Pemphigoid Gestationis - Gestational Pemphigoid

Diagnosis

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
  • Pemphigus vulgaris
  • Bullous pemphigoid
  • Linear IgA disease
  • Dermatitis herpetiformis
  • Epidermolysis bullosa acquisita
• Bullous or urticarial drug reaction
• Contact dermatitis
• Erythema multiforme
• Impetigo herpetiformis
• Bullous lupus erythematosus

Monitoring

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

Background

Epidemiology

• 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
  • Graves disease most common
  • Pernicious anemia
  • Hashimoto thyroiditis
  • Autoimmune thrombocytopenia