Nonspecific ulcerative colitis. Crohn's disease in children

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

RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols 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)

Pediatric gastroenterology, Pediatrics, Pediatric surgery

general information

Short description

Approved by the Expert Commission

On health development issues

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- nonspecific primary chronic, granulomatous inflammatory disease involving all layers of the intestinal wall, characterized by intermittent (segmental) damage to various parts gastrointestinal tract. The consequence of transmural inflammation is the formation of fistulas and abscesses.

I. INTRODUCTORY PART

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

Protocol code

ICD code(s) - 10:

K50.0 Crohn's disease small intestine

K50 Crohn's disease (regional enteritis)

K50.1 Crohn's disease of the colon

K50.8 Other types of disease

K50.9 Crohn's disease, unspecified Crohn's

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

CBC - complete blood count

OAM - general urine analysis

PT - prothrombin time

PTI - prothrombin index

PCR - half-merase chain reaction

RFMC - soluble fibrin monomer complexes

CRP - C-reactive protein

ESR - erythrocyte sedimentation rate

TV - thrombin time

Ultrasound - ultrasound examination

TNF - tumor necrosis factor

FEGDS - fibroesophagogastroduodenoscopy

ECG - electrocardiography

UC - ulcerative colitis

5-ASA - 5-aminosalicylic acid

ANCA - antineutrophil cytoplasmic antibodies

IgG - class G immunoglobulins

PUCAI - Pediatric Ulcerative Colitis Activity Index

РCDAI - Pediatrics Crohn's Disease Activity Index

Date of development of the protocol: 2014

Protocol users- pediatricians in hospitals and clinics, pediatric gastroenterologists, doctors general practice, emergency medical assistants.

Classification

Clinical classification

Ulcerative colitis:

By length inflammatory process:

Proctitis,

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

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

According to the nature of the flow:

Recurrent (often, rarely);

Continuous

By attack severity:

Easy,

Average,

Heavy)

Based on response to steroid therapy:

Steroid resistance - persistence of disease activity despite intravenous administration or oral administration of an adequate dose of GCS 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 Ulcerative Colitis Activity Index (PUCAI) (Table 1)

Table 1 Pediatric Ulcerative Colitis Activity Index (PUCAI)

Symptoms	Points
(1) Abdominal pain
No pain	0
Moderate pain	5
Severe pain	10
(2) Rectal bleeding
Absent	0
Minor volume of blood, found in less than 50% of stools	10
A 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 formed	10
(4) Number of stools per day
0-2	0
3-5	5
6-8	10
>8	15
(5) Night stool (any event causing awakening)
No	0
Yes	10
(6) Activity level
No activity limit	0
Rare activity restrictions	5
Acute activity restrictions	10
Total PUCAI points (0-85)

Interpretation of scores:

High activity: 65 and above

Moderate activity: 35-64

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

Crohn's disease

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

When calculating, only clinical (but not endoscopic) criteria are taken into account. Maximum amount points - 600 (Table 2). РCDAI<150 баллов расценивается как ремиссия БК, индекс >150 points - as an active disease, divided 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 times a day	10
Well-being, activity	No activity limit	0
	Moderate activity limitation	5
	Significant activity restriction	10
Body mass	No weight loss	0
	Reduce body weight by 1-9%	5
	Loss of body weight more than 10%	10
Height	Below one centel	0
	From 1-2 cents	5
	Below two cents	10
Abdominal pain	No pain	0
	Soreness, thickening is noted	5
	Severe pain	10
Pararectal manifestations	No	0
Pararectal manifestations	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 and 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

Basic (mandatory) diagnostic examinations performed on an outpatient basis:

UAC (6 parameters);

Determination of total protein and protein fractions;

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

Coprogram;

Bacteriological research stool for dysbacteriosis;

Ultrasound of the abdominal organs;

Additional diagnostic examinations performed on an outpatient basis:

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

Examination of stool for helminth eggs;

Determination of HIV p24 antigen in blood serum using the ELISA method;

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

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

UAC (6 parameters);

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

Stool examination (coprogram);

Fibrorectosigmoidoscopy with examination of histological specimen

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, PT-PTI-INR, RFMC, TV, fibrinogen);

Determination of blood electrolytes;

Fecal occult blood test;

Fibrorectosigmoidoscopy with examination of histological specimen;

Total fibrocolonoscopy;

Irrigoscopy/irrigography (double contrast);

Histological examination of biopsy specimens

Additional diagnostic examinations carried out at the hospital level(in case of emergency hospitalization, diagnostic examinations are carried out that were not carried out 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;

Frequent bowel movements;

Constant urge to defecate;

Stool mainly at night;

Abdominal pain mainly in the left iliac region;

Tenesmus.

Physical examination:

Underweight;

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, increased alpha-2 globulins

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

Instrumental studies:

Colonoscopy, sigmoidoscopy: the presence of transverse ulcers, aphthae, limited areas of hyperemia, edema in the form of a “geographical map”, fistulas localized 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 tracts, uneven narrowing of the intestinal lumen up to the “lace” symptom. With UC: granulation (granularity) of the mucosa, erosions and ulcers, jagged contours, wrinkling.

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

Ultrasound: wall thickening, decreased echogenicity, anechoic thickening of the intestinal wall, narrowing of the lumen, weakened peristalsis, segmental disappearance of haustra, abscesses.

Indications for consultation with specialists:

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

Rheumatologist - if joints are involved in the autoimmune process);

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

Oncologist (if signs of dysplasia or cancer appear).

Phthisiatrician - to resolve the issue of conducting 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 rare
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 - constant	Rarely, more often - when the distal parts of the colon are involved in the process
Diarrhea	Frequent, loose stools, often with nighttime bowel movements	Stools are rarely observed, more often than 4-6 times, mushy, mainly during the daytime
Constipation	Rarely	More typical
Stomach ache	Only during the period of exacerbation, intense before defecation, subside after defecation	Typical, often low-intensity
Palpation of the abdominal area	Spasmodic, painful colon	Infiltrates and conglomerates of intestinal loops, most often in the right iliac zone
Perforations	With toxic dilatation into the free abdominal cavity, they are asymptomatic	Covered ones are more typical
Remission	Characteristic, possible long-term absence of exacerbations with reverse development of structural changes in the intestines	There are improvements, there is no absolute remission, the intestinal structure is not restored
Malignancy	If the disease lasts more than 10 years	Rarely
Exacerbations	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
Lesions of the perianal area	In 20% of patients, maceration, cracks	In 75% of patients, perianal fistulas, abscesses, ulcers are sometimes the only manifestations of the disease
Prevalence of the process	Colon only: distal, left-sided, total	Any part of the digestive tract
Strictures	Not typical	Occur frequently
Haustration	Low, smoothed or absent	Thickened or normal
Mucosal surface	Grainy	Smooth
Microabscesses	Eat	No
Ulcerative defects	Irregular shape without clear boundaries	Aphtha-like ulcerations with a rim of hyperemia or fissure-like longitudinal defects
Contact bleeding	Eat	No
Barium evacuation	Normal or accelerated	Slowed down
Shortening of the colon	Often, the lumen is tube-shaped	Not typical
Small intestine damage	Most often absent, with retrograde ileitis - uniform as a continuation of colitis	Intermittent, uneven, with wall rigidity, often to a significant extent 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 food is recommended with limited fiber, fat and individually intolerant foods (usually milk). Diet No. 4 (b, c). Milk and dairy products, fats (medium- and short-chain), fried, spicy and salty foods, foods containing coarse plant fiber (mushrooms, bran, plums, dried apricots, kiwi, white cabbage, radishes, etc.) are excluded from the diet. products containing gluten (wheat, rye, oats, etc.). In patients with dehydration, additional fluid administration is indicated. In case of total intestinal damage, in order to ensure functional rest, it is possible to transfer to total parenteral nutrition with a transition to tube or enteral nutrition using polymer and elemental diets.

