Topics on Continuous Training

M.L. Cilleruelo Pascual, A. García Díaz

Gastroenterology, Hepatology and Pediatric Nutrition Service. Puerta de Hierro Majadahonda University Hospital. Madrid

Abstract This article focuses on the assessment and management of chronic diarrhea according to its pathophysiological mechanism, symptoms, complementary examinations and treatment. Diarrhea is classified as osmotic diarrhea and secretory diarrhea. It can also be divided into diarrhea due to maldigestion, when the digestive enzymes that hydrolyze proteins, fats and carbohydrates are not produced, and diarrhea due to malabsorption, when there is an alteration of the intestinal epithelium that prevents the transport of already digested nutrients. The warning signs and symptoms must be considered to make an initial diagnostic approach to diarrhea of organic or functional origin. The clinical history should define the characteristics of the stools, watery, bloody or greasy, which will help to orientate the possible pathophysiological mechanism. In the physical examination severity of malnutrition is specifically assessed. The differential diagnosis is broad and the complementary examinations numerous, but they must be carried out based on the clinical findings. First level investigations can lead to the diagnosis of the most common causes. In addition to nutritional support, specific treatment of the underlying disease is provided, which will often, but not always, be exclusively nutritional. Correct and early diagnosis and treatment of these patients will minimize the morbidity and nutritional consequences of chronic diarrhea.

 

Resumen Valoración y manejo de la diarrea crónica en función de su mecanismo fisiopatológico, síntomas, exploraciones complementarias y tratamiento. La diarrea se clasifica en diarrea osmótica y diarrea secretora. También puede dividirse en diarrea por maldigestión, cuando no se producen las enzimas digestivas que hidrolizan las proteínas, grasas y carbohidratos, y diarrea por malabsorción, cuando existe una alteración del epitelio intestinal que impide el transporte de los nutrientes ya digeridos. Deben considerarse los signos y síntomas de alarma para efectuar una aproximación diagnóstica inicial de diarrea de origen orgánico o funcional. En la historia clínica se definirán las características de las heces, acuosas, con sangre o con grasa, lo que permitirá orientar el posible mecanismo fisiopatológico. En la exploración física se valorará especialmente la repercusión nutricional. El diagnóstico diferencial es muy amplio y las exploraciones complementarias numerosas, pero deben efectuarse en función de los hallazgos clínicos. Con las exploraciones de primer nivel se puede llegar al diagnóstico de las causas más frecuentes. Aparte del soporte nutricional, se efectuará el tratamiento específico de la enfermedad de base, que con frecuencia, pero no siempre, será exclusivamente nutricional. El correcto y temprano diagnóstico y tratamiento de estos pacientes minimizará la morbilidad y las consecuencias nutricionales de la diarrea crónica.

 

Key words: Chronic diarrhea; Functional diarrhea; Organic diarrhea; Malabsorption; Maldigestion; Complementary tests; Management.

Palabras clave: Diarrea crónica; Diarrea funcional; Diarrea orgánica; Malabsorción; Maldigestión; Exploraciones complementarias; Tratamiento.

 

 

Pediatr Integral 2024; XXVIII (8): 493 – 502

 

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Chronic diarrhea

Introduction

Chronic diarrhea lasts more than 14 days and has an insidious onset. Differential diagnosis is complex due to the multiplicity of causes.

Diarrhea is not easy to define in children, as the frequency and consistency of stools will vary with age and with the introduction of food. It is expected that the number of stools will decrease and their consistency will increase over time. The WHO defines diarrhea as the passage of 3 or more stools per day, soft or liquid, or with a frequency greater than the patient’s previous rate(1).

Prolonged diarrhea is diarrhea that lasts more than 14 days. It usually has an acute onset and is more common in children under 5 years of age. Chronic diarrhea is diarrhea that lasts more than 14 days, has an insidious onset and slow progression(2).

Chronic diarrhea can have multiple etiologies and different pathophysiological mechanisms, so the differential diagnosis is not simple. A detailed clinical history and a physical examination focused on the nutritional status and potential specific nutritional deficiencies are necessary to select complementary tests aimed at determining the cause.

Pathophysiology

Chronic diarrhea is classified into osmotic diarrhea and secretory diarrhea. It can also be divided into diarrhea due to malabsorption and diarrhea due to maldigestion.

