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Laboratory tests that may be indicated for evaluation of children age >6 months with chronic diarrhea

Laboratory tests that may be indicated for evaluation of children age >6 months with chronic diarrhea
Test Indication/implications
General screening tests
All patients
Tissue transglutaminase (tTg-IgA)
  • tTg-IgA is a sensitive and specific screen for celiac disease.
  • Many clinicians also measure total IgA to exclude the possibility of IgA deficiency (present in approximately 2% of children with celiac disease).
CBC
  • Useful for assessment of anemia, inflammation, neutropenia, and lymphopenia.
Fecal calprotectin or lactoferrin
  • Elevated in intestinal inflammation, including IBD. These are markers of fecal leukocytes.
Stool cultures
  • Stool cultures are usually obtained early in the evaluation of prolonged diarrhea. Persistent bacterial or viral pathogens suggest an immunodeficiency.
Atypical characteristics*
Systemic inflammatory markers (eg, ESR, CRP)
  • Markers for systemic inflammation (eg, IBD).
ALT, AST
  • Abnormal liver enzymes may indicate a significant underlying systemic disorder.
Albumin
  • Low albumin levels may indicate impaired liver function or loss of protein in the urine or stool. In patients with diarrhea, low albumin may indicate protein-losing enteropathy; a common cause is extensive IBD.
Tests for patients with specific characteristics
Bloody stools and/or suspected infectious or inflammatory diarrhea
Stool cultures, C. difficile toxin, G. lamblia
  • If not already done.
Fecal occult blood
  • Confirms the presence of blood in stool. However, occult blood also may be caused by cutaneous irritation due to severe diarrhea, so its presence is not sufficient to confirm inflammatory diarrhea. We, therefore, do not recommend its use in initial testing.
Known or suspected malabsorptive disease
Fecal fat
  • Qualitative (spot) fecal fat is a helpful initial test for fat malabsorption. Elevated neutral fats suggest pancreatic insufficiency. Elevated split fats (free fatty acids) suggest intestinal fat malabsorption.
  • Quantitative measurement of fat in the stool is more sensitive for detecting fat malabsorption but the stool collection is cumbersome and difficult to perform accurately.
Fat-soluble vitamins
  • Low levels of fat-soluble vitamins suggest fat malabsorption, especially if steatorrhea is present.
Vitamin B12
  • Vitamin B12 deficiency (and macrocytic anemia) is associated with Crohn disease, celiac disease, and SIBO.
Serum calcium
  • Hypocalcemia is associated with fat malabsorption. Hypercalcemia is seen in polyglandular autoimmune syndrome.
Breath test
  • Breath tests provide evidence of carbohydrate malabsorption. However, they are not generally required for the diagnosis of lactase deficiency, congenital sucrase-isomaltase deficiency, or SIBO.
Severe unexplained diarrhea
Stool electrolytes
  • Stool electrolytes (specifically Na+ and K+), obtained while subject with diarrhea is on their usual diet, can help to distinguish between an osmotic (diet-induced) diarrhea and an electrolyte transport-related (secretory) diarrhea:
    • Normal stool osmolarity is approximately 290 mOsm.
    • Calculated stool osmotic gap = 290 mOsm/kg – 2 × (stool Na+ + stool K+).
    • If the calculated osmotic gap is >50 mOsm, other unmeasured osmoles are present (ie, nutrients), indicating an osmotic/malabsorptive type of diarrhea.
    • If the calculated osmotic gap is minimal (<50 mOsm), a high concentration of luminal electrolytes contributes to the stool volume, suggesting an electrolyte transport-related (secretory) diarrhea.
    • For details, refer to UpToDate content on pathophysiology of acute diarrhea in children.
Stool-reducing substances and pH
  • Reducing substances >0.5% indicates malabsorption of monosaccharides.
  • Low pH (<5.3) results from an abundance of short-chain fatty acids that are fermentation products and indicate carbohydrate malabsorption.
  • However, these must be interpreted in the context of the child's age and diet since some amount of carbohydrate malabsorption is normal in neonates and toddlers.
Stool magnesium and phosphorus
  • If laxative abuse or excessive antacids are suspected.
Stool alpha-1 antitrypsin
  • A low serum albumin level should prompt the assessment of fecal alpha-1 antitrypsin. Elevated alpha-1 antitrypsin in stool reflects intestinal protein loss (ie, protein-losing enteropathy) because it is not degraded by intestinal proteases (unless it is secreted in the stomach).
Anti-enterocyte antibodies
  • Elevated in a subset of subjects with autoimmune enteropathy.
Secretin stimulation test
  • Measures exocrine pancreatic function by quantifying trypsin, amylase, lipase, and chymotrypsin following secretin stimulation; requires endoscopy.
Serum vasoactive intestinal peptide (VIP)
  • Some neuroblastomas secrete VIP and are classified as VIPomas.
Urinary catecholamines (HVA and VMA) levels
  • Produced by neuroblastomas.
Suspected bowel obstruction
Abdominal radiograph
  • Partial bowel obstruction is suggested by severe abdominal distension and/or vomiting; causes include dysmotility, Hirschsprung disease, or malrotation with intermittent volvulus.
Suspected immune deficiency
Serum immunoglobulins, T and B cells subsets
  • T cell defects are associated with recurrent or persistent viral or parasitic infection, while B cell disorders are more often associated with bacterial infections. Depletion of IgG/IgA (and albumin) may be seen in CVID and protein-losing enteropathy.
Suspected bile acid malabsorptionΔ
Serum 7-alpha-hydroxy-4-cholesten-3-one (C4), a bile acid precursor
  • Elevated C4 level is associated with bile acid-induced diarrhea. Risk factors include terminal ileal disease or resection, after cholecystectomy, or SIBO.
IgA: immunoglobulin A; CBC: complete blood count; IBD: inflammatory bowel disease; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; ALT: alanine aminotransferase; AST: aspartate aminotransferase; C. difficile: Clostridioides difficile; G. lamblia: Giardia lamblia; SIBO: small intestine bacterial overgrowth; Na+: sodium ion; K+: potassium ion; mOsm: milli-osmoles; VIPoma: vasoactive intestinal peptide-secreting tumor; HVA: homovanillic acid; VMA: vanillylmandelic acid; IgG: immunoglobulin G; CVID: common variable immunodeficiency.
* Characteristics that are atypical for functional diarrhea include severe or nocturnal diarrhea, bloody stools, and any warning signs (weight loss or growth faltering, fever, abdominal distension or tenderness). Evaluation for such patients should include these general laboratory tests (tTg-IgA, ESR, CBC, ALT, AST, albumin), in addition to any relevant more specific tests in the remainder of this table.
¶ Chronic electrolyte transport-related (secretory) diarrheas are rare. They may be caused by bile acid malabsorption and certain medications (magnesium sulfate, lubiprostone) or by rare congenital disorders and enteropathies such as congenital chloride diarrhea (refer to UpToDate content on chronic diarrhea in infants <6 months).
Δ Bile acid malabsorption should be suspected in patients with terminal ileal disease or resection, after cholecystectomy, or in SIBO due to deconjugation of the bile salts by small intestinal bacteria.
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