Pruritus in Third Trimester of Pregnancy with Normal LFTs

Diagnostic Algorithm

Overview

• No primary lesions (only excoriations from scratching) → Think Intrahepatic Cholestasis of Pregnancy (ICP), but...
• With primary skin lesions in the third trimester → Consider PEP/PUPPP, Gestational Pemphigoid, or AEP

The Critical Point: Normal LFTs Does NOT Rule Out ICP

"Pruritus can precede abnormal findings of liver function tests or total serum bile acids, and follow-up testing for obstetric cholestasis may be needed for itchy pregnant patients with initially normal findings."

• Creasy & Resnik's Maternal-Fetal Medicine, p. 1716

"Cholestatic itching correlates better with elevated serum bile acid levels than with the results of other biochemical liver function tests such as alkaline phosphatase, AST, ALT, and bilirubin."

• Creasy & Resnik's Maternal-Fetal Medicine, p. 1716

Differential Diagnosis: Pruritic Conditions in Third Trimester

1. Intrahepatic Cholestasis of Pregnancy (ICP)

• Occurs in 1.5-2% of pregnant women
• Presents with generalized pruritus without rash, worse on palms and soles, worse at night
• Jaundice in only 0.02% of pregnancies
• Key diagnostic test: fasting serum bile acids (>10 µmol/L = ICP; >40 µmol/L = severe ICP with higher fetal risk)
• LFTs lag behind bile acid elevation - always order bile acids even with normal LFTs
• Resolves within 2 weeks of delivery; recurs in ~50% of subsequent pregnancies
• Treatment: Ursodeoxycholic acid (UDCA) - reduces pruritus and improves fetal outcomes
• Creasy & Resnik's Maternal-Fetal Medicine, p. 1716

2. Polymorphic Eruption of Pregnancy (PEP / PUPPP)

• Most common pregnancy rash
• Onset in 3rd trimester, begins in abdominal striae
• Erythematous urticarial papules and plaques; umbilicus typically spared
• Spreads to thighs, buttocks, proximal arms; face spared
• Associated with: primigravida, multiple gestation, increased weight gain
• All labs normal (DIF, H&E, LFTs all nonspecific)
• No fetal risk
• Does NOT recur in subsequent pregnancies (unlike ICP)
• Treatment: Topical corticosteroids + antihistamines; oral steroids for severe cases
• Creasy & Resnik's Maternal-Fetal Medicine, p. 1717

3. Gestational Pemphigoid (Pemphigoid Gestationis)

• Rare autoimmune blistering disorder
• Periumbilical involvement - vesiculobullous + urticarial eruption
• DIF: linear C3 deposition along the dermal-epidermal junction (diagnostic)
• Associated with small-for-dates babies and prematurity
• Treatment: Corticosteroids + antihistamines

4. Atopic Eruption of Pregnancy (AEP)

• Typically presents before the third trimester (75% < 3rd trimester)
• 80% are first occurrence of atopic disease; 20% are flares of pre-existing atopic dermatitis
• Trunk and extremities involved
• ± elevated IgE; no fetal risk
• Treatment: Corticosteroids + antihistamines + UVB

5. Benign Pruritus Gravidarum

• Generalized itching without cholestasis, without rash
• Associated with: twin pregnancy, fertility treatments, diabetes, nulliparity
• Up to 14% of pregnant women experience itching; most is benign
• No adverse perinatal outcomes when there is no cholestasis
• Treatment: emollients, topical antipruritics, oral antihistamines, UV light

Clinical Approach with Normal LFTs

Normal LFTs + Pruritus in 3rd trimester
          ↓
Check SERUM BILE ACIDS (fasting)
          ↓
├── Bile acids >10 µmol/L → ICP → UDCA + fetal monitoring
│   (LFTs may normalize or lag - bile acids are the gold standard)
│
└── Bile acids normal → Does patient have primary skin lesions?
         ├── Urticarial papules in striae, umbilicus spared → PEP/PUPPP
         ├── Vesiculobullous, periumbilical → Gestational Pemphigoid (DIF)
         ├── Eczematous, trunk+limbs, early onset → AEP
         └── No lesions, no bile acid elevation → Benign Pruritus Gravidarum

Key Takeaways

1. Normal LFTs do not exclude ICP - serum bile acids must always be checked separately
2. ICP = pruritus without primary skin lesions - excoriations are secondary
3. PEP/PUPPP is the most common rash in 3rd trimester and is benign
4. ICP carries real fetal risk (prematurity, fetal distress, stillbirth) - must not be missed
5. If initial bile acids are normal but suspicion remains high, repeat testing as levels can fluctuate
6. Serum glutathione S-transferase-α is a specific marker distinguishing ICP from benign pruritus gravidarum