The intestine handles a large amount of fluids that come from food intake and from secretions of saliva, gastric juice, bile, pancreatic and intestinal juice. There are numerous processes of transporting fluids, electrolytes and solutes that take place mainly in the small intestine. The rest of the fluids are reabsorbed in the large intestine to form the fecal bolus. Any imbalance in these processes will lead to diarrhea.

The most important mechanism for regulating fluid transport is through the active transport of ions (sodium, chloride and bicarbonate) through the enterocyte. The movement of sodium promotes absorption and that of chloride promotes fluid secretion. The integrity of the epithelial barrier is also necessary to prevent electrolytes and, therefore, fluid, from being passively transported after absorption or secretion. Finally, normal intestinal motility is necessary to ensure adequate contact between nutrients and the intestinal epithelium. The digestion process begins with the action of luminal enzymes and is completed by the action of brush border enzymes in the intestinal mucosa (Table I).

Chronic diarrhea is classified, according to its pathophysiological mechanism, into osmotic diarrhea and secretory diarrhea.

• Osmotic diarrhea: This is the result of malabsorption of solutes. As in all diarrhea, osmotic forces are produced; some authors prefer the term food-induced diarrhea(3). The increase in osmolarity in the intestinal lumen produces movements in favor of the gradient of water and electrolytes. This type of diarrhea characteristically improves with fasting(3).

• Secretory diarrhea: In these diarrheas there is an increase in the secretion of liquids carried by anions (chlorine or bicarbonate) or potassium or by the loss of the mechanism of absorption of liquids through sodium. For this reason, some authors prefer to use the term of diarrhea related to the transport of electrolytes(3).

Chronic diarrhea can also be classified according to the digestive process by which the alteration occurs:

• Maldigestion: When the production of digestive enzymes, both intraluminal and brush border, which hydrolyze proteins, fats and carbohydrates, fails. Pancreatic enzymes are primarily involved and clinically steatorrhea predominates.

• Malabsorption: When there is an alteration of the intestinal epithelium that prevents the transport of already digested nutrients. The fermentation of unabsorbed food in the colon produces short-chain fatty acids, which have a cathartic effect in the small intestine, giving rise to very voluminous stools.

Etiology

Diarrhea of functional or organic origin should be suspected and the possible causes of organic diarrhea should then be assessed, taking into account the age of onset and the warning symptoms.

There are many causes of chronic diarrhea. It is important to take into account the patient’s age in order to logically consider the different etiological possibilities. Table II shows the main causes of chronic diarrhea by age group.

Chronic diarrhea may be of functional or organic origin. Warning signs and symptoms (Table III) should be sought, the absence of which indicates a diagnosis of functional diarrhea, with the consequent limitation of the complementary examinations to be performed.

 

Functional diarrhea

• Functional diarrhea in infants: It is characterized by the passage of at least 4 stools per day, abundant, unformed, with recognizable and light-colored foods, without pain, loss of appetite or alteration in weight gain. It begins at 6 months and usually resolves by 5 years, but can persist throughout childhood and adolescence(4,5).

• Irritable bowel syndrome: It is characterized by at least 4 days per month for 2 months of abdominal pain associated with one or more of the following symptoms: pain with defecation, change in frequency and change in appearance of stools, in this case with a predominance of diarrhea(6).

Organic diarrhea

The most important clinical characteristics of each disease are shown in table IV.

 

Diarrhea and congenital enteropathies

These are monogenic disorders, some of them extremely rare, with autosomal recessive inheritance, which manifest in the days immediately after birth and even in utero, although there are exceptions, such as the case of saccharase-isomaltase deficiency that begins with the introduction of complementary feeding (fruits, juices and starchy foods)(7). They mainly cause liquid diarrhea, but they can also cause bloody diarrhea (very early-onset inflammatory bowel disease) or steatorrhea (primary deficiency of bile salts and alterations in the transport or metabolism of fat). Congenital diarrhea can be divided into 5 groups in relation to their pathophysiological mechanism:

1. Alterations in epithelial transporters(3,8,9).

2. Alterations in epithelial enzymes and metabolism(3,7,10,11).

3. Structural and functional alterations of absorption(3,8).

4. Enteric neuroendocrinopathies(3).

5. Enteropathies associated with alterations in immunoregulation(3,12) (Table IV).

The most common disorder in this group is primary lactase deficiency, adult-type hypolactasia or lactase non-persistence. It is due to a decrease in the function of lactase-phlorizin hydrolase, an enzyme present in the most apical area of the intestinal villi. It is an autosomal recessive disorder that can appear in Caucasians from the age of 5 years. Symptoms begin with the ingestion of milk or dairy products, when the percentage of enzyme activity is less than 50% and vary greatly in intensity, since the adaptation of the intestinal flora contributes to tolerance. Secondary lactase deficiency is temporary and acquired after injury to the intestinal mucosa.

