss of more than 100 ml of blood per day, according to objective laboratory methods (scintigraphy, determination of hemoglobin in feces by the hemoglobin cyanide method), or with a volume of feces with a visually determined admixture of blood more than 800 ml / day. Indirectly, intestinal bleeding is evidenced by a progressive decrease in hemoglobin levels against the background of adequate therapy, however, clear threshold values ​​for reducing its level, indicating intestinal bleeding, have not been defined. With the development of this complication, an emergency operation is indicated;
- toxic dilatation of the colon (toxic megacolon), which is an expansion of the colon not associated with obstruction up to 6 cm or more with symptoms of intoxication. Risk factors for toxic dilatation include hypokalemia, hypomagnesemia, bowel preparation for colonoscopy with osmotic laxatives, and antidiarrheal medications. Indirectly, the development of toxic dilatation is evidenced by a sudden decrease in stool frequency against the background of diarrhea, bloating, as well as a sudden decrease or disappearance of pain and an increase in symptoms of intoxication (increase in tachycardia, decrease in arterial pressure):
- with the development of toxic dilatation against the background of adequate intensive therapy, an emergency operation is indicated;
- if toxic dilatation is detected in a patient who has not previously received full-fledged drug (primarily hormonal) therapy, conservative treatment is possible: intravenous glucocorticosteroids at a dose equivalent to 2 mg/kg of prednisolone per day, infusion therapy (correction of electrolyte disturbances), metronidazole 1.5 g/day IV. In the absence of positive dynamics (normalization of the diameter of the intestine), colectomy is indicated during the day;
- Colon perforation is the most dangerous complication of ulcerative colitis with almost 50% mortality. If threatening symptoms (peritoneal symptoms, free gas in the abdominal cavity according to plain radiography) are detected, emergency colectomy is indicated.

Colorectal cancer and screening recommendations
In patients with a long history of ulcerative colitis, the risk of colorectal cancer is significantly increased, which necessitates regular examination to detect dysplasia of the colon epithelium. The following factors influence the likelihood of developing cancer.
- Duration of history of ulcerative colitis: The risk of colorectal cancer is 2% at 10 years, 8% at 20 years, and 18% at 30 years.
- Onset in childhood and adolescence, although this factor may only reflect the duration of history and not be an independent predictor of colorectal cancer.
- The extent of the lesion: the risk is most increased in patients with total ulcerative colitis, while in patients with proctitis the risk does not differ from the average in the population.
- The presence of primary sclerosing cholangitis.
- Family history of colorectal cancer.
- Severe exacerbations of ulcerative colitis in history or continuous course of ulcerative colitis. The consequence of the high activity of ulcerative colitis can be inflammatory polyposis, which is also a risk factor for the development of colorectal cancer.

In general, screening for colorectal cancer in patients with ulcerative colitis should begin after 6-8 years from the onset of the disease. In patients suffering from primary sclerosing cholangitis, regular follow-up examinations should be started earlier due to the high risk of cancer. Patients with lesions limited to the rectum can be seen at the same frequency as healthy individuals, provided that past or active inflammation proximal to the rectum is excluded by endoscopic examination and biopsy of the remaining parts of the intestine. The frequency of routine endoscopic examinations is dictated by the degree of risk assessed at colonoscopy 6–8 weeks after the onset of ulcerative colitis.

Two approaches are used to screen for neoplastic mucosal changes.
1. Biopsy of the mucous membrane, 4 fragments from every 10 cm of the colon and rectum (with endoscopy in white light). This approach does not exclude the mandatory biopsy of all suspicious formations.
2. With the proper qualification of the endoscopist and the availability of a high-resolution endoscope, chromoendoscopy with targeted biopsy of areas suspected of neoplasia.

The results of the screening biopsy influence the tactics of further treatment and follow-up.
- High-grade dysplasia found in intact mucosa (i.e., not in raised masses) is an absolute indication for colectomy. The presence of dysplasia must be confirmed by a second independent pathologist.
- For mild dysplasia in intact mucosa (not in raised masses), the decision is made on a case-by-case basis: colectomy should be discussed, but continuation of regular endoscopic screening with a reduction in the interval between studies to 1 year may be acceptable.
- If an adenomatous polyp is found proximal to the lesion (which is determined by endoscopic/histological examination), then a standard polypectomy can be performed, followed by routine follow-up.
- The presence of a polyp with dysplasia in the area of ​​the colon affected by ulcerative colitis is not an indication for colectomy, provided that its histological structure corresponds to an adenoma, and there are no signs of dysplasia in the surrounding intact mucosa or anywhere in the intestine, as well as in the edges of the remote polyp. Types of surgical interventions

In most patients with ulcerative colitis, modern conservative therapy makes it possible to control the course of the inflammatory process, however, in 10-30% of patients, due to the ineffectiveness of drug treatment, one has to resort to surgical intervention aimed at removing the colon. Until the early 1980s. Coloproctectomy with ileostomy was the standard of care despite the occasional use of ileorectal anastomosis. Over the past 20 years, the new "gold standard" has become a reconstructive plastic surgery - coloproctectomy with ileoanal reservoir anastomosis. If successfully performed, this operation provides the possibility of controlled defecation through the anus with a satisfactory quality of life: the average frequency of defecation after the formation of an ileoanal reservoir anastomosis is from 4 to 8 times a day, the daily volume of semi-formed / loose stools is about 700 ml / day (compared to 200 ml/day in a healthy person).

Choice of type of surgical treatment
Restorative plastic surgery with the formation of an ileoanal reservoir anastomosis, despite the obvious attractiveness for the patient, is not possible in all cases, since a number of factors worsen the functional outcome of the operation and increase the risk of complications, leading to the need to remove the reservoir in 3.5-10.0% sick.

Factors affecting the possibility of forming an ileoanal reservoir anastomosis
Despite a higher incidence of comorbidities after age 65, ileoanal reservoir anastomosis surgery itself is safe and effective in older individuals. However, the function of anal holding, which plays a key role in the normal functioning of the ileoanal reservoir anastomosis, apparently deteriorates with older age. In addition, older patients are more likely to develop complications, in particular pouchitis and anastomotic strictures. At the same time, there is no specific age threshold for refusing to form an ileoanal reservoir anastomosis. The formation of an ileoanal reservoir anastomosis by 30-70% increases the risk of infertility in women of childbearing age with ulcerative colitis, probably due to adhesions involving the fallopian tubes. The planned pregnancy and the young age of the woman are not contraindications in the formation of an ileoanal reservoir anastomosis, however, the patient should be warned about the potential risk of infertility. In some cases, it is possible to consider the formation of an ileorectal anastomosis as an intermediate stage of surgical treatment.

Approximately 10% of patients with colitis, even when studying the surgical material obtained during colectomy, fail to make a differential diagnosis between Crohn's disease and ulcerative colitis, and therefore they are diagnosed with undifferentiated nonspecific colitis. The decision to form an ileoanal reservoir anastomosis in such cases is made individually, while the patient should be warned about the risks of ineffective plastic surgery and other complications associated with Crohn's disease. Obvious contraindications to the formation of an ileoanal reservoir anastomosis are colon cancer and severe anal sphincter insufficiency.

Two- and three-stage surgical treatment with the formation of an ileoanal reservoir anastomosis
Three-stage treatment (with colectomy in the first stage) is recommended in cases of severe attack in patients who have not responded to conservative treatment, or if the patient takes 20 mg of prednisolone for more than 6 weeks. Subtotal colectomy with ileostomy relieves intoxication caused by colitis, which improves the general condition of the patient, restores metabolism, and the study of the surgical preparation also makes it possible to clarify the diagnosis and exclude Crohn's disease. Subtotal colectomy is a relatively safe intervention even in critically ill patients, while minimally invasive or laparoscopic operations are also safe if the surgeon is sufficiently skilled.

