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SUMMARY Background: Recent studies have shown both interleukin 2 (IL-2) and interferon gamma (IFN) to be elevated in patients with active Crohn's disease compared to ulcerative colitis or non-inflammatory bowel disease controls. However the effect of treatment on these lymphokines has not been studied. Patients and methods: Using a reverse haemolytic plaque assay the percentage of lymphokine-secreting cells was determined in the intestinal mucosa of children with Crohn's disease before and after 8 weeks of treatment with either enteral nutrition, cyclosporin or steroids. Results: Before treatment, a high percentage of cells isolated from mucosal biopsies secreted IL-2 or interferon-gamma. Eight weeks’treatment with the immunosuppressive agents cyclosporin, or with corticosteroids, produced a significant reduction in the percentage of IL-2 secreting cells, although only for the former was there also a reduction in interferon-gamma secreting cells. Enteral nutrition however, produced a reduction in lymphokine-secreting cells equivalent to cyclosporin and produced the best histological and clinical improvement. Conclusion: Enteral nutrition and cyclosporin can down-regulate lymphokine secretion in the gut in Crohn's disease.

Objectives: Indeterminate intestinal inflammation may result from a variety of inflammatory conditions in addition to ulcerative colitis and Crohn disease. The primary systemic vasculitides may present with intestinal inflammation and an indeterminate colitis. We set out to describe a series of children with primary systemic vasculitis who initially presented with clinical features suggestive of inflammatory bowel disease (IBD) to establish criteria that might help discriminate between IBD and primary systemic vasculitis. Methods: Ten children (6 boys, median age at presentation 8.9 years, range 0.9-14.5 years) satisfied inclusion criteria. Results: All had abdominal pain, weight loss, diarrhea (6 of 10 bloody) and laboratory evidence of a severe acute phase response. Extraintestinal clinical features included vasculitic rash, renal impairment, myalgia, testicular pain and polyarthritis. Endoscopy showed vascular changes or other macroscopic findings suggestive of vasculitis in 5 of 10 patients. Gut histology revealed indeterminate chronic inflammatory mucosal changes and one patient with small artery fibrinoid necrosis in the submucosal vessels. Extraintestinal biopsy was performed in 6 patients and had a higher yield for the demonstration of vasculitis than intestinal biopsy. The results of selective visceral angiography was suggestive of vasculitis in all patients, but was normal in 7 cases of treatment-unresponsive classic IBD. Treatment comprised corticosteroid and azathioprine in all patients. Cyclophosphamide was given to 7 of 10 patients. Conclusions: Extraintestinal manifestations and inflammatory responses that may be disproportionate to the degree of intestinal inflammation provide clues to the presence of an underlying primary systemic vasculitis, and these data suggest that selective visceral angiography plays a key role in the diagnosis of vasculitis in this context. It is important to identify and treat any vasculitic component because failure to do so may result in consequential morbidity or mortality.

Food allergy may affect the gastrointestinal tract of children and adults too, albeit less commonly. The changing clinico-pathological expression of such food allergy in children over a 30 year period is related, from the eye witness perspective of a paediatric gastroenterologist in London. Tissue diagnosis by biopsy, related to dietary elimination and challenge has been the basis for the first clinico-pathological descriptions and accurate clinical diagnosis of these syndromes as they affect the gastrointestinal tract. In the 1970s cow's milk sensitive enteropathy presenting as chronic diarrhoea and failure to thrive in infancy often after infective gastroenteritis, especially with enteropathogenic Escherichia coli, was an important problem. By the late 1990s such presentations had become most uncommon in developed communities but they continue to occur in developing communities. By contrast in more recent times, multiple food allergy associated with minor small intestinal enteropathy and gastro-oesophageal reflux in older children has become an important clinical problem in children seen in developed communities. Accompanying these changes has been a dramatic fall in the number of children with clinically severe gastroenteritis with severe dehydration requiring hospital admission. Furthermore, the widespread diagnostic use of endoscopy of the upper and lower gastrointestinal tract in children with multiple biopsies has expanded gastroenterological diagnosis in children. This approach gives information about the oesophagus and ileo-colon not available in the earlier studies, which largely concentrated upon small intestinal biopsies, obtained by Crosby capsule biopsy. So, over this 30 year period clinico-pathological expression has altered but also the diagnostic approach has technically changed.

SUMMARY T cell hypersensitivity has been implicated in the tissue damage in Crohn’s disease (CD). All studies to date have examined mucosal T cells, although much of the tissue damage occurs in the submucosa and muscle layers. The aim of this work was to study T cell proliferation throughout the intestinal wall in children with IBD. Surgical resection material from 19 children with CD (10 ileal, 10 colonic), seven with ulcerative colitis (UC), and 12 normal controls was studied. The distribution of dividing T cells was investigated by double-immunohistochemistry using Ki67 to identify proliferating cells, and CD3 to identify T cells. In ileal and colonic lamina propria virtually no Ki67+, CD3+ cells were seen in control, UC or CD tissue. In contrast, there were significantly more Ki67+, CD3+ cells within the lymphoid follicles of ileal and colonic CD than in the follicles in UC and controls. Increased numbers of Ki67+, CD3+ cells were present in the submucosa, muscle layers (M) and serosa in Crohn’s ileitis and colitis compared with the lamina propria (LP), although only in the muscle of the colon was the difference statistically significant (LP, 0.4% (0–1%); M, 1.6% (0–5.2%); P = 0.03). Pooling data from ileal and colonic CD, however, did show significantly increased Ki67+, CD3+ cells in both serosa and muscle layers compared with the LP. Dividing T cells have been identified in the deeper layers of the gut wall in CD. These may contribute to the fibrosis and muscle hyperplasia characteristic of the condition.

