Interesting Case Rounds

July 31, 2008

Sean CaineCCFP-EM Resident

The Case

90 d F referred from urgent care for FTT and prolonged jaundice

History

History

Pregnancy Mother was 23 yo Caucasian female G1P0 O neg Routine serology was normal GBS negative Nonsmoker. No EtOH Uncomplicated pregnancy (no PIH or GDM)

Delivery SVD @ 39wks GA ROM x 3 hrs BW=3220 Apgar 91,95

DAT negative Newborn metabolic screen was normal Tbili at discharge =190 d/c home 24hrs postpartum

History

Followed by GP qweekly x 6 wks

Jaundiced noted again at 6wk follow up with maternity care clinic

1 oz wt loss in past month

Exclusively breast fed. Feeds well.

~6-8 BM/day. Stools are typically yellow. Recently have become more pale.

~6-8 wet diapers/day. Urine is brown.

ROS otherwise unremarkable for sleep, appetite, activity, or symptoms indicative of focus for infection etc

On exam

VS: 36.6 119 88/47 36

No apparent distress. Awake. Alert. Interactive and pleasant

++scleral icterus. +jaundice

Firm liver edge. Palpable spleen tip.

CV, Resp, CNS, Abdo exam otherwise unremarkable

Labs/Investigations

Labs/Investigations

CBC Hb 110 (90-140) WBC 21.5 H (5-19.5) Plt 569 H (150-400) Neut 9.2 H (1-9)

Lytes, Cr, Urea – NORMAL

Urinalysis/R&M LARGE Leuks, SMALL blood 20-30 WBC/hpf 0-5 RBC Few bacteria

LFT/enzymes Tbili 178 H (0-23) Direct bili 118 H (0-7) ALT 199 H (1-35) AST 262 H (10-65) ALP 461 H (40-390) GGT 796 H (8-35) Albumin 38 INR 1.1 PTT 40.5 H (27-36)

Ammonia 61 H (12-47)

Objectives

Review features of physiologic and pathologic jaundice

Review approach to neonatal cholestasis

Highlight some common pitfalls

Return to the case to review the work up and diagnosis

Hyperbilirubinemia

Has increasingly become a presenting complaint to ER due to early postpartum discharge

However, still rare to encounter in Calgary ER

Screened by PHN/GP in first 3-5 days postpartum Direct admit to PLC Unit 31 for assessment +/-

phototherapy

Hyperbilirubinemia

Physiologic vs. Pathologic Jaundice in the Newborn

Physiologic vs. Pathologic Jaundice in the Newborn1

Physiologic

Unconjugated hyperbilirubinmia

60% term & >80% preterm neonates in first week

Rises at rate <85 umol/L/day

Appears on 2nd or 3rd day of life

Typically peaks btwn days 2-4

Begins to decline on days 5-7 at rate of 34 umol/L/day

Pathologic

Appears <24 hrs

Excessive for infant’s age (Tbili > 205 umol/L)

Elevated direct bilirubin

Jaundice present at or beyond 3 wks

Sick infant

Tbili rising >85 umol/L/day

Unexplained jaundice following phototherapy

Jaundice in the presence of risk factors

Ddx Conjugated vs. Unconjugated Hyperbilirubinemia

UNCONJUGATED CONJUGATED

Physiologic Pathologic

Non-hemolyticCephalohematomaPolycythemiaSepsisHypothyrodismGilbert’sCrigler- Najjar

Hemolytic Intrinsic

Membrane Spherocytosis ElliptocytosisEnzyme G6PD PK deficiencyHemoglobin Alpha thal

Hemolytic Extrinsic

Immune ABO-incompatibility Rh-incompatibility Kelly-Duffy etcNon immune Splenomegaly Sepsis AV malformation

HepaticInfectious Sepsis Hep B, TORCHMetabolic Galactosemia Tyrosinemia Alpha-1-antitrypsin Hypothyroidism CFDrugsTPNIdiopathic neonatal CholestasisBile duct paucityAbN Bile acid metabolism

Extra HepaticBiliary atresiaCholedocal cyst

Ddx of Hyperbilirubinemia According to Time of Onset

First 24 hours 24-72 hours 72-96 hours > 1 week

Often pathologic•Hemolysis (Rh or ABO)

•Sepsis (GBS, TORCH)

•Cephalohematoma

•Spherocytosis

•Hemorrhagic disease of thenewborn

•Physiologic

•Polycythemia

•Dehydration

•Hemolysis•G6PD•PK def

•Cephalohematoma

•Spherocytosis

•Sepsis/TORCH

•Physiologic

•Dehydration

•Sepsis

•Gilbert’s

•Crigler-Najjar

•Hypoxia/resp distress/hypoG

Often pathologic

•Breast milk jaundice

•Prolonged Physiologic

•Hypothyroidism

•Neonatal Hepatitis

•Galactosemia

•Familial Cholestasis

•Biliary atresia•Paucity of bile ducts

Neonatal Cholestasis

Defined as the impaired canalicular biliary flow resulting in acumulation of biliary substances (bilirubin, bile acids, and cholesterol)2