Ileorectal anastomosis
The formation of an ileorectal anastomosis does not lead to a cure for the patient and does not exclude the possibility of recurrence of inflammation in the rectum and the development of cancer. This operation for ulcerative colitis can only be performed in exceptional cases in women planning a pregnancy. A prerequisite is the consent of the patient to a regular examination of the rectum with a biopsy of the mucous membrane.

Features of surgical intervention in the formation of ileoanal reservoir anastomosis
Reconstructive plastic surgery with the formation of an ileoanal reservoir anastomosis in ulcerative colitis should be performed in specialized hospitals, since the frequency of complications and the functional outcome of such operations significantly depend on the surgeon's qualifications (in particular, on the number of similar interventions performed).

Length of the retained rectum and/or sigmoid colon
If an ileoanal reservoir anastomosis is planned after colectomy for urgent indications in ulcerative colitis, the entire rectum and inferior mesenteric vessels should be preserved. It is advisable to cross the rectum at the level of the promontory (i.e., at the level of the “rectosigmoid junction”) or additionally preserve the distal sigmoid colon (the decision is made by the operating surgeon). While maintaining the distal sigmoid colon, it is displayed on the anterior abdominal wall in the form of a sigmostoma. The latter option is the safest, since there is no intestinal stump left in the abdominal cavity. When crossing the rectum at the level of the cape for several days, it is recommended to drain the stump through the anus to prevent suture failure due to the accumulation of mucus in the stump. intestines. Controlled trials of drugs in patients after colectomy have not been conducted, empirical treatment consists in the use of local mesalazine, prednisolone, washing the disconnected rectum with antiseptic solutions.

Imposing an anastomosis in the formation of an ileoanal reservoir anastomosis
Preservation of an extended rectal area (more than 2 cm above the dentate line) when using a stapler to form an ileoanal reservoir anastomosis can cause chronic inflammation in the rectum with reservoir dysfunction, and also contributes to the persistence of the risk of dysplasia and (very rarely) cancer. The maximum length of the anorectal mucosa between the dentate line and the anastomosis should not exceed 2 cm. Although a small piece of mucosa is preserved with the stapling device, the risk of cancer is low and similar to that of a manual anastomosis). The formation of an ileoanal reservoir anastomosis in the vast majority of cases is carried out under the cover of a loop ileostomy.

Follow-up of patients with ileoanal reservoir anastomosis
Morphological changes in the epithelial lining of the pouch usually develop 12–18 months after closure of the ileostomy and are characterized by flattening and reduction in the number of villi, leading to their atrophy (“colonic metaplasia”), which is potentially associated with the risk of malignant transformation of the pouch mucosa. In addition, when applying a hardware ileoanal reservoir anastomosis, a small area of ​​the rectal mucosa is preserved. The risk of reservoir cancer is increased in patients operated on for cancer or dysplasia against the background of ulcerative colitis (and when dysplasia is detected in the surgical material), and in patients with primary sclerosing cholangitis. Scientific substantiation of the frequency of control examinations of patients with ileoanal reservoir anastomosis was not performed, however, in patients with the above risk factors, it is advisable to conduct control endoscopic studies (reservoiroscopy) with a biopsy of the mucous membrane at least once every 2 years. Drug therapy during surgical treatment

The impact of drug therapy on the risk of surgical complications
Taking prednisone greater than 20 mg for more than 6 weeks increases the risk of surgical complications. Preoperative azathioprine does not worsen the outcome of surgical treatment, while the introduction of infliximab and cyclosporine shortly before surgery may increase the incidence of postoperative complications, although data on infliximab remain controversial.

Hormone therapy before surgery and in the early postoperative period
Abrupt cessation of glucocorticosteroid therapy can cause a withdrawal syndrome (acute adrenal insufficiency, the so-called Addisonian crisis), which necessitates a temporary continuation of hormonal therapy after surgery until complete withdrawal. At the time of surgery and in the early postoperative period until the patient can take oral glucocorticosteroids, intravenous administration of glucocorticosteroids at a dose equivalent to 2 mg / kg of prednisolone is recommended (the dose, therefore, may exceed that taken before surgery).

Currently, there is no reliable scientific basis to justify any regimen for stopping hormone therapy after colectomy for ulcerative colitis. The dose of glucocorticosteroids for further oral administration during the period of withdrawal of hormonal therapy is determined by the duration of the previous therapy and the size of the doses used. According to the recommendations of the European Society for the Study of Ulcerative Colitis and Crohn's Disease, if hormonal therapy before surgery was carried out for no more than 1 month, it is possible to stop taking glucocorticosteroids immediately after surgery.

If the patient received glucocorticosteroids for more than 1 month before surgery, after surgery it is advisable to switch from the high parenteral dose of glucocorticosteroids described above to oral administration of glucocorticosteroids at a dose not lower than the upper limit of daily cortisol production, i.e. not less than 20 mg of prednisolone. Further dose reduction and withdrawal of glucocorticosteroids are carried out under the supervision of an endocrinologist.

Colostomy bags and stoma care
Surgical treatment of ulcerative colitis is inextricably linked with the need for a temporary or permanent ileostomy. There is a wide range of ileostomy care products that allow the patient to practically rehabilitate socially. The means of medical rehabilitation of a patient with an ileostomy (or colostomy) include adhesive (adhesive) colostomy bags and their accessories.

All colostomy bags can be divided into two main types - one-component and two-component. Along with them, aids are used to care for the stoma (medical or adhesive paste, powder, deodorants, odor absorbers, protective films, sealing rings, rods for a double-barreled ostomy, irrigators, absorbents, etc.) and skin care products around the stoma. Stomatized patients need a comprehensive medical and social rehabilitation program. Its basis is an individual patient rehabilitation program - a set of measures aimed at compensating for impaired or lost body functions and restoring the ability to perform certain types of activities.

Reservoir and other complications of surgical treatment with the formation of a small bowel reservoir
A reservoir is a nonspecific inflammation of the small bowel reservoir and is the most common complication of ileoanal reservoir anastomosis. The frequency of its occurrence varies in a wide range from 15 to 50% within 10 years after the formation of an ileoanal reservoir anastomosis in large specialized centers. Such differences may be due to a significantly higher risk of pouchitis in ulcerative colitis, exceeding the frequency of this complication in the formation of ileoanal reservoir anastomosis for other diseases.

Diagnosis of pouchitis
The diagnosis is established on the basis of clinical symptoms, as well as characteristic endoscopic and histological changes. The risk of pouchitis appears to be higher in non-smokers and non-steroidal anti-inflammatory drug users, as well as in patients with advanced ulcerative colitis and extraintestinal manifestations (primary sclerosing cholangitis).

The symptoms of pouchitis include increased bowel movements, including liquid feces, spastic abdominal pain, stool incontinence (may be an independent symptom) and tenesmus. In rare cases, fever and extraintestinal manifestations may occur. The release of blood is not characteristic and, as a rule, occurs with inflammation of the preserved mucous membrane of the rectum.

In patients with symptoms consistent with pouchitis, pouchoscopy with biopsy of the pouch mucosa should be performed to confirm the diagnosis. Patients with ileoanal reservoir anastomosis often have a stricture of the reservoir-anal anastomosis, so it is preferable to use a fistuloscope rather than a colonoscope for reservoiroscopy. An attempt should always be made to pass the device into the afferent ileum. It should be noted that when clinical remission is achieved, routine reservoiroscopy is not required.