Background Central to the management of cow's milk allergy in infancy is the complete elimination of cow's milk protein from the infant's diet for a variable period of time. The principal part of this approach is to provide nutrition for the child by means of hypoallergenic feeding formulas. Although a number of formulas are indeed marketed as hypoallergenic, it is not known with certainty how hypoallergenic they really are. A variety of ways of testing for hypoallergenicity have been developed, including the use of in vivo and in vitro animal model systems, chemical analyses, and patient studies, which are the ultimate test. Objective The purpose of the present report was to review the various ways of testing sensitizing capacity of infant feeding formulas for the treatment of children with cow's milk allergy. Data Sources English language articles were selected from PubMed, as were selected abstracts that would have immediate, practical clinical implications. The review focuses on themes related to animal models, chemical analysis, and clinical testing and clinical studies of intolerance to hydrolysates. Results Sensitizing capacity can be tested first in animal models either by in vivo or in vitro techniques. Although the information gained is valuable for preliminary evaluation, such techniques are intrinsically artificial. Second chemical analyses indicate that absence of larger peptides greater than 1,500 Da provides a critical industrial cutoff point. Third clinical effectiveness in child patients is of paramount importance. Conclusions The results of the present review demonstrate that extensively hydrolyzed formulas are usually effective, but recently intolerance to hydrolysates has been observed. However, use of amino acid-based formulas free of antigens is highly effective in such infants.

Growth impairment of undefined aetiology occurs in approximately 30% of children with chronic inflammatory bowel disease. We measured urinary growth hormone concentrations in 36 children with chronic inflammatory bowel disease and 51 normal controls. The median urinary concentration of growth hormone in the stunted children with chronic inflammatory bowel disease was 15.8 ng/g creatinine (range 4.3-32.6), compared with 11.7 ng/g creatinine (range 4.1-35.9) in those with normal growth. The difference was statistically not significant (p = 0.15). Moreover, there was no significant difference between the patients and the control group. One stunted patient had a urinary growth hormone (UGH) concentration below the normal range, whereas four patients with normal height were also below the normal range. Four of these five patients (80%) were on corticosteroid treatment at the time of urinary collection, whereas only 26% of the patients with normal UGH were also on corticosteroid treatment. We conclude that growth retardation in children with chronic inflammatory bowel disease is probably not related to growth hormone deficiency but must involve other mechanisms.

SUMMARY Gamma/delta T cells are increased in the gut epithelium of patients with coeliac disease compared with normal controls. The aim of this study was to determine whether the increase in yd intraepithelial lymphocytes (IEL) is specific for coeliac disease, in which case it could be of diagnostic importance. Biopsies were obtained from children with no intestinal disease, coeliac disease, cow-milk-sensitive enteropathy/post-enteritis syndrome (CMSE/PES) and miscellaneous other enteropathies (n = 67). Intraepithelial CD3+ and γδ T cells were identified in frozen sections using peroxidase immunohisto-chemistry. In normal biopsies there were 0-7 γδ IEL/100 cells in the epithelium. In untreated coeliac patients this increased to 9-22 γδ IEL/100 cells in the epithelium (P=0.000004). Of 27 patients with morphologic intestinal damage which was not due to coeliac disease, four with CMSE/PES had γδ IEL/100 cells in the epithelium in the same range as the patients with coeliac disease. Of these, two had high densities of CD3+ IEL in the epithelium and were indistinguishable from patients with untreated coeliac disease. The other two could be excluded as possible coeliacs because their CD3f IEL/100 epithelial cells were in the normal range. Thus an increase in γδ IEL is not specific for coeliac disease. However, enumeration of both of γδ IEL and CD3+ IEL densities will be useful in the exclusion of coeliac disease as a diagnosis in some children.

Between 1966 and 2000 the pattern of gastroenterological disease in children in developed communities changed. Clinically severe infective gastroenteritis has declined in incidence. Infection of children with the conventional serotypes of Escherichia coli dramatically declined. During this period many new infective agents notably rota virus were recognised. By contrast, more children with chronic inflammatory bowel disease (IBD), especially Crohn's disease, have been diagnosed than ever before. Gastrointestinal allergy is increasingly recognised but the pattern of disease has changed. Technological advance in accurate diagnosis occurred with an emphasis upon tissue diagnosis. Introduction to clinical practice of ileocolonoscopy in the late 1970s immensely increased the ability to make the diagnosis of chronic IBD in children. Therapeutic advance has seen development of parenteral nutrition and enteral feeding as major therapies for children. In the UK there has been a rise and fall in university departments of paediatric gastroenterology.

