Pemphigoid Gestationis - Gestational Pemphigoid
- Diagnosis
- Algorithms
- Monitoring
- Background
- Lab Tests
- References
- Related Topics
- Videos
Indications for Testing
- Urticarial, blistering, and/or pruritic lesions during pregnancy
- Prompt, accurate diagnosis is essential for planning therapy to minimize morbidity and patient discomfort
Laboratory Testing
- 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 immunofluorescence (IFA) with fresh complement demonstrates C3 on the epidermal side of human split skin substrate (herpes gestationis factor or HGF)
- Highly sensitive and specific testing for pemphigoid gestationis
- Testing by 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
- Perilesional skin biopsy for cutaneous direct immunofluorescence
- Biopsy
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
Pemphigoid gestationis (herpes gestationis) is a rare disease of pregnancy and puerperium.
Epidemiology
- Incidence – 1/40,000-50,000 pregnancies; 1-2/1,000,000 people (Huilaja, 2014)
- 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 ELISA
Clinical Presentation
- Typically presents in the second to third trimester
- Often flares with labor
- Resolves within several weeks to months after delivery
- Rarely – chronic, severe disease
- 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
Cutaneous Direct Immunofluorescence, Biopsy 0092572
Method: Direct Immunofluorescence
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
For skin involvement, biopsy perilesional skin
For mucous membrane involvement, biopsy nonlesional mucosa
May be inaccurate if tissue not taken from correct perilesional location (attached/intact epithelium or epidermis is needed)
Not possible to reliably distinguish pemphigoid from epidermolysis bullosa acquisita or to distinguish pemphigus subtypes based on direct immunofluorescence (DIF); concurrent serum testing needed
Tissue must be submitted in Michel’s or Zeus' medium; this test cannot be performed on formalin-fixed tissue
Monitor herpes gestationis factor, including IgG BP180 antibody levels in serum
Herpes Gestationis Factor (Complement-Fixing Basement Membrane Zone Antibody IgG) 0092283
Method: Quantitative Indirect 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)
Use along with perilesional skin biopsy for DIF to diagnose pemphigoid (herpes) gestationis
Use to follow persistent or recurrent disease activity with antibody titers
Because of clinical overlap among immunobullous diseases and similar names, pemphigoid testing may be confused with pemphigus testing and inadvertently misordered
Use herpes gestationis factor test to monitor disease, including IgG BP180 antibody levels; use relevant tests to monitor other immunobullous disease activity
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 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 & 230 antigens
To order individual component tests, refer to antibody testing for IgG BMZ, IgA BMZ, and/or IgG bullous pemphigoid BP 180 & 230 antigens
To screen for pemphigoid along with other possible immunobullous diseases, order concurrently with the pemphigus antibody panel IgG collagen type VII antibody, AND perilesional skin biopsy for DIF
Concurrent perilesional skin biopsy for DIF is important for diagnosis because of increased sensitivity (85-100% of pemphigus, pemphigoid, linear IgA disease, epidermolysis bullosa acquisita, and dermatitis herpetiformis cases are positive)
Clinical correlation necessary because the incidence of false positives, although rare, increases with age
Because of clinical overlap among immunobullous diseases and similar names, pemphigoid testing may be confused with pemphigus testing and inadvertently misordered
Use pemphigoid panel to monitor pemphigoid disease activity; use relevant tests to monitor other immunobullous disease activity
Repeat pemphigoid panel for indeterminate results and/or continuing clinical consideration of immunobullous disease
Pemphigus Antibody Panel - Epithelial Cell Surface Antibodies and Desmoglein 1 and Desmoglein 3 Antibodies, IgG 0090650
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
Concurrent perilesional skin biopsy for DIF is important for diagnosis because of increased sensitivity (85-100% of pemphigus, pemphigoid, linear IgA disease, epidermolysis bullosa acquisita, and dermatitis herpetiformis cases are positive)
Clinical correlation is necessary because cell surface antibodies by IFA, usually in low titers, may be found in normal individuals (possible blood group reactivity) or in patients with fungal infections, burns, drug reactions, and other dermatoses, including other immunobullous diseases
Because of clinical overlap among immunobullous diseases and similar names, pemphigoid testing may be confused with pemphigus testing and inadvertently misordered
Testing for IgG pemphigus antibody types (most common) also may be confused with IgA pemphigus testing (rare disorder)
Use pemphigus panel to monitor pemphigus disease activity; use relevant tests to monitor other immunobullous disease activity
Repeat pemphigus panel for indeterminate results and/or continuing clinical consideration of immunobullous disease
Epithelial Skin Antibody 0090299
Method: Indirect Immunofluorescence
(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 & 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
Does not include testing for antibodies to target pemphigoid antigens, BP180 and BP230, or to target pemphigus antigens desmoglein 1 and 3 which may be more sensitive diagnostic markers in some cases (levels correlate with disease activity)
Although helpful in screening for immunobullous disease, test is not as sensitive as combination of pemphigus and pemphigoid panels
Use epithelial skin antibody test or both pemphigoid and pemphigus panels to follow patients with changing clinical features because antibody profiles may change over time
Epithelial Basement Membrane Zone Antibody IgG 0092056
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 & 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 the panel tests for pemphigus antibodies or pemphigoid antibodies and will not detect IgA BMZ antibodies
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
Medical Reviewers
Last Update: August 2016