Drug treatment

5-ASK

Oral 5-ASA preparations are recommended as first-line therapy for induction and maintenance of remission in children with mild to moderately 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 doses; rectally 25 mg/kg (up to 1 g once); (children over 6 years old) for 8-12 weeks with a gradual dose reduction.

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

Oral corticosteroids for 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 during therapy with the optimal dose of 5-ASA. In severe attacks, intravenous steroid therapy is given.

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

Upon appointment hormone therapy The following must be taken into account:

Concomitant intake of calcium and vitamin D supplements is mandatory.
. During treatment, regular monitoring of blood glucose levels is necessary.

Thiopurines

Recommended for maintaining remission in children with intolerance to 5-ASA 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 therapy with 5-ASA in maximum doses; thiopurines are ineffective in inducing remission. Thiopurines are recommended for maintenance therapy in acute severe colitis after induction of remission with steroids, as these patients are more likely to develop aggressive disease. However, in children with acute severe colitis who have not previously received 5-ASA, maintenance monotherapy with 5-ASA may be considered if there is a rapid response to steroids. Therapeutic effect Thiopurines are 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 if clinically significant myelosuppression or pancreatitis occurs.

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

Biological therapy

In patients with a chronic continuous or hormone-dependent course of 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, the possibility of prescribing infliximab should be considered. Infliximab should be prescribed for hormone-resistant forms of the disease (resistant to both oral and intravenous drugs). If infliximab was prescribed for an acute attack in a patient who has not previously received thiopurines, biological therapy can be used as an adjuvant to switch 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 and is prescribed 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 selection may be required. Adalimumab should only be used in patients with loss of response to infliximab or intolerance 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 increases the duration of remission

Infliximab 5 mg/kg (3 induction doses over 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 subcutaneous infusions (40 mg every 2 weeks)

Before starting biological therapy, consultation with a phthisiatrician - screening for tuberculosis (chest x-ray, quantiferon test, if it is not possible - Mantoux test, Diaskin test)

Drug treatment provided on an outpatient basis

Mesalazine 250 mg, 500 mg, tablet;

Sulfasalazine 500 mg, tablet;

Prednisolone 0.05 tablet.

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

Metronidazole 250 mg, tablet;

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 solution for oral administration.

Drug treatment provided at the inpatient level

List of essential medicines(having a 100% probability of application):

Mesalazine 250 mg, 500 mg, tab.

Sulfasalazine 500 mg, tab.

Prednisolone 0.05 tablet.

Ulcerative colitis is a chronic inflammatory bowel disease characterized by superficial inflammation of the mucous membrane, 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 mucous membrane. The disease affects all age groups from infants to the elderly, with a maximum peak incidence between the ages of 15 and 30 years and between 50 and 70 years.

The mechanism of occurrence and development of ulcerative colitis

Although the exact mechanism of the onset and development of the disease (etiopathogenesis) of ulcerative colitis has not yet been precisely 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 intestinal microbiota and the protective mechanisms of the intestinal barrier, the mucosal layer and the mucosal immune system. Ulcerative colitis can be considered an immune-mediated disorder that develops in genetically predisposed individuals due to dysregulated immune responses against intraluminal antigens in the intestine.

A recent meta-analysis of genome-wide association studies for Crohn's disease and ulcerative colitis identified more than 160 inflammatory bowel disease-associated loci. Many are associated with both ulcerative colitis and Crohn's disease. The lower heritability in monozygotic twins of 15% for ulcerative colitis and 30% for 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 the 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 a high incidence of ulcerative colitis 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. Diets high in saturated fat, common in modern everyday foods, alter the composition of the intestinal microflora, leading to an increase in the incidence of colitis.

Diagnostic criteria for nonspecific ulcerative colitis

Diagnosis of ulcerative colitis is based on medical history and clinical assessment, and then confirmed by laboratory, radiological, endoscopic, histological and serological results.

The most important diagnostic criteria

1. Clinical symptoms that must be present for at least 4 weeks:
- Diarrhea
- Obvious or occult (hidden) rectal bleeding. Occult bleeding is only recognized by stool occult blood testing
- Abdominal pain before, after or during bowel movements
- 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 depending on the prevalence and severity of the disease, age, features of manifestations and genetic markers. Before making a diagnosis, infectious, ischemic and other causes of colitis should be excluded.

However, there is no generally accepted catalog of well-defined criteria or scoring for the classification of ulcerative colitis. Therefore, 5-10% of patients with inflammatory bowel diseases are unable 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, since first-degree relatives of patients with UC have a 10-15 times increased risk of developing the disease. Clinically, UC is characterized by bloody diarrhea and chronic abdominal pain; nonspecific inflammation of the mucous membrane in the terminal ileum occurs in 10-20% of patients with ulcerative colitis. Involvement of the upper gastrointestinal tract is controversial, 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 of 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

When diagnosed, patients should undergo endoscopic evaluation, ileocolonoscopy and gastroduodenoscopy. Based on the severity of the disease, patients are classified as having proctitis, left-sided colitis, or pancolitis. Unlike adults, UC in children more often affects the entire colon (pancolitis) and is therefore more often associated with acute colitis.

Laboratory and serological markers

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

In patients with unclassified inflammatory bowel disease, determination of ANCA and ASCA may help in establishing a definitive diagnosis. Another serologic marker specific for ulcerative colitis is intestinal goblet cell antibody GAB, which occurs in 15–28% of patients with ulcerative colitis. If the autoantigen targets used for testing are properly selected and prepared, GABs are highly specific for UC.

Ulcerative colitis activity indices

There are several activity indices for the classification and prognosis of UC treatment, although for clinical practice it is sufficient to describe disease activity as mild - bloody stools up to four times a day, moderate - stools four to six times a day, and severe - stools more than six times a day temperature, tachycardia. With fulminant colitis (rapidly progressive, acute), as the most severe form, bloody stools 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, LLC Association of Coloproctologists of Russia and the Society for the Study of Inflammatory Bowel Diseases under the Association of Coloproctologists of Russia, consisting of:

Ivashkin Vladimir Trofimovich
Shelygin Yuri Anatolievich
Abdulganieva Diana Ildarovna
Abdulkhakov Rustem Abbasovich
Alekseeva Olga Polikarpovna	Nizhny Novgorod
Baranovsky Andrey Yurievich	Saint Petersburg
Belousova Elena Alexandrovna
Golovenko Oleg Vladimirovich
Grigoriev Evgeniy 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 Aleksandrovna
Rumyantsev Vitaly Grigorievich
Timerbulatov Vil Mamilovich
Tkachev Alexander Vasilievich	Rostov-on-Don
Khalif Igor Lvovich
Khubezov Dmitry Anatolievich
Chashkova Elena Yurievna
Shifrin Oleg Samuilovich
Shchukina Oksana Borisovna	Saint Petersburg

ABBREVIATIONS 4

1. INTRODUCTION 4

2. DEFINITION AND CLASSIFICATION OF ULCERATIVE COLITIS 5

3. DIAGNOSIS 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 pouch anastomosis

IFM – infliximab

NSAIDs – non-steroidal anti-inflammatory drugs

PSC – primary sclerosing cholangitis

RCT – randomized controlled trial

IRR – irritable pouch syndrome

LE – level of evidence

UC – ulcerative colitis

1. Introduction

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

Ulcerative colitis (UC) is a chronic disease that affects only the large intestine and never spreads to the small intestine. An 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 thousand population. The annual increase in incidence is 5-20 cases per 100 thousand 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 prevalence of the disease among people of young working age - the peak incidence of UC occurs at 20-30 years of age, as well as a deterioration in the quality of life due to the chronicity of the process, and, consequently, frequent hospital treatment 4.

