Immunobullous Skin Diseases Screening

Diagnosis

Indications for Testing

  • Blistering and other inflammatory disease without obvious etiology
  • See Immunobullous Skin Diseases Testing algorithm

Laboratory Testing

  • Initial testing
    • Perilesional skin biopsy for direct immunofluorescence (DIF) plus appropriate serum antibody tests by indirect immunofluorescence (IFA) and enzyme-linked immunosorbent assay (ELISA) are important for initial diagnosis of immunobullous skin diseases
      • Skin tissue biopsy specimens are more sensitive than serum tests but serum tests permit distinguishing the various disorders and monitoring disease activity
    • Serum antibody tests – distinguish between the various disorders and permit monitoring of disease activity
      • Pemphigus and pemphigoid panels (tissue transglutaminase [tTG] or epithelial antibodies for dermatitis herpetiformis)
        • Autoantibodies correlate with disease activity and are useful in monitoring response to therapy after established diagnosis
        • Autoantibodies may be present in normal individuals, although usually in low titers and/or levels – correlate with clinical findings
Predictive Value of Immunodermatology Tests

Disease

Serology
(Cutaneous IFA and ELISA)

Histology
(Cutaneous DIF)

Pemphigus

70-80% of patients demonstrate IgG antibodies to epithelial cell surface components by IFA; 90% or more have desmoglein 1 and/or desmoglein 3 IgG antibodies by ELISA (desmoglein 1 IgG antibodies predominate in pemphigus foliaceus, and desmoglein 3 IgG antibodies predominate in pemphigus vulgaris)

Respective antibodies correlate with disease activity

>90% of patients have epidermal or epithelial cell surface IgG and/or C3 staining in perilesional skin

(Rarely, IgA cell surface antibodies in IgA pemphigus; note that IgA pemphigus is much less common than other pemphigus types)

Bullous pemphigoid

70-80% of patients demonstrate IgG antibodies to basement membrane zone (BMZ) components by IFA, with epidermal or combined epidermal-dermal staining on split skin

80% or more have BP230 (BPAg1) and/or BP180 (BPAg2) IgG antibodies by ELISA, which may be more sensitive than IFA and may correlate with disease activity

>90% of patients have characteristic linear deposition of IgG and C3 (also IgA) along the BMZ in perilesional skin
Epidermolysis bullosa acquisita~50% of patients demonstrate IgG antibodies to BMZ components, with dermal staining on split skin by IFA>95% of patients show strong IgG and C3 in a thick linear BMZ band in perilesional skin; other immunoglobulins may also be present
Linear IgA disease70-80% of patients demonstrate IgA antibodies to BMZ components by IFA, with epidermal, combined epidermal-dermal, or (rarely) dermal staining on split skin100% of patients have characteristic linear staining of IgA along the BMZ in perilesional skin; C3 and/or IgG and IgM linear staining may also be present
Dermatitis herpetiformis

70-80% of patients demonstrate IgA endomysial antibodies by IFA (highly sensitive and specific for the disease)

IgA tissue transglutaminase antibodies by ELISA – slightly less specific but highly sensitive

Respective antibodies correlate with disease activity

>95% of patients have granular and/or fibrillar IgA in dermal papillae of perilesional skin
Bullous lupus erythematosus

Antinuclear antibodies and circulating antibodies to BMZ components by IFA are typically IgG in a combined epidermal-dermal or dermal staining pattern on split skin; IgG BP180 antibodies detected by ELISA may be present (but are rarely IgG BP230 antibodies); type VII collagen antibodies are also commonly present (dermal pattern staining on split skin)

Rare disorder – predictive values not available

Linear and/or dense granular IgG, IgM, and often IgA staining along BMZ in perilesional skin; immunohistological findings are often used to make the diagnosis (>95% likely have these findings)

Rare disorder – predictive values not available

Chronic ulcerative stomatitis

IgG stratified epithelial-specific antinuclear antibodies on specific esophagus substrates

Newly described entity; predictive values not available

100% have IgG antibodies to nuclei of basal and lower 1/3 of keratinocyte cell layers, with stratified epithelial-specific antinuclear antibody pattern

