Chronic diarrhea in children

Acute diarrhea is a leading cause of under-five mortality in developing countries like India. Most of the diarrheal episodes recover within 14 days. However in certain cases acute diarrhea may last for more than 14 days in which it is termed as persistent diarrhea if presumed to be of infectious origin. Various malabsorptive syndromes due to carbohydrate, fat and protein malabsorption can result in chronic malnutrition in a child. This entity is known as chronic diarrhea. Correspondence to: Dr. Mohit Kehar, Clinial Fellow, Division of Pediatric Gastroenterology, hepatology, Nutrition and Transplant, Hospital for Sick Children, University of Toronto Toronto, Canada; E-mail: [email protected] Received: April 07, 2016; Accepted: May 09, 2016; Published: May 13, 2016 Definitions Diarrhea is defined as stool volume >10 g/kg per day in infants and toddlers, and >200 g/day in older children. [1]. Persistent diarrhea is an episode of diarrhea which is of presumed infectious etiology, which starts acutely and it lasts for more than 14 days. Chronic Diarrhea is one which lasts for more than 14 days, is usually noninfectious and associated with malabsorptive features. Epidemiology The exact incidence of chronic diarrhea is not known in India, however large-scale studies indicate that the prevalence of chronic diarrhea illnesses worldwide ranges from 3% to 20%, and the incidence is around 3.2 episodes per child year [2]. The causes of chronic vary amongst different age of children . In an Indian study on 137 children with chronic diarrhea, celiac disease was most common causes accounting for 26%, parasitic infections in 9% and tuberculosis in 5% of children [3]. Patho-physiology The basic patho-physiology is incomplete absorption of water from the intestinal lumen either because of a reduced rate of net water absorption (related to impaired electrolyte absorption or excessive electrolyte secretion) or because of osmotic retention of water in the lumen. It is seen that reduction of net water absorption by as little as one percent may be sufficient to cause diarrhea [4]. Hence even modest compromise of absorptive function can lead to loose stools and many conditions can be associated with diarrhea, the frequencies and characteristics of which vary depending on age and socioeconomic status. Osmotic diarrhea is caused by a failure to absorb a luminal solute and hence osmotic retention of water in the lumen. It can be seen because of dissacharidase deficiencies or because the absorptive capacity of the intestine for that sugar may be overwhelmed by excessive consumption [5], eg, fructose and sorbitol. It is seen in young children with excessive intake of simple sugars like fruit juices. Disaccharides deficiencies, such as lactase deficiency are usually seen as a result of gut mucosal injury secondary to some process later in infancy, like acute enteritis (bacterial/ viral). The osmotic diarrhea usually cease when the offending dietary nutrients are removed or after fasting within 24 hours. On the contrary secretary diarrhea occurs when there is a net secretion of electrolyte and fluid from the intestine. Children with a pure secretary diarrhea will continue to experience diarrhea even while fasting. Examples include multiple congenital diarrheal disorders associated with identified genetic mutations that affect gut epithelial ion transport like congenital chloride diarrhea (Table 1). Common causes of chronic diarrhea in children Causes of chronic diarrhea can be divided into following subgroups (Table 2). Infections Infective causes: Infective causes of chronic diarrhea can be seen in any age and common organisms implicated includes Salmonella, Yersinia, E.coli, Campylobacter, Aeromonas, Plesiomonas, Giardia, Cryptosporidium, viral causes (Rota, Entero, Norwalk). They have associated fever, abdominal pain, exposure history, blood/mucus in stool. The protozoa Giardia intestinalis may affect immunocompetent as well as immunodeficient children and adolescents. The resultant infection affects the duodenum and upper small bowel, leading to mild villous blunting, dissacharidase deficiency, and resultant osmotic and secretory diarrhea. Infections are linked to contaminated food and water. Many such outbreaks may occur in childcare centers. Microscopic examination of a freshly passed stool on three consecutive Secretary diarrhea Osmotic diarrhea Volume of stool >200 ml/24 hr <200 mL/24 