Chronic Nonspecific Diarrhea Research Articles

Effect of Bismuth Subsalicylate on Chronic Diarrhea in Childhood: A Preliminary Report

Stools collected from 39 infants and children with chronic nonspecific diarrhea and from 10 age-matched controls were examined for bile acid content with use of gas-liquid chromatography. Values were correlated with stool color. Mean concentration of bile acids in green stools (7.7 +/- 1.52 mg/g dry weight) was significantly higher than that in brown stools (3.76 +/- 0.7 mg/g dry weight) and in control stools (1.42 +/- 0.35 mg/g dry weight). In patients with green diarrhea, treatments with cholestyramine and bismuth subsalicylate (Pepto-Bismol) were equally effective in decreasing stool frequency, with the latter being more effective in decreasing water content. Patients with brown stools had an insignificant response to therapy.

Apple juice, fructose, and chronic nonspecific diarrhoea.

Apple juice contains fructose and sorbitol, substances that have been shown to be incompletely absorbed by most people. As this might have clinical consequences, especially in young children, we investigated the absorption of the carbohydrate content of apple juice in apple juice consuming toddlers with chronic nonspecific diarrhoea as compared to controls, using the breath hydrogen (H2) test. Incomplete absorption of the carbohydrates from 250 ml of apple juice, as indicated by a maximum breath H2 increase of greater than or equal to 20 parts per million (ppm), was found in all nine patients (mean +/- SEM 57 +/- 8 ppm), and in five out of eight controls (22 +/- 7 ppm) (P less than 0.01). Six patients were retested with apple juice "enriched" with glucose, which is known to improve fructose absorption. The maximum breath H2 increase as well as the area under the breath H2 curve decreased significantly. It was thus estimated that fructose accounted for 80% of the incomplete absorption and sorbitol for 20%. Elimination of apple juice from the diets of the nine patients resulted in normalisation of both the frequency and the consistency of the stools. Incomplete absorption of the carbohydrates, particularly fructose, from apple juice seems to be quite common, and may contribute to chronic diarrhoea in young children.

What Happens to Fructose in the Gut?

There is a separate transport system for fructose in the intestinal brush border. Fructose absorption takes place by facilitated diffusion, independently of the presence of energy supply or sodium. Until recently, the human fructose absorption capacity has been considerably overrated. It has been demonstrated with breath hydrogen tests that a dose of 50 g (2 g/kg body weight in children) is incompletely absorbed by most people; some actually absorb only 5g. Glucose, however, strongly facilitates fructose absorption. Diminished absorptive capacity for fructose may become of clinical relevance in case of consumption of apple juice, pear juice, or beverages sweetened with high-fructose corn syrups, and in case of concomitant consumption of, for instance, sorbitol. Fructose (and sorbitol) may have an aetiologic role in the irritable bowel syndrome in adults, and in recurrent abdominal pain and especially chronic nonspecific diarrhoea (toddler's diarrhoea) in children.

Relationship of Endomysial Antibodies to Jejunal Mucosal Pathology

SummarySerum immunoglobulin A class antibodies reactive to the endomysial lining of the smooth muscle bundles of the gastrointestinal tract have recently been reported to be specific and sensitive indicators of celiac disease (CD). A total of 203 subjects were examined for serum endomysial antibodies (EmA) and in 103 small bowel biopsies were obtained. EmA were detected in 43 cases including 26 CD patients evaluated during the gluten challenge phase of diagnosis by European Society for Pediatric Gastroenterology and Nutrition criteria, 11 of 53 symptomatic patients, and 6 asymptomatic family members. All patients with detectable antibody at the time of biopsy exhibited grade III‐IV villous atrophy. Disaccharidase activities performed in 19 cases revealed severe deficiencies. EmA were not detected in 160 subjects including 42 infants and children with chronic nonspecific diarrhea. Eighteen of these possessed grade II‐III villous atrophy with moderate disaccharidase deficiency and 24 were found to have normal histology and enzymes. The EmA were also not detected in 3 CD patients who were well maintained on a gluten‐free diet for > 1 year and 25 asymptomatic family members exhibiting normal histology and enzymes. An additional 90 infants and children with other gastrointestinal and liver diseases were also negative for the serum EmA. Fourteen of these patients underwent biopsies and were demonstrated to have normal histology.

Relationship of endomysial antibodies to jejunal mucosal pathology: specificity towards both symptomatic and asymptomatic celiacs.

