Pemphigoid Gestationis - Gestational Pemphigoid

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

Tabs Content

Clinical Overview

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
Histology
- Biopsy
  - Subepidermal blister
  - Eosinophilic spongiosis
  - Dermal infiltrate of eosinophils and lymphocytes
- Immunohistology
  - Perilesional skin biopsy for cutaneous direct immunofluorescence – 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 fluorescent antibody (IFA) 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
  - Testing by enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to BP180 supplements testing by IFA
    - BP180 (BP Ag2) has been identified as a major antigenic target
    - BP230 (BP Ag1) is less commonly an antigenic target

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 (BP Ag2) and, less commonly, IgG BP230 (BP Ag1) 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

ARUP Lab Tests

Order concurrently with serum antibody testing and fixed tissue histopathology for assessment of patient with pruritic, urticarial, blistering, and/or erosive disorders, including possible pemphigoid and pemphigoid variants, pemphigus and pemphigus subtypes, dermatitis herpetiformis, epidermolysis bullous acquisita, porphyria, and pseudoporphyria

Order concurrently with fixed tissue histopathology for assessment of patient with inflammatory, immune-mediated cutaneous disease, including possible lupus and lupus variants, vasculitis, drug reactions, lichen planus, and lichenoid reactions

Refer to Immunobullous Skin Diseases Testing algorithm

Tissue must be submitted in Michel’s or Zeus medium; this test cannot be performed on formalin-fixed tissue

Cutaneous Direct Immunofluorescence, Biopsy 0092572

Method: Direct Immunofluorescence

Assess and monitor patient with possible pemphigoid gestationis (herpes gestationis); consider other types of immunobullous disease testing, (eg, IgA epithelial BMZ, IgG collagen type VII, and/or pemphigus antibody panel)

Refer to Immunobullous Skin Diseases Testing algorithm

Herpes Gestationis Factor (Complement-Fixing Basement Membrane Zone Antibody IgG) 0092283

Method: Quantitative Indirect Immunofluorescence

Initial diagnostic panel for skin and mucous membrane disorders that present with blistering, erosions, eczema, pruritus, and/or urticaria, including pemphigoid, pemphigoid variants, epidermolysis bullosa acquisita, linear IgA bullous dermatosis, linear IgA disease variants, and IgG-pemphigus subtypes

Order concurrently with perilesional skin biopsy for direct immunofluorescence for initial diagnosis

Use for disease monitoring with semiquantitative antibody level assessments and tracking and for persistent unexplained disease and/or worsening disease activity

Immunobullous Disease Panel, Epithelial 3001409

Method: Indirect Fluorescent Antibody/Enzyme-Linked Immunosorbent Assay

Initial diagnostic panel for skin and mucous membrane disorders that present with blistering, erosions, eczema, pruritus, and/or urticaria from suspected basement membrane zone antibody-associated disease (eg, bullous pemphigoid, pemphigoid variants, epidermolysis bullosa acquisita, linear IgA bullous dermatosis, and linear IgA disease variants)

Order concurrently with perilesional skin biopsy for direct immunofluorescence for initial diagnosis

Use for disease monitoring with semiquantitative antibody assessments and tracking

Basement Membrane Zone Antibody Panel 3001410

Method: Indirect Fluorescent Antibody/Enzyme-Linked Immunosorbent Assay

Preferred antibody panel for initial diagnostic assessment and disease monitoring in pemphigoid, epidermolysis bullosa acquisita, and linear IgA bullous dermatosis

Panel components include IgG and IgA epithelial BMZ antibodies and IgG bullous pemphigoid BP180 and 230 antigens

To order individual component tests, refer to antibody testing for IgG BMZ, IgA BMZ, and/or IgG bullous pemphigoid BP180 and 230 antigens

To screen for pemphigoid along with other possible immunobullous diseases, order concurrently with pemphigus antibody panel, IgG collagen type VII antibody, AND perilesional skin biopsy for direct immunofluorescence (DIF)

Refer to Immunobullous Skin Diseases Testing algorithm

Pemphigoid Antibody Panel - Epithelial Basement Membrane Zone Antibodies, IgG and IgA, BP180 and BP230 Antibodies, IgG 0092001

Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody

Preferred panel for initial assessment and disease monitoring in IgG-variant pemphigus

Panel components include antibody testing for IgG epithelial cell surface and IgG desmoglein 1 and 3; to order individual component tests, refer to epithelial skin antibody and/or desmoglein 1 and 3 antibodies in pemphigus, IgG

To screen for pemphigus along with other possible immunobullous diseases, order concurrently with antibody panel test for pemphigoid, IgG collagen type VII antibody, AND perilesional skin biopsy for DIF