These recommendations for the diagnosis and treatment of patients with UC are a guide for practitioners caring for and treating such patients. Recommendations are subject to regular review in accordance with new scientific research in this area. These recommendations are based on literature data and the European evidence-based consensus on the diagnosis and treatment of ulcerative colitis, which is the main guideline for the treatment of UC in the European Union.

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

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

Level	Diagnostic test	Therapeutic study
	Systematic review of homogeneous level 1 diagnostic studies	Systematic review of homogeneous RCTs
	Validation cohort study with gold standard quality	Single RCT (with narrow CI)
	The specificity or sensitivity is so high that a positive or negative result allows one to exclude/establish the diagnosis	All or Nothing Study
	Systematic review of homogeneous diagnostic studies >2 levels	Systematic review of (homogeneous) cohort studies
	Exploratory cohort study with gold standard quality	Single cohort study (including low quality RCTs; i.e.<80% пациентов, прошедших контрольное наблюдение)
		Outcomes research; environmental studies
	Systematic review of homogeneous studies at level 3b and above	Systematic review of homogeneous case-control studies
	A study with inconsistent recruitment or without conducting a gold standard study in all subjects	Single case-control study
	Case-control study or study with poor quality or non-independent gold standard	Case series (and cohort or case-control studies) Low quality)
	Expert opinion without careful critical evaluation or based on physiology, laboratory animal studies or development of "first principles"	Expert opinion without careful critical evaluation, laboratory animal studies or development of "first principles"
A Level 1 Consistent Studies IN Consistent level 2 or 3 studies or extrapolation from level 1 studies WITH Level 4 studies or extrapolation from Level 2 or 3 D Level 4 evidence or difficult to generalize or poor quality studies 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 the incidence of inflammatory bowel diseases is significantly inferior to other gastroenterological diseases, in terms of severity, frequency of complications and mortality throughout the world they occupy one of the leading places in the structure of diseases of the gastrointestinal tract. The constant interest in inflammatory bowel diseases is primarily due to the fact that, despite the long history of study, their etiology remains unknown, and the pathogenesis is not well understood.

Ulcerative colitis is a chronic disease that affects only the large intestine and never spreads to the small intestine. An exception is the condition designated by the term “retrograde ileitis,” however, this inflammation is temporary and is not a true manifestation of ulcerative colitis.

The prevalence of ulcerative colitis ranges from 21 to 268 cases per 100 thousand.

population. The annual increase in incidence is 5-20 cases per 100 thousand 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 of age, as well as a deterioration in the quality of life due to the chronicity of the process, and therefore, frequent hospital treatment.

SCOPE OF APPLICATION OF THE RECOMMENDATIONS
These clinical recommendations are applicable when carrying out medical activities within the framework of the Procedure for providing medical care to the adult population with coloproctological diseases of the colon, anal canal and perineum, as well as within the framework of the Procedure for providing medical care to the population for gastroenterological diseases.

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

With 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 in nature.

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 supported by medication.

An early relapse is a relapse that occurs less than 3 months after drug-induced remission. In practice, signs of clinical exacerbation include an increase in the frequency of bowel movements with bloody discharge and/or characteristic changes detected during endoscopic examination of the colon. Remission of ulcerative colitis is considered to be the disappearance of the main clinical symptoms of the disease and healing of the colon mucosa.

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

Classification
Proper classification of ulcerative colitis by 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 evaluates the extent of macroscopic changes during endoscopic examination of the colon.

According to the nature of the flow, they are distinguished:
- acute (less than 6 months from the onset of the disease):
- with a fulminant onset;
- with a gradual onset;
- chronic continuous (absence of more than 6-month periods of remission against the background of adequate therapy);
- chronic relapsing (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 a diagnosis and determine treatment tactics, the severity of the current exacerbation (attack) should be determined, for which simple Truelove-Witts criteria, usually used in everyday clinical practice, and the Ulcerative Colitis Activity Index), usually used in clinical trials, should be used. There are mild, moderate and severe attacks of ulcerative colitis.

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 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 prednisolone for more than 7 days, or
- in the case of a moderate attack, maintaining disease activity when taking oral glucocorticosteroids at a dose equivalent to 1 mg/kg per day of prednisolone for 4 weeks.

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

Formulation of 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. Below are examples of diagnosis formulations.
- Ulcerative colitis, chronic relapsing course, proctitis, moderate attack.
- Ulcerative colitis, chronic continuous course, left-sided lesion, moderate attack. Hormonal dependence. 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 voiding of blood, tenesmus and urgency, and nocturnal bowel movements. In a severe attack of ulcerative colitis, general symptoms may occur, 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 performed:
- 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 examination of the small intestine with a 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 surgery with a stoma, etc.);
- endocrinologist (steroid diabetes mellitus, adrenal insufficiency in patients on long-term hormonal therapy);
- dermatologist (differential diagnosis of erythema nodosum, pyoderma, etc.);
- rheumatologist (arthropathy, 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 proximally, with a clear boundary of inflammation. The endoscopic activity of ulcerative colitis is best reflected by contact vulnerability (bleeding upon contact with the endoscope), the absence of a vascular pattern and the presence or absence of erosions and ulcerations. Detection of persistent narrowing of the intestine against the background of ulcerative colitis requires mandatory exclusion colorectal cancer.

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

DIFFERENTIAL DIAGNOSTICS
Inflammatory bowel diseases are a group of chronic inflammatory bowel diseases of 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 medications, 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 damage to the colon, the presence of extraintestinal manifestations, the duration of the medical history, the effectiveness and safety of previous therapy, as well as the risk of developing complications of ulcerative colitis.

The goal of therapy is to achieve and maintain steroid-free remission (cessation of glucocorticosteroids within 12 weeks after the start of therapy), prevention of complications of ulcerative colitis, prevention of surgery, and if the process progresses, as well as with the development of life-threatening complications, timely prescription of surgical treatment. Since 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 for the selection 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 heavy attack
Therapy consists of prescribing suppositories with mesalazine (1-2 g/day) or mesalazine rectal foam (1-2 g/day). The therapeutic response is assessed within 2 weeks. If there is a response, therapy at the indicated doses is prolonged to 6-8 weeks.

If treatment is ineffective, adding rectal forms of clueocorticosteroids (suppositories with prednisolone 10 mg x 1-2 times a day) is effective. When remission is achieved, maintenance therapy is carried out - local administration of mesalazine (suppositories 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 administration 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 remission induced with glucocorticosteroids 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 (develops extremely rarely)
Treatment of an attack consists of prescribing systemic corticosteroids at a dose equivalent to 1 mg/kg prednisolone in combination with local therapy with mesalazine or prednisolone (suppositories, rectal foam). When remission is achieved, maintenance therapy is carried out with local preparations of mesalazine (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 re-prescription 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 administration of mesalazine orally 3 g/day in combination with mesalazine in enemas 2-4 g/day (depending on endoscopic activity). The therapeutic response is assessed within 2 weeks. If there is a response, therapy continues for up to 6-8 weeks. If there is no effect from local and oral preparations of 5-aminosalicylic acid, it is advisable to use rectal forms of glucocorticosteroids (enemas with a suspension of hydrocortisone 125 mg x 1-2 times a day). Failure to respond to oral 5-ASA therapy in combination with local treatment is usually an indication for systemic glucocorticosteroids.

