Table 12.7:"Red ag’ signs or features that init ina child with abdominal pain Pain localized away from umbilicus in right upper or lower quadrant Noctural pain Failure to thrive; weight loss significant vornting; biious vomiting Gastrointestinal blood loss Chronic diarrhea Persistent fever Jaundice ‘tts; rash Dysphagia Secondary amenortea Family history of inflammatory bowel disease Examination: Anemia, clubbing, edema, tenderness oF mass covganomegaly, perianal fitlaefags ‘Abnormal laboratory testing: Low hemoglobin, elevated CRP and, ESR, occult blood in stool, raised fecal calprotectin, ‘Among the various types of functional pain mentioned above, FAP-NOS is the most common. When evaluating fa child with abdominal pain, efforts should be made to differentiate functional from organic causes. The history should include not only details of pain but also family details, child’s emotional environment in home and school, personality, coping skills, school performance and stress factors. The presence of ‘red flag’ signs (alarming symptoms and signs) (Table 12.7) increases the probability of an organic disorder and justifies further diagnostic testing as per the likely diagnosis. Only limited investigations like hemogram, inflammatory markers (ESR/CRP), urine examination and stool for ova/parasite are needed for patients with suspected functional pain disorders. Fecal calprotectin may be done in select cases; normal levels ‘suggest functional pain. Abdominal ultrasonography is not helpful and the presence of small mesenteric lymph nodes (<10 mm in short axis) is not a cause of concern. ‘The aim of management of children with FAP-NOS is to make a positive diagnosis, normalize the lifestyle to not allow pain to curtail daily activities or school performance, and to rectify psychological factors. The crux of management is counseling the parents and the child, both jointly and separately. Parents need to be reassured about the benign nature of the ailment and emphasis is laid upon avoiding too much attention to the child. The concept of visceral hyperalgesia should be explained to parents. Provision of a nutritious diet with adequate fiber and avoiding intake of carbonated beverages and refined food helps in reducing bloating, The role of amitriptyline and hypnotherapy is restricted to refractory cases. Suggested Reading 1. Andrews ET, Beattie RM, Tighe MP. Functional abdominal pain: ‘what clinicians need to know Arch Dis Child 2020; 105: 938-44. 2. Koppen IIN, Nurko S, Saps M, et al. The pediatric Rome IV criteria, Expert Rev Gastroenterol Hepatol 2017; 1:193-201, 3, Raymond M, Marsicovetere P, DeShaney K. Diagnosing and ‘managing acute abdominal pain in children. JAAPA2022:35:16-20, 4,Uc A, Husain SZ. Pancreatitis in children. Gastroenterology 2019;156:1969-1978. Competencies: PE2S.1; PE24.2; PE24.3; PE24.4 PE24.5;PEZ4.8; PERG; 24.10; PE24.14; PED7.23 ey Diarrhea is defined as.a change in consistency and frequency of stools, ie. liquid or watery stools, that occur >3 times a day. In the vast majority of cases, these acute episodes subside within 7 days. If there is associated blood in stools, it is termed dysentery. Acute diarthea may persist for >2weeksin5-15% cases, which is labeled as persistent diarrhea. ‘The global annual burden of diarrhea is huge, affecting 17 billion cases every year and accounting for ~11% of all childhood deaths world-wide. The two most important consequences of diarzhea in children are malnutrition and dehydration. Malnutrition and diarthea form a vicious cycle, since malnutrition increases the risk and severity of diarrhea. Impaired absorption, loss of nutrients, increased catabolism and improper feeding in diarrhea aggravate the severity of malnutrition. A child may lose as much water and electrolytes from the body during an episode of diarrhea as an adult, which translates into a higher proportion of total body water loss in the child. Significant dehydration with abnormal electrolyte and acid-base status occurs in 2-5% of cases of diarthea, which may be fatal Etiology Intestinal infections are the most common cause of acute diarrhea (AD). However, certain drugs, food allergy, systemic infections (e.g. urinary tract infection and otitis media) and surgical conditions (e.g. appendicitis or Hirschsprung disease) can also present as AD. Causative agents of AD (Table 12.8) can be identified in nearly “able 12.8: Causes of acute diarrhea a. | Bacterial + Escherichia col: Enterotoxigenic, enteropathogenic, entero- invasive", enterohemorshagic* and enteroaggregative types + Shigella: S, sonnei, 5. flexneri, S. boyd and S. dysenteriae + Vibrio cholerae serogroups O1 and 0139 + Salmonella: Chiefly 5. typhi and S.paratyphi A, B or C + Campylobacter species* Viral + Rotavieus + Human caliciviruses: Norovirus spp; Sapovirus pp. + Enteric adenoviruses serotypes 40 and 41 + Others: Astoviruses, coronaviruses, cytomegalovins, pcomavis Parasitic + Giardia lamblia + Cryptosporidium parvum + Ftamoeba histolytica + Cyclospora cayetanensis + Isospora bell “Cause dates with or withou dysentery pe BO Diseases of Gastrointestinal System and Liver70-80% episodes. Rotavirus remains the leading cause of severe, dehydrating gastroenteritis worldwide. In India, rotavirus and enterotoxigenic E. coli account for nearly half of the diarrheal episodes among children. In rotavirus diarthea, vomiting is an early feature and diarrhea is more severe. Cholera accounts for 5-10% cases; it is endemic in some parts and may occur in outbreaks. In cholera, stools are like rice water, vomiting is common and severe dehydration occurs rapidly within hours. Apart from enterotoxin producing E. coli (TEC), which accounts for nearly 20% of childhood diarthea, enteroinvasive E. coli (EIEC) and enterohemorthagic E. coli (EHEC) can cause dysentery. EHEC may also cause hemolytic uremic syndrome. Shigella and Salmonella species are isolated in 3-7% of childhood diarrheas. Shigella accounts for majority of cases of dysentery whereas Entamoeba histolytica accounts for only 5% ofdysentery. Giardia lamblia rarely causes AD. Infection with Candida albicans can cause AD in patients 2 With malnutrition, immunocompromised state or after prolonged antibiotic treatment. Clostridium dificile should be suspected in patients who have received broad-spectrum z antibiotics. SS Pik Factors © Factors determining susceptibility to diarrhea include 5 poor sanitation and personal hygiene, non-availability B of safe drinking water, unsafe food preparation practices 4 and low rates of breastfeeding and immunization. Young (<2 years) and malnourished children are more susceptible to AD, and tend to have severe and prolonged episodes. Other risk factors for prolonged and recurrent episodes of diarrhea include hypo- or achlorhydria (due to Helicobacter, pylori infection or therapy with proton pump inhibitors) and immunodeficiency (selective IgA deficiency, HIV, etc) Pathogenesis and Clinical Features Approximately 60% of a child’s body weight is water, present in two fluid compartments—extracellular fluid (ECF) and intracellular fluid (ICF). The ECF includes circulating blood, intestinal fluid and secretions. Diarrheal losses come from ECE, which is relatively rich in sodium and has low potassium. Loss of water from the body causes a reduction or shrinkage of ECF volume. In half of these cases, the concentration of sodium in the plasma remains nearly normal (about 140 mEq/L); in another 40-45% cases, excessive sodium is lost in the stools leading to a relative decline in serum sodium (hyponatremia) and a fall in ECF osmolality. This causes movement of water from the ECF to ICF compartment, causing further shrinkage of, the already reduced extracellular compartment volume in hyponatremic dehydration. In about 5% cases of diarrhea, especially if the child has been given fluids with extra salt, serum sodium increases to >150 mEq/L and ECF ‘osmolalilty is also increased. Normaily, skin turgor or elasticity is maintained by tissue water and fat. Shrinkage of extracellular water in both hypo- and isonatremic dehydration impairs skin elasticity. On pinching, it takes a few seconds for the skin fold toreturn to normal. In patients with hypernatremic dehydration, water moves from inside the cells to the ECF compartment due tothe increased osmolality of ECE, and therefore, partially masks the loss of skin turgor. The skin appears soggy, doughy or leathery. Thus, a severe case of hypernatremic dehydration is likely to be erroneously underestimated as mild dehydration, unless severe sequelae of dehydration such as circulatory or renal impairment are noted. ‘As the ECF compartment is depleted, the blood volume is reduced. This results in a weak, thready pulse, low blood pressure