The findings on barium follow through, ileoscopy and biopsy of the terminal ileum in 46 children with suspected chronic inflammatory bowel disease have been compared to the final clinical diagnosis. Ileoscopy and barium follow through agreed in 91%, barium follow through and biopsy in 80% and barium follow through, ileoscopy and biopsy in 76% of cases. A pronounced lymphoid hyperplasia pattern was present radiologically in 24%, and was a source of error in two cases. Barium follow through compared favourably to ileoscopy or biopsy individually, detecting 18 of 20 and 17 of 20 cases respectively; however, ileoscopy combined with biopsy diagnosed every case. The sensitivity of the barium follow through was 0.90 with a specificity 0.96 for the diagnosis of Crohn's disease in the terminal ileum.

Background Because of the high prevalence of cow's milk allergy as one of the most frequent clinical presentations of food allergy in infancy and early childhood, it is important to define the condition accurately. Allergy must be distinguished from the broader term food intolerance , which may be defined as a reproducible adverse reaction to the ingestion of a food or to any of its components, ie, proteins, carbohydrates, fats, and additives, and which includes toxic, metabolic, and allergic reactions. By contrast, food allergy may be defined as an adverse clinical reaction to a specific food component and that is immunologically mediated. The rapid increase in knowledge resulting from research in immunology in recent years has not only led to a better understanding of the basis for cow's milk allergy in infancy, but has also yielded considerable promise for improved diagnosis and management of the condition. Objective To review recent developments in immunology which demonstrate how they may lead to a better understanding of the clinical spectrum of cow's milk allergy in infants and children. Data Sources English language articles were selected from PubMed and selected abstracts that would have immediate, practical clinical implications. The review focuses on themes related to gastro-enterology, focusing upon the esophagus and small intestine. Results In cow's milk-sensitive esophagitis, there is dense infiltrate of eosinophils and increased T cell activation with upregulation of the chemokine eotaxin. In cow's milk-sensitive enteropathy, there is T cell activation, and it often results as a sequela of gastro-enteritis. Changing patterns in recent years suggests that sensitization occurs via mother's breastmilk to cow's milk and multiple food antigens. There is evidence of reduced Th 1 response in these children. This is related to associated IgA deficiency and low levels of cytokine transforming growth factor β. Conclusions The results of the present review demonstrate that the clinical manifestations of cow's milk allergy are very diverse, with differences between developing and developed countries. Understanding the immunologic mechanisms is of key importance in understanding this diversity.

In children with complicated inflammatory bowel disease, conventional ultrasound imaging may not define the extent of extraluminal disease and the involvement of other viscera. Three children with chronic inflammatory bowel disease are presented, where computed tomography was well tolerated and provided valuable information on extraluminal disease, involvement of other organs, and the state of the bowel wall and mesentery. In children in whom ultrasound examination is inconclusive or limited by gas or tenderness, computed tomography can provide important information that may determine clinical management.

Twenty children with active ulcerative colitis were assessed before and after 8 weeks of medical therapy with 5-aminosalicylic acid (5-ASA) derivatives and corticosteroids. Local therapy was given for distal disease (seven cases) ; other disease was treated with oral prednisolone (1-2 mg/kg/day, maximum 40 mg). Eighteen of the children showed a clinical improvement on therapy, and complete remission of clinical disease activity by 8 weeks was seen in 17 (85%). C-reactive protein was elevated initially in 10 of 20 children and returned to normal posttreatment in all but one. Reassessment of the colon after treatment showed an improved endoscopic appearance in 15 and complete remission in eight (40%). Histological improvement was seen in 13, with full remission in only three (15%). In conclusion, remission of clinical disease activity by corticosteroid therapy in ulcerative colitis may not be accompanied by endoscopic remission and uncommonly by mucosal healing. This finding may be important prognostically because of the risk of dysplasia in long-standing persistent mucosal inflammation.

SUMMARY Background: Corticosteroids are widely used to treat children with inflammatory bowel disease although the response is variable, side-effects are common, and many patients develop a partial or complete steroid resistance. The mechanism underlying these phenomena are unclear. Corticosteroids mediate some of their actions through lipocortin-l, and the inductic of autoantibodies to lipocortin has been proposed as a possible mechanism by which steroid efficacy is suboptimal in vivo. Patients and methods: We have measured serum lipocortin-1 antibody concentration by ELISA in 38 children with Crohn's disease, 12 with ulcerative colitis and in 15 controls. Results: IgG and IgA anti-lipocortin-1 antibody levels were higher in the Crohn's group than in the ulcerative colitis or control groups. Elevated concentrations did not relate to disease activity, history of steroid therapy or steroid-responsiveness. Lipocortin IgM antibody status was similar in all three groups. Conclusion: It is therefore unlikely that serum antibodies to lipocortin-1 have a role in the development of steroid-resistance in children with inflammatory bowel disease.

