BeginningArticles The modern principles of treatment of children with nonspecific ulcer colitis
The modern principles of treatment of children with nonspecific ulcer colitis
M. F. Denisova
Nonspecific ulcer colitis belongs to the most serious inflammatory illness of a large intestine which is characterized by the progressing current, development of abenteric complications, involvement in pathological process of other digestive organs that negatively influences quality of life of the child. In spite of the fact that questions of diagnosis and treatment of nonspecific ulcer colitis reside in the center of attention of both domestic, and foreign researchers, were repeatedly discussed at the international forums, the cardinal solution of this problem is not found. It is explained, apparently, first of all by an illness pathogeny ambiguity though there is a number of theories of developing of nonspecific ulcer colitis — infectious, allergic, nervous, hormonal, vascular, alimentary, psychosomatic, autoimmune aggressions. Many of these theories did not find confirmation in clinic, however their separate provisions can be used for an explanation of releasers of an illness. In particular, the theory of autoimmune aggression is confirmed by essential changes of the immune status of patients and nature of pathological processes in a mucous membrane of a large intestine: plentiful infiltration of a wall of a gut plasmocytes, lymphoid elements, eosinophilic granulocytes.
The great attention is deserved by the point of view of Textur stated in 1957 that observed at nonspecific ulcer colitis hypostasis, the hyperemia, superficial abscesses and ulcerations of a mucous membrane of a large intestine are a consequence of a vasculitis. Pointed to it also Enge L (1954), connecting emergence of early intestinal bleedings with defeat of vessels of a wall of a gut. Extremely important in this plan the researches of not changed intestinal wall at the operated patients with nonspecific ulcer colitis described by V.A. Zhelman and Yu.V. Baltaytis (1986) are represented. At microscopic examination of a remote site of a gut authors recorded change of a gleam of intramural vessels, vasodilatation of a submucosal layer (veins, arteries), a weak diffusion lymphoid infiltration of blankets of a mucous membrane and increase in quantity of scyphoid cells in crypts.
Results of our kliniko-eksperimentalny researches of microhaemo circulation in a mucous membrane of a large intestine and the found changes of walls of capillaries and small veins allow to suggest that in genesis of nonspecific ulcer colitis at children the leading role is played by a hemorrhagic vasculitis and immunopathological reactions in which initiation, perhaps, the same etiological factor takes part (enteropathogenic bacteria or viruses, mycoplasmas, etc.).
It is impossible to exclude that along with an infectious factor the big role in a pathogeny of an illness belongs to genetic mechanisms, in particular the phenotype of histocompatibility antigens of HLA defining character of an individual immune response of an organism. This assumption is spoken well by results of a tipirovaniye of HLA antigens at patients with nonspecific ulcer colitis (And, B, C, DR): in 21% of cases HLA-B12 antigen was found.
The psychogenic theory of developing of nonspecific ulcer colitis offered Michchau which did not find recognition at therapists, apparently, is least acceptable for an explanation of value of psychogenic factors in developing of a disease at early children's age. However psychopathological frustration at children pre-and pubertal age can play a part in synchronization of pathological process, provoke palindromias.
In recent years in literature the nitrogen oxide role in a pathogeny of many diseases including nonspecific ulcer colitis is actively discussed. According to L. Rachmielwitz (1993), N0 — one of basic reasons of development of ulcer colitis and illness Krone. This situation is based on the analysis of results of researches of the author who established that the mucous membrane of a large intestine of patients with the specified pathology cosecretes at 5-20 times more NO, than a mucous membrane of healthy people. It is suggested that the nitrogen oxide, reacting with free radicals of oxygen, forms peroxynitrites which decomposition products (N02 and ON") cause an ulceration of a mucous membrane of a digestive tract. Thus, despite numerous researches of various genetic, immunological, microbic and psychogenic factors, an origin of nonspecific ulcer colitis still it was not succeeded to establish. The etiology ambiguity substantially influences the current and an outcome of a disease, and modern therapy at nonspecific ulcer colitis consists in impact on the pathogenetic links known today defining a clinical picture and a patomorfologiya of an illness.