and cold extremities. Because of low hydrostatic pressure, the filtration of urine is reduced. This is ominous because poorly functioning kidneys cannot regulate metabolic derangements. Urine flow is a good indicator of the severity of diarthea. Severe cases are associated with acute kidney injury. Diartheal stools contain large amounts of potassium. Therefore, serum potassium invariably falls, if diarthea persists for more than a few days. Thisis more pronounced in children with severe malnutrition with already depleted potassium stores. Affected children present with abdominal distension, paralyticileus and muscle hypotonia. Electrocardiogram may show ST depression and flat ‘Twaves, Since intestinal secretions are alkaline, considerable bicarbonate is lost in diarrheal stools and acidosis usually accompanies dehydration. Patients remain asymptomatic till the base excess falls to 12 mEq/L. Below this level, breathing becomes deep and rapid (Kussmaul breathing). The child is thirsty and slightly irritable in early and mild cases of diarrhea. As the diarrhea continues and dehydration worsens, the child becomes more irritable with depressed fontanelle (if open), sunken eyes and dry tongue and the inner side of cheeks. Abdomen may become distended in hypokalemia. As acidosis worsens, the breathing becomes deep and rapid. In extreme cases, the child appears moribund, with weak and thready pulses, low blood pressure and oliguria. ‘Assessment of Child with Acute Diarrhea Goals of assessment: These are to: (i) determine the type of diarthea, ie. acute watery diarrhea, dysentery or persistent diarrhea; (i) look for dehydration and other complications; (ii) assess for malnutrition; (iv) rule out non-diarheal illness especially systemic infection; and (v) assess feeding, both pre-iliness and during illness. History: This should include information on: (i) Onset of diarrhea—duration and number of stools per day; i) blood in stools; (ii) number of episodes of vomiting: (iv) presence of fever, cough, or other significant symptoms (eg. convulsions, recent measles); (v) type and amount of fluids (including breast milk) and food taken during the illness and pre-illness feeding practices; (vi) drugs or other local remedies taken (including opioids or anti- motility drugs like loperamide that may cause abdominal distension); and (vii) immunization history. Examination: The most important assessment is for dehydration. The degree of dehydration is assessed as per Table 12.9. One should look at the child’s general condition and sensorium (alert, restless, irritable,Table 12.9: Assessment of dehydration in patients with diarthea Look at Condition’ Well alert Eyes Normal Sunken Tears Present Absent Mouth and tongue! Moist Dy Thirst Drinks normally; not thirsty Feel ‘kin pinch* Goes back quickly Decide ‘The patient has no signs of dehydration Treat Use treatment Plan A. Restless, initable Thirsty, drinks eagerly Goes back slowly lf the patient has two or more signs, there is some dehydration ‘Weigh the patient, if possible, and Use treatment Plan B Lethargic or unconscious; floppy Very sunken and dry Absent Very dey ‘Drinks poorly’ or isnot able to drink Goes back very slowly lithe patient has two or more signs, there is severe dehydration Weigh the patient and use treatment Plan C urgently "lethargic childs not simply asleep; the child cannot be fully awakened; hasa dll metal state andthe child may appear tobe criting into unconsciousness. 2in some infants and children, the eyes normally appear somewhat sunken, Its helpful to ask the mather, ifthe child’ eyes are normal or more sunken than usual "Dryness of the mouth and tongue can also be palpated with a clean finger. The mouth may be dry ina child who habitually breathes through the mouth “The mouth may be wet ina dehycated child owing to recent vomiting or dinking, “The skin pinch is less sel in infants or children with marasmus (severe wasting), kwashiorkor (severe malnutition with edema) and in obese children lethargic or unconscious). Other assessments include appearance of eyes (normal or sunken) and the ability to drink water or ORS solution (normal, taken eagerly, refused or unable to drink due to lethargy or coma). Dehydration is assessed by feeling for skin turgor; following pinching, the abdominal skin may flatten immediately, go back slowly or return very slowly (more than 2 seconds). Based on the degree of dehydration after history and examination, the estimated fluid loss is calculated as follows: Degree of dehydration Assessment of fluid loss No dehydration <50 mUkg Some dehydration 50-100 mLikg, Severe dehydration 100 mL/kg In addition, we look for features of malnutrition and for for systemic infection. Laboratory investigations: Most episodes of acute diarrhea can be managed even in absence of laboratory investigations. Stool microscopy is not helpful except in selected situations, such as cholera (darting motion suggests Vibrio cholerae) and giardiasis (trophozoites). Stool culture is of little value in routine management. It helps decide ‘on antibiotic therapy in patients with Shigella dysentery who do not respond to initial antibiotics. Tests for stool pH and reducing substances are not indicated routinely. Hemogram, pH, bicarbonate, electrolytes and renal function tests are performed, only if the child has pallor, labored breathing, altered sensorium, seizures, paralytic ileus or oliguria. Principles of Management Management of acute diarrhea has four components: (i) Rehydration and maintaining hydre feeding; (ii) oral supplementation of zinc; and (iv) early recognition of danger signs and treatment of complications. The cornerstone of management is the use of oral rehydration solutions. The dehydration status is classified asno dehydration, some dehydration or severe dehydration and appropriate treatment is started. Physiological Bosts for Oral Rehydtration Therapy In most cases of acute diarrhea, sodium and chloride are actively secreted from the gut mucosa due to pathogen- induced dysfunction of several actively functioning absorption pumps. However, glucose dependent sodium pump remains intact and functional, transporting one molecule of glucose and dragging along a molecule of sodium and of water across the intestinal mucosa resulting in repletion of sodium and water losses. ‘The glucose dependent sodium and water absorption is the principle behind replacing glucose and sodium in 1:1 molar ratio in the WHO oral rehydration solution (ORS). An important consideration in making ORT is that the osmolarity of the replacement fluid should not exceed that of blood (290 mOsm/L). Keeping the intestinal lumen at lower osmolarity as compared to blood allows for greater absorption of fluids into the bloodstream across concentration gradient, which also results in electrolyte absorption (by solvent drag). Since the concentration of glucose increases osmolarity, it is suggested that glucose concentration should not exceed 11 mmol/L. Meta- analyses have shown that use of low osmolarity ORS causes reduction of stool output, decrease in vomiting and reduced use of intravenous fluids, without increasing the risk of hyponatremia. For this reason, the recommendation for use of standard ORS (osmolarity of 311 mOsm/L) was changed to low osmolarity ORS (osmolarity of 245 mOsm/L). Since 2004, based on the WHO/UNICEF and LAP recommendations, the Government of India has adopted the low osmolarity ORS as the single universal ORS to be used for all ages and all types of diarrhea. The composition of the low osmolarity ORS is given in Table 12.10. In the i Diseases of Gastrointestinal System and Liver a maaaaaaaammmmcmmmmmaaaaalsTable 12.10: Compostion of WHO recommended ORS Constituent g/L Osmole or ion mimo Sodium chloride 2.6 Sodium 75 Glucose, anhydrous 13.5. Chloride 65 Potassium chloride 1.5. Glucose, anhydrous 75 Trisodium citrate, 2.9 Potassium 20 dihydrate Citrate 10 Total osmolarity 245. Table 12.1: Home available ids for acute arts Acceptable home available fuids Fluids that Salted drinks (e.g. salted rice water, yoghurt contain salt drink), vegetable or chicken soup with salt (preterred) 12 Fluids that do rot contain salt (acceptable) Plain water, water in which a cereal has been cooked (e.g. unsalted rice water), unsalted soup, yoghurt drinks without salt, green coconut water, weak unsweetened tea, unsweetened fresh fruit juice ‘Commercial carbonated beverages, commercial fruit juices, sweetened tea Unsuitablehome & available fluids Pediatrics § absence of WHO ORS, one may administer culturally acceptable appropriate homemade fluids (Fable 12.11). Oral 4 olutions should be given by a spoon or katori and in sips ‘orsmall volumes rather than a large volume at one time