Eighteen children and adolescents, of a total of 90 treated in our unit between 1982 and 1992, underwent colectomy for ulceractive colitis. Six (6.7%) of the 90 patients had short stature, i.e., a height below the 3rd centile, and 8 of the 18 who had surgery had a subnormal height velocity, i.e., below the 25th centile for age at the time of surgery. Surgery was performed for resistance to medical therapy (n = 13) or toxic megacolon (n = 5). Surgery was followed by catch-up growth, i.e., increasing height velocity, in eight subjects and cessation of the trend of diminishing height velocity, but without catch-up growth, in five. In 11 of the subjects who were prepubertal, the median height velocity increased from 3.85 cm/year preoperatively to 7.35 cm/year postoperatively (p < 0.01). One year after surgery, 14 of the 18 patients were either asymptomatic or substantially improved. Surgery therefore led to improved linear growth and a prolonged symptom-free period in most of the children and adolescents with ulcerative colitis undergoing this treatment.

Soluble interleukin-2 receptor (IL-2R) concentrations were measured in 110 serum samples from 102 children undergoing routine small bowel biopsy for a wide range of gastrointestinal symptoms. Young children in the control group who had no gastrointestinal disease and a normal intestinal mucosa were found to have high concentrations of IL-2R. There was a significant inverse relationship between IL-2R concentration and age in the control group. Children with a gastrointestinal diagnosis appeared to have increased IL-2R concentrations, although some of the diagnostic groups were too small in size for statistical analysis. Children with cow's milk sensitive enteropathy had IL-2R concentrations equivalent to those of age-matched controls. High concentrations of IL-2R in young healthy children implies that serum IL-2R is of no clinical use as an index of inflammation in this age group.

There are two types of food sensitive enteropathy; permanent and temporary. Celiac disease belongs to the former, the temporary food sensitive enteropathies of early childhood to the latter. A food sensitive enteropathy is characterized by an abnormal small intestinal mucosa while having the offending food in the diet; the abnormality is reversed by an elimination diet, only to recur once more on challenge with the relevant food. These disorders are temporary and may follow gastroenteritis. Cow's milk sensitive enteropathy is the most frequent and best known example but soy protein, egg, fish, chicken meat, ground rice and probably gluten may also temporarily damage the small intestinal mucosa in infancy. Treatment is with an elimination diet and protein hydrolysates as a cow's milk substitute. The reason why these enteropathies are temporary has not yet been established.

Childhood Crohn's disease may cause significant morbidity. T cell activation is considered to be central to Crohn's disease pathology, and as cyclosporin is a powerful inhibitor of T cell activation, and has been used in adult Crohn's disease with encouraging results, it may offer the prospect of remission if given early in the course of disease. Children with newly diagnosed Crohn's disease or those relapsing off treatment were therefore given cyclosporin or conventional treatment (enteral nutrition or corticosteroids) by random allocation. Evaluation was performed initially and at two months. Twenty four children were studied (10 on cyclosporin and 14 on conventional treatment; one child on cyclosporin withdrew). Significant clinical improvement occurred in the group on conventional treatment, but not in the cyclosporin group. Colonoscopic improvement was noted in 5/9 on cyclosporin and 8/14 on conventional treatment, but neither group produced a significant fall in median colonoscopic index. Histological improvement was seen in 7/8 on cyclosporin and 8/13 on conventional treatment, but cyclosporin was not significantly better. Cyclosporin produced improved clinical and histological appearance without matched improvement in blood disease indices. It was not better than conventional treatment, and simple oral administration is probably not suitable for newly diagnosed patients with Crohn's disease.

Factors influencing outcome after surgery have been studied in 67 children requiring bowel resection or diversion of the faecal stream for Crohn's disease. Patients were divided into four groups on the basis of disease location at time of surgery, and mean follow-up was 4–5 years. All three children with panenteric disease (group 1) have relapsed. Best results were observed in cases with disease confined to the small bowel (group 2) and ileocaecal region (group 3), in whom surgery was followed by sustained remission in six out of seven and 24 out of 30 patients respectively. In the 27 children with colitis (group 4), results were mixed. Six of the seven patients who had staged colonic resections with a primary anastomosis relapsed, as did three out of four patients given a loop ileostomy to divert the faecal flow; in contrast, 15 out of 16 children who had a subtotal colectomy with ileostomy as the primary procedure have remained well, with only minor problems involving the rectal stump. An acceleration in growth velocity was observed during the first year after operation in 89 per cent of 40 children studied. Outcome after surgery for Crohn's disease in childhood depends mainly on disease location, but is influenced by the type of primary operation performed. In addition to symptomatic relief the principal early benefit of surgery is improved growth.

A retrospective analysis of pubertal parameters of 30 children with Crohn's disease (N = 26) or ulcerative colitis (N = 4) was compared with standards. Four parameters were analyzed

42 children requiring surgery for Crohn's disease before 17 yrs of age were studied to determine the effect of bowel resection on their growth and pubertal development. Height, weight, pubertal status and bone age were recorded by an auxologist for at least 1 yr post-operatively (mean 3.12 yrs). 20 (48%) were below the 3rd centile for height at surgery, and 13 (31%) had pubertal delay of 2 yrs or more. 6 cases had a small bowel resection, 22 right hemicolectomy, and 14 sub-total colectomy (8 with ileostomy). The children were divided into 3 groups according to pubertal status at surgery - group A (prepubertal), group B (breast/genitalia stages 2+3), and group C (stages 4+5). Mean annual growth velocities (GV, cm/yr) for the 12 months before and after surgery were: Groups A+B showed a highly significant increment in GV after surgery, and pubertal acceleration was seen in 8 of the 13 with delay. GV correlated well with weight gain, and inversely with disease activity index and serum C-reactive protein. Poor growth in the first year post-operatively was a predictor of early disease relapse. GV varied little with site of disease or the type of operation performed. These findings suggest that surgery has an important role in the management of growth failure in CD, but should be performed before puberty becomes too advanced.