Subset also demonstrates linear to shaggy fibrinogen BMZ staining pattern

Pemphigoid (herpes) gestationis

~85% of patients demonstrate HG factor (HG IgG) by complement fixing IFA and BP180 (BPAg2) antibodies by ELISA

~25% have IgG BMZ antibodies

>95% of patients have intense linear C3 at BMZ; 25-50% show linear IgG BMZ staining in perilesional skin
VasculitisAntinuclear antibodies and/or antineutrophilic cytoplasmic antibodies50-60% of patients with immune-mediated vasculitis demonstrate antibodies in dermal blood vessels in early lesion (24-48 hours old)
Clinical presentation and diagnostic testing for immunobullous skin diseases
Clinical Presentation and Diagnostic Testing for Immunobullous Skin Diseases

PEMPHIGUS

Clinical presentation

Serum autoantibodies

Perilesional biopsy staining

Pemphigus vulgaris

Mucosal involvement is prominent; flaccid bullae with Nikolsky sign; erosions and crusting

Pemphigus vegetans

Variant with vegetating intertriginous plaques and oral involvement including cerebriform tongue

IgG epithelial cell surface by IFA; correlates with disease activity

Desmoglein 1 and desmoglein 3 IgG antibodies by ELISA also correlate with disease activity and can help distinguish pemphigus subtypes  

Epidermal IgG and C3 cell surface (intercellular substance) staining

Pemphigus foliaceus

Superficial bullae, erosions, and scale with crusting; Nikolsky sign present

Pemphigus erythematosus 

Variant  of pemphigus foliaceus with lupus features

IgG epithelial cell surface by IFA; correlates with disease activity

Desmoglein 1 and desmoglein 3 IgG antibodies by ELISA also correlate with disease activity and can help distinguish pemphigus subtypes

Epidermal IgG and C3 cell surface (intercellular substance) staining; in pemphigus erythematosus variant, IgG, IgM, IgA and/or complement granular immune deposits at the BMZ

Drug-induced pemphigus

Pemphigus vulgaris or pemphigus foliaceus

Implicated drugs:

  • Thiol-containing medication implicated in 80% – penicillamine or captopril, pyritinol, thioproline, piroxicam, thiamazole, and gold sodium thiomalate
  • Masked thiols – penicillin, piroxicam, cephalosporins, rifampin
  • Others – enalapril and dipyrone

IgG epithelial cell surface by IFA; correlates with disease activity

Desmoglein 1 and desmoglein 3 IgG antibodies by ELISA also correlate with disease activity and can help distinguish pemphigus subtypes

Epidermal IgG and C3 cell surface (intercellular substance) staining

IgA pemphigus

  • Pruritic vesicles and pustules in subcorneal pustular dermatosis variant
  • Variable skin lesions with numerous pustules in intraepidermal neutrophilic IgA dermatosis variant

IgA epithelial cell surface by IFA; correlates with disease activity

Epidermal IgA cell surface staining

Paraneoplastic pemphigus

Flaccid bullae, lichenoid or erythema multiforme-like; usually involves mucosa, often extensively; esophageal and respiratory involvement

IgG epithelial cell surface and BMZ by IFA (staining on rodent bladder epithelium is characteristic); correlates with disease activity

Epidermal IgG and C3 cell surface and BMZ staining

PEMPHIGOID

Clinical presentation

Serum autoantibodies

Perilesional biopsy staining

Bullous pemphigoid and variants (urticarial, localized, drug-induced)

Tense bullae, often on urticarial base, prominent pruritus; variant forms may not have bullae and may resemble other more common dermatoses; oral involvement; most cases are idiopathic

Minority are drug induced

  • Antibiotics – penicillins, ciprofloxacin, chloroquine
  • Angiotensin converting enzyme inhibitors – captopril, enalapril
  • Sulfasalazine
  • Phenacetin
  • Nifedipine
  • Terbinafine
  • Furosemide

IgG BMZ, epidermal or combined by IFA; BP180 and/or BP230 IgG antibodies by ELISA correlate with disease activity

Linear BMZ IgG (linear and n-serrated patterns) and linear C3; linear IgM, IgA and IgE may be present

Mucous membrane (cicatricial, ocular, antiepiligrin, anti-laminin-332)