Endoscopic findings consistent with pouchitis include diffuse erythema, which may be focal, in contrast to that seen in ulcerative colitis. Edema and granulation of the mucous membrane, spontaneous and contact bleeding, erosion and ulceration are also characteristic endoscopic manifestations. Erosions and/or ulcers along the staple line are not necessarily indicative of pouchitis. Biopsy specimens should be taken from the mucosa of the reservoir and the afferent loop above the reservoir, but not from the line of brackets. Histological manifestations of pouchitis are also nonspecific and include signs of acute inflammation with polymorphonuclear leukocyte infiltration, crypt abscesses and ulceration against the background of chronic inflammatory infiltration.

Complications of pouchitis include abscesses, fistulas, pouch stenosis, and pouch adenocarcinoma. The latter complication is extremely rare and almost always occurs when dysplasia or cancer is detected in the surgical preparation obtained during colectomy.

The differential diagnosis for suspected pouchitis is with irritable pouch syndrome, ischemic lesions, Crohn's disease, and other rare causes of pouch dysfunction such as collagenous, cytomegalovirus, and Cl. difficile-associated pouchitis. Consideration should be given to the possibility of developing non-specific ileitis caused by the use of non-steroidal anti-inflammatory drugs and the syndrome of excessive bacterial growth.

Treatment of pouchitis and maintenance of remission
Antibiotics remain the main drugs used to treat pouchitis, which makes it possible to classify pouchitis as antibiotic-sensitive, antibiotic-dependent, and antibiotic-resistant. The first line of therapy includes a 14-day course of oral metronidazole (15-20 mg / kg per day) or ciprofloxacin (1000 mg / day). Adverse events are much more common when taking metronidazole. In the absence of effect or with the development of dependence on the intake of these drugs, it is possible to prescribe reserve drugs - rifaximin (2000 mg / day), tinidazole, rectal glucocorticosteroids, rectal mesalazine, azathioprine. In cases of antibiotic-resistant pouchitis, it is possible to prescribe oral budesonide (9 mg) for 8 weeks. A prerequisite for effective treatment of resistant pouchitis is a reliable exclusion of alternative causes of reservoir dysfunction.

Inflammation of the mucous membrane of the preserved area of ​​the rectum and irritable reservoir syndrome
Another potential complication of an ileoanal reservoir anastomosis is inflammation of the rectal mucosa, which is preserved when an instrumental anastomosis is performed. Treatment of cuff inflammation is carried out with mesalazine suppositories 500 mg 2 times a day and / or rectal glucocorticosteroids.

Irritable pouch syndrome is a functional disorder with symptoms similar to those of pouchitis. It occurs in patients who took anxiolytics or antidepressants before colectomy, which indirectly indicates the manifestations of irritable bowel syndrome in such patients before surgery. Treatments for these two functional disorders overlap and include psychotherapy and antidepressants, dietary fiber, antidiarrheals, antispasmodics, and nonabsorbable antibiotics to correct bacterial overgrowth syndrome.

Forecast
The lifetime risk of severe exacerbation of ulcerative colitis is 15%, while the likelihood of a severe attack is higher in patients with total colon damage. When conducting adequate anti-relapse therapy for 5 years, exacerbations can be avoided in half of the patients, and within 10 years - in 20% of patients. Within 1 year after diagnosis, the probability of colectomy is 4-9% (with a severe attack - about 50%), in the future, with each year of the disease, the risk of colectomy increases by 1%. Temporary, procedural and preventive criteria are used to assess the quality of medical care. Temporary characterize the timeliness of the provision of certain stages of medical care. The performance by the patient of a number of medical manipulations, instrumental and laboratory studies necessary for the quality of medical care is evaluated in procedural criteria. Preventive criteria are used to analyze measures aimed at preventing the development of complications.

UDK 616.348-002.44-07-08

nonspecific ulcerative colitis: current approaches to diagnosis and treatment

S.R.Abdulkhakov1, R.A.Abdulkhakov2

1 Department of General Medical Practice, 2 Department of Hospital Therapy

Gou VPO "Kazan State Medical University of Roszdrav", Kazan

Abstract. The article discusses the classification, clinical picture, approaches to diagnosis and modern standards for the treatment of non-specific ulcerative colitis, based on international and Russian recommendations. Criteria for assessing the severity of ulcerative colitis according to Truelove/Witts and the Mayo scale, recommended depending on the severity of the dose of 5-ASA and glucocorticosteroids, are given; indications for surgical treatment.

Keywords: nonspecific ulcerative colitis, assessment of activity and severity, treatment.

NoN-spEOiFiO uLOERATivE coLiTis: up-TO-DATE APPROACHES TO DIAGNOSTiOS AND TREATMENT

S.R. Abdoulkhakov1, R.A.Abdoulkhakov2

1 Department of General Medical Practice, 2 Department of Hospital Therapy,

^zan State Medical University, Kazan

abstract. The article deals with classification, clinic, approaches to diagnostics and modern standards of non-specific ulcerative colitis treatment, based on international and Russian recommendations. Criteria of assessment of severity stages of non-specific ulcerative colitis according to Truelove/Witts and Mayo score; 5-ASA and corticosteroids recommended doses depending on severity stages; and indications for surgical treatment are presented.

Key words: non-specific ulcerative colitis, assessment of activity and severity, treatment.

Nonspecific ulcerative colitis (NUC) is a chronic inflammatory disease of the colon, characterized by ulcerative-destructive changes in its mucosa.

The prevalence in the world is 50-230 cases per 100 thousand population. The epidemiology of NUC in Russia as a whole is unknown; the prevalence in the Moscow region is 22.3 cases per 100,000 population. The annual increase in UC patients in the world is 5-20 cases per 100,000 population. Epidemiological studies in the United States have shown that UC occurs 3-5 times more often in the white population than in African Americans, and in Jews - 3.5 times more often than in non-Jewish people. The disease occurs in all age groups, but the main incidence peak occurs in 20-40 years. Men and women get sick with the same frequency. In smokers, NUC occurs 2 times less frequently than in non-smokers. Mortality from inflammatory bowel diseases, including UC, is 6 cases per 1 million population in the world, and 17 cases per 1 million population in Russia. In Russia, in most cases, the diagnosis is made several years after the onset of the first clinical symptoms of the disease.

Classification

I. According to the clinical course:

Sharp form.

Fulminant (lightning) form.

Chronic form.

Recurrent (episodes of exacerbation lasting 4-12 weeks are replaced by periods of remission).

Continuous (clinical symptoms persist for more than 6 months).

II. By localization:

Distal colitis (proctitis, proctosigmoiditis).

Left-sided colitis (up to the level of the middle of the transverse colon).

Total colitis (in some cases with retrograde ileitis).

III. According to the severity of clinical manifestations (disease activity):

Light form.

Medium form.

Severe form.

IV. By response to steroid therapy1:

Steroid addiction.

Steroid resistance.

The severity of NUC exacerbation is assessed according to the criteria of Truelove and Witts (1955), supplemented by M.Kh. Levitan (Table 1).

In addition, the Mayo Clinic Severity Scoring System (Mayo Index) can be used.

Mayo index \u003d stool frequency + presence of rectal bleeding + endoscopy data + general medical opinion

Stool Frequency:

0 - stool frequency normal for this patient;

1 Important for deciding whether to add

immunosuppressive agents, biological agents, or surgical treatment.