When remission is achieved, maintenance therapy is carried out with oral mesalazine 1.5 g/day. Additional administration of mesalazine in enemas of 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 in tablets 4-5 g/day in combination with mesalazine in enemas 2-4 g/day (depending on endoscopic activity). The therapeutic response is assessed within 2 weeks. If there is a response, therapy is extended to 6-8 weeks. When remission is achieved, maintenance therapy is carried out with mesalazine 1.5-2 g/day orally + mesalazine in enemas 2 g 2 times a week. It is acceptable to prescribe sulfasalazine 3 g/day instead of mesalazine.

If there is no effect from 5-ASA, the administration of systemic steroids is indicated at a dose equivalent to 1 mg/kg prednisolone in combination with azathioprine 2 mg/kg or 6-MP 1.5 mg/kg. 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 within 4 weeks, biological therapy is indicated (infliximab 5 mg/kg at weeks 0, 2, 6, or golimumab 200 mg at week 0, 100 mg at week 2, and then 50 or 100 mg at depending on body weight monthly) in combination with azathioprine 2 mg/kg or 6-MP 1.5 mg/kg. Maintenance therapy consists of azathioprine (or 6-MP) in combination with infliximab every 8 weeks or golimumab every month for at least 1 year. If prolonged use of infliximab/golimumab is impossible, maintenance therapy is carried out only with thiopurines, in case of intolerance to thiopurines - with 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, increased body temperature over 37.8 ° C, anemia less than 105 g/l, a patient with ulcerative colitis should be hospitalized in a multidisciplinary hospital with subsequent mandatory observation by a specialist -gastroenterologist and coloproctologist. In case of 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-electrolyte disturbances, detoxification (hypokalemia and hypomagnesemia increase the risk of toxic dilatation of the colon).
- Correction of anemia (blood transfusions for anemia below 80 g/l, then therapy with iron supplements, preferably parenterally).
- Endoscopic examination of the colon upon admission of the patient should be performed without preparation, since its implementation increases the risk of toxic dilatation.
- Connection of additional enteral nutrition in malnourished patients. Complete parenteral nutrition and/or temporary restriction of oral intake is not advisable.
- If there is a fever or suspected intestinal infection, prescribe antibiotics.
- 1st line - metronidazole 1.5 g/day + fluoroquinolones (ciprofloxacin, ofloxacin) intravenously for 10-14 days;
- 2nd line - intravenous cephalosporins for 7-10 days.

Continuing hormonal therapy for more than 7 days if there is no effect is not advisable. If there is a clinical response after 7 days, the patient is transferred to oral glucocorticosteroids: prednisolone 1 mg/kg or methylprednisolone 0.8 mg/kg, followed by a reduction until 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 added 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.

If there is no 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 (administered as part of an induction course at weeks 0, 2 and 6) or golimumab at a dose of 200 mg in week 0, then 100 mg in week 2, and then a month after the second injection (at a dose of 100 mg for body weight more than 80 kg or 50 mg for body weight less than 80 kg);
- administration of cyclosporine A intravenously or orally 2-4 mg/kg for 7 days with monitoring of kidney function indicators and determination of drug concentration in the blood.

If there is a response to an 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). Upon response to the induction course of golimumab, further maintenance therapy is carried out using monthly injections of 100 mg for patients weighing more than 80 mg and 50 mg for patients weighing less than 80 mg. If treatment with cyclosporine A is effective 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 achieved. 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, 2nd golimumab injection or 7 days of cyclosporine A therapy, surgical treatment options should be considered.

Predicting the effectiveness of conservative therapy in severe attacks of ulcerative colitis
Joint monitoring of the patient by an experienced gastroenterologist and coloproctologist remains key to the safe management of a severe attack of ulcerative colitis. Although medical therapy is effective in many cases, there is evidence that delays in providing necessary surgical treatment have a detrimental effect on patient outcome, particularly by increasing the risk of surgical complications. Most studies of predictors of colectomy were conducted before the widespread use of biological therapy and cyclosporine and predict failure of glucocorticosteroids rather than infliximab and immunosuppressants.
- Stool frequency >12 times per day on day 2 of IV hormone therapy increases the risk of colectomy to 55%.
- If on the 3rd day of hormonal therapy the frequency of stool 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 the 3rd day, you can also determine the Swedish index using the formula: stool frequency x 0.14 x C-reactive protein level. Its value of 8 or more increases the likelihood of colectomy to 75%.
- The risk of colectomy also increases 5-9 times in the presence of hypoalbuminemia and fever on admission, as well as in the absence of more than 40% reduction in stool frequency after 5 days of IV hormone therapy.
- The presence of deep ulcerations of the colon (against which the residual mucous membrane is determined only in the form of “islands”) increases the risk of colectomy to 86-93%.

The effectiveness of infliximab against hormonal resistance, according to various sources, ranges from 25 to 80%, which may be explained by differences in the effectiveness of the drug in individual patients. Research into predicting the effectiveness of biological therapy remains limited, but it has been established that:
- 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 with severe hypoalbuminemia, a hemoglobin level of less than 95 g/l and a C-reactive protein level of 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 the start of infliximab therapy predicts its further ineffectiveness with 78% accuracy.

In patients at high risk for colectomy, an individual decision should be made regarding second-line therapy with cyclosporine or infliximab, or surgical treatment immediately after an ineffective course of IV corticosteroids.

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

When prescribing immunosuppressants and biological therapy, the following is necessary:
- before starting biological therapy, consultation with a phthisiatrician - screening for tuberculosis (chest x-ray, quantiferon test, if it is not possible - Mantoux test, Diaskin test);
- biological therapy requires strict adherence to doses and schedule of administration (irregular administration increases the risk of infusion reactions and ineffectiveness);
- during therapy with immunosuppressants, it is mandatory to monitor the level of leukocytes (complete blood count monthly).

Prevention of opportunistic infections
Risk factors for the development of opportunistic infections include:
- taking 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;
- accompanying illnesses: chronic diseases lungs, alcoholism, organic diseases brain, 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 vaccine prophylaxis.

Required minimum vaccination prophylaxis:
- recombinant vaccine against HBV;
- polyvalent inactivated pneumococcal vaccine;
- trivalent inactivated vaccine against influenza virus. For women under 26 years of age who do not have the virus at the time of screening, vaccination against human papillomavirus is recommended.