Tense bullae and erosions, scarring sequelae, ocular and oral

IgG BMZ, epidermal or combined, rare dermal; IgG BP180 antibodies by ELISA

Linear BMZ IgG (n-serrated) and C3

PEMPHIGOID (HERPES) GESTATIONIS
Clinical presentationSerum autoantibodiesPerilesional biopsy staining
Variable skin lesions ranging from urticarial to vesicles to tense blisters on skin with pronounced pruritus; onset during or after pregnancyIgG complement-fixing BMZ antibodies and IgG BP180 antibodiesC3 and, less commonly, IgG linear BMZ staining

EPIDERMOLYSIS BULLOSA ACQUISITA

Clinical presentation

Serum autoantibodies

Perilesional biopsy staining

Tense bullae commonly occurs in areas of trauma and in oral mucosa

IgG BMZ, rarely IgA, dermal

Linear BMZ IgG (u-serrated) and C3; may show linear IgA and IgM BMZ staining

LINEAR IgA DERMATOSIS
(Linear IgA bullous dermatosis and chronic bullous disease of childhood)
Clinical presentationSerum autoantibodiesPerilesional biopsy staining

Tense bullae, similar to bullous pemphigoid; oral involvement common in adult disease; annular blisters (“cluster of jewels” or “string of pearls”); most cases are idiopathic

Some cases are drug induced

  • Antibiotics – vancomycin, ceftriaxone, cefamandole, trimethoprim and sulfamethoxazole, penicillins, rifampin
  • Cardiac drugs –captopril, benazepril,  furosemide, atorvastatin, amiodarone
  • NSAIDs – diclofenac, piroxicam
  • Chemotherapeutic agents – interleukin-2, interferon-gamma, somatostatin, gemcitabine
  • Antiseizure – vigabatrin, phenytoin
  • Glibenclamide
  • Diethylcarbamazine
  • Cyclosporin
  • Lithium
IgA BMZ, epidermal, or combined (rarely dermal)Linear BMZ IgA (n-serrated and u-serrated) may have IgG and C3 (less-intense BMZ staining)
DERMATITIS HERPETIFORMIS
Clinical presentationSerum autoantibodiesPerilesional biopsy staining
Small bullae or erythematous papules, patches, plaques on extensor surfaces (elbows and knees, also scalp and buttocks); markedly pruritic; associated with intestinal gluten sensitivity; often nontypical presentation because of severe pruritus with eczematous features (distribution is important in making the diagnosis)IgA endomysial and transglutaminase antibodies; correlates with disease activity and compliance with gluten-free dietGranular BMZ IgA with stippling in dermal papillae; occasionally fibrillar IgA staining
BULLOUS LUPUS ERYTHEMATOSUS
Clinical presentationSerum autoantibodiesPerilesional biopsy staining
Tense bullae, photodistributedIgG BMZ, dermal or combinedLinear BMZ IgG; also may show granular IgM and C3 BMZ as in lupus band
LICHEN PLANUS
Clinical presentationSerum autoantibodiesPerilesional biopsy staining

Multiple subtypes; classical lesions are polygonal, flat-topped, violaceous papules and plaques with reticulated white scale (called Wickham striae); oral mucosa and/or cutaneous; may blister and/or erode

No specific serum antibodiesCytoid bodies staining with IgM and/or IgG, IgA, C3, and fibrinogen; prominent shaggy fibrinogen BMZ staining
CHRONIC ULCERATIVE STOMATITIS
Clinical presentationSerum autoantibodiesPerilesional biopsy staining
Pain and erosive lesions commonly involving tongue, also buccal mucosa and gingival tissue with desquamative gingivitis; less frequently involves labial mucosa and hard palateIgG stratified epithelial specific antinuclear antibodies on specific esophagus substratesIgG antibodies to nuclei of basal and lower 1/3 of keratinocyte cell layers with stratified epithelial-specific antinuclear antibody pattern and linear to shaggy fibrinogen BMZ staining pattern

Clinical Background

Immunobullous skin diseases are autoimmune blistering diseases affecting skin and mucous membranes and are caused by or associated with the deposition of specific antibodies on cutaneous structures. They include the following

