What are the differential diagnoses and treatment options for itching in a pregnant patient?

Differential Diagnoses for Itching in Pregnancy

Most Critical Diagnosis to Rule Out First

Intrahepatic cholestasis of pregnancy (ICP) must be immediately excluded in any pregnant woman presenting with itching, as this condition carries substantial risk of stillbirth and requires specific management with ursodeoxycholic acid and timed delivery. 1

Diagnostic Algorithm for Pruritus in Pregnancy

Step 1: Immediate Laboratory Evaluation

When a pregnant woman presents with itching, order the following tests immediately:

• Serum bile acids (most sensitive test; diagnostic when >10 μmol/L) 1
• Liver transaminases (ALT and AST) to assess for hepatic involvement 1
• Total bilirubin and GGT for comprehensive hepatobiliary assessment 1

Do not delay testing even if symptoms seem mild—stillbirth can occur suddenly without warning signs in ICP. 1

Step 2: Clinical Pattern Recognition

Red flag features suggesting ICP:

• Pruritus developing in second or third trimester (80% after 30 weeks, though 5.6% can present in first trimester) 1, 2
• Itching predominantly affecting palms and soles that worsens at night 1
• Pruritus WITHOUT a primary rash (skin changes are secondary to scratching only) 1, 3
• Generalized itching severe enough to disrupt sleep or cause excoriations 1

Complete Differential Diagnosis List

1. Intrahepatic Cholestasis of Pregnancy (ICP)

• Affects 0.3-2.0% of pregnancies in Europe; up to 5.6% in Latina women in the United States 2
• Diagnosed when bile acids exceed 10 μmol/L with pruritus 1
• Most cases present with mild to moderately elevated AST/ALT (2-fold to 30-fold elevation) and total bilirubin <6 mg/dL 1, 2
• Fetal risks include prematurity and stillbirth, particularly when bile acids ≥100 μmol/L 1

2. Atopic Eruption of Pregnancy (AEP)

• Presents with eczematous rash on face, eyelids, neck, antecubital/popliteal fossae, trunk, and extremities 4
• Most common pregnancy-specific dermatosis 3
• Has visible primary rash (unlike ICP) 4
• Usually associated with personal or family history of atopy 1

3. Polymorphic Eruption of Pregnancy (PEP)

• Previously called PUPPP (pruritic urticarial papules and plaques of pregnancy) 5, 3
• Presents with pruritic urticarial papules and plaques on abdomen and proximal thighs in third trimester 4
• Typically begins in abdominal striae 3
• No fetal risks associated 3

4. Pemphigoid Gestationis

• Rare autoimmune condition 1, 3
• Presents with vesicles and bullae (blistering lesions) 1, 4
• Associated with fetal risks including prematurity and stillbirth 3, 6
• Requires immunofluorescence testing for definitive diagnosis 3

5. Physiologic Pruritus of Pregnancy

• Affects approximately 23% of all pregnancies 1
• Most cases have no underlying pathologic process 1
• Typically presents as generalized dry, itchy skin without specific pattern 7
• Normal bile acids and liver function tests 3

6. Pre-existing or Acquired Dermatoses

• Atopic dermatitis or eczema (usually with visible rash and history of atopy) 1
• Contact dermatitis 7
• Scabies or other parasitic infestations 7

7. Systemic Causes

• Pre-eclampsia (has other systemic features including hypertension and proteinuria) 1
• Acute fatty liver of pregnancy (has other systemic features) 1
• Medication-related pruritus (particularly narcotics) 1

Treatment Approach Based on Diagnosis

For Confirmed ICP (Bile Acids >10 μmol/L):

First-line treatment:

• Initiate ursodeoxycholic acid (UDCA) 10-15 mg/kg/day in divided doses for all confirmed cases 1
• UDCA improves pruritus, serum bile acid levels, liver transaminases, and meta-analyses demonstrate decreased adverse outcomes including preterm birth and stillbirth 1

Second-line treatment:

• Add cholestyramine if UDCA alone is insufficient 1
• Monitor prothrombin time regularly due to vitamin K deficiency risk with cholestyramine 1, 2

Third-line treatment:

• Rifampicin can be attempted for refractory pruritus 1

Delivery timing based on bile acid levels:

• Bile acids ≥100 μmol/L: Deliver at 36 0/7 weeks due to substantially increased stillbirth risk (GRADE 1B recommendation) 1
• Bile acids <100 μmol/L: Deliver between 36 0/7 and 39 0/7 weeks (GRADE 1C recommendation) 1
• Administer antenatal corticosteroids if delivering before 37 0/7 weeks (GRADE 1A recommendation) 1

For Pregnancy-Specific Dermatoses Without Fetal Risk:

Topical treatments (safest options for localized pruritus):

• Emollients for dry skin 5, 7
• Topical corticosteroids (hydrocortisone can be applied to affected areas not more than 3-4 times daily) 8, 5
• Topical antipruritics 5

Systemic treatments for generalized pruritus:

• Restricted number of antihistamines may be administered in severe cases 5, 7
• Systemic corticosteroids for severe cases 5, 7
• UV phototherapy is adequate for generalized pruritus 5, 7

Critical Pitfalls to Avoid

• Never delay delivery in confirmed ICP with bile acids ≥100 μmol/L beyond 36 weeks—stillbirth risk increases substantially 1
• Do not perform preterm delivery based on clinical suspicion alone without laboratory confirmation of elevated bile acids 1
• If initial bile acid levels are normal but clinical suspicion remains high, repeat testing after excluding other causes 1
• Never assume ICP has resolved if pruritus persists beyond 6 weeks postpartum—this indicates underlying chronic liver disease (primary biliary cholangitis, primary sclerosing cholangitis, ABCB4 deficiency, or chronic hepatitis C) requiring workup 2
• Do not miss vitamin K deficiency in patients on cholestyramine—monitor PT regularly 1, 2

Recurrence Risk Counseling

• ICP recurs in 40-92% of subsequent pregnancies in women with personal history 2
• Family history is significant, as familial clustering suggests genetic susceptibility 2
• Consider genetic testing in women with severe ICP (bile acids >100 μmol/L), recurrent ICP, or early-onset ICP 2