What is the most likely diagnosis in a patient with significant pruritis, especially at night, in a 21-week pregnancy with normal liver function tests and bile acid levels?

Most Likely Diagnosis: Atopic Eruption of Pregnancy or Polymorphic Eruption of Pregnancy

In a 21-week pregnant patient with significant pruritus (especially nocturnal) but normal bile acid levels, the most likely diagnosis is a pregnancy-specific dermatosis—either atopic eruption of pregnancy or polymorphic eruption of pregnancy—rather than intrahepatic cholestasis of pregnancy (ICP), which is effectively ruled out by normal bile acids. 1, 2

Why ICP is Unlikely Despite Classic Symptoms

While the clinical presentation of nocturnal pruritus at 21 weeks gestation initially suggests ICP, the normal bile acid levels make this diagnosis highly improbable:

• ICP requires elevated bile acids (>10 μmol/L) for diagnosis, and bile acids are the most sensitive and specific marker for this condition 1, 2, 3
• The American College of Obstetricians and Gynecologists states that ICP diagnosis is based on pruritus symptoms supported by elevated total serum bile acid levels 1
• Normal bile acids effectively exclude ICP as the primary diagnosis at this time 2, 3

Important Caveat: Consider Repeat Testing

However, pruritus can precede bile acid elevation by several weeks in ICP, so if symptoms persist or worsen, repeat bile acid testing is essential 3:

• Bile acid levels can increase rapidly, particularly as pregnancy progresses toward term 3
• Early-onset ICP (presenting in the first or early second trimester) is rare but documented, and may be associated with genetic mutations 4, 5
• If clinical suspicion remains high despite normal initial testing, repeat bile acids after excluding other causes 2

Most Likely Alternative Diagnoses

With normal bile acids, consider these pregnancy-specific dermatoses:

Atopic Eruption of Pregnancy

• Most common dermatosis of pregnancy, affecting approximately 23% of pregnancies 2, 6
• Presents with pruritus that may worsen at night 6
• Often associated with personal or family history of atopy (eczema, allergic rhinitis, asthma) 1
• Typically presents with visible eczematous rash, though pruritus may precede visible changes 6

Polymorphic Eruption of Pregnancy (PEP)

• Second most common pregnancy-specific dermatosis 1
• Characterized by pruritic urticarial papules and plaques on the abdomen and proximal thighs 1
• Usually presents in third trimester but can occur earlier 6
• Associated with visible rash (unlike ICP) 1

Diagnostic Algorithm

Immediate evaluation should include:

1. Detailed skin examination to identify any rash, excoriations, papules, plaques, or vesicles that would distinguish dermatologic conditions from ICP 1

2. Assess for excoriations from scratching versus primary skin lesions 1, 3

3. Obtain detailed history including:

   • Personal or family history of atopy (eczema, allergic rhinitis, asthma) 1
   • Recent medication changes, particularly narcotics which can cause pruritus 1, 3
   • Amount of bathing and use of new soaps or lotions 1
   • Household contacts and pets 1

4. Verify bile acid testing was appropriate:

   • Confirm total serum bile acids were measured (not just liver enzymes) 2, 3
   • Random (non-fasting) samples are acceptable 3
   • Enzymatic assay is preferred for faster results 3

Management Approach

If skin examination reveals a rash:

• Diagnose based on rash morphology and distribution 1, 6
• Treat symptomatically with topical corticosteroids and antihistamines 6
• No specific fetal monitoring required for dermatologic conditions 6

If no rash is present (only excoriations):

• Repeat bile acid testing in 1-2 weeks if symptoms persist or worsen, as ICP cannot be definitively excluded with a single normal result when clinical suspicion is high 2, 3
• Consider empiric symptomatic treatment with antihistamines while awaiting repeat testing 2
• Do not initiate ursodeoxycholic acid without confirmed elevated bile acids 2, 3

Critical Pitfall to Avoid

Never assume ICP is excluded permanently based on one normal bile acid level if pruritus persists, especially given the patient is only at 21 weeks gestation 3:

• ICP typically presents in late second or third trimester, so bile acids may rise later in pregnancy 1, 7
• Early-onset ICP, while rare, can occur and may be associated with more severe disease and genetic mutations 4, 5
• Serial monitoring is warranted if symptoms continue despite normal initial testing 3

When to Escalate Concern

Repeat bile acids urgently if the patient develops:

• Worsening pruritus, particularly affecting palms and soles 1, 2
• Dark urine or jaundice (though these are uncommon even in ICP) 1
• Elevated liver transaminases on routine testing 2, 3
• Any of these findings would increase suspicion for ICP despite initially normal bile acids 1, 2