Evaluation of the severity of UC

Signs Mild Moderate Severe

Stool frequency< 4 раз в сут >4 times a day > 6 times a day

Rectal bleeding Insignificant Pronounced Pronounced

Temperature Normal< 37,8°С >37.8°C for 2 days out of 4

Pulse rate Normal< 90 в мин >90 per min

Hemoglobin, g/l More than 111 105-111 Less than 105

ESR, mm/h Less than 20 20-30 More than 30

1 - stool frequency exceeds the usual by 1-2 in

2 - stool frequency exceeds the usual by 3-4 in

3 - stool frequency exceeds the usual by 5 or more per day.

Rectal bleeding:

0 - no visible blood;

1 - traces of blood in less than half of the bowel movements;

2 - visible blood in the stool in most bowel movements;

3 - predominant allocation of blood.

Endoscopic picture:

0 - normal mucous membrane (remission);

1 - mild degree (hyperemia, blurred vascular pattern, graininess of the mucous membrane);

2 - medium degree (severe hyperemia, lack of vascular pattern, granularity, erosion of the mucous membrane);

3 - severe (ulceration, spontaneous bleeding).

General clinical characteristics (based on the doctor's conclusion according to three criteria: the patient's daily reports of sensations in the abdomen, the patient's general well-being and the characteristics of the patient's objective status):

0 - norm (remission);

1 - easy form;

2 - moderate form;

3 - severe form.

Mayo index interpretation:

0-2 - remission/minimum disease activity;

3-5 - mild form of UC;

6-10 - moderate form of UC;

11-12 - severe form of UC.

Etiology and pathogenesis. The etiology of NUC is not fully known. In the pathogenesis of the disease, the significance of changes in immunological reactivity, dysbiotic changes, allergic reactions, genetic factors, and neuropsychiatric disorders is assumed.

There is a genetic predisposition to UC (familial cases of ulcerative colitis) and an association of UC with HLA histocompatibility complex antigens. Among the closest relatives, UC occurs 15 times more often than in the general population.

Pathological anatomy. Morphologically, inflammation of various parts of the colon is determined. The mucous membrane is hyperemic, edematous, ulcerated; ulcers of a rounded shape, various sizes. Microscopic changes are characterized by infiltration of the lamina propria by plasma cells, eosinophils, lymphocytes, mast cells, and neutrophils.

clinical picture. In the clinical picture, there are three leading syndromes associated with intestinal damage: stool disorders, hemorrhagic and pain syndromes (Table 2). The onset of the disease may be acute or gradual.

The main symptom is multiple (in severe cases up to 20 times a day) watery stools mixed with blood, pus and mucus, combined with tenesmus and false urge to defecate. Often, only bloody mucus is excreted when the urge to defecate. Diarrhea is most pronounced when the right half of the large intestine is affected, where water and electrolytes are absorbed. In the case of the spread of the inflammatory process in the proximal direction to a large part of the colon, the disease is accompanied by significant bleeding. In the initial period of the disease, which occurs in the form of proctosigmoiditis, constipation may occur, mainly due to spasm of the sigmoid colon. During remission, diarrhea may completely stop.

Pain in the abdomen - usually aching, less often - cramping. Localization of pain depends on the extent of the pathological process. Most often, this is the area of ​​​​the sigmoid, colon and rectum, less often - the paraumbilical or right iliac region. Typically, pain increases before a bowel movement and eases after a bowel movement. In many patients, the intensity of pain increases 30-90 minutes after eating. As the disease progresses, the connection between meals and abdominal pain is lost (i.e., the gastrocolytic reflex fades, in which increased intestinal motility occurs after eating).

Tenesmus - false urges with the release of blood, mucus and pus ("rectal spit") with little or no stool; are a sign of high activity of the inflammatory process in the rectum.

Constipation (usually combined with tenesmus) due to spastic contraction of the intestinal segment above the lesion, is characteristic of limited distal forms of UC.

Later, general symptoms join: anorexia, nausea and vomiting, weakness, weight loss, fever, anemia.

The fulminant form is almost always characterized by a total lesion of the colon, the development of complications (toxic dilatation of the colon, perforation), in most cases it requires urgent surgical intervention. The disease begins acutely, within 1-2 days a pronounced clinical picture unfolds with a frequency of bloody stools more than 10 times a day, a decrease in hemoglobin level less than 60 g/l, an increase in ESR more than 30 mm/h.

Table 2 The frequency of intestinal symptoms at the onset of the disease and one year after the onset of the disease (according to M. Roth, V. Bernhartd, 2006)

Extraintestinal manifestations are detected in 10-20% of patients with UC, more often with total damage to the colon (Table 3).

Erythema nodosum and pyoderma gangrenosum are due to the presence of circulating immune complexes, bacterial antigens, and cryoproteins.

Aphthous stomatitis is observed in 10% of patients with UC, aphthae disappear as the activity of the underlying disease decreases.

Eye damage - episcleritis, uveitis, conjunctivitis, keratitis, retrobulbar neuritis, choroiditis - occurs in 5-8% of cases.

Inflammatory lesions of the joints (sacroiliitis, arthritis, ankylosing spondylitis) can be combined with colitis or occur before the onset of the main symptoms.

Bone manifestations: osteoporosis, osteomalacia, ischemic and aseptic necrosis are complications of corticosteroid therapy.

All extraintestinal manifestations, with the exception of ankylosing spondylitis and hepatobiliary disease, disappear after coloproctectomy.

Complications of UC: toxic dilatation of the colon, perforation, profuse bleeding, strictures, malignancy, sepsis, thrombosis and thromboembolism.

Toxic dilatation of the colon is an acute expansion of the colon, predominantly descending and transverse, with an increase in pressure in its lumen. It is clinically characterized by a sharp and progressive deterioration of the patient's condition: hyperthermia, rapidly increasing weakness, abdominal pain, frequent liquid stools with copious discharge of blood, pus, tachycardia, arterial hypotension, bloating and weakening / absence of intestinal noise during auscultation. Against the background of steroid therapy, clinical symptoms may be erased. The diagnosis is confirmed with

Plain radiography of the abdominal organs. Depending on the diameter of the large intestine,

3 degrees of toxic dilatation:

I degree - the diameter of the intestine is less than 8 cm;

II degree - intestine diameter 8-14 cm;

III degree - the diameter of the intestine is more than 14 cm.

Perforation usually develops against the background of toxic dilatation of the colon and is diagnosed by the presence of free gas in the abdominal cavity during x-ray examination. Characteristic symptoms - abdominal pain, bloating, palpation tenderness, symptoms of peritoneal irritation - can be erased while taking steroid drugs.

Thrombosis and thromboembolism are a manifestation of the high activity of the inflammatory process and develop against the background of hypercoagulation. Most often, thrombosis of the superficial or deep veins of the lower leg or iliofemoral thrombosis is observed. The presence of recurrent thromboembolism is an indication for colectomy.

Diagnostics

Endoscopic examination (colonoscopy) with biopsy is the main method to confirm the diagnosis, assess the degree of activity of the inflammatory process, establish the extent of the process, and monitor the effectiveness of treatment. NUC is characterized by the absence of a vascular pattern, granularity, hyperemia and edema of the mucous membrane, the presence of contact bleeding and / or erosions and ulcers. Histological examination of biopsy specimens is carried out in order to confirm the diagnosis: signs of nonspecific immune inflammation are revealed, which, however, are not pathognomonic for UC.

In the remission phase, endoscopic changes may be completely absent.

In severe exacerbations, colonoscopy is not always possible due to the risk of complications.

When conducting an endoscopic examination, the activity of the inflammatory process in UC is assessed (Table 4, Fig. 1).

