Pemphigoid Gestationis - Gestational Pemphigoid

Content Review: July 2015 Last Update:

Pemphigoid gestationis (herpes gestationis) is a rare disease of pregnancy and puerperium. Biopsy and immunohistology are both used in the workup of the disease.


Indications for Testing

Urticarial, blistering, and/or pruritic lesions during pregnancy

Laboratory Testing

  • Prompt, accurate diagnosis is essential for planning therapy to minimize morbidity and patient discomfort
  • Histopathology
    • Biopsy 
      • Subepidermal blister
      • Eosinophilic spongiosis
      • Dermal infiltrate of eosinophils and lymphocytes
    • Immunopathology
      • Perilesional skin biopsy for cutaneous direct immunofluorescence (DIF) – characteristic pattern shows linear C3 basement membrane zone (BMZ) staining with or without linear IgG BMZ staining
      • Serum testing for complement-fixing IgG BMZ antibodies by indirect immunofluorescence (IIF) testing with fresh complement
        • Demonstrates C3 on epidermal side of human split skin substrate (herpes gestationis factor [HGF])
        • Highly sensitive and specific testing for pemphigoid gestationis
      • Serum testing by enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to BP180 supplements testing by IIF
        • BP180 (BPAg2) has been identified as a major antigenic target
        • BP230 (BPAg1) is less commonly an antigenic target
      • Consider serum testing for celiac disease (CD) because positive CD serologies have been identified in a subset of patients with pemphigus gestationis

Differential Diagnosis

  • Polymorphic eruption of pregnancy (PEP) – also known as pruritic urticarial papules and plaques of pregnancy (PUPPP)
  • Atopic eruption of pregnancy – also known as prurigo gestationis (prurigo of pregnancy or PP) and pruritic folliculitis of pregnancy
  • Intrahepatic cholestasis of pregnancy
  • Viral exanthems (eg, varicella)
  • Urticaria
  • Scabies
  • Autoimmune skin disorders
  • Bullous or urticarial drug reaction
  • Contact dermatitis
  • Erythema multiforme
  • Impetigo herpetiformis
  • Bullous lupus erythematosus


Antibody levels may be helpful but may lag behind clinical response and may not reflect disease activity.



  • Incidence (Huilaja, 2014)
    • 1/40,000-50,000 pregnancies
    • 1-2/million people
  • Age – onset in childbearing years
  • Sex – exclusively females
  • Ethnicity – no racial distribution

Risk Factors

  • Previous pregnancy with pemphigoid gestationis
  • HLA-DR3, HLA-DR4, or both
    • DRB1*0301 and DRB1*0401/040X
  • C4 null allele
  • Increased HLA-DR2 in father

Pathology and Immunopathology

  • Subepidermal blistering process
  • Linear C3 at the basement membrane zone (BMZ) on direct immunofluorescence of perilesional tissue in all cases; also linear IgG in 25-30%
  • Complement fixing IgG BMZ serum antibodies (herpes gestationis factor [HGF]) – 50% of patients show epidermal localization on split skin substrate
  • IgG BP180 (BPAg2) and, less commonly, IgG BP230 (BPAg1) antibodies present by enzyme-linked immunosorbent assay (ELISA)

Clinical Presentation

  • Typically presents in the second to third trimester
    • Often flares with labor
    • Resolves within several weeks to months after delivery
    • Chronic, severe disease is rare
  • Variable skin lesions ranging from urticaria to vesicles to tense blisters on skin
    • Abdominal lesions common; usually begins with periumbilical lesions
    • Usually spares mucous membranes, face
    • Pronounced pruritus
  • Recurrence
    • Likely in subsequent pregnancies – earlier and greater severity
    • May also recur with
      • Menstrual cycles
      • Hormonal medications (oral contraception)
  • Infants of affected mothers
    • Increased risk of preterm birth
    • Intrauterine growth retardation
    • ~10% of infants have lesions from passive transfer of transplacental antibodies
      • Mild disease – urticarial and/or vesicular skin lesions
      • Usually resolves spontaneously within days or weeks
    • Blisters in small percentage of infants
  • May develop or recur in gestational trophoblastic disease
    • Molar pregnancy (hydatidiform mole)
    • Choriocarcinoma
  • Autoimmune-associated diseases

ARUP Laboratory Tests

Additional detail about the tests below, including components and recommended use, can be found in the ARUP Immunobullous Disease Testing Comparison table.  


Additional Resources

Medical Experts



Kristin M. Leiferman, MD
Co-Director, Immunodermatology Laboratory, Professor of Dermatology, and Adjunct Professor of Pathology, University of Utah
Medical Director, Immunodermatology, ARUP Laboratories