Epidemiology & Risk Factors

  • Occurs primarily in the late 2nd and 3rd trimesters (typically >30 weeks GA).
  • Resolves rapidly postpartum.
  • Risk factors:
    • Personal or family history of ICP (strong genetic component).
    • Multifetal gestation.
    • Advanced maternal age (AMA) >35.
    • History of gallstones or HCV.

Clinical Features

  • Intense pruritus:
    • Characteristically starts/worst on palms and soles, then generalizes.
    • Typically worse at night.
  • No primary rash:
    • Skin examination reveals only secondary excoriations from scratching.
  • Systemic signs (rare, <10%):
    • Mild jaundice.
    • Right upper quadrant (RUQ) abdominal pain.
    • Dark urine and pale stools.

Diagnosis

  • Initial & Best Diagnostic Test: ↑ Total serum bile acids (TBA) (≥10 µmol/L is diagnostic).
    • TBA >40 µmol/L associated with increased fetal risk.
    • TBA ≥100 µmol/L indicates severe disease (critical threshold for fetal mortality).
  • Key Labs:
    • ↑ LFTs (ALT and AST can be mildly elevated up to 10x ULN).
    • ↑ Direct bilirubin (mildly elevated in <20% of cases).
    • Normal to minimally increased GGT (helps differentiate from other biliary pathologies).
  • Imaging: RUQ US not required for diagnosis, but done if biliary colic/cholecystitis is suspected.

Differential Diagnostics

  • Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP):
    • Diff: Presents with an intense pruritic rash (erythematous papules/plaques) starting within abdominal striae with periumbilical sparing. Normal LFTs and TBA.
  • Atopic Eruption of Pregnancy (AEP):
    • Diff: Presents with eczematous or papular lesions on trunk/limbs. Normal TBA.
  • Acute Fatty Liver of Pregnancy (AFLP):
    • Diff: A life-threatening 3rd-trimester emergency. Presents with hypoglycemia, DIC, encephalopathy, acute kidney injury (AKI), and significantly higher LFT elevations.
  • HELLP Syndrome:
    • Diff: Characterized by hemolysis (schistocytes, ↑ LDH), elevated liver enzymes, and low platelets (<100,000), usually associated with preeclampsia. No isolated severe pruritus.

Management

  • Medical Therapy:
    • First-line: Ursodeoxycholic acid (UDCA).
      • Mechanism: Increases bile flow, decreases serum bile acid concentration, and relieves maternal pruritus.
    • Symptomatic relief: Antihistamines (hydroxyzine, diphenhydramine).
  • Fetal Surveillance:
    • Weekly or biweekly Nonstress Test (NST) and/or Biophysical Profile (BPP) starting at diagnosis or 32 weeks GA.
  • Timing of Delivery (to prevent stillbirth):
    • TBA <100 µmol/L: Scheduled delivery at 36 0/7 to 39 0/7 weeks GA.
    • TBA ≥100 µmol/L: Scheduled delivery at 36 0/7 weeks GA (or earlier if additional complications arise).

Complications

  • Maternal:
    • Minimal risk except for severe sleep deprivation (due to pruritus) and increased risk of future gallstones/recurrence in subsequent pregnancies (up to 90%).
  • Fetal (driven by toxic bile acid transfer across placenta):
    • Intrauterine fetal demise (IUFD) / Stillbirth (sudden cardiac arrest/vasospasm of placental vessels).
    • Meconium-stained amniotic fluid (bili-induced colonic hypermotility).
    • Preterm delivery (spontaneous or iatrogenic).
    • Neonatal respiratory distress syndrome (RDS).