In addition to congenital diarrhea, newborns may present diarrhea due to congenital digestive malformations, such as short intestine (<75 cm in length) and enterocolitis as a complication of Hirschsprung’s disease. Other chronic diarrheas are acquired and more frequent in premature infants, such as intestinal anatomical defects (atresia) or necrotizing enterocolitis(3).

Abnormal immune response

This group includes diseases that are much more common in clinical practice, such as celiac disease, non-IgE-mediated cow’s milk protein allergy (CMPA)(13) and inflammatory bowel disease (IBD). Primary eosinophilic gastrointestinal disorders produce a wide variety of symptoms, including chronic diarrhea, and are becoming more prominent in specialized units. The two entities that cause diarrhea are eosinophilic gastritis and eosinophilic colitis(14). Finally, in microscopic colitis, which includes lymphocytic colitis and collagenous colitis, the mucosa has a normal appearance and specific histological findings are what allow the diagnosis, as both diseases are clinically indistinguishable(15).

Exocrine pancreatic insufficiency

In exocrine pancreatic insufficiency, there is a decrease in the secretion of pancreatic enzymes, bicarbonate, or both, leading to maldigestion of nutrients. The main enzymes secreted are amylase for carbohydrate digestion, lipase for fat digestion, and proteases (trypsinogen and chymotrypsin) for protein digestion. Amylase insufficiency does not cause symptoms, since it is compensated by the secretion of amylase from the salivary glands and from the small intestine. When trypsin secretion is less than 5-10% of normal, there is an excess loss of nitrogen in the feces. Therefore, the main consequence of pancreatic insufficiency is fat malabsorption.

The most characteristic symptoms are chronic diarrhea, steatorrhea and weight loss associated with abdominal distension, which appear when pancreatic function is less than 10%. There is also a deficiency of fat-soluble vitamins (A, D, E, K) and trace elements, such as magnesium and zinc(16).

Drug-induced diarrhea

• Antibiotic-associated diarrhea: It appears up to 2 weeks after the start of antibiotics, such as cephalosporins, ampicillin and amoxicillin/clavulanic acid.

• Pseudomembranous colitis: Caused by Clostridium difficile in children treated with antibiotics (clindamycin, penicillin, fluoroquinolones and cephalosporins). It can also occur in children with inflammatory bowel disease or immunodeficiencies(17).

• Non-antibiotic-associated diarrhea: Laxative abuse (Polyethylene glycol, magnesium hydroxide), sorbitol and artificial sweeteners, and treatment with erythromycin, which accelerates intestinal transit, do not alter the intestinal mucosa. However, non-steroidal anti-inflammatory drugs and proton pump inhibitors (PPIs) can cause enteritis(17).

Miscellaneous

Small intestine bacterial overgrowth syndrome (SIBO) is characterized by an excessive growth of microorganisms in the small intestine, either colonic (coliforms) or oropharyngeal and respiratory bacteria. In a recent study, the two factors most frequently associated with its development were a history of gastrointestinal infection in the previous year and the use of PPIs in the previous month. Only 7.4% had a history of previous intestinal surgery and up to 22.2% had recurrence after treatment(18).

Diagnosis

The diagnosis of chronic diarrhea is based on a complete history and physical examination and on the performance of complementary tests and first and/or second level diagnostic tools.

Medical history and physical examination

When assessing a patient with chronic diarrhea, it is very important to evaluate the age of onset and its possible relationship with the introduction of new foods, previous or current drug treatments, stool characteristics, and family history of digestive diseases.

The characteristics of the stools can provide information about the mechanisms responsible for diarrhea: carbohydrate intolerance (liquid, explosive and acidic stools, which may be associated with perianal erythema); maldigestion of fats (sticky, shiny, pale and floating stools); autoinflammatory origin (frequent, small stools with mucus and/or blood, which may be associated with tenesmus and/or nocturnal habits) and functional origin (soft stools, whose consistency decreases throughout the day and which may contain food remains, sometimes alternating with normal or hard stools).