Serum immunoglobulin A class antibodies reactive to the endomysial lining of the smooth muscle bundles of the gastrointestinal tract have recently been reported to be specific and sensitive indicators of celiac disease (CD). A total of 203 subjects were examined for serum endomysial antibodies (EmA) and in 103 small bowel biopsies were obtained. EmA were detected in 43 cases including 26 CD patients evaluated during the gluten challenge phase of diagnosis by European Society for Pediatric Gastroenterology and Nutrition criteria, 11 of 53 symptomatic patients, and 6 asymptomatic family members. All patients with detectable antibody at the time of biopsy exhibited grade III-IV villous atrophy. Disaccharidase activities performed in 19 cases revealed severe deficiencies. EmA were not detected in 160 subjects including 42 infants and children with chronic nonspecific diarrhea. Eighteen of these possessed grade II-III villous atrophy with moderate disaccharidase deficiency and 24 were found to have normal histology and enzymes. The EmA were also not detected in 3 CD patients who were well maintained on a gluten-free diet for greater than 1 year and 25 asymptomatic family members exhibiting normal histology and enzymes. An additional 90 infants and children with other gastrointestinal and liver diseases were also negative for the serum EmA. Fourteen of these patients underwent biopsies and were demonstrated to have normal histology.

Carbohydrate Malabsorption Following Fruit Juice Ingestion in Young Children

We performed breath hydrogen analyses in 13 healthy children (9 to 36 months of age) and seven children (14 to 27 months of age) with chronic nonspecific diarrhea after they had ingested pear, grape, and apple juices and a 2% sorbitol solution. Excess breath H2 excretion was found in virtually all study subjects following the ingestion of either pear juice (with approximately 2% sorbitol content) or the 2% sorbitol solution, in approximately 50% of those ingesting apple juice (0.5% sorbitol), and in 25% of those ingesting grape juice (no sorbitol) (P less than .001, analysis of variance). No differences were noted between the healthy children and those with chronic nonspecific diarrhea. Forty percent of all study subjects in whom excess breath hydrogen excretion occurred also had diarrhea and abdominal cramping. Carbohydrate malabsorption appears to be frequent following the ingestion of common fruit juices and in some children may be associated with nonspecific gastrointestinal symptoms.

The preschool child: developmental themes and clinical issues

The preschool years are a remarkable period of dramatic growth in the areas of physical, affective, and cognitive development. Physical development is characterized by a slow but steady rate of somatic growth and the mastery of motor skills that facilitate the child's achievement of autonomy and independence. Major themes in affective development include the achievement of autonomy and independence from family, a lessening of attachment to parents and the alleviation of separation anxiety, and the acquisition of impulse control and socialization skills. Cognitive development during the so-called preoperational period is best characterized by the mastery of language. The remarkable developmental gains achieved during this dynamic period culminate in a child who can function independently and competently and begin the major occupation of childhood—attending school. Health maintenance issues during the preschool years directly reflect the child's developmental stage. For example, nutritional issues reflect not only physical growth and motor skills, but also negativism and the child's struggle to achieve autonomy. Similarly, safety and injury prevention relate to the “motor-minded” behavior so characteristic of children at this age, as well as the illogical, egocentric thought that predominates during this period of cognitive development. Examples of other stage-related issues addressed during health maintenance visits include discipline and behavior problems, sleep problems and night awakening, and toilet training. The unique aspects of development during the preschool years also have implications for other components of child health maintenance, including developmental screening, procedures and immunizations, and physical assessment. A number of clinical issues are of special significance during the preschool years. For example, the most common causes of children's short stature, constitutional delay in growth and familial short stature, may result in major parental concerns at this time. Recurrent otitis media is an important problem during this period of language acquisition. Among preschool children with urinary tract infections, the risk of an underlying structural anomaly of the urinary tract and the danger of irreversible renal damage is greater than for older children. Although chronic nonspecific diarrhea of childhood is mainly a problem for infants and toddlers, such diarrhea may persist during the early preschool years. Examples of behavioral and developmental issues of particular significance include language impairment, depression, hyperactivity, and such social stressors as the death of a loved one and parental separation or divorce. The early identification of children who are not ready to begin the formal task of classroom learning has been increasingly emphasized by educators, psychologists, parents, and pediatricians. Reasons for this emphasis on early identification include the critical influence of the early childhood years on later competence, the policy of determining school entry by chronological age rather than developmental status, and legislative factors such as P.L. 94–142. The pediatrician, as the professional concerned with monitoring children's growth and development, is uniquely suited to participate in the identification of children unready for school. Effective participation requires recognition of the various factors influencing school readiness, including general health, developmental competencies, temperament and behavior, and social and environmental issues. Possible pediatric roles include screening children for school readiness and clinical problem-solving when issues or concerns arise.