SURGERY
Indications for surgical treatment
Indications for surgical treatment of ulcerative colitis include the ineffectiveness of conservative therapy (hormonal resistance, ineffectiveness of biological therapy) or the impossibility of continuing it (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 indicated 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 in case of hormonal resistance, the administration 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, surgical treatment can be performed without attempting to use biological drugs or immunosuppressants. This issue is described in detail in the section “Predicting the effectiveness of conservative therapy in severe attacks of ulcerative colitis.” Intestinal complications

Intestinal complications of ulcerative colitis requiring surgical treatment include:
- intestinal bleeding, the presence of which is determined when there is a loss of more than 100 ml of blood per day, according to objective laboratory methods (scintigraphy, determination of hemoglobin in stool using the hemoglobin cyanide method), or when the volume of stool with a visually detectable admixture of blood is more than 800 ml/day. Indirectly, intestinal bleeding is evidenced by a progressive decrease in hemoglobin levels against the background of adequate therapy, but clear threshold values for reducing its level, indicating intestinal bleeding, have not been defined. If this complication develops, emergency surgery is indicated;
- toxic dilatation of the colon (toxic megacolon), which is an expansion of the colon up to 6 cm or more not associated with obstruction with symptoms of intoxication. Risk factors for toxic dilation include hypokalemia, hypomagnesemia, bowel preparation for colonoscopy with osmotic laxatives, and antidiarrheal medications. Indirectly, the development of toxic dilatation is evidenced by a sudden reduction in the frequency of stool against the background of existing 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 care, emergency surgery 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 prednisolone per day, infusion therapy (correction of electrolyte disturbances), metronidazole 1.5 g/day i.v. In the absence of positive dynamics (normalization of intestinal diameter), colectomy is indicated within 24 hours;
- colon perforation is the most dangerous complication of ulcerative colitis with almost 50% mortality. If threatening symptoms are detected (peritoneal symptoms, free gas in the abdominal cavity according to plain radiography), 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 colon epithelial dysplasia. The following factors affect your likelihood of developing cancer.
- Duration of history of ulcerative colitis: the risk of colorectal cancer is 2% with a 10-year history, 8% with a 20-year history and 18% with a 30-year history.
- Onset of the disease in childhood and adolescence, although this factor may only reflect the duration of the medical history and is not an independent predictor of colorectal cancer.
- Length of 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.
- Presence of primary sclerosing cholangitis.
- Family history of colorectal cancer.
- History of severe exacerbations of ulcerative colitis or continuous course of ulcerative colitis. A consequence of 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 begin earlier due to the high risk of cancer. Patients with lesions limited to the rectum can be monitored at the same intervals as healthy people, 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 changes in the mucosa.
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 mandatory biopsy of all suspicious formations.
2. With proper qualifications of the endoscopist and the presence of a high-resolution endoscope, chromoendoscopy with targeted biopsy of areas suspicious for neoplasia.

The results of a screening biopsy influence the tactics of further treatment and observation.
- High-grade dysplasia found in intact mucosa (i.e., not elevated lesions) is absolute indication to colectomy. The presence of dysplasia must be confirmed by a second independent pathologist.
- For dysplasia mild degree in intact mucosa (not in elevated lesions), the decision is made individually: the possibility of 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 proximal to the affected area (which is determined by endoscopic/ histological examination) an adenomatous polyp is detected, then a standard polypectomy can be performed followed by routine monitoring.
- 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 it is histological structure corresponds to an adenoma, and there are no signs of dysplasia in the surrounding unchanged mucosa or anywhere in the intestine, as well as in the edges of the removed polyp. Types of surgical interventions

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

Choosing the type of surgical treatment
Carrying out reconstructive 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 influencing the possibility of forming an ileoanal pouch anastomosis
Despite the higher incidence of concomitant diseases after 65 years, surgery itself with the formation of an ileoanal pouch anastomosis in older people is safe and effective. However, the anal holding function, which plays a key role for normal functioning ileoanal pouch anastomosis apparently worsens in older age. In addition, older patients are more likely to develop complications, such as pouchitis and anastomotic strictures. At the same time, any specific age threshold for refusing the formation of an ileoanal reservoir anastomosis has not been defined. The formation of an ileoanal pouch anastomosis increases the risk of infertility in women by 30-70% childbearing age with ulcerative colitis, probably due to adhesions involving the fallopian tubes. Planned pregnancy and a woman's young age are not contraindications for 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.

In approximately 10% of patients with colitis, even when studying the surgical material obtained during colectomy, it is not possible 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 pouch anastomosis in such cases is made individually, and the patient should be warned about the risks of ineffective reconstructive 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 has been taking 20 mg 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 specimen 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, and minimally invasive or laparoscopic operations are also safe if the surgeon is sufficiently qualified.

Ileorectal anastomosis
The formation of an ileorectal anastomosis does not lead to healing of 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 pregnancy. Required condition is the patient’s consent to 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 surgeries with the formation of 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 qualifications of the surgeon (in particular, on the number of similar interventions performed).

Length of rectum and/or sigmoid colon preserved
If, after colectomy for urgent indications for ulcerative colitis, the formation of an ileoanal reservoir anastomosis is planned, 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). If the distal part of the sigmoid colon is preserved, it is brought to 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 promontory, drainage of the stump through the anus is recommended for several days to prevent failure of the sutures due to the accumulation of mucus in the stump. If the rectum or rectum and sigmoid colon remain disconnected, secondary inflammatory changes in the mucous membrane, such as disconnected colitis, may develop intestines. Controlled trials of drugs in patients after colectomy have not been conducted; empirical treatment consists of the use of local mesalazine, prednisolone, and rinsing the disconnected rectum with antiseptic solutions.

Anastomosis during the formation of ileoanal reservoir anastomosis
Preservation of an extended section of the rectum (more than 2 cm above the dentate line) when using a stapler to form an ileoanal pouch anastomosis may be the cause chronic inflammation in it with dysfunction of the reservoir, and also contributes to the preservation 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. If it is impossible to form an anastomosis using a stapler, mucosectomy should be performed and a manual anastomosis should be performed. Although a small fragment of mucous membrane is preserved when using a stapler, the risk of cancer is low and corresponds to that when forming 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.

Monitoring of patients with ileoanal pouch anastomosis
Morphological changes in the epithelial lining of the reservoir 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 (“colic metaplasia”), which is potentially associated with the risk of developing malignant transformation of the mucous membrane of the reservoir. In addition, when applying a hardware ileoanal reservoir anastomosis, a small area of the rectal mucosa is preserved. The risk of developing pouch 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 has not been carried out, however, in patients with the presence of the above risk factors, it is advisable to conduct control endoscopic examinations (reservoiroscopy) with a biopsy of the mucous membrane at least once every 2 years. Drug therapy during surgical treatment

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

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

There is currently no reliable scientific basis to support any hormonal therapy discontinuation regimen following colectomy for ulcerative colitis. The dose of glucocorticosteroids for further oral administration during the period of discontinuation of hormonal therapy is determined by the duration of 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 was administered before surgery for no more than 1 month, it is possible to stop taking glucocorticosteroids immediately after surgery.

If before surgery the patient received glucocorticosteroids for more than 1 month, after surgery it is advisable to switch from the high parenteral dose of glucocorticosteroids described above to oral administration of glucocorticosteroids orally 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 discontinuation of glucocorticosteroids are carried out under the supervision of an endocrinologist.

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

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

Reservoiritis and other complications of surgical treatment with the formation of a small intestinal reservoir
Reservoiritis is a nonspecific inflammation of the small intestinal reservoir and the most common complication of ileoanal reservoir anastomosis. The frequency of its occurrence ranges from wide range from 15 to 50% within 10 years after the formation of the ileoanal reservoir anastomosis in large specialized centers. Such differences may be due to the significantly greater risk of pouchitis in ulcerative colitis, which exceeds the frequency of this complication in the formation of ileoanal pouch anastomosis for other diseases.

Diagnosis of pouchitis
The diagnosis is made based on clinical symptoms, as well as characteristic endoscopic and histological changes. The risk of pouchitis appears to be higher in nonsmokers and those taking nonsteroidal anti-inflammatory drugs, as well as in patients with extensive ulcerative colitis and extraintestinal manifestations (primary sclerosing cholangitis).

Symptoms of pouchitis include increased bowel movements, including liquid stool, cramping abdominal pain, stool incontinence (which can be an independent symptom) and tenesmus. In rare cases, fever and extraintestinal manifestations may occur. Discharge of blood is not typical and, as a rule, occurs when the preserved mucous membrane of the rectum is inflamed.