A child, aged 6 years 3 months, with a triglyceride storage disorder in peripheral adipose tissue, microcephaly, and gross emaciation has been studied at autopsy. The mean triglyceride content of adipocytes in hand and foot was 0.17 ± 0.02µg/cell and 0.18 ± 0.02µg/cell. Adipocytes from abdominal tissue were small, irregular, and difficult to measure accurately, reflecting the degree of cachexia. Basal tissue contents of cyclic AMP and release of glycerol and fatty acid from peripheral tissue of the child were in the same range as adult tissues. None of these measurements, however, were increased by incubation with isoprenaline (105 M), compared to a three- to seven-fold increment in adult subcutaneous tissues and to a four- to ten-fold increment of glycerol and cyclic AMP in peripheral adipose tissue of a control child aged 10 years. We postulate that the proband may have had a defect of adenyl cyclase or catecholamine receptor, which has a role in the abnormal storage of triglyceride in peripheral adipose tissue.

This chapter discusses miscellaneous disorders of the small intestine. Hartnup disease is an uncommon disease that is inherited as an autosomal recessive trait. Clinically, its typical features are cerebellar ataxia, a pellagra-like skin rash, and photosensitivity. There is a defect of absorption of neutral amino acids from the small-intestinal mucosa, and there is also a renal tubular defect for the re-absorption of the neutral amino acids. Children with cystinuria have a selective malabsorption of the amino acid cystine and the basic amino acid lysine, ornithine, and arginine. There is also a renal tubular defect for these amino acids characterized by aminoaciduria. Cystinosis is an autosomal recessively inherited disorder in which large amounts of intracellular free cystine are found. Acrodermatitis enteropathica is a rare autosomal recessively inherited disorder usually presenting in infancy because of a defect in zinc absorption. The small-intestinal lymphangiectasia syndrome of idiopathic hypoproteinemia without proteinuria and with normal hepatic function results from excessive loss of plasma protein into the alimentary tract. There is also a syndrome of congenital short intestine in association with pyloric hypertrophy and malrotation. This syndrome is caused by the absence or diminution of argyrophil ganglion cells in the small-intestinal wall. These cells normally organize peristalsis and ensure that the bolus moves forward at the correct speed.

A careful history is the most vital step in the investigation of children with diseases of the small intestine. There are two aspects to this history taking. First is the narrative history concerning the child's illness from its onset up to the present and second is the specific questioning about the child's symptoms and past history. A detailed dietary history also is of particular importance in such children, including details such as what formula the child is feeding on as well as the time of introduction and nature of solids in the infant's diet. The symptoms and signs of disease of the small intestine in children can be placed into three broad groups: (1) those symptoms and signs that direct immediate attention to the alimentary tract, that is, gastrointestinal symptoms such as diarrhea, vomiting, abdominal pain, abdominal protuberance, and anorexia; (2) those clinical features that result because of nutritional disturbance and growth and developmental slowing, such as failure to thrive and weight loss, shortness of stature and delayed development, as well as the various deficiency states such as anemia, rickets, edema, tetany, and skin changes; and (3) clinical features that occur because of disturbances in water and electrolyte balance. Useful information about small-intestinal disease can be obtained from a careful physical examination. All body systems should be examined thoroughly, but examination of the skin, particularly for signs of dehydration in young infants, is vital because the skin may also indicate weight loss and malnutrition.

Summary A 10-week-old male infant presented with a history of recurrent diarrhoea and vomiting and in a state of collapse. After much fruitless investigation he was challenged with a wheat rusk and developed life-threatening anaphylactic shock followed by watery diarrhoea due to monosaccharide intolerance. This immediate type hypersensitivity to wheat rusk was transient, the infant being able to tolerate dietary wheat at the age of 14 months.

A study was undertaken in paediatric patients suffering from ulcerative, Crohn's or indeterminate colitis. This aimed to compare the occurrence and tolerance of side-effects arising during treatment with position-release mesalazine (Asacol) with those occurring during previous treatment with sulphasalazine (Salazopyrin). The drugs were used to maintain remission from colitis. The occurrence of adverse reactions was also monitored. Sixty-seven children were assessed for a period of 6 months; 45 of these children received mesalazine after previous treatment with sulphasalazine. The results show that the majority of patients were maintained in remission with either drug, but they reported a preference for position-release mesalazine with respect to ease and frequency of administration when compared to sulphasalazine. No serious adverse reactions arose during mesalazine treatment, compared with three such events during previous sulphasalazine treatment.