Treatment at all forms of nonspecific ulcer colitis, except for demanding surgical intervention, should be begun with conservative therapy which has to be strictly individual. At its appointment it is necessary to consider data of the anamnesis (the instruction on intolerance or hypersensitivity to separate foodstuff, medicines), a degree of activity and prevalence of inflammatory process, existence local (proctal cracks, a gut stricture) and abenteric (reactive hepatitis) complications.
In the period of an aggravation of the severe forms of nonspecific ulcer colitis which are characterized by the profuse ponosa which are sharply expressed by the dispeptic phenomena appoint a diet with restriction of fats (to 55 g a day) and carbohydrates (to 250 g a day), the increased protein content (110-120 g a day) — a diet No. 4. Milk, eggs, salty and hot dishes, a cellulose are excluded from a diet. Patients receive mucous soups, limited amount of meat (steam cutlets, quenelles and frikadel), low-fat grades of fish (a pike perch, a pike, a perch, the bream) in a boiled look, the wiped porridges welded on water, steam puddings, kissels from bilberry, dried fruit, tea, cocoa on water, unsweetened fruit juice (in limited quantity, warm). When strengthening fermentative or putrefactive processes limit carbohydrates to 100-120 g a day (diet No. 4a). All dishes move in a warm look, the number of meals — 5 times a day.
When subsiding inflammatory process, and also to patients who have no sharply expressed manifestations of a syndrome of a hemocolitis appoint a diet No. 4b. It is physiologically full-fledged diet with the normal content of proteins, fats, carbohydrates and restriction of table salt to the lower bound of physiological norm (4-5 g a day), with an exception of the products and dishes strengthening processes of rotting and fermentation in intestines. White loaf (yesterday's), croutons, butter, fresh not acid cottage cheese, rather weak broth, the wiped vegetable soups, low-fat grades of meat (boiled or baked), cutlets, boiled fish, not strong cheese, jelly and kissels, the wiped compotes, fruit juice in a warm look, the boiled and wiped vegetables and fruit are resolved. Whole milk is excluded; eggs — no more than two in a week.
During recovery as transition to a table d'hote the diet No. 4v is shown. A daily diet and culinary processing of products — same, as well as at a diet No. 4b; in limited quantity enter crude vegetables and fruit; whole milk is excluded.
During permanent compensation of pathological process in intestines and in the absence of associated diseases of a stomach, duodenum, zhelchevydelitelny system apply option of a diet No. 2 with not wiped dishes, in the presence of the specified diseases appoint a diet No. 4v to a long span.
Thus, duration of use of diets at nonspecific ulcer colitis has to be strictly individual and be defined by severity of a disease, nature of functional disturbances of intestines, dominance in it fermentative or putrefactive processes, existence of dysbacteriosis, etc. At the medium-weight and especially severe forms of nonspecific ulcer colitis which are characterized by diarrhea, anorexia, exhaustion, long fever and intoxication it is necessary to resort to the parenteral food (PF).
Total parenteral food at children is applied for a long time rather seldom because of fast development of a liver failure. In pediatric practice generally use partial parenteral food on system of a giperalimentation which essence is that the settlement daily allowance kalorazh is reached by means of introduction of strong solutions of glucose (fructose, sorbitol) (tab. 1). Basic element of software — daily liquid loading which is very dynamic size and depends on age of the child, mass of his body and a specific clinical situation (tab. 2).