Refer to Immunobullous Skin Diseases Testing algorithm

Pemphigus Antibody Panel - Epithelial Cell Surface Antibodies and Desmoglein 1 and Desmoglein 3 Antibodies, IgG 0090650

Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody

General screen for immunobullous diseases

Test includes IgG and IgA BMZ antibodies (pemphigoid, epidermolysis bullosa acquisita, linear IgA disease) and IgG and IgA cell surface antibodies (IgG and IgA pemphigus subtypes)

Consider ordering concurrently with IgG bullous pemphigoid (BP180 and 230) antigens for suspected pemphigoid and/or IgG desmoglein 1 and 3 antibodies for suspected pemphigus

For more sensitive and specific testing for pemphigoid or pemphigus, refer to antibody panels for pemphigus or pemphigoid

Refer to Immunobullous Skin Diseases Testing algorithm

Epithelial Skin Antibody 0090299

Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

Monitor disease in patient with pemphigoid or epidermolysis bullosa acquisita who has positive IgG BMZ antibodies by indirect immunofluorescence, either epidermal (roof) pattern or dermal (floor) pattern, on split skin substrate

Consider ordering concurrently with IgG antibody testing for bullous pemphigoid (BP180 and 230) antigens and/or collagen type VII

May use to screen for pemphigoid and other immunobullous diseases; however, this test has decreased sensitivity and specificity when compared to panel tests for pemphigus antibodies or pemphigoid antibodies and will not detect IgA BMZ antibodies

Refer to Immunobullous Skin Diseases Testing algorithm

Epithelial Basement Membrane Zone Antibody IgG 0092056

Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

Related Tests

Monitor disease in patient previously diagnosed with pemphigoid and increased antibodies for IgG BP180 and/or BP230; IgG BP180 antibody levels correlate with disease activity

For initial diagnosis and assessment of disease progression or changes, preferred test is pemphigoid antibody panel; panel components include IgG and IgA epithelial basement membrane zone (BMZ) antibodies and IgG bullous pemphigoid (BP180 and 230) antigens

To determine involvement of IgG BMZ antibodies and pattern of reactivity on split skin substrate, order with antibody testing for IgG epithelial BMZ; also, consider other types of BMZ antibody-associated disease testing, (ie, IgA epithelial BMZ, IgG collagen type VII, or herpes gestationis factor)

Bullous Pemphigoid Antigens (180 kDa and 230 kDa), IgG 0092566

Method: Enzyme-Linked Immunosorbent Assay

Medical Experts

Leiferman, Kristin M., MD, Consultant, Immunodermatology at ARUP Laboratories; Co-Director, Immunodermatology Laboratory, Professor of Dermatology, University of Utah

References

General References

Huilaja L, Mäkikallio K, Tasanen K. Gestational pemphigoid. Orphanet J Rare Dis. 2014; 9: 136. PubMed

Intong LR, Murrell DF. Pemphigoid gestationis: pathogenesis and clinical features. Dermatol Clin. 2011; 29(3): 447-52, ix. PubMed

Lipozenčić J, Ljubojevic S, Bukvić-Mokos Z. Pemphigoid gestationis. Clin Dermatol. 2012; 30(1): 51-5. PubMed

Roth M. Pregnancy dermatoses: diagnosis, management, and controversies. Am J Clin Dermatol. 2011; 12(1): 25-41. PubMed

Semkova K, Black M. Pemphigoid gestationis: current insights into pathogenesis and treatment. Eur J Obstet Gynecol Reprod Biol. 2009; 145(2): 138-44. PubMed

Testing Algorithms

Epithelial Antibody-Associated Immunobullous Diseases Testing

Read more about Epithelial Antibody-Associated Immunobullous Diseases Testing

Immunobullous Diseases Testing Algorithm – Pregnancy

Read more about Immunobullous Diseases Testing Algorithm – Pregnancy

Educational Videos

Last Update: October 2019

Pemphigoid Gestationis - Gestational Pemphigoid

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Monitoring

Background

Epidemiology

Risk Factors

Pathology and Immunopathology

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

General References

Epithelial Antibody-Associated Immunobullous Diseases Testing

Immunobullous Diseases Testing Algorithm – Pregnancy

ARUP Laboratories

ARUP Websites

ARUP Consult


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	Pemphigoid Gestationis - Gestational Pemphigoid. ARUP Consult^©. Retrieved January 15, 2020, from: https://arupconsult.com/content/pemphigoid-gestationis

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Pemphigoid Gestationis - Gestational Pemphigoid

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Monitoring

Background

Epidemiology

Risk Factors

Pathology and Immunopathology

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

General References

Epithelial Antibody-Associated Immunobullous Diseases Testing

Immunobullous Diseases Testing Algorithm – Pregnancy

ARUP Laboratories

ARUP Websites

ARUP Consult