Publisher Summary Defective digestion and absorption of ingested carbohydrate are common and important problems in infants and children. They may result from a primary inherited enzyme defect and thus be a permanent disorder, or they may be a secondary phenomenon of temporary duration and a sequel to small-intestinal mucosal damage or to colonization of the small intestine with bacteria. Sugar intolerance is a clinical syndrome occurring in infants and children that is characterized by the development of diarrhea and/or vomiting, abdominal pain, and failure to thrive when a particular sugar or sugars are ingested. Sugar malabsorption refers to a situation where a carbohydrate is not absorbed from the small intestine but may not necessarily cause any symptoms as the clinical effects may be overcome by large bowel scavenging of the malabsorbed sugar. Sucrase–isomaltase deficiency is an inherited enzyme deficiency of the small-intestinal mucosa, characterized by undetectable sucrase activity and absent or greatly reduced isomaltase. Congenital glucose–galactose malabsorption is a rare, genetically determined disorder. It is inherited as an autosomal recessive trait. The absorptive defect is confined to the two structurally similar hexoses—glucose and galactose.

This chapter discusses dietary protein intolerance. Clinical food intolerance has many causes and many manifestations, including psychological aversion to the sight, smell, or taste of food as well as psychological intolerance to one or more of the many constituents of food. Dietary protein intolerance is the clinical syndrome resulting from the sensitization of an individual to one or more proteins that have been absorbed via a permeable mucosa in the small intestine. Intolerance to various food proteins, especially to cows' milk, has been recognized in children for many years. Such food intolerance may be the result of a variety of causes—for example, a congenital digestive enzyme defect such as sucrase–isomaltase deficiency or an acquired lactase deficiency secondary to small-intestinal mucosal damage, which in turn can be the result of a food allergy. The incidence of gastrointestinal food allergy diseases is greatest in the first few months and years of an infant's life and decreases with age. The acute syndrome is usually characterized by the sudden onset of vomiting, after cows' milk ingestion, occasionally followed by pallor and a shock-like state; however, acute anaphylaxis is rare. Acute abdominal pain seems to be a particular feature of fish hypersensitivity, while peanuts often produce immediate reactions in the oral mucosa as well as abdominal pain.

Publisher Summary Celiac disease may be defined as a disease of the proximal small intestine characterized by an abnormal small-intestinal mucosa and associated with a permanent intolerance to gluten. The removal of gluten from the diet leads to a full clinical remission and restoration of the small-intestinal mucosa to normal. Celiac disease is a lifelong disorder that affects both children and adults. Environmental factors influence the incidence of celiac disease, because it cannot occur unless gluten is present in the child's diet. Hypoproteinemia is a common complication of celiac disease and is found in children with celiac disease is because of protein-losing enteropathy. When there is severe hypoproteinemia, the child may present with generalized edema mimicking the nephrotic syndrome. The edema is relieved by therapy that includes a gluten-free diet. An abnormal prothrombin time caused by the malabsorption of vitamin K may occur in celiac disease. Some authorities recommend calculating prothrombin time along with other parameters of coagulation before small-intestinal biopsy is performed.

Publisher Summary There are three parasites that can damage the small-bowel mucosa of children. These are Giardia lamblia, Strongyloides stercoralis, and Cryptosporidium. Infestation with these parasites may be related to structural damage to the small-bowel mucosa. Giardia lamblia is a motile flagellate protozoon. It is a biphasic parasite with trophozoite and cystic stages. It has four pairs of flagellae and a sucker disc. Being a trophozoite, it may infest the proximal small intestine in children and may be found in the glandular crypts of the duodenojejunal mucosa. Giardia lamblia can cause diarrhea, steatorrhea, and variable small-intestinal mucosal damage in children with giardiasis. The mucosal inflammatory response in giardiasis may also play a role in the development of enteropathy. Infestation with the nematode Strongyloides sterocoralis is often found in aboriginal and part-aboriginal children in Australia and tropical countries. During the life cycle of this parasite, the larvae invade the mucosa of the proximal small intestine and develop into adult worms within the wall of the small bowel. However, unlike infestation with Ascaris lumbricoides, the adult Strongyloides worms are not usually found in the bowel lumen. The ova are laid in the gut wall and the hatched larvae subsequently migrate into the bowel lumen; these may then re-infect the gut farther down the bowel. Cryptosporidium is a coccidian parasite related to Toxoplasma. Transmission may occur from direct contact with infected animals. Direct person-to-person spread is also likely to occur. Cryptosporidial infection may cause chronic watery diarrhea and malabsorption in patients with immunodeficiency. Cryptosporidium infection can cause severe abdominal pain before the onset of diarrhea, sometimes even mimicking appendicitis in a manner similar to infection with Yersinia and Campylobacter.

Publisher Summary Chronic diarrhea can be defined as the passage of an increased volume of stool water for a period greater than 2 weeks. Chronic diarrhea may be associated with malabsorption of one or more essential nutrients. If diarrhea and malabsorption are severe and persistent, then malnutrition may result with important secondary complications. These include secondary immunoincompetence and further impairment of gastrointestinal function such as failure of pancreatic secretion. The intractable diarrhea syndrome of infancy is a heterogeneous syndrome with a diverse etiology. Intractable diarrhea has very important nutritional consequences resulting in a deteriorating spiral of malnutrition and malabsorption. The management of intractable diarrhea in infancy is one of the most difficult problems in the whole of pediatric gastroenterology, and it has two aspects to it—first, the establishment of a diagnosis when possible; and second, the institution of treatment for dehydration if present and for the associated malnutrition. Autoimmune enteropathy is a syndrome of intractable diarrhea associated with a severe proximal small-intestinal enteropathy and the production of specific autoantibodies against gut epithelium. The autoantibody that has lead to the designation of this disorder as autoimmune enteropathy could be a primary or secondary phenomenon.

