Treatment of inflammatory bowel diseases

Treatment of inflammatory bowel diseases in children is similar to that of adults, should comply with modern principles of evidence-based medicine. The tactics of treating inflammatory bowel diseases are different from those in adults only with regard to individual doses and some other limitations. To date, relatively few controlled studies have been published, and the strategy of treating inflammatory bowel diseases in children is based on the results obtained in the treatment of adults. Doses are calculated based on body weight, with the exception of methotrexate, the dose of which is calculated based on body surface area. The maximum dose corresponds to the recommended dose in adults.

The goals of treatment of inflammatory bowel diseases

Achieving remission, bringing physical and neuro-psychological development in line with the age standard, preventing unwanted side effects and complications.

Medication for inflammatory bowel disease

Drugs can be used both as monotherapy. And in various combinations according to individual need. It has been shown that simultaneous administration of systemic glucocorticosteroids and preparations of 5-aminosalicylic acid (5-ASA) or salazosulfapyridine does not have special advantages in comparison with monotherapy with glucocorticosteroids.

Given the significantly lower incidence of adverse reactions of 5-ASA preparations (mesalazine), their use is preferred. The dose of 5-ASA should be 50-60 mg / kg of body weight per day, the maximum - 4.5 g per day.

Glucocorticosteroids are indicated for patients in whom the use of 5-ASA and SASP does not give the desired effect, as well as patients with upper gastrointestinal tract damage (from the esophagus to the jejunum), with extraintestinal symptoms. The course of inflammatory bowel diseases in children is usually more severe, which is associated with a high percentage of steroid-dependent patients.

Given the severe side effects of systemic glucocorticosteroids, researchers have high hopes for preparations of the topical glucocorticoid budesonide (budenofalk). About 90% of the drug is metabolized at the first passage through the liver, and therefore the frequency of side effects is significantly lower (= 2.4 times). Budesonide is indicated in patients with mild and moderate forms of the disease in the acute phase, as well as in patients with distal ileal and ascending colon damage. The optimal dose of budesonide is 9 mg per day.

In patients with chronic continuous inflammatory bowel disease, the additional use of azathioprine or its active metabolite 6-mercaptopurine (6-MP) can help reduce the dose of glucocorticosteroids by an average of 60%. Fistulas on the background of the use of these drugs are closed in 40% of cases. The recommended dose of azathioprine is 2.5 mg / kg, 6-MP - 1-1.5 mg / kg per day. Side effects occur quite often, including fever, pancreatitis, dyspeptic disorders, an increased incidence of infectious diseases. Pancreatitis is a contraindication to the appointment of azathioprine. The occurrence of these side effects can be avoided with a gradual increase in the dose (appoint half the dose in the first 4 weeks of treatment), as well as on the condition of regular monitoring of laboratory indicators and the activity of thiopurine methyltransferase. In patients with low enzyme activity, the risk of adverse reactions is increased.

The effect of treatment is noted already in the first 2-4 months, in some cases through bmes.

The use of antibiotics in the treatment of inflammatory bowel diseases is based on the assumption that some bacterial antigens act as a trigger for the pathological immune defense of the intestinal mucosa. Nevertheless, up to the present time there are no results of studies confirming the role of antibiotics in achieving remission or a decrease in the activity of inflammatory bowel diseases. Only metronidazole at a dose of 20 mg / kg per day in patients with Crohn's disease proved to be more effective than placebo; the preparation is highly effective in the treatment of prianal fistulas.

Cyclosporin A is not considered a drug suitable for long-term treatment, it is prescribed for exacerbation for the period of accumulation of azathioprine concentration.

Reports of local application of tacrolimus in the form of ointments in children with oral and perianal lesions refractory to other drugs are of interest.

Methotrexate is considered the drug of choice for ineffectiveness of glucocorticosteroids or severe adverse reactions to treatment. Assign subcutaneously at a dose of 15 mg / kg 1 time per week.