Estimated incidence of 1/2500 live births

Jaundice at 2-3 weeks of age increases suspicion2

2.4-15% of newborns are jaundice at 2 weeks of age6

Estimated that 60-375 jaundiced infants at 2 weeks of age would need to be tested to detect one case of cholestasis 26

Common Pitfalls

Breast feeding jaundice Exaggeration of physiologic jaundice Day 2 7 Premature babies: can last up to 10 days

Breast milk jaundice 2% of breast fed babies Starts ~ day 7, persists until week 2-3 May persist for 3-10 weeks at low levels Unconjugated Theory: glucuronidase in breast milk increased

enterohepatic bilirubin re-circulation

Neonatal Cholestasis

Clinical Presentation

Prolonged jaundice

Pale stools

Dark urine

Coagulopathy

Hepatomegaly

Splenomegaly

RUQ mass

FTT

Less specific suggestive of underlyingmetabolic, CNS, or infectious aetiology:

Fever Irritability Lethargy, Seizures Poor feeding Dysmorphic features

Ddx Neonatal CholestasisObstruction

Biliary Atresia

Choledochol cyst

Tumor

Inspissated bile/plug sybdrome

Gallstone

Biliary Sludge

Infectious

Bacterial

Protozoal

TORCH

Echovirus

Adenovirus

Parvovirus B18

Metabolic/Genetic

Alagille Syndrome

α-1-Antitrypsin

Galactosemia

Tyrisonemia

Lipid metabolism disorders

Bilae acid metabolism disorders

Mitochondrial Disease

Citrin deficiancy

Approach to Neonatal Cholestasis

1. Initial investigations: Establish cholestasis and determine severity of disease

Detailed hx, exam Fractioned serum bili Tests for liver injury (AST, ALT, ALP, GGT) LFT (Albumin, INR, PTT, serum ammonia, glucose)

2. Detect conditions that require immediate treatment CBC, blood & urine cultures to r/o sepsis Serum T4 and TSH Metabolic Screen: lactate, ammonia, iron, ferritin, urinalysis,

urine amino acids and organic acids Viral serologies, VDRL, and cultures

Approach to Neonatal Cholestasis

3. Differentiate extrahepatic disorders from intrahepatic causes of cholestasis

U/S Hepatobiliary scintigraphy Perc liver bx, Exploratory laparotomy with intraoperative

4. Establish other specific diagnosis α-1-antitrypsin, CF, Alagille, PFIC, storage

disorders

Back to the Case

1. Initial investigation: establish cholestasis

2. Detect conditions that require treatment

3. Differentiate extrahepatic disorders from intrahepatic causes of cholestasis

4. Investigate for the rare diagnosis

BiliaryAtresia

Inflammation of bile ducts leading to progressive obliteration of the extrahepatic biliary tract

Most common cause of cholestasis in the first few weeks of life

Incidence of 1/10,000 to 1/20,000 births

Cause remains unknown though various infectious (CMV, reovirus, rotavirus) and genetic causes have been proposed

Biliary Atresia

Jaundice typically develops in weeks 3-6

Uncommon for jaundice to be present at birth

10-15% association with congenital malformations (polysplenia, malrotation, etc)

Biliary Atresia

Diagnosis U/S can be suggestive Liver biopsy is the most useful test HIDA useful

Specificity improved with phenobarb 5d before scan

Duodenal aspirate Exploratory laparotomy & intraoperative

cholangiogram ERC and MRC likely to have future

Ultrasound

Main utility is to r/o other extrahepatic causes (ie choledochol cyst)

Findings suggestive of biliary atresia Absence of gallbladder Abnormal gallbladder size and shape “Triangular cord” sign Absence of a common bile duct

Ultrasound

Ultrasound

Abnormally small and contracted gallbladder and irregular contour and septations in the gallbladder neck.

Common bile duct not visualized

Consistent with biliary atresia

Biliary Atresia

Treatment Primary treatment is Kasai procedure Early diagnosis and surgery is critical

Narrow window for optimal short and longterm outcomes

bile drainage achieved in >80% of patients <60 days of age vs. 20% of infants >90 days

4 yr survival with native liver 49% with sx <30 days of age 36% with sx at 31-90 days of age 23% with sx at >90 days of age

Kasai

Pearls

Recognize pathologic features of jaundice

Obtain fractioned serum bili level (ie total and direct) on all 2-3 week old jaundiced infants

Infants with biliary atresia will often appear to be well in the first 1-2 weeks of life

Neonatal cholestasis is rare, but timely diagnosis is crucial!

References

1. Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the Newborn Infant 35 or More weeks of Gestation. Pediatrics. 2004;114:297-316.

2. Venigalla S, Gourley GR. Neonatal Cholestasis. Seminars in Perinatology.2004;28:348-355.

3. Suchy F. Neonatal Cholestasis. Pediatrics in Review. 2004;25:388-395.

4. Schreiber RA, Barker CC, Roberts EA, et al. Biliary Atresia: the Canadian Experience. Journal of Pediatrics. 2007;151:659

5. Abrams S, Shulman R. Causes of Neonatal Cholestasis. UpToDate. Last updated June 12, 2008.

6. Abrams S, Shulman R. Approach to Neonatal Cholestasis. UpToDate. Last updated September 26, 2006.

The End