Forty children (less than or equal to 2 years of age) were admitted to hospital with acute gastroenteritis and were randomly assigned to receive either an oral rehydration solution (ORS) containing bicarbonate (Na 35, K 20, Cl 37, HCO3 18, glucose 202 mmol litre-1) or an identical solution in which bicarbonate was replaced by chloride ions. Groups were matched for age, sex, ethnic origin, duration of diarrhoea and nutritional status. On admission, degree of dehydration, biochemical and haematological parameters were similar. The majority had minimal or no dehydration and only 30% had moderate to severe dehydration. All children were treated successfully with no complications. Oral rehydration solution intake by each group was similar. Clinical outcome, as judged by speed of rehydration or maintenance of hydration, duration of diarrhoea, stool frequency and length of hospital stay, was the same in both groups. After 24 h of ORS there was no difference between groups in venous pH, serum bicarbonate, urea and electrolytes. In hospitalized children with acute gastroenteritis in the United Kingdom an ORS without bicarbonate is a safe, effective means to prevent dehydration and maintain hydration and acid-base status where dehydration is not severe. Exclusion of bicarbonate would simplify production, increase stability and reduce the cost of ORS without apparent impairment of efficacy.

Crohn's disease is a chronic inflammatory disorder that may affect any part of the alimentary tract and has a characteristic pattern of clinical and pathological features. Crohn's disease may affect any part of the alimentary tract from the mouth to the anus. The pathological lesion in Crohn's disease is typically transmural, although submucosal thickening is a characteristic. The gastrointestinal symptoms that occur in children with this disorder include abdominal pain, anorexia, nausea, vomiting, and diarrhea. The abdominal pain is characteristically periumbilical and colicky, and it is often brought on by eating. It is caused by a combination of intestinal obstruction and inflammatory reaction. Pain is extremely variable in duration, severity, and site. A proportion of patients present with colicky pain typical of small-intestinal obstruction. Some of these may present acutely with intestinal obstruction or occasionally with peritonitis because of cecal perforation.

During routine lower gastrointestinal endoscopy of children for suspected chronic inflammatory bowel disease, it is possible to visualize lymphoid follicles (Peyer's patches) in the last few centimeters of the terminal ileum. Biopsy specimens have been taken from these Peyer's patches and the lymphoid cells have been isolated by collagenase digestion. The mean cell yield of Peyer's patch cells was 1.7 x 10(8) lymphocytes/g tissue. Isolated Peyer's patch cells were 26%-54% CD3+ (pan T cells), 14%-34% CD4+ (helper/inducer T cells), and 9%-17% CD8+ (suppressor/cytotoxic T cells). Twenty six percent to 48% of the Peyer's patch cells were B cells; less than 1% contained cytoplasmic immunoglobulin A. When stimulated in vitro with phytohemagglutinin or pokeweed mitogen, cells from Peyer's patches proliferated. The successful isolation of functional cells from Peyer's patches will now allow studies to be done at the afferent limb of mucosal immunoregulation in humans.

A massive resection of the small intestine may be defined as a resection of more than 30 cm. Resection in the pediatric age group usually occurs following surgical catastrophes in the neonatal period. These include volvulus neonatorum secondary to a developmental anomaly, such as omphalocele or malrotation; obstruction from multiple atretic areas requiring resection; necrotizing enterocolitis; and sometimes meconium ileus, intussusception, or long-segment Hirschsprung's disease with small-intestinal involvement. Extensive Crohn's disease in the older child may sometimes require massive small-intestinal resection. The clinical syndrome resulting from massive small-intestinal resection is referred to as the “short-gut syndrome.” It is characterized by diarrhea and reduced absorption of all nutrients, minerals, and vitamins. The characteristic disabilities suffered by these children are the result of gross alterations in nutrient absorption. The resection of the entire duodenum frequently results in anemia and osteomalacia. The problems encountered following massive small-intestinal resection fall into two groups—first, the immediate post-operative problems and, second, the long-term problems. The major immediate problems are severe diarrhea with associated fluid and electrolyte losses and the resultant inability to retain enough calories to maintain weight. The long-term problems relate more to the severity of the malabsorption state resulting from loss of absorptive capacity and the effect this has on nutrition and growth.