Chronic Diarrhea and Soy Formulas

Soy protein formulas are often poorly tolerated by infants with chronic nonspecific or postinfectious diarrhea syndrome. We found that these adverse responses may be prevented by using lactose, instead of sucrose or dextrimaltose, in soy formula. We studied 40 infants diagnosed as soy intolerant. They were given soy formula with differing carbohydrate contents in a randomized, blinded prospective study. Stool output, stool sodium content, and symptoms were significantly improved in infants receiving a soy-lactose formula; no difference was seen in formulas with sucrose or maltose. Improvement occurred in three to five days in most infants. Furthermore, the characteristic frequency distribution of the favorable response to lactose suggested a specific mechanism for the inhibition of water and electrolyte losses through the bowel. The results indicate that, in the absence of lactose intolerance, a soy-lactose formula could be useful in treating chronic diarrhea and secondary protein intolerance.

71. CHRONIC NON-SPECIFIC DIARRHEA OF INFANCY-SUCCESSFULLY TREATED WITH TRIMETHOPRIM-SULFAMETHOXAZOLE

18 children who fullfilled the criteria of chronic non-specific diarrhea of infancy were evaluated for intestinal bacterial overgrowth as a cause of their diarrhea. The children were randomized into group I (n=10), who were treated with trimethoprim-sulfamethoxazole (TMX) and group II (n=5>, three children were excluded because of Yersinia enterocolitica infection) treated with low lactose diet only. The aim of the study was to investigate whether colonization of the small intestine with upper respiratory tract microflora was related to the diarrhea and if treatment with TMX resolved the diarrhea.

Morphometric studies and eosinophil cell counts in the duodenal mucosa of children with chronic nonspecific diarrhoea and cow's milk allergy.

Morphometric studies and eosinophil counts in the lamina propria of the duodenal mucosa have been performed in patients with chronic nonspecific diarrhoea and with persistent diarrhoea due to a cow's milk allergy, using a semiautomatic image analysing system. The results have shown that the mean eosinophil count was significantly higher in both of these groups of patients compared with a control group (p less than 0.001), and some of the patients with chronic nonspecific diarrhoea had partial villous flattening. These findings in patients with chronic nonspecific diarrhoea could be related to the pathogenesis of this disorder.

Morphometric Studies and Eosinophil Cell Counts in the Duodenal Mucosa of Children With Chronic Nonspecific Diarrhoea and Cow's Milk Allergy

SummaryMorphometric studies and eosinophil counts in the lamina propria of the duodenal mucosa have been performed in patients with chronic nonspecific diarrhoea and with persistent diarrhoea due to a cow's milk allergy, using a semiautomatic image analysing system. The results have shown that the mean eosinophil count was significantly higher in both of these groups of patients compared with a control group (p < 0.001), and some of the patients with chronic nonspecific diarrhoea had partial villous flattening. These findings in patients with chronic nonspecific diarrhoea could be related to the pathogenesis of this disorder.

APPLE JUICE: INCOMPLETE ABSORPTION, BUT OF WHICH CARBO HYDRATE?

Apple juice (AJ) is a popular drink in toddlers. Due to the wide-spread belief that it has an anti-diarrhoeal effect, it frequently is advocated in case of chronic diarrhoea. Recently, however, it has been suggested that AJ promotes diarrhoea in toddlers either due to fructose (F) or to sorbitol (S). AJ contains about 60g/l of F, 20g/l of glucose, and possibly up to 10g/l of S. Aim of this study was to investigate the incidence of incomplete absorption of AJ carbohydrates and to identify the responsible carbohydrate, using breath hydrogen (BH) tests. Methods. We studied 10 children, 7 without and 3 with chronic nonspecific diarrhoea (CNSD), all AJ consumers, ages l-4½y. BH tests were done with 150-250ml of AJ. In 7 (2 CNSD), tests were repeated with F (10g); in 4/7 (1 CNSD) also with S (5g). BH increase >10ppm indicated positive (+ve) tests. Results. AJ tests were +ve in 5/7 controls (20-55ppra) and in all 3 CNSD patients (42-69ppm). In addition, 2/5 controls and 2/2 CUSD patients had +ve F tests (16-55ppm). The 3 controls with negative F tests had +ve S tests (16-29ppm); one CNSD patient had a negative S test. Actual S content of AJ (assessed by GLC) was 4.3g/l. In the CNSD patients, stools became normal after AJ elimination. Conclusions. These results indicate that AJ absorption frequently is incomplete in toddlers and may result in CNSD, and that neither F nor S can be held solely responsible for this phenomenon.

