Associated professor Masyuta D.I.

1. M.Gorky Donetsk National Medical UniversityDepartment No. 2 of PediatricsHead of the Department Dr. Churilina A.V., Ph.D.Malabsorption syndromesin children Associated professor Masyuta D.I.

2. Gluten-Sensitive Enteropathy (Celiac Disease) • Gluten-sensitive enteropathy is a disorder in which small-bowel mucosal damage is the result of a permanent sensitivity to dietary gluten. • The disorder does not present until gluten products have been introduced into the diet. • Typically, the most common period of presentation is between 6 mo and 2 yr of age.

3. PATHOGENESIS • Three components interact in the pathogenesis: • toxicity of certain cereals, • genetic predisposition, and • environmental factors. • The disorder develops only after chronic dietary exposure to the protein gluten, which is found in wheat, rye, oats, and barley. • The activity of gluten resides in the gliadin fraction, which contains certain repetitious amino acid sequences (motifs) that lead to sensitization of lamina propria lymphocytes.

4. PATHOGENESIS • The evidence that there is a genetic predisposition is that • (1) up to 2–5% of first-degree relatives have symptomatic gluten-sensitive enteropathy, • (2) as many as 10% of first-degree relatives have asymptomatic damage to small-bowel mucosa consistent with this disorder, and • (3) there is an association of the disorder with certain human leukocyte antigen (HLA) types (B8, DR7, DR3, and DQw2).

5. PATHOGENESIS • Environmental factors must influence the expression of this genetic predisposition because • (1) there is a 30% rate of discordance in monozygotic twins, • (2) there is a 70% rate of discordance in HLA-identical siblings, • (3) the age of onset among siblings is variable, and • (4) the onset of symptoms can be precipitated by gastrointestinal surgery, pregnancy, antibiotic use, or a coincidental diarrheal illness.

6. PATHOGENESIS • The immunologic response to gluten results in • villus atrophy, • crypt hyperplasia, and • damage to the surface epithelium in the small bowel.

7. Histology of a jejunal biopsy showing lymphocytic infiltration and villous atrophy confirming coeliac disease.

8. Normal jejunal histology is shown for comparison.

9. PATHOGENESIS • The injury is greatest in the proximal small bowel and extends distally for a variable distance. The latter observation is undoubtedly the explanation for the variable degree of symptoms and findings of malabsorption among individuals with gluten-sensitive enteropathy. • A decrease in absorptive and digestive capacity results from a decrease in small intestinal surface area and a relative increase in immature epithelial cells. • Pancreatic secretion is decreased as a result of lowered serum cholecystokinin and secretin levels.

10. CLINICAL MANIFESTATIONS • The mode of presentation is variable; the majority present with diarrhea. • Children can have failure to thrive or vomiting as the only manifestation. • Perhaps as many as 10% of children referred to endocrinologists for growth retardation without an endocrine or overt gastrointestinal disorder have gluten sensitivity. • Anorexia is common and may be the major cause of weight loss or lack of weight gain.

11. CLINICAL MANIFESTATIONS • Infants with gluten-sensitive enteropathy are often, but not always, clingy, irritable, unhappy children who are difficult to comfort. • In contrast to infants with cystic fibrosis, they are not interested in food, although this is not always the case. • Pallor and abdominal distention are common. • Large, bulky stools have been described in some children with this condition. • Digital clubbing can occur.

12. Rickets in a 3-year-old boy secondary to coeliac disease. He has frontal bossing, a Harrison's sulcus and bow legs.

13. Coeliac disease causing wasting of the buttocks and distended abdomen.

15. Celiac Disease (a 4-year-old child)

16. Celiac Disease (a 6-year-old child)

17. Celiac Disease (a 23-year-old man after treatment)

20. EVALUATION • Screening tests for malabsorption are not particularly helpful because they may be normal in a child with gluten-sensitive enteropathy. • Anemia and hypoproteinemia may be present. • The first serologic tests, including antigliadin antibodies, were not reliable enough. • However, the sensitivity and specificity of serum IgA-endomysial antibody testing have approached 100% (except in IgA-deficient patients).

21. EVALUATION • Histologic findings on small-bowel biopsy remain the gold standard for diagnosis and biopsy should be performed if one has a high suspicion of gluten-sensitive enteropathy or if serum endomysial antibody is found. • The strictest approach to diagnosis is to demonstrate that the biopsy returns to normal within 1–2 yr after starting a gluten-free diet and then to rechallenge with a gluten diet and repeat the biopsy. • This approach is now in evolution because it is possible to demonstrate antibody conversion while on a gluten-free diet and only an initial small-bowel biopsy may be necessary.

22. TREATMENT • Treatment requires a lifelong, strict gluten-free diet. • All wheat, rye, and barley products should be eliminated from the diet; many children tolerate oats. • Initially, vitamin and iron supplementation is advisable. • When the disorder presents with fulminant diarrhea, initial treatment with oral prednisone can be useful; this approach is rarely necessary.