as this increases the retention of oral fluids. Treatment Plan A: Treatment of "No Dehyctration® Such children may be treated at home after explanation of feeding and the danger signs to the mother /caregiver. ‘The mother may be given WHO ORS for use at home as per Table 12.12. Danger signs requiring medical attention are continuing diarrhea beyond 3 days, increased volume/ frequency of stools, repeated vomiting, increasing thirst, decreased urine output, refusal to feed, fever or blood in stools. Treatment Plan B: Treatment of “some Dehydration” All cases with obvious signs of dehydration need to be treated in a health center or hospital. However, oral fluid therapy must be commenced promptly and continued during transport. Fluid requirement is calculated under the following three headings: i, Provision of normal daily fluid requirements: Up to 10 kg = 100 ml./kg, 10-20 kg = 50 mL/kg, >20 kg = Table 12.1 }: Guidelines for treating patients with some dehydration (Plan B). Table 12.12:Olrehyaton therapy to preven eye EA Age (ORS or other culturally ORS to provide for appropriate ORT fluids use at home after each loose stool <24mo 50-100 mL 500 mUday 2-10ye 100-200 mL 1000 muiday >1yr Adib 2000 mUday Explain use of ORS, ie. the amount to be given, how to mix. Give a teaspoonful every 1-2 min for a child under 2 years. Give frequent sips from a cup for an olde chile Ifthe child vomits, wat for 10 min. Then give the solution more slovy (lor ‘example a spoontul every 2-3 min) If diarrhea continues after the ORS packets ae used up, tll the mother to sive other fluids as described above or return for more ORS 20 mL/kg. As an example, the daily fluid requirement ina child weighing 15 kg, will be 1250 mL (first 10 kg, 10x 100 = 1000 mL; another 5 kg, 5 x 50= 250 mL, total 1000 + 250 = 1250 mL). Rehydration to correct the existing water or electrolyte deficits: Calculated as75 mL/kg of ORS, tobe given over 4 hours. IFORS cannot be taken orally, then nasogastric tube canbe used. Ifchild’s weight cannotbe taken, then only age may be used to calculate fluid requirement as showninTable 12.13.If,after4 hours, the child still has some dehydration, then another treatment with ORS (asin rehydration therapy) is to be given. This therapy is effective in 95% cases, Oral rehydration therapy may be ineffective in children witha high stool purge rate of >5mL/kgbody weight hr, persistent vomiting >3/hr, paralytic ileus and incorrect preparation of ORS (very dilute solution). iii, Maintenance to replace ongoing losses to prevent recurrence of dehydration: This phase should begin when signs of dehydration disappear, usually within 4 hours. ORS should be administered in volumes equal to diarrheal losses, usually to a maximum of 10 mL/kg per stool. Breastfeeding and semisolid food are continued after replacement of deficit. Plain water can be offered in between. Treatment Plan C: Children with "Severe Dehydration” Intravenous fluids should be started immediately using Ringer lactate with 5% dextrose. Normal saline or plain Ringer solution may be used as an alternative, but 5% dextrose alone is not effective. A total of 100 mL/kg of fluid is given, over 6 hours in children <12 months and over 3 hours in children >12 months as shown on page 315. Age Binge oe estima fii Ree PS Weight Sig slg pitkg U-I6kg «620K OS, mL aeooo 400-400 —~+-600-800—-600-1200-—~/ 1200-2200 >2200 Number of lasses 1-2 2 34 “6 on 12-20 ‘The approximate amount of ORS required in some dehydration is 75 mkg, When body weigh isnot known, the approximate amount of ORS solution to give inthe fist 4 hours is given according to age For infants under-6 months who are not breastfed, also give 100-200 ml clean water during this period Encourage breastfeeding Te iAge 30 mike 70 mukg <12z mo he Shr >i2 mo 30 mint 2s be ‘The above canbe repeated, if child continues to have feeble/non- palpable racial pulse (ORS solution should be started simultaneously, if the child can take orally. If TV fluids cannot be given (for reasons of access, logistic availability or during transport), nasogastric feeding is given at 20 mL/kg/hr for 6 hours (total 120 mL/kg). The child should be reassessed every 1-2 hours; if there is repeated vomiting or abdominal distension, the oral or nasogastric fluids are given more slowly. If there is no improvement in hydration after 3 hours, IV fluids should be started as early as possible. The child should be reassessed every 15-30 min for pulses and hydration status after the first bolus of IV fluid. Management following the first bolus of intravenous hydration is as follows: i. Persistence of severe dehydration: Intravenous infusion is repeated. fi, Hydration is improved but some dehydration is present: 1V fluids are discontinued; ORS is administered over 4 hours according to Plan B. There is no dehydration: IV fluids are discontinued; treatment Plan A is followed. The child should be observed for atleast 6 hours before discharge, to confirm that the mother is able to maintain the child's hydration by ORS. Unique problems in infants below 2 months of age: Breastfeeding must continue during the rehydration process, whenever the infantis able to suck. Complications like septicemia, paralytic ileus and severe electrolyte disturbance are more likely in young infants with diarrhea than at later ages. Diarthea in these infants should be ideally treated as inpatient by experienced physicians at treatment centers with appropriate facilities. This allows for careful assessment of need of systemic antibiotics and monitoring. Nutritional Management of Diarrhea Children with severe malnutrition (marasmus or kwashiotkor) are at an increased risk of acute diarrhea and its complications, such as severe systemic infection, dehydration, heart failure, vitamin and mineral deficiencies. Feeding should not be restricted in such patients as this aggravates complications and increases morbidity and mortality. Early feeding during diarrhea not only decreases the stool volume by facilitating sodium and water absorption along with the nutrients, but also facilitates early gut epithelial recovery and prevents malnutrition. Once the child’s status starts improving, a higher than recommended intake is given to facilitate complete catch- up growth. Following are the recommendations on dietary ‘management: i, In exclusively breastfed infants, breastfeeding should continue asit helps in better weight gain and decreases the risk of persistent diarrhea. ii, Optimally energy dense foods with the least bulk, recommended for routine feeding in the household, should be offered in small quantities but frequently (every 2-3 hours) ili, Staple foods do not provide optimal calories and should be enriched with fat or oil and sugar, eg, Khichri with oil, rice with milk or curd and sugar, mashed banana with milk or curd, mashed potatoes with oil and lentil. iv. Foods with high fiber content, e.g. coarse fruits and vegetables should be avoided. v. In non-breastfed infants, cow or buffalo milk can be given undiluted after correction of dehydration together with semisolid foods. Milk should not be diluted with water during any phase of diarrhea. Alternatively, milk cereal mixtures, e.g. dalia, sago or rilk-rice mixture, are preferable. vi. Routine lactose-free feeding, e.g. soy formula is not required, even when reducing substances are detected in the stools. Also, do not use cold drinks, fruit juices or glucose solutions as they have high osmolarity and can aggravate diarrhea, nausea and vomiting. During recovery, an intake of at least 125% of recommended dietary allowances should be attempted with nutrient dense foods; this should continue until, the child reaches pre-illness weight and ideally until the child achieves a normal nutritional status. vii. Zine Supplementation Zinc deficiency is widespread among children in developing countries. Intestinal zinc losses during diarthea aggravate pre-existing zinc deficiency. Zine supplementation is now part of the standard care along with ORS. It is helpful in decreasing severity and duration of diarrhea and the risk of persistent diarrhea. Zinc is supplemented as sulfate, acetate or gluconate formulation, at a dose of 20 mg of elemental zinc per day for children >6 months for 14 days. Symptomatic Teatment ‘An occasional vomnit in a child with acute diarrhea does not need antiemetics. If vomiting is severe or recurrent and interferes with ORS intake, then a single dose of oral ondansetron (0.15 mg/kg/dose) should be given. Preferably wait for 45-60 minutes before restarting ORT. Children with refractory vomiting despite administration of ondansetron may require intravenous fluids. Abdominal distension does not require specific treatment, if bowel sounds are present