Epidemiology

  • Incidence – 1-2/1,000,000
    • Pemphigoid – 10-13/1,000,000
    • Pemphigus – 1-5/1,000,000
  • Age – usually occurs in 40s-50s; can occur in childhood
    • Linear IgA disease – most common immunobullous childhood disease; appears as a chronic bullous disease
    • Pemphigoid (herpes) gestationis occurs in females during childbearing years
    • Incidence of bullous pemphigoid significantly increases after age 70 (15-18/100,000)
  • HLA class II associations

Clinical Presentation

  • Although the various immunobullous skin diseases are characterized by clinical and histological features, presentation is often atypical and shows overlap with other immunobullous diseases or with more common skin diseases (eg, eczema, urticaria)
  • Classic features – blistering or erosive lesions
  • Wide range and variability of lesional types, often with prominent itching, secondary lesions, eczema, or urticaria
  • Histology varies with each immunobullous disease
    • Eosinophil infiltration and eosinophil-associated spongiosis common in IgG autoantibody immunobullous disease
    • Neutrophil infiltration common in IgA autoantibody immunobullous disease

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Cutaneous Direct Immunofluorescence, Biopsy 0092572
Method: Direct Immunofluorescence
(Direct Fluorescent Antibody Stain)

Use to determine the presence and characteristic staining pattern of immunoglobulins (IgG, IgM, IgA), third component of complement (C3) and fibrinogen in skin or mucous membrane biopsy specimens (biopsy site is critical; see below) from patients suspected of having immunobullous skin and/or mucous membrane disease; perform this test with serum pemphigoid and pemphigus panel tests

For skin involvement, biopsy perilesional skin

For mucous membrane involvement, biopsy nonlesional mucosa

See Immunobullous Skin Diseases Testing algorithm

May be inaccurate if tissue not taken from correct perilesional location (attached/intact epithelium or epidermis 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

Initial concurrent and repeat serum testing with pemphigoid and pemphigus panels is the most sensitive for diagnosis, for determining antibody profiles, and for following disease activity

Patients with indeterminate results should have repeat DIF biopsy

Patients with changing clinical features should have repeat DIF biopsy because antibody profiles may change over time

See 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

Panel includes epithelial basement membrane zone (BMZ) IgG & IgA antibodies by indirect immunofluorescence (IFA) on split human skin and monkey esophagus substrates, BP180 & BP230 IgG antibodies by ELISAs

Use to diagnose most types of pemphigoid, epidermolysis bullosa acquisita, linear IgA disease (including linear IgA bullous dermatosis and chronic bullous disease of childhood), mixed immunobullous disease

Use along with pemphigus panel and endomysial antibody IgA testing to initially diagnose and discriminate among the immunobullous skin diseases in patients suspected or known to have any type of immunobullous disease

Use in pemphigoid to monitor disease activity and therapeutic response

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)

See Immunobullous Skin Diseases Testing algorithm

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

See 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

Panel includes epithelial cell surface IgG antibodies by IFA on intact human skin and monkey esophagus substrates, and desmoglein 1 and desmoglein 3 antibodies in pemphigus, IgG

Use to diagnose most major types of pemphigus and to monitor disease activity and therapeutic response

Use along with pemphigoid panel and endomysial IgA antibody tests to initially diagnose and distinguish various immunobullous disorders in patients suspected or known to have any type of immunobullous disease

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)

See Immunobullous Skin Diseases Testing algorithm

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)

Panel includes epithelial BMZ IgG and IgA antibodies by IFA and IgG and IgA cell surface antibodies by IFA on split human skin, intact human skin, and monkey esophagus substrates

Use as alternate to pemphigoid and pemphigus panel tests to initially diagnose and discriminate among clinically similar immune-mediated skin diseases such as pemphigus, linear IgA disease, pemphigoid, epidermolysis bullosa acquisita, and dermatitis herpetiformis in patients suspected of having or known to have any type of subepidermal immunobullous disease

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

Herpes Gestationis Factor (Complement-Fixing Basement Membrane Zone Antibody IgG) 0092283
Method: Quantitative Indirect Immunofluorescence

Test includes complement-fixing BMZ antibodies, IgG BMZ antibodies, and IgG BP180 antibody level

Use along with perilesional skin biopsy for DIF to diagnose pemphigoid (herpes) gestationis

Use to follow persistent or recurrent disease activity with antibody titers

  Use herpes gestationis factor test to monitor disease, including IgG BP180 antibody levels; use relevant tests to monitor other immunobullous disease activity
Paraneoplastic Pemphigus Antibody Screen 0092107
Method: Indirect Fluorescent Antibody