Physical examination and anthropometric assessment are essential to evaluate the possible nutritional impact of diarrhea and to detect warning signs and symptoms. The patient’s weight and height should be plotted on a growth chart, since a decrease in height may be a sign of organic pathology.

In functional disorders, a compatible clinical picture and the absence of alarming data are sufficient to establish the diagnosis; whereas, if organic pathology is suspected, complementary tests are usually necessary based on the patient’s age, clinical picture and findings on examination.

First level complementary tests

These are sufficient to establish the diagnosis of the most frequent causes of chronic diarrhea in Primary Care.

• Blood tests: Complete blood count, biochemistry with blood glucose, urea, creatinine, total proteins, albumin, cholesterol, triglycerides, ions, calcium, phosphorus, alkaline phosphatase and ferritin. In addition, it is recommended to request: immunoglobulins, TSH, celiac disease serology and acute phase reactants, such as ESR and C-reactive protein. These parameters will allow us to diagnose diseases such as celiac disease and hyperthyroidism, as well as assess the possible malabsorption of nutrients or the biochemical impact. Thus, in inflammatory processes we can find anemia (of multifactorial origin), thrombocytosis, hypoalbuminemia and elevated acute phase reactants. Anemia may also be present in cases of malabsorption of iron, folic acid and/or vitamin B12, and low levels of total protein and serum albumin may indicate protein-losing enteropathy(8).

• Microbiological stool examination:

– Stool culture and viral antigens: Although these pathogens usually produce acute diarrhea, they can become chronic, mainly in children with immunodeficiencies.

– Parasites in feces: Their determination is essential, since the Giardia lamblia infection is the most common infectious cause of chronic diarrhea in developed countries. Because of the intermittent shedding of the parasite cysts, collecting stool from three different days increases the sensitivity of the study.

– Clostridium difficile toxin: Indicated if diarrhea is accompanied by blood in the stool, mainly in immunosuppressed patients, with inflammatory bowel disease or who have recently received antibiotic treatment.

• Exclusion-provocation therapeutic test: An empirical exclusion test and subsequent provocation may be considered if a non-IgE-mediated allergy or digestive intolerance is suspected, as may occur with cow’s milk proteins (in infants) or with some carbohydrates (lactose or fructose).

Second level complementary tests

If a complete clinical assessment and a first-level study do not lead to a diagnosis of chronic diarrhea, specific studies must be performed by a pediatric gastroenterologist. The choice of tests to be performed will be guided by the diagnostic suspicion based on the symptoms and characteristics of the diarrhea.

• Blood tests guided by clinical suspicion:

– Certain antibodies may be positive in IBD, such as anti-Saccharomyces cerevisiae (ASCA), more frequent in Crohn’s disease, and anti-neutrophil cytoplasmic antibodies (p-ANCA), which may be elevated in ulcerative colitis(2).

– Low levels of fat-soluble vitamins (A, E and D) are detected in cases of pancreatic insufficiency.

– Low zinc levels, in the context of chronic diarrhea associated with acrodermatitis, may guide to acrodermatitis enteropathica.

• Stool studies:

– Van de Kamer test: It consists of determining fat in 72 hour feces. Newborns and infants excrete between 15 and 20% of fat in their diet in their feces. The fat absorption coefficient increases with age and reaches adult values of >95% after one year of age. Normal values are <3 g/24 hours in children and <6 g/24 hours in adults. It is advisable to carry out a three-day dietary survey with determination of the fat absorption coefficient (fat ingested/fat excreted) to avoid false negatives due to low fat intake. Although it is the gold standard, other techniques have appeared, such as near-infrared reflection analysis (NIRA), which facilitates sample handling and also provides data on the absorption of sugars (normal values <2.5%), starch (normal values <1%) and water content (normal values <85%).

– Stool osmolality: Stool electrolytes are used to calculate the fecal osmotic gap. In secretory diarrhea, the stool osmotic gap is <50 mOsm/kg, whereas in osmotic diarrhea it is >125 mOsm/kg(2).

– Reducing substances (>1%) and stool pH (<5.3) indicate carbohydrate malabsorption. It should be noted that sucrose is a non-reducing sugar.

