Diarrhea, chronic

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Chapter 14 DIARRHEA, CHRONIC

Theodore X. O’Connell

General Discussion

The term diarrhea refers to an increase in the frequency, fluidity, or volume of bowel movements relative to the usual habit of an individual. The World Health Organization (WHO) defines diarrhea as the passage of three or more loose or watery stools per day. Diarrhea may be considered chronic if it persists for 14 days or longer.

Gastrointestinal (GI) infection is the most common cause of chronic diarrhea in children. The major pathogens are outlined below. Protein intolerance, usually to cow’s milk or soy protein, is a common cause of chronic diarrhea and usually manifests before 6 months of age. Protein intolerance may be accompanied by bloody diarrhea, anemia, and manifestations of allergy, such as eczema, hives, or asthma.

Chronic nonspecific diarrhea of childhood primarily affects children between 1 and 5 years of age. Although the parents may be concerned, children with chronic nonspecific diarrhea do not suffer from their ailment and appear healthy. The syndrome is characterized by persistent or recurrent episodes of voluminous loose stools, often with undigested food particles in the stools. Nocturnal diarrhea is absent. The pathophysiology of chronic nonspecific diarrhea remains unclear.

Overfeeding results in an osmotic diarrhea, often from the excessive intake of fluids containing sorbitol and fructose. Primary disaccharidase deficiencies are rare. However, secondary disaccharidase deficiencies occur more commonly as a result of damage to the brush-border membrane and may be associated with infection, allergies, and celiac disease. The diarrhea typically is explosive and watery and may be accompanied by bloating, flatulence, and abdominal pain.

Celiac disease is associated with villous atrophy of the proximal small intestine as a result of intolerance to gluten protein. Most children with celiac disease begin to show symptoms at 6 to 24 months of age, although symptoms can develop anytime after gluten is introduced into the diet in the form of wheat, barley, or rye. In addition to chronic diarrhea, children with celiac disease may have failure to thrive, irritability, muscle wasting, abdominal distention, and anorexia.

Cystic fibrosis may manifest as steatorrhea with malabsorption. The history may include meconium inspissation in the neonatal period, prolonged neonatal jaundice, and recurrent or chronic chest infections.

Inflammatory bowel disease usually develops in late childhood or during adolescence. Bloody diarrhea, abdominal pain, and weight loss should raise suspicion for ulcerative colitis or Crohn’s disease. Both conditions may be accompanied by extraintestinal manifestations such as arthritis, intermittent fever, erythema nodosum, and pyoderma gangrenosum.

Pseudomembranous enterocolitis is infrequently diagnosed in children but may be seen following antibiotic administration. Antibiotics may also cause diarrhea as a result of bacterial overgrowth.

Endocrine causes of chronic diarrhea include hyperthyroidism, diabetes mellitus, adrenal insufficiency, and hypoparathyroidism. Functional tumors may result in chronic diarrhea by secreting hormones. These tumors are outlined below. Other less common causes of chronic diarrhea are also outlined below.

Causes of Chronic Diarrhea

Acquired monosaccharide malabsorption

Adrenal insufficiency

Anatomic lesions

• Blind loop syndrome

• Hirschsprung disease

• Intestinal pseudo-obstruction syndrome

• Lymphoma

• Lymphosarcoma

• Malrotation

• Partial small bowel obstruction

• Polyposis

• Short bowel syndrome

Antibiotics

Carbohydrate malabsorption

Celiac disease

Chronic constipation with overflow diarrhea

Chronic nonspecific diarrhea of childhood

Congenital chloride-losing diarrhea

• Milk protein hypersensitivity

• Overfeeding

• Sorbitol intolerance

• Soy protein hypersensitivity

Disaccharidase deficiencies

Enterokinase deficiency

Eosinophilic gastroenteropathy

Glucoamylase deficiency

Glucose-galactose malabsorption

Hormone-secreting tumors

• APUDomas

• Carcinoid tumor

• Ganglioneuroma

• Medullary carcinoma of the thyroid

• Neuroblastoma

• Pancreatic islet cell tumor (Zollinger-Ellison syndrome)

Hyperthyroidism

Hypoparathyroidism

Immunodeficiency states

• Acquired immunodeficiency syndrome (AIDS)

• Agammaglobulinemia

• Autoimmune enteropathy

• Combined immunodeficiency

• Defective cellular immunity

• Isolated IgA deficiency

Infections

• Bacterial

• Campylobacter jejuni

• Escherichia coli

• Salmonella species

• Shigella spp.

• Yersinia enterocolitica

• Parasitic

• Cryptosporidium species

• Entamoeba histolytica

Intestinal lymphangiectasia

• Primary bile acid malabsorption

Metabolic abnormalities

• Abetalipoproteinemia

• Acrodermatitis enteropathica

• Familial chloride diarrhea

• Folic acid malabsorption

• Galactosemia

• Hypobetalipoproteinemia

• Selective vitamin B₁₂ malabsorption

• Sodium-hydrogen exchange defect

• Tyrosinemia

• Wolman’s disease

Microvillus inclusion disease

Necrotizing enterocolitis

Pancreatic disorders

• Chronic pancreatitis

• Cystic fibrosis

• Johanson-Blizzard syndrome

• Lipase deficiency

• Shwachman-Diamond syndrome

• Trypsinogen deficiency

Pseudomembranous enterocolitis

Sucrase-isomaltase deficiency

Toxic diarrhea

Tropical sprue

Ulcerative colitis

Urinary tract infection (UTI)

Whipple disease

Suggested Work-up

Stool analysis for the following:

pH and reducing substances	The presence of reducing substances with a pH less than 6 suggests carbohydrate malabsorption
Occult blood	To evaluate for bleeding
Fatty acid crystals	Suggests a mucosal problem such as celiac disease
Fat globules	The presence of fat globules in an older child suggests steatorrhea but may be normal in the first few months of life
Microscopic exam for red blood cells (RBCs) and white blood cells (WBCs)	Neutrophils and RBCs may suggest infection or inflammatory bowel disease
	Eosinophils suggest parasitic infestation or protein intolerance
Microscopic exam for ova and parasites	To evaluate for parasite infection
Stool culture	To evaluate for infectious etiologies
Complete blood cell count (CBC)	To evaluate for infection, neutropenia, or eosinophilia. May also reveal microcytic or macrocytic anemia.
Erythrocyte sedimentation rate	To evaluate for infection or inflammatory bowel disease
Serum electrolytes	To evaluate for electrolyte disturbance
Serum protein and albumin levels	To evaluate for malnutrition (proportional decrease) or protein-losing enteropathy (greater loss of albumin)
Serum carotene level	To evaluate for fat malabsorption

Additional Work-up

Endomysial and tissue transglutaminase antibodies	If celiac disease is suspected
Giardia stool antigen	If giardiasis is suspected
Serum immunoglobulins	If immunodeficiency is suspected
HIV test	If HIV infection is suspected
Hydrogen breath test	If carbohydrate malabsorption is suspected
72-hour fecal fat test	If fat malabsorption is suspected
Sweat chloride test	If cystic fibrosis is suspected
Upper GI series with small-bowel follow-through	If Crohn’s disease or anatomic abnormalities are suspected
Barium enema	If Hirschsprung’s disease or inflammatory bowel disease is suspected
Sigmoidoscopy	If inflammatory bowel disease or pseudomembranous colitis is suspected
Jejunal biopsy	To confirm the presence of celiac disease