What is the workup for intrahepatic cholestasis of pregnancy (ICP) and Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)?

Workup for Intrahepatic Cholestasis of Pregnancy (ICP) and Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)

For pregnant women presenting with pruritus, laboratory testing for serum bile acids and liver transaminases is essential for diagnosing ICP, while PUPPP is primarily a clinical diagnosis based on characteristic skin findings.

Intrahepatic Cholestasis of Pregnancy (ICP) Workup

Clinical Presentation

• Pruritus without rash, typically in second or third trimester
• Predominantly affects palms and soles
• Worse at night
• May develop excoriations from scratching (can be mistaken for a rash)

Laboratory Evaluation

• Serum bile acid levels (≥11 μmol/L is diagnostic) 1
  • Most sensitive indicator for ICP
  • May precede other liver test abnormalities
  • Levels >40 μmol/L associated with increased fetal complications
  • Levels ≥100 μmol/L indicate severe disease requiring earlier delivery
• Liver function tests
  • ALT (usually elevated)
  • AST
  • Bilirubin (elevated in 10-15% of cases)
  • GGT (typically normal in ICP unless ABCB4 variants present) 1
• Prothrombin time/INR (to assess coagulation)

Important Considerations

• If initial testing is normal but pruritus persists, repeat testing in 1-2 weeks as bile acid elevation may lag behind symptom onset 1
• Some clinicians diagnose based on clinical symptoms alone and start empiric UDCA treatment
• Liver biopsy is generally not warranted 1
• If abnormalities persist 4-6 weeks postpartum, additional workup for other liver diseases is indicated 1

Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP) Workup

Clinical Presentation

• Intensely pruritic eruption typically in third trimester 2, 3
• More common in primigravidas and multiple gestations 2
• Characteristic distribution: begins on abdomen (especially in striae), then spreads to thighs, legs, back, buttocks, arms, and breasts
• Spares face and palms/soles
• Skin findings: erythematous urticarial plaques, papules, and sometimes target-like lesions 3

Diagnostic Approach

• Primarily a clinical diagnosis based on characteristic appearance and distribution
• No specific laboratory tests are diagnostic for PUPPP
• Consider skin biopsy in atypical cases to rule out other conditions
  • Histology shows mild nonspecific lymphohistiocytic perivasculitis 3

Differential Diagnosis Testing

• To exclude other conditions, especially when presentation is atypical:
  • Serum bile acids (to rule out ICP)
  • Direct immunofluorescence (to rule out pemphigoid gestationis)
  • Liver function tests

Key Differential Diagnoses

For ICP:

• Pre-eclampsia
• Acute fatty liver of pregnancy
• Viral hepatitis
• Other chronic liver diseases (PBC, PSC)
• PUPPP with excoriations

For PUPPP:

• Pemphigoid gestationis
• Atopic eruption of pregnancy
• Drug eruption
• Viral exanthem
• Scabies

Common Pitfalls and Caveats

1. Misdiagnosis of ICP: Pruritus can precede laboratory abnormalities by several weeks. If clinical suspicion is high but initial tests are normal, repeat testing is essential 1.

2. Confusing PUPPP with pemphigoid gestationis: Pemphigoid gestationis is an autoimmune blistering disease that can resemble PUPPP but has different treatment requirements and fetal implications. Direct immunofluorescence can help differentiate.

3. Overlooking ICP due to absence of jaundice: Only 10-15% of ICP patients develop jaundice; absence of jaundice should not exclude the diagnosis 1.

4. Failing to recognize the significance of bile acid levels: Levels ≥100 μmol/L indicate need for delivery at 36 weeks due to increased stillbirth risk 1.

5. Stopping workup after normal transaminases: Bile acids can be elevated with normal transaminases in early ICP; always check bile acids when ICP is suspected 1.

6. Inadequate follow-up: Persistent abnormalities after delivery require further investigation for underlying chronic liver disease 1.