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

Endoscopic findings consistent with pouchitis include diffuse erythema, which may be focal, in contrast to that of ulcerative colitis. Characteristic endoscopic manifestations are also swelling and granularity of the mucous membrane, spontaneous and contact bleeding, erosion and ulceration. Erosions and/or ulcers along the staple line do not necessarily indicate pouchitis. Biopsies should be taken from the mucous membrane of the reservoir and the afferent loop above the reservoir, but not from the line of staples. Histological manifestations of pouchitis are also nonspecific and include signs acute inflammation with polymorphonuclear leukocyte infiltration, crypt abscesses and ulcerations against the background of chronic inflammatory infiltration.

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

Differential diagnosis for suspected pouchitis is carried out 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. The possibility of developing nonspecific ileitis caused by taking non-steroidal anti-inflammatory drugs and bacterial overgrowth syndrome should be taken into account.

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 significantly more common when taking metronidazole. If there is no effect or if dependence on taking these drugs develops, it is possible to prescribe reserve drugs - rifaximin (2000 mg/day), tinidazole, rectal glucocorticosteroids, rectal medications 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 exception alternative reasons reservoir dysfunction.

Inflammation of the mucous membrane of the preserved area of the rectum and irritable pouch syndrome
Another potential complication of ileoanal pouch anastomosis is inflammation of the rectal mucosa, which is preserved during the hardware anastomosis. 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 whose symptoms coincide with those of pouchitis. It occurs in patients who took anxiolytics or antidepressants before colectomy, which indirectly indicates manifestations of irritable bowel syndrome in such patients before surgery. Treatment methods for these two functional disorders are the same and include psychotherapeutic assistance and antidepressants, dietary fiber, antidiarrheal drugs, antispasmodics, as well as non-absorbable antibiotics to correct bacterial overgrowth syndrome.

Forecast
The lifetime risk of severe exacerbation of ulcerative colitis is 15%, with the likelihood of a severe attack being higher in patients with total colon involvement. With 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%), then with each year of illness the risk of colectomy increases by 1%. To assess the quality of medical care, temporary, procedural and preventive criteria are used. Temporary characterize the timeliness of providing certain stages of medical care. Performing a series on the patient medical manipulations, instrumental and laboratory research necessary for quality medical care are assessed in procedural criteria. To analyze measures aimed at preventing the development of complications, preventive criteria are used.

UDC 616.348-002.44-07-08

Nonspecific ulcerative colitis: modern approaches to diagnosis and treatment

S.R.Abdulkhakov1, R.A.Abdulkhakov2

1 department of general medical practice, 2 department of hospital therapy

Go VPO "Kazan State medical University Roszdrav", Kazan

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

Key words: 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 (UC) is a chronic inflammatory disease of the colon, characterized by ulcerative-destructive changes in its mucous membrane.

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

Classification

I. According to the clinical course:

Acute form.

Fulminant (fulminant) form.

Chronic form.

Recurrent (episodes of exacerbation lasting 4-12 weeks are followed 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.

Moderate form.

Severe form.

IV. Based on response to steroid therapy1:

Steroid addiction.

Steroid resistance.

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

In addition, the Mayo Clinic severity rating system (Mayo Index) can be used.

Mayo index = stool frequency + presence of rectal bleeding + data endoscopic examination+ general doctor’s opinion

Stool frequency:

0 - normal stool frequency for this patient;

1 Important for deciding whether to add

immunosuppressants, biological agents or surgical treatment.

Assessing the severity of UC

Signs Mild Moderate Severe

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

Rectal bleeding Minor Severe Severe

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

Pulse rate Normal< 90 в мин >90 per minute

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 is 1-2 higher than usual

2 - stool frequency is 3-4 higher than usual

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

Rectal bleeding:

0 - no visible blood;

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

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

3 - preferential release of blood.

Endoscopic picture:

0 - normal mucous membrane (remission);

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

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

3 - severe degree (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 a description of the patient’s objective status):

0 - normal (remission);

1 - mild form;

2 - moderate form;

3 - severe form.

Interpretation of the Mayo index:

0-2 - remission/minimal 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 UC is not completely known. In the pathogenesis of the disease, the importance of changes in immunological reactivity, dysbiotic changes, allergic reactions, genetic factors, neuropsychiatric disorders.

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

Pathological anatomy. Inflammation of various parts of the colon is morphologically determined. The mucous membrane is hyperemic, edematous, ulcerated; ulcers are round in shape, of 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 can be acute or gradual.

The main symptom is repeated (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, when you have the urge to defecate, only bloody mucus is released. Diarrhea is most pronounced when the right half of the large intestine is affected, where water and electrolytes are absorbed. If the inflammatory process spreads proximally to most of the colon, the disease is accompanied by significant bleeding. IN initial period a disease that occurs in the form of proctosigmoiditis, constipation may occur, mainly due to spasm of the sigmoid colon. During remission, diarrhea may completely stop.

Abdominal pain is usually aching, less often cramping. The 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 periumbilical or right iliac region. Typically, the pain intensifies before defecation and decreases after bowel movement. In many patients, the intensity of pain increases 30-90 minutes after eating. As the disease progresses, the connection between food intake and abdominal pain is lost (i.e., the gastrocolytic reflex fades, in which a increased peristalsis intestines).

Tenesmus - false urges with the release of blood, mucus and pus (“rectal spitting”) with virtually no feces; are a sign of high activity of the inflammatory process in the rectum.

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

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

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

Table 2 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 caused by the presence of circulating immune complexes, bacterial antigens and cryoproteins.

Aphthous stomatitis is observed in 10% of patients with UC; aphthous stomatitis disappears as the activity of the underlying disease decreases.

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

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

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

All extraintestinal manifestations, with the exception of ankylosing spondylitis and hepatobiliary diseases, 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 of the descending and transverse sections, with increased pressure in its lumen. Clinically characterized by a sharp and progressive deterioration of the patient's condition: hyperthermia, rapidly increasing weakness, abdominal pain, frequent loose stools with copious discharge blood, pus, tachycardia, arterial hypotension, bloating and weakening/absence bowel sounds upon auscultation. During steroid therapy clinical symptoms may be erased. The diagnosis is confirmed when

plain radiography of the abdominal organs. Depending on the diameter of the colon, there are

3 degrees of toxic dilatation:

I degree - intestinal diameter less than 8 cm;

II degree - intestinal diameter 8-14 cm;

III degree- intestinal diameter 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 high activity of the inflammatory process and develop against the background of hypercoagulation. Most often, thrombosis of the superficial or deep veins of the 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 for confirming the diagnosis, assessing the degree of activity of the inflammatory process, establishing the extent of the process, and monitoring the effectiveness of treatment. UC is characterized by the absence of a vascular pattern, granularity, hyperemia and swelling of the mucous membrane, the presence of contact bleeding and/or erosions and ulcers. Histological examination of biopsy specimens is carried out 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 case of severe exacerbation, colonoscopy is not always possible due to the risk of complications.

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

X-ray examination (irrigoscopy, irrigography) allows you to determine the extent of the process by characteristic signs: smoothness or absence of haustra (the “water pipe” symptom), shortening of the colon; it is possible to identify barium depots corresponding to ulcerative defects, pseudopolyps, and 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 intestines Aphthous stomatitis. Erythema nodosum. Arthritis. Eye lesions. Thrombosis, thromboembolism Gangrenous pyoderma

Not related to the activity of the inflammatory process in the intestines 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 Expressed

Edema Yes - -

Vascular pattern Absent Absent Absent

Bleeding Petechial hemorrhages Contact, moderate Spontaneous, severe

Erosions Single Multiple Multiple with ulcerations

Ulcers No Single Multiple

Fibrin No Yes Abundant

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

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

Rice. 2. X-ray picture with UC (water pipe symptom)

Bacteriological examination of stool is carried out to exclude infectious colitis.