X-ray examination (irrigoscopy, irrigography) allows you to establish the length of the process according to characteristic features: smoothness or absence of gaustra (symptom of the "water pipe"), shortening of the colon; it is possible to identify barium depots corresponding to ulcerative defects, pseudopolyps, strictures (Fig. 2).

Symptoms At the onset of the disease, % After 1 year, %

Intestinal bleeding 80 100

Diarrhea 52 85

Abdominal pain 47 35

Anal fissures 4 4

Anal fistulas 0 0

Table 3

Symptoms Frequency 5-20% Frequency below 5%

Associated with the activity of the inflammatory process in the intestine Aphthous stomatitis. Nodular erythema. Arthritis. Eye damage. Thrombosis, thromboembolism Pyoderma gangrenosum

Not associated with the activity of the inflammatory process in the intestine Sacroiliitis. Psoriasis Ankylosing spondylitis. Rheumatoid arthritis. Sclerosing cholangitis. Cholangiogenic carcinoma. Amyloidosis

Consequences of malabsorption, inflammation, etc. Steatohepatitis. Osteoporosis. Anemia. Cholelithiasis

UC activity according to endoscopic examination

Activity

Sign minimal (I degree) moderate (II degree) high (III degree)

Hyperemia Diffuse Diffuse Diffuse

Graininess No Yes Pronounced

Edema Yes - -

Vascular pattern Absent Absent Absent

Bleeding Petechial hemorrhages Contact, moderate Spontaneous, severe

Erosions Single Multiple Multiple with ulceration

Ulcers None Single Multiple

Fibrin No Yes Abundant

Pus (in the lumen and on the walls) No No or a small amount Much

Rice. 1. Endoscopic picture in UC (a - minimal, b - moderate, c - high activity)

Rice. 2. X-ray picture in NUC (symptom of "water pipe")

Bacteriological examination of feces is carried out in order to exclude infectious colitis.

Laboratory research methods are important for establishing the severity of NUC. In addition, with a long course of the disease due to diarrhea, hyponatremia, hypochloremia, hypoalbuminemia develop, weight loss progresses; anemia is often observed. Severe forms of the disease are characterized by an increase in ESR, the presence of leukocytosis.

Differential Diagnosis

Nonspecific ulcerative colitis is differentiated primarily from infectious lesions of the intestine, ischemic colitis, Crohn's disease.

In differential diagnosis with infectious pathology, microbiological examination of feces is of paramount importance.

Ischemic colitis. Characterized by the elderly age of patients, typical x-ray signs (symptom of "finger impressions", pseudodiverticula), detection of hemosiderin-containing macrophages in histological examination of biopsy specimens of the colon mucosa.

The greatest difficulties may arise when distinguishing between nonspecific ulcerative colitis and Crohn's disease (granulomatous colitis) with localization in the large intestine (Table 5).

Differential diagnosis of ulcerative colitis and Crohn's disease

Signs of UC Crohn's disease

Clinical: Bloody diarrhea 90-100% 50%

Tumor-like masses in the abdominal cavity Very rare Often

Perianal localization Does not happen 30-50%

Colonoscopy: Presence of proctitis 100% 50%

Histology: Spread Mucosa Transmural

Cellular infiltrates Polymorphonuclear Lymphocytic

Glands Disturbed Normal

Decreased goblet cells Often when the process is active Absent

Granulomas Absent Have diagnostic value

X-ray: Distribution Expressed Localized

Symmetry Yes No

Ulcers Superficial Deep

Strictures Very rare Common

Fistulas Never Often

Treatment. Diet

Various diet options are prescribed, slowing down intestinal transit (4, 4a, 4b), rich in protein, with restriction of fats.

The goals of UC treatment are induction and maintenance of clinical and endoscopic remission, improvement of the patient's quality of life, prevention of relapses and prevention of complications.

Medical therapy

Currently, the doctor has a fairly large arsenal of drugs that are effective in the treatment of patients with chronic inflammatory bowel diseases. The choice of drugs and method of treatment depends on the following characteristics of the disease in a particular patient:

1. Prevalence (localization) of the pathological process in the intestine.

2. The severity of the exacerbation (mild, moderate, severe), which does not always correlate with the prevalence of the inflammatory process. Determining the severity of the disease is necessary, first of all, to resolve the issue of the need for hospitalization of the patient and the appointment of hormone therapy.

3. The effectiveness of previously used drugs (with a previous exacerbation and before the start of the prescribed therapy).

4. The presence of complications.

Basic in the treatment of NUC are two groups of drugs:

Preparations of 5-aminosalicylic acid (sulfasalazine, mesalazine).

Glucocorticosteroids (GCS).

Preparations of 5-aminosalicylic acid (5-ASA)

Before the advent of mesalazine, the drug of choice in the treatment of patients with UC was sulfasalazine, introduced into clinical practice in the early 1940s. After entering the large intestine, about 75% of sulfasalazine is cleaved into two components by the action of bacterial azoreductases - 5-aminosalicylic acid and the sulfonamide component sulfapyridine. Late 70s - early

80s it has been shown that sulfapyridine has no intrinsic anti-inflammatory activity. Most of the side effects when taking sulfasalazine are associated precisely with the systemic action of sulfapyridine and they are observed most often in individuals with genetically determined "slow" acetylation in the liver of sulfapyridine to N-acetylsulfapyridine. The frequency of side effects when using sulfasalazine (nausea, vomiting, itching, dizziness, headache, allergic reactions, etc.) reaches, according to some reports, 55%, averaging 20-25%. These effects are often dose-dependent, therefore, it is recommended to stop taking sulfasalazine for 1-2 weeks, followed by the resumption of taking the drug at a dose of 0.125-0.25 g / day, gradually increasing the dose by 0.125 g / week until a maintenance dose of 2 g / day is reached. Serious side effects (agranulocytosis, leukopenia, impotence) when using sulfasalazine are observed in 12-15% of patients. After it was found that the only active anti-inflammatory component of sulfasalazine is 5-aminosalicylic acid (5-ASA), further prospects in the development of an effective drug for the treatment of chronic inflammatory bowel diseases were associated with it.

Preparations of "pure" 5-ASA are represented by three groups of pharmacological agents. The first of them is mesalazine (salofalk, pentasa, mesacol), in which 5-ASA is enclosed in shells of different chemical composition, gradually dissolving in the gastrointestinal tract. occurs under the action of microorganisms of the large intestine. Preparations of the third group consist of 5-ASA and an inert non-absorbable conductor; the release of 5-ASA also occurs under the action of the intestinal microflora. Nevertheless, despite the existence of a number of 5-ASA preparations, mesalazine preparations form the basis of drug therapy for UC.

As for the mechanism of action of 5-ASA preparations, most studies are devoted to the study

the effect of these drugs on the metabolism of arachidonic acid and the suppression of cyclooxygenase activity. However, given that non-steroidal anti-inflammatory drugs, which are based on the inhibition of cyclooxygenase, do not affect the course of the inflammatory process in the intestine, this mechanism can hardly be considered the leading one. At the same time, both sulfasalazine and “pure” 5-ASA preparations have been shown to increase the local concentration of prostaglandins, which are known to have a cytoprotective effect. Among other possible mechanisms of action, the influence of 5-ASA on the production of immunoglobulins, interferons, pro-inflammatory cytokines, suppression of the activity of oxygen free radicals, a decrease in increased cell permeability, etc.

Currently, mesalazine preparations are available in the form of 3 dosage forms: tablets, suppositories and microclysters.

Topical application of 5-ASA preparations

Topical treatment is indicated in the case of distal colitis (proctitis, proctosigmoiditis or left-sided colitis) and as part of a combination therapy for advanced colitis (given that the inflammatory process in UC always affects the distal intestine).