A new drug for the treatment of inflammatory bowel diseases refractory to the standard treatment regimen is infliximab. The composition of the drug includes chimeric antibodies to the tumor necrosis factor a - one of the most powerful pro-inflammatory cytokines. The effectiveness of this drug is proven only in adult patients, experience with children is limited. In children's practice, the drug is allowed only for the treatment of Crohn's disease.

In patients with lesions of the distal colon, local treatment is preferable to systemic therapy, since the effectiveness helps to avoid or reduce the severity of adverse reactions. Unfortunately, in children's practice nonspecific ulcerative colitis is more often (up to 70-80%) represented by pancolitis, as a result of which local therapy has to be combined with the administration of systemic drugs.

Complications and an inadequate response to ongoing medication are usually considered indications for surgical treatment.

Algorithm for choosing treatment for nonspecific ulcerative colitis

Features of the disease	Treatment
Exacerbation	Mild exacerbation - mesalazine or sulfasalazine Aggravation of moderate severity - glucocorticosteroids, mesalazine or sulfasalazine Severe exacerbation - glucocorticosteroids, mesalazine or sulfasalazine, parenterally or enterally
Maintaining remission	Mesalazine or sulfasalazine, a diet rich in dietary fiber, compensation of vitamin and micronutrient deficiency
Chronic active and complicated course, steroid dependence, maintenance of remission after treatment with cyclosporin or tacrolimus	Azathioprine

Age dosages of essential medicines for ulcerative colitis in children

A drug	Dose
Prednisolone and others.	1-2 mg / kg per day inside or in / in (40-60 mg)
Sulfasalazine	25-75 mg / kg daily (4 g / day)
Mesalazine	30-60 mg / kg daily (4.8 g / day)
Azathioprine	1-2 mg / kg per day, subject to control of the content of metabolites of 6-MP in serum
6-Mercaptopurine	1-1.5 mg / kg per day, provided that the content of 6-MP metabolites in the blood serum is controlled
Cyclosporin	4-8 mg / kg per day inside or in / in (serum content of 200-250 μg / ml)
Tacrolimus	0.15 mg / kg per day inward (serum content of 10-15 μg / ml)
Infliximab	5 mg / kg IV

Algorithm for the choice of therapy for Crohn's disease

Features of the disease	A drug
Exacerbation	HA topical (budesonide) and systemic (prednisolone), mesalazine or sulfosalazine. Immunosuppressants (azathioprine, 6-mercaptopurine). Elemental Diet
Maintaining remission	Mesalazine or sulfasalazine. A diet rich in dietary fiber, compensation of vitamin and micronutrient deficiency, cholestyramine in case of cholera diarrhea
Chronic active and complicated course	Azathioprine, antibodies to tumor necrosis factor a

Age Dosages of Essential Medicines for Crohn's Disease in Children

A drug	Dose
Prednisolone, hydrocortisone	1-2 mg / kg per day inside or in / in (40-60 mg)
Budesonide	9 mg - starting dose, 6 mg - maintenance
Sulfasalazine	25-75 mg / kg daily (4 g / day)
Mesalazine	30-60 mg / kg daily (4.8 g / day)
Metronidazole	10-20 mg / kg daily
Azathioprine	1-2 mg / kg per day, subject to control of the content of metabolites of 6-MP in serum
6-Mercaptopurine	1-1.5 mg / kg per day, provided that the content of 6-MP metabolites in the blood serum is controlled
Methotrexate	15 mg / m2 (25 mg / day)
Thalidomide	1-2 mg / kg (single dose at night)
Infliximab	5 mg / kg IV

Forecast

The prognosis for most forms of inflammatory bowel disease is unfavorable, especially in case of complications (with ulcerative colitis - toxic dilatation or perforation of the colon, intestinal bleeding, sepsis, thrombosis and thromboembolism, colon cancer, with Crohn's disease - stenoses and strictures, fistulas, abscesses, sepsis, thrombosis and thromboembolism, colon cancer).