Use along with perilesional skin biopsy for DIF to aid in diagnosis of paraneoplastic pemphigus

Use to follow persistent or recurrent disease activity with antibody titers

   
Tissue Transglutaminase (tTG) Antibody, IgA with Reflex to Endomysial Antibody, IgA by IFA 0050734
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Use along with pemphigoid and pemphigus panel tests, or use with epithelial skin antibody testing to initially diagnose and discriminate among the immunobullous skin diseases in patients suspected or known to have any type of immunobullous disease

Does not detect IgG or IgA BMZ or cell surface antibodies that characterize immunobullous diseases other than dermatitis herpetiformis

Use tissue transglutaminase (tTG) antibody, IgA with reflex to endomysial antibody, IgA by IFA for initial diagnosis of dermatitis herpetiformis and to follow disease activity in dermatitis herpetiformis; use relevant tests to monitor other immunobullous disease activity

Repeat test for indeterminate results and/or continuing clinical consideration of immunobullous disease

Epithelial Basement Membrane Zone Antibody IgA 0092057
Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

This test comprises components included in pemphigoid panel and epithelial skin antibody tests

Use to establish or confirm diagnosis of linear IgA bullous disease, chronic bullous disease of childhood and mixed immunobullous disease

Use to discriminate among clinically similar immunobullous diseases, linear IgA disease (linear IgA bullous dermatosis, childhood immunobullous disease), pemphigoid, epidermolysis bullosa acquisita, mixed immunobullous disease, pemphigus, and dermatitis herpetiformis

Follow persistent or recurrent disease activity with antibody titers

Although helpful in screening for immunobullous disease, not as sensitive as combination of pemphigus and pemphigoid panels

Clinical correlation necessary because incidence of false positives, although rare, increases with age

Specific for IgA BMZ antibodies found in linear IgA disease and will not detect IgG BMZ antibodies found in pemphigoid and epidermolysis bullosa acquisita or cell surface antibodies found in pemphigus

Use epithelial IgA BMZ IgA antibody or pemphigoid panel tests to monitor linear IgA disease activity and response to therapy; use relevant tests to monitor other immunobullous disease activity

Repeat epithelial IgA basement membrane zone IgA antibody or pemphigoid panel for indeterminate results and/or continuing clinical consideration of linear IgA disease

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Epithelial Basement Membrane Zone Antibody IgG 0092056
Method: Indirect Immunofluorescence
(Indirect Fluorescent Antibody)

This test comprises components included in pemphigoid panel, epithelial skin antibody, and pemphigoid gestationis tests

Use to establish or confirm diagnosis of epidermolysis bullosa acquisita or pemphigoid in patients suspected of having or known to have any type of disorder with IgG BMZ antibodies

Use to distinguish epidermolysis bullosa acquisita from pemphigoid

This test alone is not as useful as pemphigoid panel or epithelial skin antibody test in initial diagnosis of immunobullous disease

Use epithelial BMZ IgG antibodies test to follow patients with pemphigoid, particularly those with normal BP180 and BP230 IgG antibody tests; use relevant tests to monitor other immunobullous disease activity

Bullous Pemphigoid Antigens (180 kDa and 230 kDa), IgG 0092566
Method: Enzyme-Linked Immunosorbent Assay

This test comprises components included in the pemphigoid panel and pemphigoid gestationis factor tests

Use to test for IgG BP180 (BP Ag2) and BP230 (BP Ag1) antibodies in patients suspected of having or known to have any type of pemphigoid, including bullous pemphigoid and variant forms, mucous membrane (cicatricial) pemphigoid and herpes gestationis

Use to measure relative levels of BP180 and BP230 IgG antibodies to diagnose pemphigoid and to monitor disease activity and therapeutic response

Use along with epithelial BMZ antibodies by IFA to identify patients with pemphigoid antibodies  to epitopes other than those in the assay

Negative, positive and borderline/indeterminate results should be correlated and confirmed with IFA, epithelial skin antibody test and indeterminate/borderline levels should be monitored

Patients with pemphigoid may show reactivity to multiple BMZ components; therefore, negative/normal IgG BP180 and BP230 antibody levels do not rule out pemphigoid or another immunobullous disease