Placebo-controlled clinical studies have shown the high efficacy of mesalazine in the form of enemas at a dose of 1-4 g / day and rectal suppositories at a dose of 0.5-1.5 g / day in inducing remission in patients with mild to moderate left-sided colitis, proctosigmoiditis and proctitis the severity of the disease. The clinical effect of the rectal method of drug administration in the treatment of left-sided lesions is almost always higher than with oral administration, the maximum effect is achieved with the combined use of oral and rectal forms of mesalazine. Foam is distributed in the rectum and sigmoid colon, suppositories - only in the rectum. With the introduction of 5-ASA in an enema, 20-30% of the total dose is absorbed and has a systemic effect, most of the drug has a local effect.

Salofalk in enemas of 2 and 4 g (30 and 60 ml) is used to treat left-sided forms of ulcerative colitis. Enemas containing 2 g of salofalk (30 ml) can be prescribed for mild and moderate forms of ulcerative colitis, especially in cases where the lesion is limited to the rectum and sigmoid colon. The contents of the enema are administered daily in the evening before bedtime [enemas of 60 ml (4 g) can be used in two doses: the second portion of the enema is administered after emptying the bowels from the first, or the next day in the morning].

In a comparison of different treatment options for distal colitis, rectal mesalazine was found to be comparable to, and in some reports even better than, corticosteroid enemas and oral mesalazine. A meta-analysis of clinical studies has shown that rectal mesalazine is more effective in inducing remission in left-sided lesions compared to rectal steroids.

Interestingly, the use of 5-ASA enemas provides a significant therapeutic effect even in the treatment of patients resistant to previous oral administration.

treatment with sulfasalazine, systemic and topical corticosteroids.

With regard to maintenance therapy with topical forms of mesalazine, it has been shown that more frequent use of drugs (suppositories 2 times a day or enemas daily) leads to a lower frequency of recurrence compared with less frequent use of drugs (suppositories 1 time per day or enemas 1 time in 2- 3 days) . Oral administration of 5-ASA preparations Placebo-controlled studies have shown high efficacy of mesalazine at a dose of 1.6-4.8 g/day in inducing remission in patients with mild to moderate UC. The results of meta-analyses confirm the presence of a dose-dependence with oral mesalazine. The effectiveness of mesalazine at a dose of 0.8-4.0 g / day and sulfasalazine at a dose of 4-6 g / day is approximately the same, however, when using the latter, a significantly greater number of side effects are observed. In mild and moderate forms, the average dose of sulfasalazine is 4-6 g / day, mesalazine - 2-4 g / day. After achieving the effect, a gradual decrease in the dose of the drug is recommended. Studies show that high doses of mesalazine used in the exacerbation phase are, in some cases, almost equivalent in effectiveness to glucocorticoids. However, high doses of 5-ASA preparations are recommended to be used for no more than 8-12 weeks.

The maximum effect of therapy can be achieved with a combination of oral and local forms of mesalazine.

In the case of long-term use, the appointment of mesalazine is preferable compared to sulfasalazine due to fewer side effects. Side effects when taking mesalazine Side effects are quite rare. Cases of toxic hepatitis, pancreatitis, pericarditis, interstitial nephritis are described. However, the observations of Hanauer et al. (1997) for patients taking mesalazine at various doses up to 7.2 g / day for up to 5.2 years, did not reveal any adverse effects on renal function. In a small number of patients, adverse events have been described in the form of increased diarrhea and abdominal pain, which are commonly associated with hypersensitivity to 5-ASA.

The use of mesalazine in children With an exacerbation of the disease, depending on the severity of the disease and the age of the child, the recommended doses of mesalazine are 30-50 mg / kg of body weight per day for 3 doses. In case of inflammation limited to the left half of the large intestine, it is possible to use local dosage forms (suppositories, enemas). For the prevention of relapses, depending on age, mesalazine is prescribed at a dose of 15-30 mg / kg of body weight per day for 2 doses. If the child weighs over 40 kg, the usual adult dose of mesalazine is prescribed. There are no official recommendations for the treatment of infants and young children due to insufficient experience with the use of mesalazine in this age group. Age under 2 years is considered a contraindication to taking mesalazine.

Mesalazine use during pregnancy and lactation

Pregnancy is not a contraindication to the use of mesalazine. Moreover, in many works

it is recommended to continue therapy with NUC without reducing the dose of mesalazine during pregnancy. The use of 5-ASA preparations during lactation is also considered safe, since only a small amount of the drug passes into milk.

Glucocorticosteroids

The effect of glucocorticosteroids (GCS) may be associated with systemic (i.v., oral or rectal administration of prednisolone, hydrocortisone) or local (non-systemic) action (rectal or oral administration of budesonide). Glucocorticoids are used in severe UC or in case of ineffectiveness of previous therapy with 5-ASA drugs. The drugs of choice are prednisolone and its methylated analogues. The most effective dose of prednisolone is 1 mg / kg per day, however, in severe cases, higher (up to 1.5-2 mg / kg per day) doses of prednisolone can be used for 5-7 days, followed by a dose reduction to 1 mg / day. kg In the case of an acute attack of UC, short courses (7 days) of intravenous steroids (prednisolone 240-360 mg/day or hydrocortisone succinate 400-500 mg/day) are effective. Reducing the dose of hormonal drugs begins when clinical improvement is achieved (on average, after 2-3 weeks of therapy).

Systemic action of glucocorticosteroids

Considering that, under physiological conditions, plasma cortisol levels are highest between 6 and 8 am, it is recommended to take a large dose of glucocorticoids in the morning. Morning oral administration at a dose of 40 mg is comparable in effectiveness to 4 times daily intake of separate doses of 10 mg In cases of disease refractory to hormone therapy, it may be effective to divide the daily dose into a higher morning dose (2/3 of the daily dose) and lower evening (1/3 daily dose). Oral administration of prednisolone begins with doses of 40-60 mg per day (until remission is achieved, usually from 2 weeks to 1 month) with a gradual decrease to 5 mg and subsequent withdrawal during therapy with mesalazine drugs.

Hydrocortisone is applied rectally (in microclysters) or intravenously. With ulcerative proctitis or proctosigmoiditis, the administration of hydrocortisone in microclysters, 125 mg 1-2 times a day, is effective. In severe cases, parenteral administration of hydrocortisone in daily doses of 300-500 mg is used.

Indications for intravenous administration of corticosteroids are severe UC and refractoriness to oral corticosteroids, since patients with UC often have impaired absorption and metabolism of orally taken corticosteroids. For example, individuals with severe UC have a smaller peak plasma concentration of corticosteroids and a slower decrease after a single dose of 40 mg of prednisolone compared with healthy volunteers. Intravenous administration leads to the same level of GCS in plasma as in healthy individuals. Intravenous use of corticosteroids for 5 days leads to the achievement of clinical remission in 55-60% of patients with severe exacerbation of ulcerative colitis.

In the event that parenteral use of GCS for 7-10 days does not lead to the achievement of clinical remission, it is recommended to raise the question of the advisability of surgical treatment.

Recently, much attention has been paid to new generation glucocorticoids (fluticasone

propionate, beclomethasone dipropionate, budesonide), the local activity of which is significantly higher than that of methylprednisolone. In addition, as a result of rapid metabolism during the first passage through the liver, the severity of their side effects due to systemic action is significantly lower than that of hormones commonly used in practice. The most studied among them is budesonide. Thus, the affinity for GCS receptors in budesonide is 195 times higher than that of methylprednisolone. Only 2% of the accepted dose of the drug circulates in the systemic circulation, more than 95% of the drug binds to tissues. Currently, budesonide is recommended for inclusion in regimens for the treatment of inflammatory bowel disease.