hr Response to fasting : Diarrhoea continues Diarrhoea stops Stool Na : >70 mEq/L <70 mEq/L Reducing substances: Negative Positive Stool pH >6 <5 Stool osmotic gap {Stool osmolarity – 2(stool Na + K )} : < 100 >100 Table 1. Difference between osmotic and secretary diarrhea. Kehar M (2016) Chronic diarrhea in children Volume 1(2): 40-43 Gastroenterol Hepatol Endosc, 2016 doi: 10.15761/GHE.1000110 days is recommended for detection of Giardia trophozoites. Giardiasis should be treated with metronidazole, tinidazole, or nitazoxanide. Emphasis should be laid on maintenance of health and hygiene especially cleans portable drinking water. Small bowel bacterial overgrowth: Overgrowths of aerobic and anaerobic bacteria in the small bowel like in condition as in short bowel syndrome, bowel strictures, pseudo-obstruction, malnutrition. There is enhanced bile acid deconjugation and fatty acid hydroxylation by bacteria. The patients present with abdominal pain and diarrhea. Whipple’s disease: Whipples disease is caused by Gram +ve bacteria: Tropheryma whippelii. The patients have Malabsorption, central nervous system, joints and cardiovascular involvement. It is a rare condition and carries a poor prognosis. Tropical sprue: It is a rare condition in children and coliform organisms are implicated in its etio-pathogenesis. Abnormal digestive processes Cystic fibrosis: In Cystic fibrosis diarrhea occurs as a result of pancreatic insufficiency. Ninety percent of patients suffering from cystic fibrosis have pancreatic insufficiency [6]. The patient suffering from cystic fiboris has repeated chest infections, abdominal bloating along with passage of large greasy rotten smelling stools with failure to thrive Sweat chloride estimation is done for screening and mutation studies are diagnostic. Other rare causes like Shwachman Diamond syndrome, Pearson syndrome, JohansonBlizzard Syndrome Nutrient malabsorption Carbohydrate malabsorption: Carbohydrate malabsorption is seen in condition like intestinal lactase deficiency which can be congenital, adult-onset and secondary lactase deficiency. Congenital lactase deficiency is rare entity. Adult onset is extremely common and ‘normal’ for most humans and has racial distribution being common among Asians. Secondary lactase deficiency is seen after infectious gastroenteritis or injury to small intestinal mucosa caused by gluten or other sensitizing substances. Lipid malabsorption: Lipid malabsorption is seen in diseases like cystic fibrosis, Shwachman Diamond syndrome, Pearson syndrome, JohansonBlizzard Syndrome, celiac disease, cholestatic liver disease, beta lipoprotenemia , lymphangectasia and short bowel syndrome. Protein malabsorption: Protein malabsorption is seen in condition like pancreatitis, cystic fibrosis, trypsionogen deficiency, enterokinase deficiency, hartnup disease, lymphangectasia, lowes syndrome and lysinuric protein intolerance. Immune and inflammatory Celiac disease: Celiac disease is an immune-mediated systemic disease that occurs in the setting of gluten ingestion in a genetically susceptible individual. It is very common in India, especially in North India with prevalence approaching 1% [7]. It is most common cause of chronic diarrhea and malabsorption in more than 2 years age group patients [8]. The typical presentation of celiac disease in children is failure to thrive, diarrhea and abdominal distension. However, the presentation of disease seems to have changed over the past few years. The typical presentation is now seen in less than 50% of newly diagnosed cases of Celiac disease. Diagnosis should begin with establishing the presence of anti-tissue transglutaminase antibody/anti endomyseal antibody and is confirmed by histologic findings in the duodenum which is graded according to Marsh Criteria. The management of celiac disease is lifelong restriction of food containing gluten in diet which includes wheat, rye, and barley. Multivitamin and mineral deficiency should also be managed appropriately. Cow’s milk protein allergy (CMPA): Cow’s milk protein allergy present in first yr of life, but may preset up to two years of age. The child present with streaks of blood and mucus in stool, in otherwise healthy infant. It typically occurs in child on top milk, however 0.5% may present in exclusive breast fed infants. CMPA is increasing being recognised in India over past decade [9]. The disease can be IgE and non IgE medicated, most of the gastrointestinal