and the distension is mild. Paralytic ileus should be suspected, if bowel sounds are absent and abdomen is distended. Paralytic ileus can occur due to hypokalemia, intake of antimotility agents, necrotizing enterocolitis or septicemia. Subjects ith paralytic ileus require IV fluids, nasogastric aspiration, correction of hypokalemia and no oral feeding. Potassium chloride (30-40 mEq/L) should be administered intravenously with parenteral fluids provided the child is passing urine. Convulsions associated with diarrhea may be due to (i) hypo- or hypernatremia; (ii) hypoglycemia; i) hypocalcemia following bicarbonate therapy for g 2 z s 2 3 3 g 3 : 8 aacidosis; iv) encephalitis; (v) meningitis; (vi) febrile seizures; or (vii) cerebral venous or sagittal sinus thrombosis. The management depends on the etiology. Most episodes of diarrhea are self-limiting and do not require any drug therapy. Antibiotics are not recommended for routine treatment of acute diarrhea in children ‘Antimicrobials are indicated in bacillary dysentery, cholera, amebiasis and giardiasis. Escherichia coli are normal gut flora and their growth on stool culture is not an indication for antibiotics. Diarrhea may be the features of systemic infection especially in malnourished, prematurely born and ‘young infants, Presence of (i) poor sucking; (ii) abdominal distension, (ii) fever orhypothermia; (iv) fastbreathing; and (v) significant lethargy or inactivity in well-nourished, ‘well-hydrated infants points towards sepsis. Antimotility agentssuch as synthetic analogues of opiates 8 (diphenoxylate hydrochloride and loperamide) reduce & peristalsis orgutmoiityand should not be used in children & with diarrhea. Reduction of gut motility allows more time for the harmful bacteria to multiply. These drugs may cause paralyticileus, bacterial overgrowth and sepsis, and can be B dangerous in infants “Antisecretory agentshave been used in AD. Racecadotril is $ anantisecretory drug that exerts its antidiartheal effects by © i ghibiting intestinal enkephalinase. Recent studies reported some evidence in favour of racecadotril over placebo in reducing the stool output and duration of diarrhea. However, the overall quality of the evidence is limited Probiotics, defined as microorganisms that exert beneficial effects when they colonize the bowel, have been proposed as adjunctive therapy in the treatment of AD. Lactobacillus rhamanosus GG >10! CFU/day or Saccharomyces boulardii 250-750 mg/day for 5~7 days can be used as an adjuvant therapy. The quality of evidence is moderate-low for L. rhamanosus GG, and very low-low for S. boulardii ‘The marginal cost-benefit advantage must be carefully considered before prescribing these agents. Prevention of Diarthea and Malnutrition Chief measures to prevent diarrhea and its nutritional consequences are: i. Proper nutrition: Since breast milk offers distinct advantages in promoting growth and development of the infant and protection from diarrheal iliness, its continuation should be encouraged. Exclusive breast- feeding may not be adequate to sustain growth beyond the first 6-months of life. Supplementary feeding with cenergy-rich natural food mixtures containing adequate amounts of nutrients should be introduced by 6-month of age, without stopping breastfeeding. ii, Adequate sanitation: Improvement of environment sanitation, clean water supply, adequate sewage disposal system and protection of food from exposure to bacterial contamination are effective long-term strategies for control of all infectious illnesses including diarrhea. Three ‘Cs’/—clean hands, clean container and clean environmentare the key messages. Complementary foods should be protected from contamination during preparation, storage, and at administration. iii, Vaccination: With improvement in sanitation and hygiene in developing countries, the burden of bacterial, and parasitic infection has decreased. The use of rotavirus vaccine is an effective strategy for preventing acute diarrhea. Suggested Reading 1. Bhatnagar, Lodha R, Choudhury P, etal. AP Guidelines 2006 fon management of acute diarrhea, Indian Pediatr 2007; 44: 380-89, 2. Kumar A, Basu S, Vashishtha V, Choudhury P. Burden of rotavirus diarrhea in under-five children. Indian Pediatr 2016; 5607-17. 3, Piescik-Lech M, Shamir R, Guarino A, Szajewska H. Review article: The management of acute gastroenteritis in children. ‘Aliment Pharmacol Ther. 2013; 37: 289-308. 4. Yachha SK, Sarma MS, Mohan N, et al. Indian Academy of Pediatrics: Consensus guidelines for probiotic use in childhood diarrhea. Indian Pediatr 2022; 59:543-51 Dysentery Dysentery refers to the presence of grossly visible blood in the stools and isa consequence of infection of the colon by either bacteria or ameba. Bacillary dysentery is much more common in children than amebic dysentery. The bacteria causing bloody diarrhea are Shigella species (S. dysenteriae, S. flexneri, 8. boydii and S. sonnei), enteroinvasive and enterohemorthagic E. coli, Salmonella and Campylobacter jejuni. S. flexneri is the commonest organism reported in developing countries and S. dysenteriae is associated with ‘epidemics of dysentery. ‘A child with bacillary dysentery presents with fever and diarrhea, Diarrhea may be watery to start with, but then shows mucus and blood mixed with stools. There is tenesmus, which refers to ineffectual defecation along with straining and suprapubic discomfort. The illness may be ‘complicated by dehydration, dyselectrolytemia, hemolytic ‘uremic syndrome, convulsions, toxic megacolon, intestinal perforation, rectal prolapse and, very rarely, Shigella encephalopathy. ‘Administration of ORS, continuation of oral diet, zinc supplementation and antibiotics are the components of treatment. Stool culture and sensitivity should be sent before starting empirical antibiotics. Antimicrobial agents are the mainstay of therapy of all cases of shigellosis. Based on safety, low cost and efficacy, ciprofloxacin (15 mg/kg/day in two divided doses for 3 days) has been recommended by World Health Organization (WHO) as the first-line antibiotic for shigellosis. However, antimicrobial resistance to fluoroquinolones had increased significantly from 2002 to 2011 and only ceftriaxone has been shown to bbe uniformly effective. Keeping this in mind, intravenous ceftriaxone (50-100 mg/kg/day for 3-5 days) should be the first line of treatment in asick child. Ina stable child, either ciprofloxacin or oral cefixime may be given, but the patient should be monitored for clinical improvement within48 hours (decrease in fever, stool frequency and blood in stools). If no improvement is seen at 48 hours, antibiotics should be changed appropriately. Oral azithromycin (10 mg/kg/day for 3 days) can be used for shigellosis, but the experience is limited. ‘Amebic dysentery is less common among children. The onset is insidious. Tinidazole or metronidazole is the drug of choice. Any young child presenting with blood in stools and persistent abdominal pain should also be suspected to have intussusception and evaluated accordingly, Competency: PE2S.6 fesoenacny Persistent diarrhea is an episode of diarrhea, of presumed infectious etiology, which starts acutely but lasts for >14 days. Itshould notbe confused with chronic diarrhea which has a prolonged duration but an insidious onset. Etiopathogenesis, Although persistent diarrhea starts as acute infectious diarrhea, the prolongation of diarrhea isnot entirely due to infection. Various factors that are implicated in pathogenesis include: i. The predominant problem is the worsening nutritional status that, in turn, impairs the reparative process in the gut. This worsens nutrient absorption and initiates a vicious cycle that can only be broken by proper therapy. Persistent diarthea is more common in malnourished children. Apart from malabsorption, malnutrition also results from inadequate calorie intake due to anorexia, faulty feeding and improper counseling regarding feeding. One of the major obstacles to nutritional recovery is secondary lactose intolerance, and in some cases, impaired digestion of other complex carbohydrates due to decrease in brush border disaccharidases. Pathogenic E. coli, especially the enteroaggregative and enteroadherent types, result in malabsorption by causing persistent infection. ‘Associated infections of the urinary tract or other sites contribute to failure to thrive and mortality. Prolongation of an acute diarrhea may rarely be ‘a manifestation of cow milk protein allergy. The increased gut permeability in diarrhea predisposes to sensitization with oral food antigens. v. The use of antibiotics in acute diarthea suppresses normal gut flora. This may result in bacterial overgrowth with pathogenic