This chapter discusses the various techniques that are used in the investigation of the small intestine. Evidence of anatomical abnormality of the small intestine can be obtained by X-ray studies. The plain X-rays of the abdomen of children with malabsorption can reveal a dilated small and large bowel. In severe malabsorption, an ileus with dilated loops and fluid levels can occur. Barium studies in such cases reveal dilation of the small intestine and the segmentation and fragmentation of the barium column. Thickening of the mucosal folds may be found in instances of intestinal lymphangiectasia and lymphosarcoma. Bleeding from the small intestine may be difficult to investigate radiologically, but duodenal ulceration, duplication of the ileum, and Meckel's diverticulum can be diagnosed from barium studies. Parasitic infestation can be diagnosed radiologically. Ascaris lumbricoides in the small intestine can be readily recognized and strongyloidiasis may produce an acute inflammation and obstruction in the ileum, which may also give an appearance that mimics Crohn's disease. Endoscopy is increasingly available in the pediatric age group. It is now possible, during the course of colonoscopy, for the endoscope to enter the distal ileum to allow an endoscopic ileal biopsy to be taken. Laparotomy can be indicated when malrotation with intermittent volvulus is suspected.

Lesions of the small intestine that are surgically correctable may be divided into those that are present during the neonatal period and those that are present during infancy and childhood. The surgically correctable lesions of the small intestine present clinically during the neonatal period in four principal ways: (1) neonatal small-intestinal obstruction, (2) small-intestinal perforation, (3) necrotizing enterocolitis, and (4) gastrointestinal bleeding. Persistent vomiting, abdominal distension, or failure to pass meconium suggest the diagnosis of intestinal obstruction in the neonatal period. Necrotizing enterocolitis in the newborn is a condition in which there is a diffuse or patchy necrosis of the mucosa or submucosa of the small and/or large intestine. It is a syndrome that probably has a multifactorial etiology. Intrinsic small-intestinal obstruction may produce either complete or partial obliteration of the bowel lumen. Complete obliteration may be caused by a diaphragm occluding the lumen.

One hundred and sixteen children (less than 2 years old) admitted to a London hospital with acute gastroenteritis were randomized to receive either an oral rehydration solution (ORS) with low sodium and high glucose concentration (Na+ 35, glucose 200 mmol/L), an ORS with a high sodium but low glucose concentration (Na+ 60, glucose 111 mmol/L), or an ORS containing glycine and a glucose polymer (Na+ 50, glucose 50, glycine 50 mmol/L). Clinical, biochemical and haematological features of the three groups were similar on admission. Rotavirus was common (31%); the majority of children had minimal dehydration or acid-base disturbance. The clinical outcome, including ORS intake, prevention of dehydration, rehydration, and duration of hospital stay was similar in the three treatment groups. All initial electrolyte abnormalities were corrected; no child developed hypernatraemia or hyponatraemia. At 24 h, the mean serum urea was higher in those who received the ORS containing glycine than in other groups, and it had not fallen significantly since admission. Eighteen per cent of children had carbohydrate intolerance: four children with greater than or equal to 2% reducing substances in their stool had all received ORS with a high glucose content and had numerous watery green stools containing rotavirus. All ORS solutions were safe and effective for rehydration and correction of biochemical abnormalities, however carbohydrate intolerance was more prevalent in children who received the ORS with a high glucose content.

SUMMARY Background: Recent studies in adults have shown that polymeric (whole protein) diets are as effective as semi-elemental and elemental formulae for the induction of remission in small bowel Crohn's disease. Whole protein diets are more palatable and cheaper. There have been no studies confirming efficacy in children. Patients and Methods: We report our experience with seven children with active small bowel Crohn's disease given a casein-based, polymeric feed rich in TGF-SbT2 (Specific Polymeric Diet; Nestl–Clintec; Vevey, Switzerland) as complete nutrition for 8 weeks. Results: Initial and follow-up assessments were performed. All children showed a significant improvement in disease activity, with C-reactive protein returning to normal, an increase in serum albumin and a good weight gain. Initial and follow-up ileal biopsies were assessed and showed reduced mucosal inflammation in six of seven children, with complete healing in two. Conclusion: In an uncontrolled descriptive study we have shown that a polymeric (whole protein) diet is a therapeutic option for small bowel Crohn's disease in children. By comprehensive follow-up we have demonstrated clinical and biochemical remission, with an improved endoscopic appearance and a reduction of mucosal inflammation in the terminal ileum.

Immune mechanisms may be important in the pathogenesis of colonic inflammation To test this hypothesis, an organ-culture model was used to study the effects of T cell activation in human colonic mucosa. Lamina propria T cells in expant cultures of human fetal colon (16-20 weeks gestation, n=10) were activated in-situ using poke-weed mitogen or anti-CD atibody, and compared with controls. After 3 days of culture, immunohistochemistry demonstrated a 2-4 fold increase in crypt epithelial cell proliferation in T cell stimulated explants compared with controls; this was associated with a decrease in crypt goblet cell numbers of up to 20 fold. After 5 days, the surface epithelium in stimulated explants appeared flttened with severe loss of goblet cells, and by day 7, severe mucosal damage was observed under both light and electron microscopy. A fall in crypt goblet cells without hyperplasia had occurred in control cultures by day 7; however, the epithelium remained intact, and the degree of mucous depletion, and the rate at which it occurred, were less than in stimulated explants. Goblet cell depletion, crypt hyperplasia, and epithelial damage are common histological findings in colonic inflammation (particularly ulcerative colitis) These experiments suggest that T cells may have an important role in the pathogenesis of colitis. The model provides a new system whereby the mechanisms of T cell-mediated damage in the human colon can be studied.