symptoms are non Ig mediated. Double blinded placebo control trial is diagnostic for the disease, however it is cumbersome and an open challenge is done in practice [10]. In open challenge the patient is advised to stop all milk and milk products and is started on extensively hydrolysed formulae for 4-6 weeks and after improvement of symptoms the child is challenged with normal milk, if the symptoms reappear it confirms the diagnosis. Treatment is extensively hydrolysed formulae (eHF) or amino acid based formulae. In exclusive breast fed infants below 6 months of age, the mother is stopped of all milk and milk products and breast feeding is continued. Soy protein–based formula may be an option in infants older than 6 months who do not accept the bitter taste of an eHF, or in cases in which the higher cost of an eHF is a limiting its factor, provided that the tolerance to soy protein has been established [10]. Inflammatory bowel disease: Inflammatory bowel diseases (IBD) can present in children and adolescents with chronic diarrhea with passage of blood or mucus in stools. The child can have weight loss, anemia, tenesmus, joint pains, and redness of eyes. In Crohn’s disease, stool may contain microscopic blood but may not be grossly bloody. In ulcerative colitis, diarrhea is a more consistent presenting feature. The patients will have raised inflammatory markers like ESR, CRP, Platelet counts, and low albumin. Evaluation involves hematological markers, serology, upper GI endoscopy and colonoscopy. Treatment includes anti-inflammatory agents like steroids, 5ASA, Azathioprine etc. Autoimmune enteropathies: Autoimmune enteropathies are rare disorders that may present as severe diarrhea during infancy or toddlerhood. The diarrhea may be isolated, or may occur in association with diabetes mellitus as part of the IPEX syndrome. Immunodeficiency: Patient with chronic diarrhea should be evaluated for primary or secondary immunodeficiency such as HIV disease. In this case, the evaluation should focus on potential infectious Infective Due to exogenous substances Abnormal digestive processes Nutrient malabsorption Immune and inflammatory Structural defects Defects of electrolytes and metabolite transport Motility disorders Neoplastic Chronic non specific dirrhoea Table 2. Causes of chronic diarrhea. Kehar M (2016) Chronic diarrhea in children Volume 1(2): 40-43 Gastroenterol Hepatol Endosc, 2016 doi: 10.15761/GHE.1000110 causes of the diarrhea, particularly parasites and opportunistic infections such as Cryptosporidium, Isospora, and Cyclospora [10]. Structural defects: These include disease like tufting enteropathy, microvillous inclusion disease , phenotypic diarrhea, lymphangiectasia, intergrin deficiency, heparan sulphate deficiency. These are rare diseases and cause neonatal diarrhea and carries a poor prognosis. Defects with effects of electrolytes of electrolytes and metabolite transport: It includes congenital chloride diarrhea (CCD) and congenital sodium diarrhoea (CSD), these disorders cause secretary diarrhea and present in 1-2 week of life and carry a poor prognosis. Chronic non specific diarrhea Chronic non specific diarrhea of infancy/Toddler’s diarrhea: Toddler’s diarrhea is most commonly seen in first 3 years after birth. It present with varied stool frequency and consistency without blood or mucus and stool contain undigested food particles. There is no failure to thrive and treatment includes decreased fruit juices (fructose) and reassurance along with liberalization of fat to encourage normal caloric intake and to slow intestinal transit time is also important [12]. Monitoring growth parameters in child with chronic diarrhea is important as disease like toddler’s diarrhea have normal growth parameters. Neoplastic causes: Neoplastic causes of chronic diarrhea are rare and includes diseases like gastrinoma, vipoma, mastocytosis, zollinger ellison syndrome, pheochromocytoma, lymphoma. Motility disorders Hirschprung’s disease Hirschprungs disease may present enterocolitis and diarrhea, and may progress to life-threatening toxic megacolon. Infant presents with history of delayed passage of meconium, constipation, failure to thrive. Per rectal examination will reveal a empty rectum and gush of air and stool following withdrawal of finger. Infants with Hirschsprung’s disease should be evaluated promptly with abdominal plain films, barium contrast studies and/or rectal suction biopsies.