Jaundice - Case 15-4: 6-Week-Old Girl
Jaundice - Case 15-4: 6-Week-Old Girl: Excerpt from Pediatric Complaints and Diagnostic Dilemmas
I. History of Present Illness
A 6-week-old, full-term female infant was brought to the hospital by her mother
because of persistence of scleral icterus. The infant had been seen during the
first week of life after the mother noted she
“looked yellow.” At that time, she was otherwise doing well and the pediatrician diagnosed
physiologic jaundice. At 2 weeks of age, the baby began having blood-tinged
stools. She was changed first from cow
's milk to soy milk formula, and then to an elemental formula, after which the
bleeding resolved.
The baby had lately been acting well, taking her feedings without difficulty,
and making a normal number of wet diapers. There was no recent history of
emesis, excessive fussiness, bleeding, or bruisability. The mother did report
that the baby
's stools had become increasingly white and pasty.
II. Past Medical History
The child was born by an uncomplicated, repeat cesarean section at 38 weeks. Her
birth weight was 3.6 kg. Her hospital stay was unremarkable, and she was
discharged home with her mother on the third day of life.
The infant had a healthy 3-year-old brother. There was no family history of
jaundice, liver disease, anemia, or familial blood disorders.
III. Physical Examination
T, 37.0°C; RR, 32/min; HR, 136 bpm; BP, 88/60 mm Hg
Weight, 4.1 kg (10th to 25th percentile); length, 56 cm (25th to 50th
percentile)
On examination, the infant was resting quietly in her mother's arms and was observed to have a mild “muddy” jaundice in her face. She was nondysmorphic and normocephalic, with an open,
flat fontanel. Scleral icterus was pleasant. There was no nasal discharge or
flaring. The oropharynx was clear, with moist mucous membranes. The lung and
cardiac examinations were normal. Her abdomen was soft and nondistended, and a
smooth, firm liver edge palpable 2 cm below the right costal margin. The
genitourinary, extremity, and neurologic examinations were all normal.
IV. Diagnostic Studies
The complete blood count revealed the following: 6,900 WBCs/mm3 (43% segmented neutrophils and 48% lymphocytes); hemoglobin, 9.2 g/dL; and
332,000 platelets/mm
3. Total bilirubin was 9.5 mg/dL, and the direct bilirubin concentration was 8.4
mg/dL. ALT and AST were 267 and 288 U/L, respectively. Albumin was 3.2 g/dL,
and the alkaline phosphatase was 641 U/L. Serum electrolytes, BUN, creatinine,
and glucose were normal. Calcium was also normal. Urinanalysis revealed a
specific gravity of 1.015 and 1+ blood but no nitrites, leukocyte esterase,
protein, or urobilinogen.
V. Course of Illness
Abdominal ultrasound studies demonstrated mild hepatomegaly but normal-appearing
kidneys, spleen, and adrenal glands. The infant was admitted for urgent
evaluation of her cholestatic hyperbilirubinemia.
Discussion: Case 15-4
I. Differential Diagnosis
The differential diagnosis for cholestatic jaundice in the infant is quite
broad, and many excellent and detailed reviews exist. General categories of
disease entities to be considered include
infections, such as hepatitis viruses, TORCH infections, and serious bacterial infections; idiopathic neonatal hepatitis; a long list of metabolic and endocrine diseases, including galactosemia, α1-antitrypsin deficiency, cystic fibrosis, hypothyroidism, hypopituitarism, and
bile acid synthesis defects;
genetic cholestatic syndromes, such as Byler disease; obstructions to bile flow, including biliary atresia, Alagille syndrome, choledochal cysts, and
cholelithiasis; and
iatrogenic causes, such as drug-induced cholestasis or cholestasis related to total parenteral
nutrition.
II. Diagnosis
The infant was sent for a hepatic scintigraphic study (diisopropyl
iminodiacetate [DISIDA] scan). It showed good tracer uptake but no intestinal
excretion at 4 or 24 hours. An obstructive etiology of cholestasis was feared,
and the baby was taken to the operating room. An intraoperative cholangiogram
confirmed the
diagnosis of extrahepatic biliary atresia (EHBA).