– Fecal elastase-1: It is a pancreatic enzyme resistant to degradation by the intestinal flora, so when the value is low (<200 µcg/g of feces) it suggests pancreatic exocrine insufficiency(8).

– Fecal α1-antitrypsin: It is a serum protein synthesized in the liver, resistant to proteolysis, which is normally present in low concentrations in the stool. Values ≥2 mg/g stool in a sample may indicate protein loss.

– Fecal calprotectin: This cytosolic protein of neutrophils is elevated in cases of intestinal inflammation, with normal values <50 µg/g. Despite its high sensitivity, this parameter may be elevated in gastrointestinal infections, juvenile polyps, use of non-steroidal anti-inflammatory drugs or gastrointestinal bleeding. In addition, calprotectin values have a significant negative correlation with age, with very high levels of up to 1,500 µg/g being observed in healthy infants and a wide variability up to 4 years of age, so caution should be exercised when interpreting it in children under this age(19).

– Fecal occult blood: Nonspecific marker indicating gastrointestinal blood loss.

• Breath test: Lactose and fructose breath tests consist of administering these labelled carbohydrates and subsequently measuring exhaled H2. In cases of carbohydrate malabsorption, carbohydrates are not absorbed and are therefore fermented in the colon, producing H2 and methane, which pass into the blood and are eliminated during exhalation. In SIBO, the bacteria in the small intestine ferment glucose before it is absorbed, with an early increase in hydrogen in the breath being detected. When carbohydrate intolerance is suspected, these tests are only indicated in cases of no conclusive clinical response to exclusion-provocation.

• Endoscopy and histological study: This test is essential in diseases such as inflammatory bowel disease, celiac disease, congenital enteropathies, microscopic colitis, primary eosinophilic gastrointestinal disorders, abetalipoproteinemia and intestinal lymphangiectasia, as well as for the study of disaccharidases in intestinal mucosa.

• Genetic studies: Most congenital diarrhea, cystic fibrosis (CF), monogenic IBD and immunodeficiency disorders have a genetic basis. Genetic analysis helps to make a definitive diagnosis and guide management.

• Sweat test: Stimulation of sweat by iontophoresis with pilocarpine. A first test is performed using conductivity and if the values are >50mmol/l, the concentration of chlorine in sweat will be measured. Two chlorine determinations of >60 mmol/L confirm the diagnosis of CF. Values between 40-60 mmol/L are considered doubtful.

• Imaging tests: Abdominal ultrasound and magnetic resonance play an important role in the study of IBD. Tc99-labeled albumin allows visualization of lymph leakage in intestinal lymphangiectasia.

At the end of the article, the diagnostic algorithm for chronic diarrhea is shown, with first and second level examinations of the different pathophysiological types of diarrhea and by etiology.

Treatment

Treatment of chronic diarrhea is based on general management of the disease, ensuring adequate nutritional support, and specific treatment of the underlying cause.

General treatment

The treatment of chronic diarrhea requires an accurate diagnosis for an adequate and specific management of the underlying cause, with nutritional rehabilitation being the most important aspect in the treatment of these patients. Adequate nutrient intake will facilitate the recovery of the intestinal mucosa, with the oral route being the route of choice. Occasionally, nutritional supplements may be necessary to cover the patient’s requirements. In cases of poor oral tolerance or compromised swallowing safety or efficacy, feeding may be administered through a nasogastric or transpyloric tube with continuous or intermittent delivery. The parenteral route will be reserved for those patients with poor enteral tolerance, severe malnutrition and intractable diarrhea. The use of drugs that inhibit intestinal peristalsis is not recommended in the pediatric population. Probiotics would only be indicated for the prevention of antibiotic-associated diarrhea and there is insufficient evidence for the prevention or treatment of SIBO.

Specific treatment

• Dietary treatment: This will be the treatment of choice in pathologies in which there is malabsorption due to a deficiency of enzymes or transport proteins, as occurs in glucose-galactose malabsorption, lactose or fructose intolerance, or saccharase-isomaltase deficiency, where the management of these clinical pictures is based on the partial or total withdrawal of the carbohydrate involved(20). It is also the treatment of choice in chronic diarrhea due to non-IgE mediated allergies, such as in CMPA(13). The strict gluten-free diet is the treatment for celiac disease. In intestinal lymphangiectasia, nutritional management is essential, indicating a low-fat diet, with medium chain triglycerides (MCT) and rich in protein(20). In alterations in the transport and metabolism of fats, such as abetalipoproteinemia, fats in the diet will be restricted and essential fatty acids will be provided(20). In Crohn’s disease, dietary treatment has an important role as an alternative to corticosteroids. In cystic fibrosis, supplementation with fat-soluble vitamins is required. In diarrhea associated with protein-losing enteropathy, a fat-free or low-fat diet is required, with MCT oil, rich in protein and supplementation with fat-soluble vitamins and essential fatty acids(20).