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

Differential diagnosis

Nonspecific ulcerative colitis is differentiated primarily from infectious intestinal lesions, ischemic colitis, and Crohn's disease.

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

Ischemic colitis. Characterized by the elderly age of patients, typical radiological signs (symptom of “finger indentations”, pseudodiverticula), detection of hemosiderin-containing macrophages during histological examination of biopsies of the colon mucosa.

The greatest difficulties may arise in distinguishing between nonspecific ulcerative colitis and Crohn's disease (granulomatous colitis) localized in the colon (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 formations in the abdominal cavity Very rare Often

Perianal localization Does not happen 30-50%

Colonoscopy: Presence of proctitis 100% 50%

Histology: Distribution Mucosa Transmural

Cellular infiltrates Polymorphonuclear Lymphocytic

Glands Disturbed Normal

Reduction of goblet cells Often when the process is active Absent

Granulomas Absent Have diagnostic value

X-ray: Spread Pronounced Localized

Symmetry Yes Absent

Ulcers Superficial Deep

Strictures Very rare Common

Fistulas Never Often

Treatment. Diet

Various diet options are prescribed that slow down intestinal transit (4, 4a, 4b), rich in protein, with limited fat.

The goals of UC treatment are to induce and maintain clinical and endoscopic remission, improve the patient’s quality of life, prevent relapses and prevent the development of complications.

Drug therapy

Currently, doctors have at their disposal a fairly large arsenal of medications that are effective in treating patients with chronic inflammatory bowel diseases. The choice of drugs and treatment method 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 decide whether the patient needs to be hospitalized and prescribe hormonal therapy.

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

4. Presence of complications.

Two groups of drugs are basic in the treatment of UC:

Preparations of 5-aminosalicylic acid (sulfa-salazine, 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 40s. After hitting colon About 75% of sulfasalazine is cleaved into two components by bacterial azoreductases - 5-aminosalicylic acid and the sulfonamide component sulfapyridine. Late 70s - early

80s It has been proven that sulfapyridine does not have its own anti-inflammatory activity. Most of the side effects when taking sulfapyridine are associated specifically with the systemic effect of sulfapyridine and they are most often observed in individuals with genetically determined “slow” acetylation of sulfapyridine in the liver into N-acetylsulfapyridine. The frequency of side effects when using sulfasalazine (nausea, vomiting, itching, dizziness, headache, allergic reactions, etc.) reaches, according to some data, 55%, averaging 20-25%. These effects are often dose-dependent, so it is recommended that sulfasalazine be discontinued for 1-2 weeks followed by resumption of 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 achieved. Serious side effects (agranulocytosis, leukopenia, impotence) when using sulfasalazine are observed in 12-15% of patients. After it was established 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 includes mesalazine (salofalk, pentasa, mesacol), in which 5-ASA is enclosed in shells of different chemical composition, which gradually dissolve in the gastrointestinal tract. In another 5-ASA preparation - olsalazine - two molecules of 5-ASA are connected by an azo bond, the destruction of which occurs under the influence of microorganisms of the large intestine. Preparations of the third group consist of 5-ASA and an inert non-adsorbable conductor; release of 5-ASA also occurs under the influence of intestinal microflora. However, despite the existence of a number of 5-ASA drugs, the basis drug therapy UC consists of mesalazine preparations.

As for the mechanism of action of 5-ASA drugs, most studies are devoted to studying

the effect of these drugs on metabolism arachidonic acid and inhibition of cyclooxygenase activity. However, given that nonsteroidal anti-inflammatory drugs, whose action is based on 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, it has been shown that both sulfasalazine and “pure” 5-ASA preparations increase the local concentration of prostaglandins, which are known to have a cytoprotective effect. Other possible mechanisms of action include the influence of 5-ASA on the production of immunoglobulins, interferons, pro-inflammatory cytokines, suppression of the activity of oxygen free radicals, reduction of increased cellular permeability, etc.

Currently, mesalazine preparations are available in 3 dosage forms: tablets, suppositories and microenemas.

Local use of 5-ASA drugs

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

Placebo-controlled clinical studies have shown the high effectiveness 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 left-sided colitis, proctosigmoiditis and proctitis with mild to moderate severity severity of the disease. The clinical effect with the rectal route 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. The foam is distributed in the rectum and sigmoid colon, suppositories are distributed only in the rectum. When 5-ASA is administered in an enema, 20-30% of the total dose is absorbed and has a systemic effect, most of the drug has local action.

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 bed [enemas of 60 ml (4 g) can be used in two doses: the second portion of the enema is administered after bowel movement from the first, or the next day in the morning].

When comparing various options treatment of distal colitis, it turned out that the effectiveness of mesalazine when administered rectally is comparable, and according to some data, even higher compared to corticosteroids in enemas and oral administration of mesalazine. A meta-analysis of clinical trials found that rectal mesalazine was more effective in inducing remission in left-sided lesions compared with rectal steroids.

It is interesting that the use of enemas with 5-ASA gives a reliable therapeutic effect even in the treatment of patients resistant to previous oral administration.

treatment with sulfasalazine, systemic and local 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 incidence of relapse compared to more infrequent use of drugs (suppositories 1 time per day or enemas 1 time every 2 days). 3 days) . Oral administration 5-ASA drugs Placebo-controlled studies have shown the high effectiveness 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 support the presence of a dose-response relationship 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, but when using the latter there is a significant larger number side effects. For 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 reduction in the dose of the drug is recommended. Studies show that high doses of mesalazine used during the acute phase are, in some cases, almost equivalent in effectiveness to glucocorticoids. However, high doses of 5-ASA drugs 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 mesa-lazine.

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

Use of mesalazine in children During 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 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). To prevent relapses, depending on age, mesalazine is prescribed at a dose of 15-30 mg/kg body weight per day for 2 doses. If the child weighs more than 40 kg, the usual adult dose of mesalazine is prescribed. There are no official recommendations for the treatment of infants and young children, which is due to insufficient experience with the use of mesalazine in this age group. Age under 2 years is considered a contraindication to taking mesalazine.

Use of mesalazine during pregnancy and breastfeeding

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

It is recommended to continue therapy for UC 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) can be associated with systemic (iv, oral or rectal administration of prednisolone, hydrocortisone) or local (non-systemic) action (rectal or oral administration of budesonide). Glucocorticoids are used for 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 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. A reduction in 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 the level of cortisol in plasma is highest between 6 and 8 am, it is recommended to take a large dose of glucocorticoids in the morning. A morning oral dose of 40 mg is comparable in effectiveness to separate doses of 10 mg taken 4 times a day. In cases of disease refractory to hormonal therapy, dividing the daily dose into a higher morning dose (2/3 of the daily dose) and lower evening dose (1/3 of the 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 reduction to 5 mg and subsequent withdrawal during therapy with mesalazine drugs.

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

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

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

IN Lately great attention is given 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 of budesonide is 195 times higher than that of methylprednisolone. Only 2% of the administered 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 treatment regimens for inflammatory bowel diseases.