bacteria and /or overgrowth of fungi, resulting in persistent diarrhea and malabsorption. Cryptosporidium infection is frequently implicated, even in immunocompetent children. Clinical Features Majority of patients with persistent diarrhea pass several loose stools daily but remain hydrated. Dehydration develops only in some patients due to high stool output ‘or when oral intake is reduced due to associated systemic infections. The major consequences of persistent diarrhea EEE eee eee eee eee eee oe eee eee rr are growth faltering, worsening malnutrition and death due to diarrheal or non-diarrheal illness. The presence of secondary lactose intolerance should be considered wien the stools are explosive (i.e. mixed with gas and passed with noise) and in presence of perianal excoriation. The stool pH is low and stool test for reducing substances is positive. Unabsorbed dietary lactose once delivered to colon isconverted to hydrogen and lactic acid by colonic bacteria. Lactic acid results in decreased stool pH, explosive stools are due to hydrogen and unabsorbed lactose gives positive reducing substances. There is no need for laboratory testing for stool pH and reducing substances when the history is classical and excoriation is marked. Secondary fungal infection should be suspected, if the anal excoriation extends to groins with or without oral thrush. Management The principles of management are: (i) Correction of, dehydration, electrolytes and hypoglycemia; (ii) evaluation for infections using appropriate investigations (hemogram, blood culture and urine culture) and their management; and (ii) nutritional therapy. Two-thirds of patients with persistent diarrhea can be treated as outpatients. Patients in need of hospital admission are those with (i) age <4 months and not breastfed; (ii) presence of dehydration; (ii) severe malnutrition (weight for height <3 SD, mid-upper arm circumference <11.5 cm for children between 6 and 60 months of age, or bilateral pedal edema); or (iv) presence or suspicion of systemic infection, Nutrition Feeding should be started at the earliest Initially 6-7 feeds are given per day and a total daily caloric intake of 100 kcal/ kg/day is ensured. Caloric intake should be increased gradually over 1-2 weeks to 150 keal/kg/day in order to achieve weight gain. Tube (nasogastric) feeding may be done initially in children with poor appetite. To ensure absorption and decreased stool output, one may attempt to overcome varying clegrees of carbohydrate maldigestion by using diets with different degrees of carbohydrate exclusion in the form of diet A (lactose reduced), diet B (lactose free) and diet C (complex carbohydrate free) diets (Table 12.14). Initial diet A (reduced lactose diet; milk rice gruel, milk sooji gruel, rice with curds, dalia): This is based on the fact that secondary lactose intolerance exists in children with persistent diarthea and malnutrition. Clinical trials have shown that reduced lactose diet is tolerated equally ie as totally lactose-free diet, without significantly incre stool output or risk of dehydration If the patient is fed entirely on animal milk, the quantity should be reduced to 50-60 ml/kg providing not more than 2 g of lactose/kg/ day. To reduce lactose concentration in animal milk, it should be mixed with cereals, but not diluted with water as that reduces the caloric content. Milk cereal mixtures, e.g. milk ot curd mixed rice gruel, milk sooj gruel, ot dala, are palatable, provide good quality proteins and some micronutrients and result in faster weight gain than milk-free diets, Second diet B (lactose-free diet with reduced starch): ‘About 65-70% of children improve on the initial diet A. System and Liver Diseases of GastrointestinalTable 12.14: Diets for persistent diarhea Diet A (reduced lactose} Constituents + Milk (1/3 katori/50 mL) + Puffed rice powder/cooked rice or Sooji Diet (lactose free) (2 tspl6 g) + Glucose (1% tsp/7 8) + Sugar (1 tsp/7 g) + Oil (1 t=p/7 g) + Oil (1 tsp/4.5 g) + Water (3/4 katori/120 mL) + Water (2/3 katori/100 mL) Preparation Mix milk, sugar and rice, add boiled water and mix well, add oil, ‘water and mix rapidly Nutrient content £85 kcal and 2.0 g protein per 100 g The remainder have impaired digestion of starch and & disaccharides other than lactose. These children, if free of 5 systemic infection, are advised dit B which is free of milk © (lactose) and provides carbohydrates as.a mixture of cereals B and glucose. Milk protein is replaced by chicken, egg or & protein hydrolysate. The starch content is reduced and & partially substituted by glucose. Substituting only part of the cereal with glucose increases the digestibility but atthe same time does not cause a very high osmolarity. G Third diet C (monosaccharide-based diet): Overall, 80-85% of patients with severe, persistent diarthea will recover with sustained weight gain with diet A or diet B. A small percentage may not tolerate a moderate intake of the cereal in diet B. These children are given diet C, which contains only glucose and a protein source as egg white or chicken or commercially available protein hydrolysates. Energy density is increased by adding oil to the diet. ‘The strategy of serial carbohydrate exclusion to varying degrees in plan A, Band C diets are meant to circumvent the problem of carbohydrate malabsorption. In addition, green (unripe) banana diet is gaining acceptance for treatment of persistent diarrhea. Fermentation of non-digestible soluble fibers in cooked green (unripe) banana by colonic bacteria ‘generates short chain fatty acids that are absorbed along with sodium in the colon, thereby facilitating water absorption by solvent drag and also conserving dietary nutrients, Indications for change from the initial diet (diet A) to the next diet (diet B or diet C): The diet should be changed to the next level, if the child shows (i) marked increase in stool frequency (usually more than 10 watery stools/day) at any time after at least 48 hours of initiating the diet; (i) features of dehydration any time after initiating treatment; or (i) failure to gain weight gain by day 7 in the absence of initial or hospital acquired systemic infection. Unless signs of treatment failure occur earlier, each diet should be given for a minimum period of 7 days. Resumption of regular diet after discharge: Children discharged on totally milk-free diet should be given small quantities of milk as part of a mixed diet after 10 days. If they tolerate this and have no signs of lactose intolerance + Egg white ( tsp/half egg white) + Puffed rice powder/cooked rice (3 tsp/9 ‘After whipping the egg white, add rice, sglucose and oil and mix well. Add boiled 90 kcal and 2.4.g protein per 100 g Diet C (monosaccharide based) * Chicken puree (5 tsp/15 g) or egg white @ tsprhalf egg white) + Glucose (1% tsp/7 g) + Ol (1% tsp/7 g) + Water (1 katori150 ml) Boil chicken and make puree after removing bones. Mix it with glucose and oil. Add to avoid clumping _ boiled water to make a smooth flowing feed 67 kcal and 3.0 g protein per 100 g (abdominal pain, abdominal distension and excessive flatulence), then milk can be gradually increased over the next few days. Age appropriate normal diet can then be resumed over the next few weeks. Supplement vitamins and. minerals: Supplemental multivitamins and minerals, at about twice the RDA, should be given daily to all children for at least 2-4 weeks. Iron supplements should be introduced only after the diarthea has ceased. Vitamin A (as a single dose) and zine are supplemented as both of them enhance the recovery from persistent diarrhea. A single oral dose of vitamin A should bbe given to those children with persistent diarrhea having severe acute malnutrition or with manifestation of vitamin A deficiency, at2,00,000 IU for children >12 months or 100,000 TU for children 6-12 months of age. Children weighing <8 kg, irrespective of their age, should be given 100,000 IU of vitamin A. Zinc is given at a dose of 10-20 mg per day for at least2 weeks to children between 6 months and 3 years ofage. Additional supplements for severely malnourished infants and children: Magnesium and potassium supplementation is provided to these children. Magnesium is given by intramuscular route at 0.2 mL/kg /dose of 50% magnesium sulfate twice a day for 2-3 days. Potassium is supplemented at 5-6 mEq/kg /day orally or as part of intravenous infusion during the initial stabilization period. Role of antibiotics: The indiscriminate use of antibiotics in the treatment of acute diarthea is one of the reasons for persistent diarrhea. Hence, the use of empirical antibiotics at admission is to be individualized and reserved for children with either severe malnutrition (majority