Oral glucocorticosteroids with non-systemic action

Comparative studies using budesonide 10 mg/day and prednisolone 40 mg/day showed comparable efficacy; the difference in the two groups of patients was only in fewer side effects when taking budesonide.

Local therapy with glucocorticosteroids (systemic effect)

Hydrocortisone, prednisolone, methylprednisolone and other steroid drugs administered rectally in the form of enemas or suppositories are absorbed as well as the drug taken per os, and, accordingly, can be the cause of all side effects characteristic of systemic corticosteroids.

A small number of studies comparing rectally administered 5-ASA with rectal hydrocortisone 100-175 mg/day or prednisolone 20-30 mg/day have shown similar clinical efficacy of these treatment options in patients with active ulcerative proctitis and proctosigmoiditis. However, this meta-analysis showed the advantage of rectally administered mesalazine preparations over rectal steroids in inducing remission of UC.

The effectiveness of local glucocorticoid therapy depends on the depth of penetration of the drug and the duration of its stay in the intestinal lumen. Studies have shown that with the introduction of GCS in the form of enemas, the drug enters the sigmoid colon and reaches the distal descending colon, and under favorable conditions - the splenic angle. The depth of penetration of the drug depends on the volume of the enema. However, when using large volume enemas, patients are often unable to hold them for a long time. The introduction of GCS in the form of rectal foam contributes to the retention of the drug in the intestine and thus makes it possible to reduce the dose of the administered drug.

Thus, short courses of rectally administered corticosteroids (prednisolone 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 to be used continuously due to the possibility of side effects. .

Rectal glucocorticosteroids (local action)

Placebo-controlled studies have shown that rectal (in the form of enemas) administration of budesonide at a dose of 2-8 mg / day leads to clinical improvement in patients with mild to moderate

severity and left-sided lesion of the colon. It turned out that enemas containing 2 mg of budesonide have the same positive effect on the clinical and endoscopic picture of the disease as enemas containing 4 g of 5-ASA.

Side effects associated with taking systemically active corticosteroids include a moon-shaped face, acne, infectious complications, ecchymosis, hypertension, hirsutism, etc. complications - in 3-5% of patients. The incidence of diabetes mellitus, requiring the appointment of hypoglycemic drugs, in persons taking GCS for a long time is 2.23 times higher than the average in the population.

Depending on the response to steroid therapy, the following conditions are distinguished: steroid resistance and steroid dependence.

Steroid resistance - the lack of the effect of adequate therapy, including prednisolone 0.75 mg / kg / day for 4 weeks, infusion therapy (erythromass, protein solutions, etc.), if necessary, broad-spectrum antibiotics.

Steroid dependence: 1) the impossibility of reducing the dose of steroids to less than 10 mg / day (in terms of prednisolone) within 3 months from the start of GCS therapy without exacerbation of the disease; 2) the presence of a relapse of the disease within 3 months after the abolition of GCS.

Immunosuppressants (azathioprine, metatrexate, cyclosporine) in the treatment of UC are reserve drugs. Indications for their appointment are steroid dependence and steroid resistance.

Azathioprine is used in UC as monotherapy for steroid-resistant and steroid-dependent forms of the disease; as an anti-relapse treatment in patients with frequent exacerbations during maintenance therapy with 5-ASA drugs; in case of activation of inflammation with a decrease in the dose of hormones. The recommended dose of azathioprine is 2 mg/kg per day (no more than 150 mg). Therapeutic effect - after 12 weeks; duration of treatment - at least 12 months. In the absence of side effects, it can be used for a long time as maintenance therapy at a minimum dose of 50 mg / day.

Metatrexate is used in steroid-resistant forms of UC; 25 mg intramuscularly is prescribed once a week for 2 weeks, then the dose can be reduced to 7.5-15 mg. The time of the expected therapeutic effect is 3-4 weeks, the duration of the active phase is 12-16 weeks, the duration of the maintenance phase is

12-16 weeks (dose 7.5 mg per week). Currently, the use of metatrexate in UC is recommended only in the absence of effect or inability to prescribe azathioprine.

Cyclosporine is effective in fulminant course and severe exacerbation of UC, administered intravenously at a dose of 2-3 mg/kg per day for 5-7 days. Causes remission in 50% of steroid-resistant patients.

The effectiveness of aminosalicylates is assessed on the 14-21st day of therapy, corticosteroids - on the 7-21st day, azathioprine - after 2-3 months.

Biological therapy for inflammatory bowel disease

Infliximab (Remicade) is an anti-cytokine drug of biological origin, which

is a chimeric human-mouse monoclonal antibody (!d G) to the pro-inflammatory cytokine - tumor necrosis factor alpha (TNF-a). Infliximab is 75% human and 25% mouse protein. Thanks to the variable "mouse" fragment, a high affinity of antibodies to TNF-a and the ability of infliximab to neutralize the effect of the cytokine are ensured. The "human" component of antibodies provides low immunogenicity of the chimeric molecule.

TNF-a exists in the body in a soluble form, and is also partially fixed on the membranes of immunocompetent cells. In this regard, a significant advantage of infliximab is its ability to neutralize both forms of TNF-a.

The clinical efficacy of infliximab is associated with its anti-inflammatory and immunomodulatory effects on the intestinal mucosa; however, there is no suppression of the systemic immune response. After intravenous administration, infliximab circulates in the blood for a long time, which allows it to be administered once every 4-8 weeks. It is known that patients with UC have elevated serum concentrations of TNF-a, which decrease during disease remission.

Indications for the appointment of infliximab in UC (since 2006) are moderate and severe forms of the disease (Mayo index - from 6 to 12) with ineffectiveness, intolerance to standard therapy or the presence of contraindications to its implementation. Infliximab (Remicade) for UC is recommended to be administered every 8 weeks after induction therapy (induction scheme - 0, 2, 6 weeks).

Maintenance therapy and maintenance of remission

The recurrence rate of ulcerative colitis after discontinuation of oral therapy or topical treatment with sulfasalazine or "pure" 5-ASA preparations reaches 74% within a year. The frequency of recurrence after discontinuation of local treatment is even higher in patients with distal colitis.

It is reliably shown that glucocorticoids do not prevent the recurrence of ulcerative colitis. The effectiveness of 5-ASA preparations in preventing relapses is considered unequivocally proven, with doses ranging from 0.75 to 4 g per day equally effective in maintaining remission. Currently, patients with UC are recommended to carry out long-term maintenance therapy with possibly lower doses of sulfasalazine (2 g/day) or mesalazine (1-1.5 g/day). The use of mesalazine as maintenance therapy is preferred due to fewer side effects compared to sulfasalazine. Enemas and oral preparations can be equally successful in prolonging remission; in the case of a distal lesion, topical 5-ASA preparations can be limited. For example, for the prevention of recurrence of ulcerative colitis, limited to damage to the rectum, the use of salofalk suppositories 250 mg 3 times a day is usually sufficient.

Long-term use (up to 2 years) of a maintenance dose of mesalazine, as a rule, ensures the maintenance of stable remission; on the contrary, in patients with a remission that persists for a year while taking the drug, when transferred to placebo, relapses are observed in 55%

cases over the next 6 months. With continued maintenance therapy, the recurrence rate over the same period is only 12%. In addition, regular use of mesalazine reduces the risk of colorectal carcinoma, which is significantly more common in ulcerative colitis and Crohn's disease. Against the background of long-term use of mesalazine, the incidence of carcinomas becomes comparable to the average in the population. That is why the question of stopping maintenance therapy after 1-2 years in the absence of relapses should be decided in each case individually.