In functional diarrhea, a diet low in oligosaccharides, disaccharides, monosaccharides and fermentable polyols (FODMAPS) may be useful in irritable bowel syndrome, although they should be prescribed with caution and closely monitored due to the risk of nutritional repercussions(20).

• Pharmacological treatment: Specific treatments will depend on the etiology of the diarrhea. Antibiotics are mainly used in diarrhea of infectious origin, although they may also be indicated in SIBO (rifaximin or metronidazole)(18). Corticosteroids and immunomodulatory drugs are widely used in IBD and in less frequent pathologies, such as microscopic colitis(15), gastrointestinal eosinophilic disorders(14), autoimmune enteropathy and intestinal lymphangiectasia(8). Other specific treatments include: enzyme replacement therapy in exocrine pancreatic insufficiency; ion exchange resins in bile acid diarrhea; and octreotide in intestinal lymphangiectasia(8).

Role of the Primary Care pediatrician

• To perform the initial clinical history and physical examination, detailing the characteristics of the stools and the nutritional status of the patient.

• To request first-level tests, which can diagnose the most common causes of chronic diarrhea.

• Referral to the pediatric gastroenterology consultation, if a diagnosis has not been reached and the patient´s symptoms remain.

Conflict of interest

There is no conflict of interest in the preparation of the manuscript.

Bibliography

Asterisks indicate the authors’ opinion of the article as being of interest.

1. World Health Organization. Diarrhoeal Disease Fact Sheet N 330. 2017. Available in: http://www.who.int/mediacentre/factsheets/fs330/en/.

2.*** Tripathi PR, Srivastava A. Approach to a Child with Chronic Diarrhea. Indian J Pediatr. 2024; 91: 472-80.

3.** Thiagarajah JR, Kamin DS, Acra S, Goldsmith JD, Roland JT, Lencer WI, et al. Advances in Evaluation of Chronic Diarrhea in Infants. Gastroenterology. 2018; 154: 2045-59.

4. Benninga MA, Nurko S, Faure C, Hyman PR, Roberts IJ, Schechter NL. Childhood Functional Gastrointestinal Disorders: Neonate/Toddler. Gastroenterology. 2016; 150: 1443-55.e2.

5. Rajindrajith S, Hathagoda W, Devanarayana NM. Functional Diarrhea in Children. Indian J Pediatr. 2024; 9: 5849.

6. Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M, et al. Childhood Functional Gastrointestinal Disorders: Child/Adolescent. Gastroenterology. 2016; 150: 1456-68.

7. Naim HY, Heine M, Zimmer KP. Congenital Sucrase-Isomaltase Deficiency: Heterogeneity of Inheritance, Trafficking, and Function of an Intestinal Enzyme Complex. J Pediatr Gastroenterol Nutr. 2012; 55: S13-20.

8.*** Shankar S, Rosenbaum J. Chronic diarrhoea in children: A practical algorithm-based approach. J Ped Child Health. 2020; 56: 1029-38.

9. Gu L, He XH, Zhu P. Analysis of similarities and differences between transient symptomatic zinc deficiency an acrodermatitis enterophatica in children: a case report of a Chinese Yi-ethnic infant. BMC Pediatr. 2024; 24: 338. Available in: https://doi.org/10.1186/s12887-024-04830-y.

10. Sissaoui S, Cochet M, Poinsot P, Bordat C, Collardeatu-Frachon S, Lachaux A, et al. Lipids reponsible for intestinal or hepatic disorder. When to suspect a familiar intestinal hypocholesterolemia? J Ped Gastroenterol Nutr. 2021; 73: 4-8.

11. Niu Y, Wu Q, Wang Y, Lu L. Feng Y, Cai W, et al. Primary intestinal lymphangiectasia in children: Twelve years of experience in the diagnosis and management. Asia Pac J Clin Nutr. 2021; 30: 358-64.