Table 1. Needs for calories at parenteral food
The number of calories on 1 kg body weights in days
Table 2. Daily need for liquid at parenteral food
Body weight, kg 1-10
Amount of liquid, ml/kg 100
11-20 of More than 20
1000 + 50 on each kg over 10 1000 + 20 on each kg over 10
Glucose or dextrose provides 3,4 kal/g and is applied in the form of 20-10% of solution which is entered into the central vein in a dose to 12 g/kg a day. The need for protein (2,5-3 g/kg a day) is satisfied at the expense of amino acids and a transfusion of plasma (albumine). The preference is given to the balanced solutions of amino acids. For the prevention of development of a giperammoniyemiya it is recommended to increase gradually doses of amino-acid solutions from 0,5 to 2,5 g/kg a day. Use of fatty emulsions for children is limited because of fast development of a fatty embolism, but in need of software on system of a giperalimentation apply MTsT/LTsT lipofundinum (srednetsepochechny and long-chain triglycerides) in a dose of 0,5-1,5 g/kg a day, controlling coagulability of blood.
For completion of the liquid lost with excrements and emetic masses, and correction of deficit of electrolytes is recommended to use the combined medicines — Acesolum (1 l of solution contains 2 g of sodium of acetate, 5 g of sodium of chloride and 1 g of potassium of chloride), disalt (1 l of solution contains 2 g of sodium acetate and 6 g of sodium of chloride) 15-20 ml/kg a day; 7,5% potassium chloride solution (in a dose of 3 mmol/kg a day).
In the absence of nausea and vomiting for a regidratation appoint inside the carbohydrate and electrolytic solutions in particular ready dosed the instant powders containing sodium-potassium salts and glucose, for example tsitroglyukosan, regidron, a gastrolith.
Hemotransfusions, packed red cells, freshly frozen plasma at the rate of 10 ml/kg a day are shown to patients with the severe form of nonspecific ulcer colitis which is followed by massive and long bleedings for achievement of haemo static effect, the improvement of microcirculation stimulating impacts on an organism. Good results in respect of correction of anemia are yielded by drugs of bivalent iron — (course duration — 5-6 weeks), and also folic, ascorbic acids, vitamins of group B in the standard doses and duration of use. However, as iron preparations render an irritant action on a mucous membrane of intestines, the parenteral way of their introduction is preferable. For this purpose it is possible to appoint aktiferrin — the drug containing sulfate of bivalent iron and L-serine amino acid which promotes more effective absorption of iron. Average doses for children of preschool age — 5 ml 1-2 times a day, for school students — 5 ml 2-3 times a day. Drugs of azo compounds 5-aminosalitsi-lovoy of acid and sulphapyridine are among cure of basic medicamentous therapy for nonspecific ulcer colitis (Sulfasalazinum and its analogs — Salazopyrinum, Salazopyridazinum, Salazodimethoxinum). They differ in ability to collect selectively in connecting fabric of a wall of intestines with release of the 5-aminosalicylic acid possessing antiinflammatory activity and the sulphapyridine possessing bacteriostatic activity — the competitive antagonist of paraamino-benzoic acid. Sulfasalazinum appoint on 1,5 — 3,0 — 6,0 g a day depending on age of the child. The initial dose of drug is applied before disappearance of pathological impurity in Calais and intoxication; then the daily dose is reduced on 1/3, and at achievement of clinical remission — for 1/3, gradually selecting the minimum dose supporting permanent clinical laboratory remission. This scheme was offered O. A. Kanshina (1974), and we, using it for many years, were convinced of its efficiency. At the same time at use of this class of medicines there is a number of side effects from digestive organs (anorexia, nausea, vomiting, pain in epigastriß area), hematologic disturbances (an agranulocytosis, anemia, a pancytopenia, met-and a sulfametgemoglobinemiya), skin rash, diagnosed in 10-25% of cases that limits duration of their use. It is possible to avoid side effects at rectal administration of Sulfasalazinum in the form of candles that was confirmed at treatment of patients with an easy form of nonspecific ulcer colitis; we appointed drug for 3-4 weeks on 1 candle to night, and further — in tablets. In recent years drugs of 5-aminosalicylic acid (5-ACK) are widely used: salofalk (consisting of one substance — 5-ACK), olsalazin (as a part of which two molecules 5-ACK are connected by azocommunication) and besalazin, consisting from 5-ACK and the inert not absorbed conductor. Kliniko-pilot studies showed that the antiinflammatory effect 5-ACK is caused by its ability to slow down formation of prostaglandins, cytokines (interleykina-1 and interleykina-6) in a mucous membrane of intestines, to suppress formation of receptors interleykina-2, to inhibit activity of a lipoxygenase of the activated neutrocytes. 5-ACK possesses also antioxidant properties, ability to slow down synthesis of the factor activating thrombocytes, and also phagocytal activity of leukocytes. Is issued in tablets, candles and enemas. According to multicenter researches, 5-ACK is effective drug of basic therapy of nonspecific ulcer colitis and it can be applied both in an aggravation phase, and during remission — to prevention of palindromias. Our first supervision over children with a medium-weight form of a disease confirm its high performance in achievement of fast and permanent clinical laboratory remission. At acute (fulminant) and severe forms of nonspecific ulcer colitis which involve system complications (hepatitises, damages of eyes, erythema nodosum) glucocorticoid therapy remains by the most effective method of treatment so far.