of these children have associated systemic infections and clinical signs of, infection may not be obvious) or those with evidence of systemic infection. A combination of cephalosporin and aminoglycoside can be started empirically and thereafter changed according to reports of culture sensitivity. Urinary tract infection is common (seen in 10-15%) and should be treated appropriately. Monitaring Response fo Treatment Successful treatment is characterized by adequate food intake, reduced frequency of diartheal stools (<2 liquid Ps eee ee ee eee eee eee ee eee oastools /day for 2 consecutive days) and weight gain. Most children will lose weight in the initial 1-2 days and then show steady weight gain as associated infections are treated and diarrhea subsides. All children should be followed regularly even after discharge to ensure continued weight gain and compliance with feeding advice. Prognosis Most patients with persistent diarrhea recover with an approach of stepped-up dietary management as discussed above. A small subgroup (<5%) may be refractory and require parenteral nutrition and extensive workup. These patients generally have high purge rate, continue to lose weight, do not tolerate oral feeds and require referral to specialized pediatric gastroenterology centers. Suggested Reading 1. Bandasma RHJ, Sadiq K, Bhutta ZA. Persistent diarthoea: Current knowledge and novel concepts. Paediatr Int Child Health 2019 Feb;39(1)-41-47. Gaffey MF, Wazny K, Bassani DG, Bhutta ZA. Dietary ‘management of childhood diarrhea in low- and middle-income countries: A systematic review. BMC Public Health. 2013;13 Suppl 3$3-S17, 3. Williams PCM, Berkley JA. Guidelines for the treatment ‘of dysentery (shigellosis) A systematic review of the evidence. Paediatr Int Child Health 2018; 38:S50-S65. Competencies: PER.7; PE25.1 rere Chronic diarthea is a common problem in children. It is defined as an insidious onset diarthea of >2 weeks duration in children and >4 weeks in adults. The term chronic diarrhea is not synonymous with persistent diarrhea, In children, diarrhea can be defined as a stool volume of >20 g/kg/d. Usually the parents can identify diarthea by the increase in frequency and fluid content of the stool ‘as compared to the normal for that child. The approach, etiology and management of chronic diarthea along with a brief outline of some common causes. discussed as follows. Approach Approach to chronic diarthea mustbe considered with the following points in mind: Age of onset: A list of common causes according to age of onset is shown in Table 12.15. Tele 12.15: Common causes of cronc dianhea according to age of onet and atu of iti a | Zaza net <6 moms Reena sae atl ‘Watery, ‘Small bowel ‘Small bowel + Cow milk protein allergy* + Lymphangiectasia + Post enteritis syndrome + Immunodeficiency’ + Anatomical defects + Urinary tact infection* + Toddler diarthea + Celiac disease + Lymphangiectasia * Giardiasis + Crohn's disease? + Immunodeficiency! Rare causes*** + Autoimmune enteropathy + Microvillus inclusion disease + Tufting enteropathy + Glucose glactose malabsorption + Congenital sodium/chloride diarrhea Bloody + Cow milk protein allergy + Cytomegalovirus colitis + Very early onset inflammatory bowel disease (VEOIBD) + Hirschsprung enterocolitis + Nectrotizing enterocolitis + Drug induced Large bowel + CMV colitis + Pseudomembranous + Ulcerative colitis, + Crohn's disease + Tuberculosis Fatty Fatty + Cystic fibrosis + Cystic fibrosis + Cholestasis + Chronic pancreatitis + Cholestasis + Cow milk protein allergy’ + Post enteritis syndrome + Autoimmune enteropathy + Abetalipoproteinemia + Short bowel syndrome** + Bacterial overgrowth + Cow milk protein allergy + Hirschsprung enterocolitis + Celiac disease + Parasitic infections: Giardiasis, BS (diarrhea), lactose intolerance + Tropical sprue + Drugs + Lymphangiectasia + Crohn's disease + Immunodeficiency" + Drug induced + Short bowel syndrome* + Bacterial overgrowth + Immunoproiferative small intestinal disease Large bowel + Ulcerative colitis * Crohn's disease + Tuberculosis, + Pseudomembranous colitis =cMv + Radiation colitis + Hirschsprung enterocolitis, ete: Fatty + Chronic pancreatitis + Cystic fibrosis + Cholestasis colitis + Shwachman-Diamond syndrome *Should be considered in young infants with chronic diarrhea, particularly i fever is noted **Consider if there is antecedent history of small bowel surgery. ‘These rare condtions should any be considered, ifthe darrhea s very erly ins onset (neonate to 3 months and common conditions have been ruled out “Some etiologies can present with watery andior bloody darthea depending onthe site of involvement =| DO : é ; é ;12 5 2 Table 12.16: Different ing small bowel from large bowel diarthea Features ‘Small bowel diarthea Stool volume; color Large; pale Blood in stool No Rectal symptoms, e.g. urgency, tenesmus No Steatorthea (greasy stools}; smell ‘Yes; offensive smell Yes, explosive stools Yes Carbohydrate malabsorption Protein malabsorption Pain (if any) Nutrient deficiency Frequent Nature of stools: Stools can be broadly divided into three main categories—watery, fatty, and bloody. Watery stool has a high liquid content and can be mistaken for urine in infants. Fatty stools are bulky, foul smelling and pale with visible oil sometimes. Bloody stools contain gross blood mixed with stools and suggest a large bowel disease. Features that help in differentiating small bowel from large ‘bowel diarrhea are shown in Table 12.16. Response to fasting: Once the baseline stool output with normal feeding has been noted, the patient can be Kept 3 nil orally for 24 hours to assess the response. If the stool ‘volume is same or minimally changed after fasting, it Suggests the presence of secretory diarthea. However, if there is significant reduction in the stool output, it suggests osmotic diarrhea Site of disease: Diarrhea is most commonly of intestinal origin (small, large or both) and sometimes pancreatic, for hepatobiliary in etiology. Cholestasis due to biliary ‘obstruction or intrahepatic causes leads to fat malabsorption ‘nd diarrhea, Pruritus and malabsorption of fat-soluble vitamins (A, D, E and K) are commonly associated. Maldigestion due to deficiency of pancreatic enzymes leads to fatty stools. Diarthea may be a systemic manifestation of other conditions like immunodeficiency states, diabetes, ff collagen vascular disorders. Other uncommon causes include Zollinger-Elison syndrome, VIPoma, carcinoid or mastocytosis ‘The approach to a case with chronic diarrhea is shown in Fig, 12.19 and the important clues to some of the etiologies are given in Table 12.17. Abrief description of the common ‘causes of chronic diarthea is given below. Celiac Disease This is an enteropathy caused by permanent sensitivity to gluten in genetically susceptible subjects. Nearly 99% of patients are positive for the human leukocyte antigen DQ2 or -DOB. Celiac disease is the most common cause of chronic diarrhea in children over 2 years of age in North India. High-risk groups include type 1 diabetes mellitus, Down syndrome, selective Ig deficiency, autoimmune thyroid disease, Turner syndrome, Williams syndrome, autoimmune liver disease and first-degree relatives of patients with celiac disease — Periumbilical, no reduction after stool Large bowel diarthea Small; normal Usually present Yes No; normal No No Hypogastric, reduced after passage of stool Can occur due to blood loss “Approach to child with chronic diarrhea Detailed history Age at onset 1 Slcharecteristics: Nature, frequency, poctumal, volume, relation ‘nth #504, presence of blood, ot «Dietary history Relabon wth introduction of animal ik, ten. Intake of ful ices: food aversions + Prewous abdominal surgery: Resection, adhesions History of repeated infections: Immunodeficiency, cystic fbrosis brug intake: Causing darthea,immunesuppressive medications can Inereaze nak of GI nfectons «Associated ilness: Diabetes metus, thyrotoxicosis, postpone ‘marrow transplant amy history 180, esac disease, cystic fbosis, immunodeficiency 1 prowous history of acu gastoenteriis: Post nfecbous IBS, post enleris syndrome += Otner manifestations: Exrantestnal ineebac disease in 180, rashephthous stomatitis Detailed examination + Anthropometry, signs of dehyeraton 1 Anemia, edema ptinginan-piting(Wmphedeme), clubbing, oral thrush, skin Infeton/ash ‘Vitamin (water off sluble)Iminera deficiency 1 Penanal. Rash, tage, fesures, tune, blood on finger, features of Hirecnsprung disease «Abdomen: Distension, ascites, seas, organomegaly, visible peristalsis Systemic examination dointeye--IBD, chest for cyst fibrosis, tuberculosis 1 Determine + Likely aiterential agnosis s per nature of darthea, age of onset ‘associated feings + Pian investigative work-up. Select from the st below Investigations: No uniform protocol; case based + Hemogram including ESR and C-reactive protein Biochemistry: Liver functions electrolytes, calcium, lipid prole 1 Stout examination, Reducing substances, microscopy and antigen test for opportuniste nfectons, GostlGtum dice toxin, fecal faelastase + Serology Celae disease, HIV, antienterocyte antibody 1 immune profile: Cellule and humoral immunity 1 Endoscopy wth biopsies: Upper Glcolonventeroscopy 1 Radiologe maging: USG, CT enterogrephy + hr Dosw cose ncgnlate ea ets, ering Fig. 12.19 Approach to a patient with chronic diarthea. 