12. Jin M, Gong Y, Liu W, Zhong X. Clinical characteristics and management of autoimmune enteropathy in children: case reports and literature review. BMC Pediatr. 2023; 23: 601. Available in: https://doi.org/10.1186/s12887-023-04435-x.

13. Vandenplas Y, Broekaert I, Domellöf M, Indrio F, Lapillonne A, Pienar C, et al. An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow’s Milk Allergy. J Ped Gastroenterol Nutr. 2024; 78: 386-413.

14. Papadopoulou A, Amil-Dias J, Auth MKH, Chehade M, Collins MH, Gupta SK, et al. Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2024; 78: 122-52. Available in: https://doi.org/10.1097/mpg.0000000000003877.

15. Khushal S, Hemker MO. Diagnosis and Management of Microscopic Colitis in Pediatric Patients. Pediatric Drugs. 2022; 24: 217-33.

16. Sankararaman S, Schindler T, Sferra TJ. Management of Exocrine Pancreatic Insufficiency in Children. Nutrition in Clinical Practice. 2019; 34: S27-42.

17.** Sathiyasekaran M, Ganesh R, Natarajan S. Other Causes of Chronic Diarrhea in Children. Indian J Pediatr. 2024; 91: 60613.

18. Cho YK, Chang J, Paik CN. Prevalence, risks factors, and treatment of small intestinal overgrowth in children. Clin Exp Pediatr. 2023; 66: 377-83.

19. Lężyk-Ciemniaka E, Tworkiewicza M, Wilczyńskaa D, Szaflarska-Popławskab A, Krogulskaa A. Usefulness of Testing for Fecal Calprotectin in Pediatric Gastroenterology Clinical Practice. Med Princ Pract. 2021; 30: 311-9.

20.*** Shankar DS, Durairaj E. Diet and Management of Diarrhea. Indian Journal of Pediatrics. 2024; 91: 590-7.

21. Ramos Boluda E, González Sacristán R. Chronic diarrhea. Diarrea crónica. Pediatr Integral. 2019; XXIII: 386-91. Available in: https://www.pediatriaintegral.es/publicacion-2019-12/diarrea-cronica-2/.

Recommended bibliography

– Tripathi PR, Srivastava A. Approach to a Child with Chronic Diarrhea. Indian J Pediatr. 2024; 91: 472-80.

Review article explaining the different clinical types of chronic diarrhea. It also updates the diagnostic procedures available and shows comprehensive diagnostic algorithms for making the differential diagnosis.

– Shankar S, Rosenbaum J. Chronic diarrhoea in children: A practical algorithm-based approach. JPed Child Health. 2020; 56: 1029-38.

Review article that, in addition to showing diagnostic algorithms, assesses the pharmacological treatments available for some types of chronic diarrhea.

– Shankar DS, Durairaj E. Diet and Management of Diarrhea. Indian Journal of Pediatrics. 2024; 91: 590-7.

Excellent review article that assesses in detail the treatment of the different causes of chronic diarrhea, whose therapy is exclusively dietary.

 

Clinical case

A 3-year-old boy with a history of atopic dermatitis and IgE-mediated egg allergy came to the clinic with diarrhea that had been ongoing for 6 months. The parents reported that he had previously had one or two episodes of Bristol type 4 stools per day. However, after starting nursery school he had multiple infectious processes, including acute gastroenteritis lasting for up to 5 days, with diarrhea, fever and vomiting. Since then, the patient has had 2-3 Bristol type 6 stools a day with abundant bloating. He has abdominal distension after meals and periumbilical discomfort. He has not had loss of appetite and has an ascending height and weight curve. They do not relate the diarrhea and the accompanying symptoms to the intake of any specific food. The parents removed lactose from the diet with partial improvement for a week. However, the symptoms described above subsequently relapsed again. The patient’s nutritional and hydration status was good, with a normal systematic examination, in which the only notable feature was a globular abdomen, although soft and depressible, without masses or megalies, and it did not seem painful to palpation. Given the chronic diarrhea, a stool culture and stool parasites were obtained, which were negative, and a blood test with a normal complete blood count and biochemistry (with immunoglobulins), except for positive anti-deaminated gliadin peptide IgG (40 U/ml), with negative anti-transglutaminase IgA and antiendomysium.