III. Incidence and Etiology
Biliary atresia occurs in about 1 in every 10,000 to 15,000 infants worldwide.
The disease is characterized by postinflammatory obliteration of some or all of
the extrahepatic biliary ducts. The extent of biliary tree involvement varies.
If the disease is limited to the distal segment, surgical correction may be
possible. Far more common, however, is diffuse involvement of the extrahepatic
biliary ducts, for which hepatic portoenterostomy (the Kasai procedure) or
liver transplantation is required.
The etiology of EHBA remains a mystery. It is presumably caused by an insult,
perhaps viral or ischemic, to the developing biliary tree. Not even the timing
of the disease onset is clear. Some children with biliary atresia are born with
other true congenital anomalies (e.g. malrotation, polysplenia, heart defects).
On the other hand, most infants with EHBA have no other malformations and are
clinically well until several weeks of age, suggesting a progressive, acquired
process with relatively late onset. Likewise, the range of histopathologic
findings seen in biliary atresia is heterogeneous. Therefore, it seems likely
that multiple etiologies of biliary atresia exist.
IV. Clinical Presentation
Infants with biliary atresia often present in the first 2 to 6 weeks of life
with acholic stools, hepatomegaly, and jaundice. Over time the urine darkens,
the jaundice persists, the liver grows (as bile stasis worsens), and even the
spleen may enlarge. In the early weeks and months, these children often appear
well and have unremarkable medical histories. If the disease goes untreated,
malnutrition, growth retardation, and liver dysfunction emerge. Portal
hypertension, coagulopathy, and hypersplenism may develop. In untreated
patients, average expected survival time is about 1 year.
In this case, the baby presented with a direct hyperbilirubinemia but also a
mild elevation of liver enzymes suggestive of hepatocellular injury. This is
common in EHBA, although these findings may also be seen with neonatal
hepatitis or other disease entities, and indeed there can be considerable
overlap in clinical and laboratory findings among the various etiologies of
conjugated hyperbilirubinemia. The complete blood count was not suggestive of
acute infection, and the urinalysis appeared benign. The absence of
urobilinogen is actually consistent with an obstructive cholestasis, because
its formation requires entry of conjugated bilirubin into the intestine for
degradation by gut bacteria. The presentation of a jaundiced but otherwise
well-appearing 6-week-old infant with conjugated hyperbilirubinemia prompted an
immediate search for an obstructive process, and hepatic scintigraphy strongly
suggested the diagnosis that was confirmed by intraoperative cholangiogram.
V. Diagnostic Approach
The differentiation of biliary atresia from other common causes of cholestatic
jaundice in the young infant (particularly
“neonatal hepatitis”) can be complex. Prompt diagnosis of biliary atresia is critical because of the
declining success of hepatic portoenterostomy performed beyond 2 months of age.
Among the other causes of cholestatic jaundice for which urgent intervention is
required are galactosemia, hormone deficiency states (specifically,
hypothyroidism and hypopituitarism), and acute infections, notably with
gram-negative organisms.
Once cholestatic jaundice has been diagnosed (with a fractionated bilirubin
measurement) and a thorough history and physical examination have been
performed, laboratory assessment of liver function should be made (e.g.,
prothrombin time, glucose, ammonia, albumin). Simultaneously, infectious and
metabolic causes of cholestasis for which immediate therapy might be necessary,
such as those mentioned previously, should be excluded. This evaluation should
include cultures of blood and urine, assessment of thyroid function, and a
measurement of urine reducing substances (in infants receiving lactose) or
other appropriate assay for galactosemia. Other helpful first-line tests
include liver enzymes (e.g., ALT, AST, alkaline phosphatase, GGT), complete
blood count, and an abdominal ultrasound study.
Abdominal ultrasonography. Although abdominal ultrasonography does not diagnose biliary atresia, it can
identify anomalies (e.g., polysplenia) that are specifically associated with
some cases of EHBA, as well as gall bladder sludge or stones, choledochal
cysts, ascites, and other disease states.