1BD inflammatory bowel disease, USG ultrasonography Clinical Features ‘The classical presentation is with small bowel diarrhea, growth failure and anemia. A temporal association of‘Clues to important causes of chronic diarthea Cow milk protein allergy + Onset of diatrhea after introduction of ‘cow or buffalo milk or formula + Rectal bleeding (due to colitis) failure to thrive + Family history of allergy or atopy + Response to milk withdrawal Lymphangiectasia + Nonpitting pedal edema suggesting lymphedema + Recurrent anasarca + Hypoalbuminemia and hypoproteinemia + Lymphopenia + Hypocalcemia Cystic fbrosis «History of meconium ileus + Predominant or associated lower respiratory tract infections + Severe failure to thrive + Clubbing + History of sibling deaths + High sweat chloride (>60 mEq/L) Immunodeficiencies + Predominant fever + Recurrent infections involving other sites + History of sibling deaths + Organomegaly + Opportunistic infections on stool exami ration diarrhea and introduction of wheat products at weaning may be present. Onset of diarrhea before introduction of, wheat products in diet negates a diagnosis of CD. Other presentations include refractory iron deficiency (not responding to oral supplements) or dimorphic anemia, short stature, delayed puberty, rickets and osteopenia. Examination reveals failure to thrive, loss of subcutaneous fat, clubbing, anemia, rickets and signs of other vitamin deficiencies. A high index of suspicion for the disease is the key to diagnosis. Diognos's vestigations required for mal 2 diagn: ogy: IgA antibody against tissue transglutaminase (tTG) is an ELISA-based test, with high sensitivity (92-10%) and specificity (91-10%) and is recommended {for initial testing. IgA antiendomysial antibody isan equally accurate test (sensitivity 88-100%; specificity 91-10%), but is difficult to perform and not readily available. Serology helps in making a diagnosis of celiac disease and also in assessing compliance to dietary therapy. Upper Gl endoscopy and histology: The endoscopy may be normal or show absence of folds or scalloped duodenal folds (Fig, 12.20a). Multiple biopsies should be taken from the second/third part of duodenum and also from the duodenal bulb. The characteristic histological changes in celiac disease are increased intraepithelial lymphocytes (230/100 enterocytes), increased crypt length, partial to total villous atrophy, decreased villous to crypt ratio and infiltration of plasma cells and lymphocytes in lamina propria (Fig, 12.20b). Both serology and biopsy should be done when the subject is on a normal gluten-containing diet. ‘The diagnostic criteria have been changing in recent years with differences in recommendations between children and adults. Traditionally, the diagnosis of celiac disease required the following: i. Clinical features compatible with diagnosis ii, Positive intestinal biopsy iii, Positive serology and iv. Unequivocal response to gluten-free diet (GFD) within 12 weeks of its initiation. Tre recent 2020 ESPGHAN guidelines suggest that in all suspected cases (symptomatic, asymptomatic, and at-risk group), the first test should be total serum Ig and IgA tTG. In patients with IgA-tTG 210 times the upper limit of normal, the diagnosis of celiac disease may be made without a duodenal biopsy provided that the antiendomysial Fig. 12.20: Celiac disease: (a) Upper gastrointestinal endoscopy showing scalloping of duodenal folds (arrow): (b) uodenal histology showing total villous atrophy Diseases of Gastrointestinal System and Liver ®antibody (EMA, separately drawn blood sample) is also positive and there is a definite response to gluten-free diet. However, in view of restricted availability and cost of EMA and multiple labs reporting IgA-tTG only as positive (without actual titers), the non-biopsy approach is not yet preferred in our country. This is especially important as it is very difficult to confirm or refute the diagnosis of celiac disease after initiation of gluten-free diet. Thus, all efforts should be made to make a correct diagnosis with full work- up at onset prior to initiation of dietary therapy. Ireatment ‘Treatment involves lifelong gluten-free diet (no intake of, wheat, rye and barley). Oats should also be avoided in the initial period due to the risk of gluten contamination, ‘Nutritional deficiency of iron, folate and other vitamins and minerals should be corrected by supplementation. After initiation of gluten-free diet, the symptoms should subside 42 (2-4 weeks) and there should be weight and height gain. & Repeated explanation to patient and parents by doctors & is essential for sustaining compliance after the child has B become asymptomatic. Celiac disease should be differentiated from nonceliac G gluten sensitivity (NCGS) which is a condition in which = gluten ingestion leads to Gl and non-GI symptoms but the § patients does not have celiac disease or wheat allergy (i.e B no enteropathy, negative serology). Gluten challenge is required to make a diagnosis of NCGS. Cow Milk Protein Allergy Cow milk protein allergy (CMPA) affects 2 to 5% of all children in the West, with the highest prevalence during the first year of life. CMPA accounted for one-third of all children with chronic diarthea of <5 years of age from a tertiary care centre in India. A family history of atopy is common. Nearly 50% children outgrow theallergy by 1 year and ~95% by 6 years. Itis the most common food allergy in small children who are top-fed but can occasionally occur in exclusively breastfed babies, due to passage of cow milk antigen in breast milk. There are two kinds of reactions to cow milk: (i) Immediate (IgE mediated). It occurs within minutes of milk intake and is characterized by vomiting, pallor, shock- like state, urticaria and swelling of lips. (ii) Delayed (cell mediated): It has an indolent course and presents mainly with GI symptoms. Clinical Features The chief presentation is with diarrhea with blood and mucus. Depending upon the site and extent of involvement, the child may have small bowel, large bowel or mixed type diarrhea. In an Indian study, 40% children presented with bloody diarrhea, 33% watery and 7% with a mixed type of diarthea. Uncommonly reflux symptoms and hematemesis may be present. Respiratory symptoms (allergic rhinitis and asthma) and atopic manifestations (eczema, angioedema) may be seen in 20-30% and 50-60% cases, respectively. Iron deficiency anemia, hypoproteinemia and eosinophilia are commonly present. Diagnosis In patients with GI symptoms, non-IgE-mediated CMPA is more common. The gold standard for diagnosis is the elimination and challenge test. Typically, the symptoms subside after withdrawal of milk and milk products and recur after re-exposure to milk, Eosinophilia and family history of atopy are suggestive. Sigmoidoscopy (aphthous ulcers and nodular lymphoid hyperplasia, Fig. 12.21a) and rectal biopsy (plenty of eosinophils, Fig. 12.21b) canbe used in patients with only gastrointestinal symptoms. Skin prick test and specific IgE levels are useful for IgE-mediated CMPA. Treatment All animal milk/milk products have to be removed from the diet. Soy or extensively hydrolyzed formula (EHF), both of which are equally effective in terms of growth and nutrient intake can be used as alternatives. Although soy is ‘more palatable and cheap, itis not recommended in infants <6 months of age. 10-15% children of CMPA have Fig. 12.21: Cow mik protein allergy: (a) Sigmoidoscopy showing aphthous ulcers; (b) Rectal biopsy showing eosinopt with crypt abscessconcomitant soy allergy, and they need extensively hydrolyzed formulae for therapy. A minority of children with severe enteropathy or intolerant to hydrolyzed formulae need amino acid formulae. CMPA is usually a mild disease in exclusively breastfed babies. A trial of continued breastfeeding tll 6 months of age while the mother is placed ona milk/milk product free diet may be done in them. Parental education regarding diet and calcium supplementation is essential. Reevaluation should be done to determine development of tolerance and avoid prolonged