Jaundice
Jaundice: Excerpt from Pediatric Complaints and Diagnostic Dilemmas
Eric J. Frehm
Approach to the Patient with Jaundice
I. Definition of the Complaint
Jaundice is the yellow discoloration of the skin, mucous membranes, and sclerae
that is caused by increased serum levels of bilirubin, a byproduct of heme
breakdown. As a lipophilic pigment, bilirubin must bind to plasma albumin for
carriage to the liver. It is taken up by hepatocytes for conjugation with
solubilizing sugars to form bilirubin diglucuronides (and, less commonly,
monoglucuronides), thus allowing for excretion into bile. Not all jaundice is
pathologic. Indeed, the vast majority of clinically encountered
hyperbilirubinemia occurs as physiologic jaundice in neonates.
II. Complaint by Cause and Frequency
Neonatal jaundice can be caused by conjugated or unconjugated hyperbilirubinemia
(Table 15-1). The differential diagnosis of cholestatic jaundice in the older
child differs from diseases that present early in life. Young infants are more
likely to have congenital anatomic anomalies, such as biliary atresia, or
inborn metabolic disorders, such as galactosemia. Older children are more
likely to experience acquired or secondary liver diseases, such as autoimmune
or toxic hepatitis, or liver impairment related to inflammatory bowel disease.
Infectious hepatitis is among the most common causes of liver disease in older
children and adolescents. Viruses causing hepatitis and jaundice in these
children include: hepatitis A, B, C, D and E; Epstein-Barr virus;
cytomegalovirus; varicella; human herpesvirus 6 (HHV-6); and herpes simplex
virus (HSV). Other infectious diseases associated with jaundice include
schistosomiasis, leptospirosis, Rocky Mountain spotted fever, ehrlichiosis, and
malaria.
Obstructive, extrahepatic causes of conjugated hyperbilirubinemia in children
and adolescents to consider include cholelithiasis, choledochal cysts,
sclerosing cholangitis, pancreatitis, and tumors and other anatomic
abnormalities along the choledocho-pancreatico-duodenal path.
III. Clarifying Questions
• Is the elevated bilirubin level all unconjugated? Is the process a conjugated
hyperbilirubinemia?
— Separating a total bilirubin measurement into its conjugated and unconjugated
components is a critical step in the evaluation of hyperbilirubinemia in a
child. Conjugated hyperbilirubinemia is present when the conjugated fraction is
at least 1.5 mg/dL or accounts for more than 15% of the total bilirubin
measurement. Conjugated hyperbilirubinemia is abnormal and merits prompt
evaluation, particularly in infants, in whom diseases such as biliary atresia
require urgent therapy. An increased unconjugated bilirubin level suggests a
very different differential diagnosis but can also be a medical emergency if
very high: unconjugated bilirubin is able to cross the blood-brain barrier and
directly injure the brain.
Sometimes the terms “direct” and “indirect” bilirubin are used interchangeably with the terms “conjugated” and “unconjugated.” The former terms derive from the van den Bergh reaction, in which the
conjugated bilirubin component is measured
directly (by colorimetric analysis after reaction with a diazo compound). The subsequent
addition of methanol allows for a measurement of total bilirubin, after which
unconjugated fraction is determined
indirectly, by subtracting the conjugated bilirubin level from the total bilirubin level. Of
note, measurement of the direct bilirubin fraction detects not just bilirubin
diglucuronides and monoglucuronides but also
“delta” bilirubin, which forms when conjugated bilirubin seeps retrograde into the
serum and binds covalently to albumin. Because of the delta component
's long half-life, the “direct fraction” can remain deceptively elevated even as a conjugated hyperbilirubinemia
improves.
• Does the jaundiced baby have other concerning physical findings?
— A significant unconjugated hyperbilirubinemia can result from the increased
bilirubin of a cephalohematoma or extensive bruising. A newborn afflicted with
a TORCH infection might have microcephaly, growth retardation,
hepatosplenomegaly, chorioretinitis, or petechiae. A heart murmur is often
heard in children with Alagille syndrome, whereas a baby with Zellweger
syndrome is hypotonic and dysmorphic. Of course, serious bacterial infection
must always be considered in any case of significant bilirubinemia.
• Is there a family history of jaundice?
— Many of the disorders that manifest with jaundice are heritable. α1-Antitrypsin deficiency, Crigler-Najjar syndrome type I and II, galactosemia,
and tyrosinemia are just a few of the autosomal recessive diseases associated
with neonatal jaundice. On the other hand, Alagille syndrome is an autosomal
dominant disorder (but with variable penetrance and expressivity). The
inheritance of glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked
but so highly polymorphic that it should be considered in the evaluation of
boys and girls alike.
• Were there changes in the child's diet or other new “exposures” that preceded the onset of jaundice?
— Deficiencies in the metabolism of galactose or fructose can lead to jaundice in
infants. Likewise, children with G6PD deficiency can have hemolytic crises
triggered by certain foods (e.g., fava beans), medications (e.g., antimalarial
agents), or other compounds (e.g., mothballs).
• Are neonatal hyperbilirubinemia risk factors present?
— Risk factors for neonatal jaundice that derive from the mother include
ethnicity (e.g., Asian, Native American) and pregnancy complications such as
gestational diabetes or blood group incompatibility. Birth trauma that results
in extravascular blood collections is also a risk factor for jaundice. Other
independent risk factors for the infant include polycythemia, prematurity,
breast-feeding, perinatal infections, and a long, heterogenous list of genetic
disorders.
IV. References
1. D'Agata ID, Balistreri WF. Evaluation of liver disease in the pediatric patient. Pediatr Rev 1999;20:376–389.
2. Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med 2001;344:581–590.
3. Gourley GR. Neonatal jaundice and disorders of bilirubin metabolism. In:
Suchy FJ, Sokol RJ, Balistreri WF, eds.
Liver disease in children, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2001:275–314.
4. Maisels MJ. Jaundice. In: Avery GB, Fletcher MA, MacDonald MG, eds. Neonatology: pathophysiology and management of the newborn, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 1999:765–819.
5. Maller ES. Jaundice. In: Altschuler SM, Liacouris CA. Clinical pediatric gastroenterology. New York: Churchill Livingstone, 1998:49–61.
Pictures
Book Source Details
- Book Title: Pediatric Complaints and Diagnostic Dilemmas
- Author(s): Samir S Shah MD; Stephen Ludwig MD
- Year of Publication: 2003
- Copyright Details: Pediatric Complaints and Diagnostic Dilemmas, Copyright © 2003 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
» Next page: Jaundice - Case 15-4: 6-Week-Old Girl (Pediatric Complaints and Diagnostic Dilemmas)
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