23. TREATMENT • Although the parents of a child with gluten-sensitive enteropathy usually become very knowledgable about diet, initially they need the help of an experienced dietitian. • National celiac support groups provide much specific information about the gluten content of foods and medications. • Processed foods must be considered carefully because it is common that they contain some gluten. • Gluten-free foods are commercially available.

24. PROGNOSIS • The clinical response to a gluten-free diet of a child with celiac disease is gratifying. • Improvement of mood and appetite is followed by lessening of diarrhea. • In most cases changes occur within 1 wk of starting therapy, but the response may occasionally be delayed. • Older patients and very ill patients tend to respond slowly, but once in remission the celiac child should be treated as a well child.

25. Growth chart showing failure to thrive and response to a gluten-free diet.

26. PROGNOSIS • Subtle manifestations of growth failure or delayed sexual maturation may take place when receiving a gluten-containing diet. • Appropriately diagnosed gluten-sensitive enteropathy is a lifelong condition requiring lifelong treatment. • No complications from long-term gluten-free diet treatment are recognized.

27. Coeliac disease: • is a gluten-sensitive enteropathy • classical presentation is at 8-24 months with abnormal stools, failure to thrive, abdominal distension and wasted buttocks, and irritability • other modes of presentation - short stature, anaemia, screening, e.g. children with diabetes mellitus • diagnosis - positive serology (tissue transglutaminase and anti-endomysial antibodies), flat mucosa on jejunal biopsy and resolution of symptoms and catch-up growth upon gluten withdrawal • treatment - gluten-free diet for life.

28. Intestinal Lymphangiectasia • This group of disorders is characterized by dilatation of intestinal lymphatic vessels and leakage of lymph into the intestinal lumen and, at times, the peritoneal cavity.

29. Causes Of Intestinal Lymfangiectasia • Intestinal lymphangiectasia can be • primary or • can result from • abdominal or thoracic surgical damage to lymphatic vessels, • chronic right-sided heart failure, • constrictive pericarditis, • retroperitoneal tumor, or • malrotation with lymphatic obstruction.

30. Causes Of Intestinal Lymfangiectasia • Primary intestinal lymphangiectasia is • the result of a congenital abnormality of lymphatic drainage from the intestine and • may be associated with abnormalities in lymphatic drainage from other regions of the body. • Turner and Noonan syndromes have been associated with intestinal lymphangiectasia.

31. PATHOGENESIS • Because absorbed fat is normally transferred from the intestine via the lymphatic vessels, children with this disorder have steatorrhea with protein-losing enteropathy and may have lymphocyte depletion.

32. CLINICAL MANIFESTATIONS • Manifestations may include any combination of • hypoalbuminemia, • hypogammaglobulinemia, • edema, • lymphocytopenia, • fat malabsorption, and • chylous ascites.

33. Diagnosis • The diagnosis is suggested by the typical findings described previously in association with an elevated fecal alpha1-antitrypsin level consistent with protein-losing enteropathy. • The characteristic radiologic findings of uniform, symmetric thickening of mucosal folds throughout the small intestine are usually, although not always, present on small-bowel contrast radiographs.

34. Diagnosis • The diagnosis is confirmed by the presence of collections of abnormal dilated lacteals with distortion of villi on peroral small-bowel biopsy. • The disorder may be seen only in the submucosa, requiring surgical biopsy of the intestine.

35. Lactose Intolerance • Lactose intolerance is the development of clinical symptoms resulting from lactase deficiency following ingestion of lactose in water in a standard dose.

37. CAUSES OF LACTOSE INTOLERANCE • Primary lactose intolerance – • An autosomal recessive condition. • Results from absence of hydrolytic activity for lactose or absence of intestinal capacity to transport glucose and galactose. • Child becomes symptomatic as soon as breast or cow’s milk is started. • Responds to elimination of lactose from diet.

38. CAUSES OF LACTOSE INTOLERANCE • Secondary lactose intolerance – results from decreased intestinal activity secondary to damage to intestinal mucosa from some primary pathology • Acute gastroenteritis • PEM • Worm infestations • Malabsorption syndromes • Animal milk allergy • Drugs like neomycin, antimetabolites, etc.

39. CONSEQUENCES OF LACTOSE INTOLERANCE. • Osmotic diarrhea • Metabolic acidosis • Bacterial proliferation • Caloric loss • Pneumatosis intestinalis

40. CLINICAL FEATURES • Diarrhea – Watery, frothy, greenish-yellow, sour smelling stools • Perinal excoriation • Failure to thrive • Abdominal distension • Borborygmi • Flatulence

41. INVESTIGATIONS • Stool pH and reducing substances – • Acidic pH < 5.5 • Reducing substances > 0.5 % • Stool chromatography • Breath hydrogen test • Lactose tolerance test • Intestinal enzyme activity by biopsy

42. TREATMENT • Primary lactose intolerance – • Elimination of lactose from diet • Life long treatment

43. TREATMENT • Secondary lactose intolerance • Treatment of primary cause • Lactose free diet if • Persistent diarrhea • Weight loss • Reducing substances > 1 %