Oral glucocorticosteroids with non-systemic action

Comparative studies the use of budesonide 10 mg/day and prednisolone 40 mg/day showed comparable effectiveness; 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 orally, and accordingly can be the cause of all the 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, a meta-analysis showed the superiority of rectally administered mesalazine 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 presence in the intestinal lumen. Studies have shown that when GCS is administered in the form of enemas, the drug enters the sigmoid colon and reaches the distal parts of the descending colon, and when favorable conditions- splenic angle. The depth of penetration of the drug also depends on the volume of the enema. However, when using large-volume enemas, patients are often unable to maintain them for long periods of time. Administration of GCS in the form of rectal foam promotes 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 for continuous use due to the possibility of developing 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 damage to the colon. It turned out that enemas containing 2 mg of budesonide have the same effect. positive influence on the clinical and endoscopic picture of the disease, as well as enemas containing 4 g of 5-ASA.

Side effects associated with taking systemically administered corticosteroids include moon face, acne, infectious complications, ecchymosis, hypertension, hirsutism, etc. Long-term therapy with systemic corticosteroids may cause the development of hypertension in 20% of individuals, steroid-associated osteoporosis in 50% of patients, neurological complications- in 3-5% of patients. Frequency of occurrence diabetes mellitus, requiring the prescription of hypoglycemic drugs, in people 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 is the lack of effect of adequate therapy, including prednisolone 0.75 mg/kg/day for 4 weeks, infusion therapy (erythromass, protein solutions, etc.), and, if necessary, broad-spectrum antibiotics.

Steroid dependence: 1) inability to reduce 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 relapse of the disease within 3 months after discontinuation of GCS.

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

Azathioprine is used for 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 when the dose of hormones is reduced. The recommended dose of azathioprine is 2 mg/kg per day (not 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 for steroid-resistant forms of ulcerative colitis; prescribed 25 mg IM once a week for 2 weeks, then the dose can be reduced to 7.5-15 mg. Time of expected therapeutic effect - 3-4 weeks, duration active phase- 12-16 weeks, duration of the maintenance phase -

12-16 weeks (dose 7.5 mg per week). Currently, the use of metatrexate in UC is recommended only if there is no effect or it is impossible to prescribe azathioprine.

Cyclosporine is effective for fulminant course and severe exacerbation of UC; it is 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 days 14-21 of therapy, corticosteroids - on days 7-21, azathioprine - after 2-3 months.

Biological therapy of inflammatory bowel diseases

Infliximab (Remicade) is an anticytokine drug of biological origin that

is a chimeric human-mouse monoclonal antibody (!d G) to the pro-inflammatory cytokine - tumor necrosis factor alpha (TNF-a). Infliximab is composed of 75% human and 25% murine protein. Thanks to the variable “mouse” fragment, the 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 ensures the 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 effectiveness 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 ulcerative colitis exhibit elevated serum concentrations of TNF-a, which decrease during remission of the disease.

The indications for prescribing infliximab for UC (since 2006) are moderate and severe forms diseases (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 regimen - 0, 2, 6 weeks).

Maintenance therapy and maintenance of remission

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

It has been reliably shown that glucocorticoids do not prevent recurrence of ulcerative colitis. The effectiveness of 5-ASA drugs 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 undergo long-term maintenance therapy with the lowest possible doses of sulfasalazine (2 g/day) or mesalazine (1-1.5 g/day). The use of mesalazine as maintenance therapy is preferable due to fewer side effects compared to sulfasalazine. Enemas and oral medications can be equally successfully used to prolong remission; in the case of distal lesions, you can limit yourself to 5-ASA preparations for topical use. For example, to prevent relapses of ulcerative colitis limited to the rectum, the use of salofalk suppositories 250 mg 3 times a day is usually sufficient.

Long-term use(up to 2 years) maintenance dose of mesalazine, as a rule, ensures the maintenance of stable remission; on the contrary, in patients with 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 relapse rate over the same period is only 12%. In addition, regular use of mesalazine reduces the risk of developing colorectal carcinoma, which is significantly more common in ulcerative colitis and Crohn's disease. With long-term use of mesalazine, the incidence of carcinomas becomes comparable to the average in the population. That is why the issue of stopping maintenance therapy after 1-2 years in the absence of relapses should be decided in each case individually.

Table 6 Doses of drugs recommended for the treatment of nonspecific ulcerative colitis

* It is recommended to reduce the prednisolone dose by 10 mg/week to a dose of 30 mg, and then a weekly reduction of 5 mg 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 discontinued; cancellation of GCS - while taking mesalazine.

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

As part of the treatment of UC, dysbiotic disorders are corrected. Additional methods of treating 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. For proctitis, the administration of steroids in suppositories is indicated.

If local therapy is ineffective - a combination of aminosalicylates (sulfasalazine, mesalazine)

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

Severe form - prednisolone orally 0.5-1 mg/kg body weight per day in combination with rectal administration of 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 clinical effect, prednisolone 1 mg/kg 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 intravenously 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 UC

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 body weight per day.

Severe form - prednisolone IV 160 mg/day or metipred 500 mg or hydrocortisone IM 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).

If conservative therapy is ineffective, surgical treatment is performed.

Indications for surgical treatment

Justified clinical signs suspicion of intestinal perforation;

Toxic dilatation of the colon that is not amenable to targeted complex therapy;

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);

There is a constant threat of complications from hormonal therapy (osteoporosis, steroid diabetes, arterial hypertension, infectious complications);

Development of persistent strictures with symptoms of partial intestinal obstruction;

Cancer against the background of a chronic inflammatory process.

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

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

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

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

Drug Dose

Exacerbation of the disease Glucocorticosteroids 60 mg ^ E0 mg ^ 10 mg*

Sulfasalazine E-4 g/day

5-ASA 2-4 g/day

5-ASA in enemas 1-2 g/day

5-ASA suppositories 500 mg 2 times a day

Prevention of relapses Sulfasalazine 2 g/day

5-ASA 1.5 g/day

5-ASA in enemas 1 g/day

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

Age of first exacerbation (under 30 years);

Combination with primary sclerosing cholangitis.

Risk of carcinoma formation in UC

Duration over 10 years 2%

disease (probability 20 years 9%

carcinoma development) 30 years 19%

Prevalence of pro- Proctitis *1.7

process (increased risk for Left-sided colitis *2.8

compared with the population) Total colitis *14.8

Cancer in UC can develop in any area

colon; for the most part they are solitary and localized in the distal sections. However, in 10-25% of patients, two or more carcinomas can be detected simultaneously.

In unoperated patients with pancolitis, after 20 years, 12-15% of cases develop colon carcinoma. 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 in case of total lesions, for the prevention of colon cancer, annual or once every 2 years colonoscopy is recommended (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. If low-grade dysplasia is confirmed, colectomy is recommended; if not, colonoscopy is recommended after a year. In the case of histological changes, when the presence of dysplasia seems doubtful, a repeat colonoscopy is recommended after a year, in the absence of dysplastic changes - after 1-2 years.

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

1.2 g/day reduces the risk of cancer by 81% (compared to patients not taking mesalazine). At lower doses, as well as when taking

2 g of sulfasalazine per day, the effect was significantly lower. Individuals with UC and primary sclerosing cholangitis have a higher risk of developing colorectal cancer compared to patients with UC without cholangitis. Prescription of ursodeoxycholic acid drugs in dose

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

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UDC 616.36-004-06-07-08

DIAGNOSIS AND TREATMENT OF COMPLICATIONS OF LIVER CIRRHOSIS. MANAGEMENT OF PATIENTS WITH EDEMA-ASCITISIC SYNDROME

I.A. Gimaletdinova

clinical hospital MChM 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