Hepatic scintigraphy. If abdominal ultrasonography is nondiagnostic, hepatic scintigraphy (e.g.,
DISIDA scan) may demonstrate biliary tract patency. A scintigraphic examination
that
fails to show hepatic excretion of the isotope, however, neither diagnoses EHBA nor
excludes intrahepatic bile duct obstruction and neonatal hepatitis. Sampling of
nasoduodenal tube aspirates for bile pigments
—or even for radioactivity, if scintigraphy was performed—can also provide evidence of bile duct patency.
Other studies. Magnetic resonance cholangiography and endoscopic retrograde cholangiography are
among the newer modalities for assessing the biliary tract anatomy. Liver
biopsy is highly sensitive and specific for biliary atresia and can also
differentiate EHBA from intrahepatic bile duct obstruction. Ultimately, if
continuity between the liver and duodenum remains unproved, exploratory
laparotomy with cholangiography is required.
If evaluation for obstructive processes and potential medical emergencies (e.g.,
galactosemia, sepsis, an endocrinopathy) is nondiagnostic, the scope of the
evaluation must be widened. Once the extrahepatic diseases are excluded, the
remainder of the differential diagnosis can be conceptualized as being related
to either
hepatocellular or intrahepatic bile duct etiologies. Multiple tests on blood and urine (in addition to sweat testing to
rule out cystic fibrosis) are available to assess for specific disease
entities. Among these are plasma amino acids, urine amino and organic acids,
α1-antitrypsin phenotype, plasma iron and ferritin (to rule out neonatal iron
storage disease), serum and urine bile acid profile, and serologic analyses for
the hepatitis virus, TORCH infections, syphilis, cytomegalovirus, human
immunodeficiency virus (HIV), HHV-6, Epstein-Barr virus, and parvovirus B19.
Liver biopsy is a safe and straightforward procedure, and the histopathologic
data it provides can discriminate among diseases of intrahepatic bile duct
hypoplasia or paucity.
VI. Treatment
The hepatic portoenterostomy (Kasai procedure) for biliary atresia involves the
anastomosis of a limb of small intestine to hepatic ducts in the region of the
porta hepatis (where the portal vein and hepatic artery enter the liver and the
hepatic ducts exit). It relies on the patency of tiny duct remnants to allow
for bile drainage from the liver. Cholangitis is among the most worrisome of
the postoperative complications of hepatic portoenterostomy; its signs and
symptoms include fever, diminished bile flow, and the return of
hyperbilirubinemia. Over time, survivors of hepatic portoenterostomy are also
at risk for liver dysfunction, portal hypertension, esophageal varices,
hypersplenism, and hepatopulmonary syndrome, in which arteriovenous shunts form
within the lung. Liver transplantation is often required for patients who have
undergone portoenterostomy for EHBA, and it is sometimes necessary as a primary
operation if liver disease is far advanced at the time of diagnosis. Estimates
of 10-year survival for patients with EHBA range from 40% to 70%. Approximately
25% to 40% of patients survive 10 years without requiring transplantation.
VII. References
1. Balistreri WF. Cholestasis. In: Behrman RE, Kleigman RM, Jenson HB, eds. Nelson textbook of pediatrics, 16th ed. Philadelphia: WB Saunders, 2000:1203–1207.
2. D'Agata ID, Balistreri WF. Evaluation of liver disease in the pediatric patient. Pediatr Rev 1999;20:376–388.
3. MacMahon JR, Stevenson DK, Oski FA. Obstructive jaundice due to biliary
atresia and neonatal hepatitis. In: Taeusch HW, Ballard RA, eds.
Avery's Diseases of the Newborn, 7th ed. Philadelphia: WB Saunders, 1998:1021–1029.
4. Nio M, Ohi R. Biliary atresia. Semin Pediatr Surg 2000;9:177–186.
5. Suchy FJ. Approach to the infant with cholestasis. In: Suchy FJ, Sokol RJ,
Balistreri WF, eds.
Liver disease in children, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2001:187–194.
6. Witzleben CL, Piccoli DA. Extrahepatic bile ducts. In: Walker WA, Durie PR,
Hamilton JR, et al., eds.
Pediatric gastrointestinal disease, 3rd ed. Hamilton, Ontario: BE Decker, 2000:915–926.
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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Jaundice - Case 15-6: 5-Week-Old Girl (Pediatric Complaints and Diagnostic Dilemmas)
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