Up to 7% of individuals unaffected by pemphigoid (including those with other immunobullous diseases) have increased IgG BP180 and/or IgG BP230 antibody levels

These tests are components of pemphigoid panel; pemphigoid panel is optimal for initial diagnosis of pemphigoid and monitoring response to therapy; otherwise, concurrent testing is advised with epithelial skin antibody test

Correlations with IFA (epithelial skin antibody test), DIF findings, and clinical presentation are important for initial diagnosis

Use bullous pemphigoid (180 kDa and 230 kDa) antigens IgG antibody tests  to follow disease activity in pemphigoid; use relevant tests to monitor other immunobullous disease activity

Desmoglein 1 and Desmoglein 3 Antibodies in Pemphigus, IgG 0090649
Method: Enzyme-Linked Immunosorbent Assay

These ELISA tests are components included in the pemphigus panel

Use to distinguish pemphigus foliaceus from pemphigus vulgaris and other immune-mediated skin disease

Use to measure relative levels of desmoglein 1 and desmoglein 3 IgG antibodies to support a diagnosis of pemphigus (may be more sensitive than IFA in some patients) and to monitor disease activity and therapeutic response

Use along with epithelial cell surface antibodies by IFA for added sensitivity and to identify patients with pemphigus antibodies  to epitopes other than those in the assay

Negative, positive and borderline/indeterminate results should be correlated and confirmed with IFA, epithelial skin antibody test or IgG epithelial cell surface antibodies test, and indeterminate/borderline levels should be monitored

Patients with pemphigus may show reactivity to various cell surface antigens; therefore, negative/normal desmoglein 1 and desmoglein 3 IgG antibody levels do not rule out pemphigus

These tests are components of pemphigus panel; pemphigus panel is optimal for initial diagnosis of pemphigus and for monitoring response to therapy; otherwise, concurrent testing is recommended with epithelial skin antibody test

Correlations with IFA (epithelial skin antibody test), DIF findings and clinical presentation are important for initial diagnosis

May not be positive in paraneoplastic pemphigus and typically not positive in IgA pemphigus, although cross expression of antibody classes may develop

Epithelial Cell Surface Antibody IgG 0090266
Method: Indirect Fluorescent Antibody

This test comprises components included in the pemphigus panel and epithelial skin antibody test

Use to test for IgG cell surface antibodies in patients suspected of having or known to have the major types of pemphigus

Use to distinguish pemphigus from other immune-mediated diseases

Use to monitor response to therapy and disease activity in pemphigus

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

Use IgG epithelial cell surface antibodies and/or desmoglein 1 and desmoglein 3 IgG antibodies or pemphigus panel tests to monitor pemphigus vulgaris and pemphigus foliaceus disease activity and response to therapy; use relevant tests to monitor other immunobullous disease activity

Repeat IgG epithelial cell surface antibodies and/or desmoglein 1 and desmoglein 3 IgG antibodies or pemphigus panel tests for indeterminate results and/or continuing clinical consideration of pemphigus vulgaris or pemphigus foliaceus

See Immunobullous Skin Diseases Testing algorithm

Pemphigus Antibody IgA 0092106
Method: Indirect Fluorescent Antibody

This test comprises components included in the epithelial skin antibody test

Use to test for IgA cell surface antibodies in patients suspected of having or known to have IgA pemphigus and have tested negative for IgG pemphigus (cell surface) antibodies

Use to distinguish IgA pemphigus from other immune-mediated diseases

Use to monitor response to therapy and disease activity in IgA pemphigus

IgA pemphigus is a rare form of pemphigus; recommend testing for IgG autoantibody types with pemphigus panel concurrently or before ordering this test

Clinical correlation is necessary; cell surface antibodies, usually in low titers, also may be found in normal individuals because of blood group reactivity

Use pemphigus IgA antibodies test to monitor disease activity in IgA pemphigus; use relevant tests to monitor other immunobullous disease activity

Use pemphigus panel  or desmoglein 1 and desmoglein 3 IgG antibodies to monitor pemphigus vulgaris and pemphigus foliaceus disease activity and response to therapy

Repeat pemphigus IgA antibodies test for indeterminate results and/or continuing clinical consideration of the disease