It is known that antiinflammatory and immunosuppressive action of glucocorticoids (Civil Code) is explained by their ability to suppress activity of a phospholipase of A2 (due to induction of synthesis of a lipokortin), an expression of genes of metal-proteinases (a collagenase, stromelizin) and synthesis of mediators of an inflammation to stimulate T apoptosis - and V-lymphocytes, to render some other effects. The main molecular mechanisms which are the cornerstone of action of group of companies is a linkng with DNA sites located in a pro-motor site of a steroidotvechayushchy gene, interaction with transcription factors (AR-1, NF kV) and inhibitory proteins.
Positive takes of treatment of group of companies are noted at various ways of their introduction: per os, parenteral or rectal. From drugs of this class we, as a rule, apply Prednisolonum (or drug equivalent to it) in a daily dose of 1,0 mg/kg of body weight; (1,5-2 mg/kg a day) resorted to higher doses extremely seldom. At achievement of positive dynamics of a diarrheal syndrome, reduction of intoxication, decrease in indicators of activity of inflammatory process (S0E, a leukocytosis, content of ostrofazovy proteins, gamma globulins) Prednisolonum dose was gradually lowered by 2,5 mg in the first two weeks, in the subsequent — on 5 mg a week, and in 6-8 weeks — cancelled.
In cases of insufficient efficiency of group of companies at patients with acute or severe forms of nonspecific ulcer colitis, and also at identification of side effects in the form of an Icenco-Cushing syndrome, a hypopotassemia, a delay of liquid, osteoporosis, strengthening of intestinal bleedings perhaps combined use of group of companies with immunodepressants which exponential action allows to reduce twice doses of both drugs. The scheme of purpose of the Civil Code in combination with cytostatics is similar to the scheme of purpose of the Civil Code.
The essential place in therapy of nonspecific ulcer colitis is taken by enterosorbents, the motility regulators, intestinal antiseptic agents which are not breaking balance of microbic flora. It is known that high performance of an enterosorbtion is provided with ability of sorbents to absorb or neutralize toxic substances, to regulate rn intestinal contents, its microbic, electrolytic and fermental structures. Thereof processes of oxidation of the intermediate metabolites possessing the expressed toxic action accelerate the quantity of antigenic irritants of immunological "board" of a mucous membrane of intestines decreases, the functional load decreases by a liver and, so its detoksitsiruyushchy function amplifies. Today in clinical practice along with such known sorbents as UVESORB, karbosorb, a karbosfer, enterosorbents of the second generation, in particular silica gel, SKN, AUVM, SKA of I, etc. are approved. Enterosorbents, as a rule, within 5-7 days, behind an exception enterosgelya which can be applied for 14 days are applied. In the period of an exacerbation of an illness it is recommended to conduct repeated courses of an enterosorbtion.