Well‐Compensated Primary Bile Acid Malabsorption Presenting as Chronic Nonspecific Diarrhea

SummaryIncreased fecal bile acid loss and defective in vitro ileal bile acid uptake were demonstrated in an 8‐year‐old boy with diarrhea starting in the neonatal period. His continuously normal physical development and good nutritional status are in keeping with a well‐preserved cholic acid pool and normal duodenal bile acid concentration. Isolated bile acid malabsorption can remain well compensated and present as the chronic nonspecific diarrhea syndrome of childhood.

Chronic diarrhea associated with hypogammaglobulinemia and enteropathy in infants and children.

In order to define the gastrointestinal manifestations and small intestinal structure and function in a group of infants with chronic nonspecific diarrhea and hypogammaglobulinemia, we retrospectively identified 55 such patients from a population of 518 children evaluated for chronic diarrhea over a 6-year span (10.6%). All patients had IgG levels 2.0 SD or more below the mean values for age. Patients with biochemical evidence of protein loss (enteropathy or nephropathy) were excluded. There was a 50% incidence of small intestinal mucosal injury among these patients, with a spectrum of morphological findings ranging from healing enteritis to severe active enteritis. Carbohydrate malasorption, and infection with Giardia lamblia or Clostridium difficile occurred in 34% and 24% of patients tested, respectively. These structural, functional, and infectious complications were all statistically more common in patients than in a control group of children with chronic diarrhea, normal growth, and normal immunoglobulin levels. This study suggests that immunoglobulin determination, in children who would otherwise carry a diagnosis of chronic nonspecific diarrhea, identifies a group with hypogammaglobulinemia, having an increased incidence of treatable intestinal dysfunction or infection, and a spectrum of small intestinal histologic abnormalities.

Apple juice. An unappreciated cause of chronic diarrhea.

Chronic nonspecific diarrhea (CNSD) remains a common pediatric problem. Previous reports have suggested disordered small intestinal motility, food intolerances, dietary fat restriction, and excessive fluid consumption as possible contributory factors. We have recently encountered a subset of children with CNSD in whom nonexcessive apple juice intake seemed to cause their diarrhea. In five subjects, ingestion of 240 mL of apple juice disclosed evidence of significant carbohydrate malabsorption by breath-hydrogen testing and resulted in diarrhea. Withdrawal of apple juice from the diets of these subjects was curative in all cases. Before embarking on an expensive and time-consuming evaluation for CNSD in otherwise healthy children, a brief restriction of apple juice intake may be warranted.

Chronic protracted diarrhea of infancy: A nutritional disease: Lo CW, Walker WA. Pediatrics 1983; 72:786–800

?? CHRONIC PROTRACTED DIARRHEA OF INFANCY: A NUTRITIONAL DISEASE, Lo CW, Walker WA. Pediatrics 1983; 72:786-800. Diarrhea1 disease is an extremely common cause of morbidity in infancy. Although its impact is especially severe in children of underdeveloped countries, in industrialized countries the mortality for infants hospitalized with diarrhea still exceeds 1%. Stool weight, consistency, and frequency are not reliable guides to etiology. Clinical findings of dehydration, malabsorption, and failure to thrive are easily recognized and require careful management. The majority of cases of intractable diarrhea seen in this country are due to postinfectious diarrhea, cow’s milk allergy, giardia and parasites, and celiac sprue. Chronic nonspecific diarrhea is easily distinguished from intractable diarrhea by the absence of malabsorption characteristics and dehydration. More common in the first 30 months of life, it is thought to be the childhood counterpart of irritable bowel syndrome and has psychologic overlay. Postinfectious and viral diarrhea are probably the most common causes of intractable diarrhea. Rotavirus has been found in 40% to 70% of infants with gastroenteritis. Bacterial pathogens (Shigelia, Salmonella, Escherichia coil) are found in 4% to 33Vo; the virulence of these agents is due to their invasiveness of the bowel mucosa. Cow’s milk allergy usually occurs before the age of 6 months and is felt to be due to an antigenic response to the milk protein, leading to villous atrophy. Symptoms resolve on milk-free formulas. Giardiasis occurs frequently in some parts of the United States. Most infections are asymptomatic. The degree of malabsorption and steatorrhea does not correlate with the number of parasites or severity of mucosal injury. Entamoeba histolytica, Strongyloides, and Ascaris are other causes of parasitic diarrhea. Celiac sprue, a toxic reaction to gluten, causes mucosal atrophy, crypt hyperplasia, and malabsorption. Gluten-free diets are essential to prevent growth failure. Treatment. of diarrhea includes glucose and electrolyte repletion. The inherent danger of standard electrolyte solutions is calorie and protein starvation after several days. Dehydration and failure to thrive require hospitalization and electrolyte replacement to break the cycle of malabsorption, failure to heal mucosal damage, and further wasting. [Ramon Pabalan, MD] Editor’s Note: Although not emphasizing emergency department diagnosis and treatment, . this article is an excellent review of the etiology and pathogenesis of chronic diarrhea in infancy.