T a b l e 6 Doses of drugs recommended in the treatment of ulcerative colitis

* It is recommended to reduce the dose of prednisolone by 10 mg/week to a dose of 30 mg, and then reduce by 5 mg weekly to a dose of 10 mg/day, etc., with a dose of 20 mg/day recommended for a month. After achieving remission, GCS should be canceled; cancellation of GCS - while taking mesalazine.

There is no unequivocal opinion on the advisability of using antidiarrheal drugs in patients with UC; some authors do not recommend their appointment due to the possibility of developing toxic dilatation of the colon and an insignificant therapeutic effect.

As part of the treatment of UC, correction of dysbiotic disorders is carried out. Additional treatments for UC also include hyperbaric oxygenation (HBO), plasmapheresis, and hemosorption.

Distal UC

Mild form - mesalazine 1-2 g / day rectally in the form of suppositories or enemas.

Moderate form - mesalazine rectally (2-4 g / day in the form of enemas or suppositories) or corticosteroids (prednisolone 20-30 mg / day or hydrocortisone 125 mg / day) in the form of enemas. With proctitis, the introduction of steroids in suppositories is indicated.

With the ineffectiveness of local therapy - a combination of aminosalicylates (sulfasalazine, mesalazine)

2-3 g / day orally with their rectal administration or corticosteroids in the form of enemas.

Severe form - oral prednisolone 0.5-1 mg / kg body weight per day in combination with rectal corticosteroids (prednisolone - 20-30 mg / day or hydrocortisone 125 mg / day).

Left sided UC

Mild form - aminosalicylates (sulfasalazine 3-4 g/day, mesalazine 2-3 g/day) orally and mesalazine

2-4 g / day rectally.

Moderate form - aminosalicylates (sulfasalazine 4-6 g / day, mesalazine - 3-4.8 g / day) orally and mesalazine 2-4 g / day rectally or corticosteroids (prednisolone 20-30 mg / day or hydrocortisone 125-250 mg / day) in the form of enemas.

In the absence of a clinical effect - prednisolone 1 mg/kg of body weight per day orally in combination with rectal administration of corticosteroids and mesalazine (prednisolone - 20-30 mg / day or hydrocortisone - 125-250 mg / day, or mesalazine - 2-4 g/day).

Severe form - prednisolone 1-1.5 mg/kg body weight per day IV and mesalazine 2-4 g/day rectally or corticosteroids (prednisolone 20-30 mg/day or hydrocortisone 125-250 mg/day) in the form of enemas .

Total NUC

Mild form - aminosalicylates (sulfasalazine

3-4 g / day, mesalazine - 2-3 g / day) orally and mesalazine 2-4 g rectally or corticosteroids (prednisolone 20-30 mg / day or hydrocortisone 125 mg / day) in the form of enemas.

Moderate form - prednisolone 1-1.5 mg/kg of body weight per day.

Severe form - intravenous prednisolone 160 mg / day or metipred 500 mg or hydrocortisone / m 500 mg / day (125 mg 4 times) 5-7 days, then prednisolone 1.5-

2 mg/kg body weight per day orally (but not more than 100 mg per day).

In case of ineffectiveness of conservative therapy, surgical treatment is performed.

Indications for surgical treatment

Suspicion of bowel perforation substantiated by clinical signs;

Not amenable to targeted complex therapy toxic dilatation of the colon;

Rare cases of profuse intestinal bleeding;

Lack of effect of adequate conservative treatment:

Hormonal resistance and hormonal dependence;

Ineffectiveness or severe side effects when taking immunosuppressants (azathioprine, methotrexate, cyclosporine);

The constant threat of the development of complications of hormonal therapy (osteoporosis, steroid diabetes, arterial hypertension, infectious complications);

The development of persistent strictures with symptoms of partial intestinal obstruction;

Cancer on the background of a chronic inflammatory process.

The most preferred operation is proctocolectomy with preservation of the natural anus.

The prognosis for NUC is determined by the severity of the disease itself, the presence of complications requiring surgical intervention, as well as a high risk of developing colon cancer.

The risk of malignancy in NUC is determined by 4 main factors:

Duration of the disease (more than 8 years with total colitis, more than 15 years with left-sided colitis);

Drug Dose

Exacerbation of the disease Glucocorticosteroids 60 mg ^ 0 mg ^ 10 mg *

Sulfasalazine E-4 g/day

5-ASA 2-4 g/day

5-ASA in enemas 1-2 g/day

5-ASA in suppositories 500 mg 2 times a day

Prevention of recurrence Sulfasalazine 2 g/day

5-ASA 1.5 g/day

5-ASA in enemas 1 g/day

The prevalence of the inflammatory process (total colitis) and the severity of the disease;

Age of first exacerbation (under 30 years old);

Combination with primary sclerosing cholangitis.

Risk of carcinoma formation in UC

Duration over 10 years 2%

disease (probability 20 years 9%

development of carcinoma) 30 years 19%

Prevalence of pro-Proctitis *1.7

process (increased risk for Left-sided colitis *2.8

population) Total colitis *14.8

Cancer in NUC can develop in any area

large intestine; for the most part they are solitary and are localized in the distal sections. However, 10-25% of patients may have two or more carcinomas at the same time.

In non-operated patients with pancolitis after 20 years in 12-15% of cases, colon carcinoma develops. Histologically, carcinomas against the background of UC are most often represented by adenocarcinomas.

With a duration of UC disease of 10 years or more in the case of left-sided colitis and 8 years or more with a total lesion, an annual or 1 time in 2 years colonoscopy is recommended for the prevention of colon cancer (with taking 3-4 biopsies every 10-15 cm of the intestine, as well as from all macroscopically suspicious areas).

The presence of signs of severe dysplasia is an indication for preventive colectomy. If mild dysplasia is detected, a follow-up study after 3 months with histological verification is recommended. In case of confirmation of low-grade dysplasia, colectomy is recommended, in the absence of a colonoscopy after a year. In the case of histological changes, when the presence of dysplasia is doubtful, it is recommended to repeat colonoscopy after a year, in the absence of dysplastic changes - after 1-2 years.

The possibility of chemoprevention of colorectal cancer in patients with UC has been proven: long-term (over 5-10 years) administration of mesalazine at a dose of at least

1.2 g/day resulted in an 81% reduction in the risk of developing cancer (compared to patients who did not take mesalazine). At lower doses, as well as when taking

2 g sulfasalazine per day, the effect was significantly lower. Individuals with UC and primary sclerosing cholangitis have an increased risk of developing colorectal cancer compared to patients with UC without cholangitis. Administration of ursodeoxycholic acid preparations at a dose

13-15 mg/kg per day leads to a significant reduction in the risk of developing carcinomas in these patients.

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UDC 616.36-004-06-07-08

DIAGNOSTICS AND TREATMENT OF COMPLICATIONS OF LIVER CIRRHOSIS. MANAGEMENT OF PATIENTS WITH EDEMATE-ASCITIS SYNDROME

I.A. Gimaletdinova

Clinical Hospital of the Ministry of Internal Affairs for the Republic of Tatarstan, Kazan

Abstract: The clinical picture of liver cirrhosis is largely determined by the development of complications: edematous-ascitic syndrome, hepatic encephalopathy, bleeding from varicose veins of the esophagus, etc. This article discusses approaches to the management of patients with edematous-ascitic syndrome in cirrhosis