What is the differential diagnosis for a pregnant female presenting with a papular rash?

Differential Diagnosis of Papular Rashes in Pregnancy

The differential diagnosis for papular rashes in pregnancy includes four primary pregnancy-specific dermatoses: atopic eruption of pregnancy (AEP), polymorphic eruption of pregnancy (PEP/PUPPP), pemphigoid gestationis (PG), and intrahepatic cholestasis of pregnancy (ICP), along with non-pregnancy-specific conditions such as cellulitis, allergic dermatitis, and infectious etiologies. 1, 2, 3

Primary Pregnancy-Specific Dermatoses

Atopic Eruption of Pregnancy (AEP)

• Most common pregnancy dermatosis, presenting with bilateral eczematous rash on face, eyelids, neck, antecubital/popliteal fossae, trunk, and extremities 1, 3
• Typically occurs in patients with personal or family history of atopy (eczema, allergic rhinitis, asthma) 4
• Characterized by pruritic papules with eczematous morphology rather than urticarial plaques 2

Polymorphic Eruption of Pregnancy (PEP/PUPPP)

• Second most common dermatosis, presenting with pruritic urticarial papules and plaques on abdomen and proximal thighs 4, 1
• Typically appears in third trimester, most frequently in primigravidas and multiple gestation pregnancies 5, 6
• Lesions begin within abdominal striae and spread to thighs, legs, back, buttocks, arms, and breasts, characteristically sparing the periumbilical area 5, 2
• Rash consists of erythematous urticarial plaques, papules, and occasionally erythema multiforme-like target lesions 6
• Benign condition with no fetal risk; resolves within 6 weeks postpartum 5, 6

Pemphigoid Gestationis (PG)

• Rare autoimmune condition caused by allogeneic immune reaction to placental basement membrane 2, 7
• Distinguished by development of vesicles and bullae, not just papules 4, 1
• May begin with urticarial papules before progressing to blistering 2
• Associated with fetal risks including prematurity and small-for-gestational-age babies 8, 2
• Requires confirmation by direct immunofluorescence showing linear C3 deposition at basement membrane zone 2
• 45% of neonates may have transient lesions at birth due to transplacental antibody transfer, resolving within 4 weeks 8

Intrahepatic Cholestasis of Pregnancy (ICP)

• Presents with generalized pruritus WITHOUT primary rash, predominantly affecting palms and soles, worse at night 4, 1
• Pruritus typically begins in second half of pregnancy 4
• Critical distinction: Excoriations from scratching may be mistaken for a rash, but no primary dermatologic lesions are present 4
• Dark urine and jaundice are uncommon; if present, suggest other hepatic diseases 4
• Poses significant fetal risk including fetal distress, prematurity, and stillbirth 2

Non-Pregnancy-Specific Conditions to Consider

Infectious Causes

• Facial cellulitis: Unilateral facial edema, erythema, warmth, and tenderness requiring urgent antibiotic therapy 9
• Erysipelas: Well-demarcated streptococcal infection potentially dangerous if untreated 9
• Viral exanthems: Consider parvovirus B19, rubella, and CMV, particularly if systemic symptoms present 1

Allergic/Contact Dermatitis

• Localized reaction to new cosmetics, hair products, or environmental allergens 9
• Can present with papular eruption and pruritus 9
• May be unilateral or bilateral depending on exposure pattern 9

Insect Bite Reactions

• Localized hypersensitivity causing papular eruption with edema and erythema 9

Diagnostic Algorithm

History Assessment

• Timing of onset: First, second, or third trimester 2, 3
• Distribution pattern: Abdominal striae vs. flexural areas vs. generalized 4, 2
• Primary lesion morphology: Papules, plaques, vesicles, or excoriations only 2, 3
• Presence or absence of primary rash before scratching 4
• Atopic history: Personal or family history of eczema, allergic rhinitis, asthma 4
• Parity: Primigravida vs. multigravida (PEP more common in first pregnancy) 5
• Multiple gestation: Increases risk of PEP 5
• Previous pregnancy history: Prior ICP or pemphigoid gestationis 4

Physical Examination Findings

• Location specificity: Periumbilical sparing suggests PEP; palmar/plantar involvement without rash suggests ICP 4, 5
• Lesion morphology: Eczematous (AEP), urticarial plaques (PEP), vesicles/bullae (PG), or excoriations only (ICP) 4, 1, 2
• Unilateral vs. bilateral: Unilateral facial involvement suggests cellulitis or contact dermatitis rather than pregnancy dermatosis 9
• Presence of jaundice or dark urine: Suggests hepatic disease other than typical ICP 4

Laboratory Evaluation

For suspected ICP (pruritus without primary rash):

• Total serum bile acid levels (diagnostic if >10 μmol/L) 4
• Transaminases (ALT, AST) may be elevated but not required for diagnosis 4

For suspected pemphigoid gestationis:

• Direct immunofluorescence of perilesional skin showing linear C3 at basement membrane 2
• Histologic examination showing subepidermal blistering 2

For facial non-blanching rash or systemic concerns:

• Complete blood count with differential and platelet count 1
• Peripheral blood smear 1
• Coagulation studies (PT/INR, aPTT) 1
• Comprehensive metabolic panel including liver function tests 1
• LDH and haptoglobin if hemolysis suspected 1
• Viral serologies: Parvovirus B19, rubella, CMV IgM and IgG 1

Critical Pitfalls to Avoid

• Do not dismiss pruritus without rash as trivial; this is the hallmark of ICP, which carries significant fetal risk 4, 2
• Do not assume all pregnancy rashes are benign PEP; pemphigoid gestationis requires immunofluorescence confirmation and carries fetal risks 8, 2
• Do not delay evaluation of unilateral facial swelling; cellulitis requires urgent antibiotic therapy 9
• Do not confuse excoriations from scratching with primary dermatologic lesions; ICP has no primary rash 4
• Do not assume PUPPP if symptoms persist beyond 2 weeks postpartum; this strongly favors pemphigoid gestationis 8
• Refer immediately if platelets <100,000/μL, active bleeding, or systemic symptoms present 1