Prevalence of attention deficit disorder, residual type, and other psychiatric disorders in patients with irritable colon syndrome.

On the basis of the observations that chronic nonspecific diarrhea is a precursor of irritable colon syndrome and that chronic nonspecific diarrhea is associated with attention deficit disorder in childhood, the authors conducted a psychiatric diagnostic evaluation of 22 adults with irritable colon syndrome. Six (27%) of the patients received a diagnosis of attention deficit disorder, residual type, six (27%) were diagnosed as having dysthymic disorder, and five (23%) had had episodes of unipolar depression. The relationship between the presence of these disorders and greater severity of irritable colon syndrome was statistically significant.

Excessive fluid intake as a cause of chronic diarrhea in young children

An increased incidence of chronic nonspecific diarrhea has been coincident with popularization of orally administered fluid-electrolyte therapy for management of diarrhea, and led up to postulate than an increase in fluid intake might be related to this increased incidence. Of 105 referred patients, 85 were found to have no clinical or laboratory evidence of malabsorption. Forty of these patients had characteristic features of CNSD: diarrhea for at least three weeks, normal growth, and no evidence of enteric pathogens. An outpatient study evaluated fecal output, dietary energy-protein intake, and nonprotein fluid intake. Patients were separated into two groups whose fluid intakes were highly different: group A, 196 +/- 32 ml/kg/day, and group B, 91 +/- 15 ml/kg/day (P less than 0.001). The nonprotein fluid intake was then reduced to 90 ml/kg/day with no change in diet. Evaluation at two weeks and again at six to eight weeks showed a decrease in stool frequency (from four to ten per day to zero to three per day) and increase in stool consistency in all patients in group A, but no significant change in stool patterns in group B. Our findings suggest a cause-and-effect relationship between excessive fluid intake and some cases of CNSD.

Chronic Nonspecific Diarrhea in Children

Investigations by scanning electron microscopy into changes of surface morphology of small bowel ***nucosa in children with chronic nonspecific diarrhea are reported. The study population comprised 56 patients, ranging in age from 5 months to 7 years: 65% were between 10 and 28 months old, and 64% of the patients were boys. The major findings were: microorganisms on he mucosal surface: excessive extrusion of cell cytoplasm and of enterocytes (cell shedding): presence of excessive mucus on the mucosal surface: damage to the brush border; and partial villous atrophy. The latter lesion was found in only four patients. All these changes are considered pathologic and, for the most part, are presumed to be due to the presence of antigens, in particular, nicroorganisms. A depression of disaccharidase activities was encountered in 64% of the patients, but prevalence was without regard to age. Most common was a combined depression of lactase, sucrase, and maltase, as well as an isolated depression of lactase. The possibility has to be considered that enteroadherent microorganisms which are usually not considered pathogenic, and microorganisms such as Mycoplasma, may emerge as intestinal pathogens in susceptible children. It is feasible that genetic traits of the host and environmental factors facilitate adherence and colonization of the small bowel mucosa which, in turn, produces chronic diarrhea. Further studies are needed to confirm the preliminary information contained in this report.

Use of Psyllium in the Management of Chronic Nonspecific Diarrhea of Childhood

SummaryThe etiology and treatment of chronic nonspecific diarrhea of childhood is still poorly understood. We evaluated 23 children with this disorder in whom other etiologies of chronic diarrhea had been ruled out. The children were treated first with an unrestricted diet for 1 week, and if no response was obtained they were then treated with psyllium bulk agents for 2 weeks (1 tablespoon b.i.d.). Eighty‐seven percent of the patients responded to therapy. Seven patients responded to an unrestricted diet only, and 13 responded to psyllium. Only three patients (13%) did not respond. Most children were on a restricted diet at presentation, but the amount of dietary fat intake did not correlate with the response, contrary to other reports. Treatment with normalization of the diet and psyllium bulk agents seems to be an effective mode of therapy for chronic nonspecific diarrhea of childhood.