restrictive diet. ‘Toildler diarrhea is a diagnosis of exclusion after common causes have been ruled out. The onset of diarrhea isbetween 6 and 36 months of age. The child passes 3-6 loose stools, ‘mostly during waking hours. Diarrhea worsens with low residue, low fat or high carbohydrate diet. The child is well thriving, there is no anemia or vitamin deficiencies and the diarrhea resolves spontaneously by about 4 years of age. Treatment is with dietary modification; a high (>40%) fat, low carbohydrate diet (reduced intake of juices) and increase in dietary fiber is recommended. Intestinal Lymphangiectasia Intestinal lymphangiectasia (IL) is an important cause of protein-losing enteropathy (PLE). Itcan either be primary ‘orsecondary to conditions causing obstruction of intestinal lymphatics. It is characterized by ectasia of the bowel lymphatic system, which on rupture causes leakage of pprotein-rich chyle into the intestinal lumen with resultant hypoproteinemia and hypoalbuminemia. Patients present with diarrhea, edema, ascites (chylous or non-chylous), pleural effusion, and failure to thrive. The edema can be bilateral and pitting due to hypoalbuminemia or asymmetrical and non-pitting due to lymphedema, Some children may present with steatorthea and fat-soluble vitamin deficiencies. Presence of hypoalbuminemia, low immunoglobulins, hypocalcemia and lymphopenia is characteristic. The risk of recurrent and opportunistic infections is increased. V ‘On UGI endoscopy (fat loading with 2 g/kg of butter at bedtime increases the yield), scattered white plaques or chyle-like substance covering the mucosa may be seen (Fig, 12.22a). Duodenal biopsy reveals dilated lacteals in villi and lamina propria (Fig. 12.22b) and confirms the diagnosis. However, in some patients, the UGI endoscopy may be normal and they need visualization and biopsy from jejunum by capsule endoscopy /enteroscopy for diagnosis. Treatment consists of a high protein, low fat diet with supplementation of MCT oil, calcium and fat-soluble vitamins. Intravenous albumin is required for symptomatic management. Total parenteral nutrition (TPN) and octreotide are used for management of chylous effusions. Bowel resection may be curative in patients with disease localized to a small segment of the intestine. Immunodeficiency Both congenital and acquired immunodeficiency can cause chronic diarrhea. It should be suspected, if there is history of recurrent infections at multiple sites (chest/ Gl/skin) and wasting. The common immunodeficiency conditions presenting with diarthea include IgA deficiency, severe combined immunodeficiency, common variable immunodeficiency and chronic granulomatous disease. ‘There is increased risk of celiac disease (100-20-fold increase) and Crohn's disease in patients with IgA deficiency. Diagnosis ismade by measuring serum immunoglobulins, Tcell counts and functions, phagocytic function (nitroblue tetrazolium reduction test) depending upon the suspected etiology. ‘Treatment depends on the cause of diarthea and includes, antimicrobials for bacterial overgrowth and opportunistic infections and therapy for underlying immunodeficiency (IV immunoglobulins, or bone marrow transplantation). Acquired immunodeficiency syndrome (AIDS): Chronic diarrhea is a common feature in children with AIDS. The impaired mucosal immunity results in recurrent opportunistic infections and the altered maturation and function of enterocytes results in increased permeability and decreased functional absorptive surface with or Fig, 12.22: Intestinal tymphangiectasia: (a) Upper gastrointestinal endoscopy showing snow-flake appearance; (b) Duodenal histology shows dilated lacteals Diseases of Gastrointestinal System and Liver a.without bacterial overgrowth. AIDS enteropathy characterized by chronic diarrhea and marked weight loss in absence of enteric pathogens. Presence of oral thrush, lymphadenopathy, hepatosplenomegaly and parotitis (10-20% cases) gives clue to the diagnosis. Common infections include: i. Viral: Cytomegalovirus, herpes simplex, adenovirus, norovirus fi, Bacterial: Salmonella, Shigella, Mycobacterium avium ‘complex (MAC), C. jejuni, C. difficile ili. Fungi: Candidiasis, histoplasmosis, cryptococcosis iv. Protozoa: Microsporidium, Isospora belli, Cryptosporidium, E. histolytica, G. lamblia, Cyclospora, Blastocystis hominis ‘Multiple stool examinations are required to identify the etiology, using special stains and PCR techniques. Colonic/ 4 2 terminal ileum biopsy and duodenal fluid examination are useful for diagnosing some infections. Treatment is with specific antimicrobials (Table 12.18) along with HAART (highly active antiretroviral therapy). 3B Drug-induced Diarrhea 2 Diarrhea can be a side effect of many pharmacologic & agents. Altered GI motility, mucosal injury and /or change B inintestinal microflora are the main etiologic factors. Anti- © biotics can cause loose watery stools by altered bacterial flora or bloody stools secondary to Clostridium difficile & overgrowth and pseudomembranous colitis. Stopping the offending agent is often enough. If suspicion of pseudomembranous colitis is present, then stool for toxin assay and sigmoidoscopy is required for confirmation. Metronidazole or oral vancomycin is the drug of choice. Inflammatory Bowel Disease (IBD) IBD is a chronic inflammatory disease of the GI tract and is of two main types—Crohn’s disease (CD) and ulcerative colitis (UC). In ~10% cases, with isolated colonic involvement, the subjects cannot be classified into UC or ‘CDand they are labeled as indeterminate colitis. 15-25% of Table 12-1: Treatment recommendations for infectious diarthea Infection causing diarrhea ‘Drug of choice for treatment all IBD presents in children $17 years of age and they are labeled as pediatric IBD. The incidence of pediatric IBD is increasing all over the worid including India. The average age of presentation in children is ~10-I1 years. Very early onset IBD is used to define children with symptoms at -<6 yr of age. The etiopathogenesis of IBD is multifactorial and includes genetic factors, environmental triggers, and altered gutmicroflora, the interaction of which initiates an abnormal ‘mucosal immune response and intestinal inflammation. Cinical Features Children with UC present with diarrhea and rectal bleeding which raises alarm and leads to early work-up and diagnosis. In CD, abdominal pain is the most common presenting symptom, followed by diarthea, poor growth ‘or weight loss, and anorexia. Patients with predominant colonic disease present as colitis. The classical triad of CD, ie. pain, diarrhea and weight loss is seen in only 25% cases. Fever, fatigue and anorexia are present in 25-50% cases, Extraintestinal manifestations (EIM) are seen in 25-30% children with IBD. Arthralgia arthritisis the most common EIM seen in 15-17% cases. Uveitis, aphthous stomatitis, erythema nodosum, pyoderma gangrenosum, and sclerosing cholangitis are the other EIM. They can precede, follow or occur concurrently with the intestinal disease and ‘may be related /unrelated to activity of the intestinal disease. Disease distribution: UC is classified as proctitis (El: rectum only), left-sided (E2: distal to splenic flexure), extensive (E3: distal to hepatic flexure), and pancolitis (E4), with majority of children having pancolitis. CD is classified as—L1: Distal one-third ileal alone + limited cecal involvement, L2: Colonic alone, L3: Ileocolonic, L4: Isolated upper GI based on disease extent and as inflammatory (B1), stricturing (B2) and penetrating (B3), based on disease behavior. Majority of patients with CD (50-70%) have ileocolonic disease. Upper GI involvement is present in 30-40% cases and perianal disease in ~15-20% cases. As the management and prognosis of CD and UC is different, soa correct diagnosis is Oral albendazole (15 mg/kg/day twice a day) for 14 days in immunocompetent. Longer therapy Giardia lamblia ‘Metronidazole 7.5 mg/kg/dose thrice daily for 5 days Entamoeba histolytica ‘Metronidazole 7.5 mg/kg/dose thrice daily for 10 days Cryptosporidium Nitazoxanide: In immunocompetent children + 1-3 years: 100 mg two times a day x 3 days + 4-11 years: 200 mg two times a day 3 days Microsporidium in immunocompromised. Cyclospora Cotrimoxazole 5/25 mg/kg/day for 7 days Isospora belli Cotrimoxazole for 7 days Cytomegalovirus Clostridium dificil Ganciclovir or valganciclovir for 14-21 days Stop other antibiotics. Oral metronidazole (30 mg/kg/day in 4 divided doses) for 7-10 days for ‘mild disease, Oral vancomycin (40 mg/kg/day in 4 divided doses; maximum, 2 g/day), with or ‘without metronidazole for severe disease Candidiasis Fluconazole for 4 weeks Cryptococcus neoformans Fluconazole 6 mg/kg/day oral once a day