The dioctahedral smectite capable to neutralize bacteria (£ possesses the expressed properties, adsorbing and protective in relation to a mucous membrane of intestines. coli, Campilobacter jejuni), viruses (rotaviruses), bile acids, undigested sugar. Depending on age of the child it appoint on 1/2 — to 1 powder in the form of the talker 3 times a day, in 15-20 minutes prior to food for 10 days.
Attapulgite — the natural purified aluminum-magnesium silicate in a colloid form has high ability to adsorb pathogenic activators and to connect toxic substances. The initial dose for children is more senior than 10 years — 2 tablets a day, further — 1 tablet a day.
An essential role in therapy of nonspecific ulcer colitis is played by correction of a diarrheal syndrome. It is known that in a diarrhea pathogeny at nonspecific ulcer colitis the leading place belongs to intestinal hypersecretion — "dumping" of water and electrolytes into a gut gleam through the injured mucous membrane and exudations of protein in a gut gleam (Parfyonov A.I., 1998). Elimination of abdominal pain, normalization of frequency and character of a chair, vermicular movement of a large intestine is promoted by regulators of a tone and motility of intestines: blockers of calcium channels, spasmolysants, fermental drugs.
It is known that nonspecific ulcer colitis is accompanied by quantitative and qualitative changes of structure of intestinal microflora which involve strengthening of disturbance of processes of digestion, gas generation, dispeptic manifestations. According to our data, children with nonspecific ulcer colitis along with considerable decrease have quantities or absence — at severe forms of a disease — obligate microflora (bifidobacteria, bacteroids) substantial increase of a vysevayemost of opportunistic microorganisms — klebsiyell (43% of cases), a protea (25%), a tsitrobakter (28,5%) took place.
Medicamentous correction of intestinal microflora is carried out in 2 steps: The I stage — microbic decontamination, II — normalization of quantitative and qualitative structure of microflora. Microbic decontamination is shown with an excess growth of opportunistic flora and is implemented by drugs which do not influence obligate microflora — nitrofurans, gidroksikhinola. A course of treatment — 5-7 days.
For the purpose of recovery of flora of intestines use a probiotics — drugs on the basis of live cultures of bacteria (V. of bifidum, V. of longum, Lactobaccillus acidophilus, V. of brevis, etc.). The mechanism of action of probiotics is based on their ability to synthesize antibacterial substances, organic acids, proteases, to stimulate an immune response of an organism — to raise products of interferon, Ig A, phagocytal activity of leukocytes. The range of probiotics is wide — bifidum-, laktobakterin, etc. It is recommended to apply them during food in 1-2 receptions; a course of treatment — 3-4 weeks. It is very effective biosporin: it is accepted, previously having dissolved contents of 1 ampoule in 1 glass of warm water, in 20-30 minutes prior to food, on 1-2 doses 2 times a day.
In literature there are data on expediency of purpose of probiotics together with prebiotics — the oligosaccharides capable to reduce rn a calla, to inhibit growth of mushrooms Candida, clostridiums and other microorganisms, to activate regeneration of an epithelium of a large intestine. From this class of medicines it is possible to recommend lactulose.
Planned surgical treatment is shown to children with the acute (fulminant) current of a severe form of nonspecific ulcer colitis, medium-weight and severe forms of an illness which are characterized by continuously recurrent current when conservative therapy is ineffective, and also with the big duration of a disease. Urgent operative measure is made at profuse intestinal bleeding, toxic dilatation of a large intestine, perforation of intestinal ulcers. In recent years there were publications about efficiency of use for adults with nonspecific ulcer colitis of an interferonoterapiya, immunomodulators from group of macroleads, korotkotsepochechny fatty acids, specific inhibitors of cytokines. And it means that methods of conservative therapy of nonspecific ulcer colitis are not settled yet, and the new directions of treatment of patients stated above with this pathology have big perspective.