Immunobullous Skin Diseases Screening

Dx
Background
Lab Tests
Algorithm

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
- For predictive value of tests, see table below

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 IgG desmoglein 1 and/or IgG desmoglein 3 antibodies by ELISA (IgG desmoglein 1 antibodies predominate in pemphigus foliaceus, and IgG desmoglein 3 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 disease	70-80% of patients demonstrate IgA antibodies to BMZ components by IFA, with epidermal, combined epidermal-dermal, or (rarely) dermal staining on split skin	100% 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
Vasculitis	Antinuclear antibodies and/or antineutrophilic cytoplasmic antibodies	50-60% 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 IgG desmoglein 3 and desmoglein 1 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 with lupus features	IgG epithelial cell surface by IFA; correlates with disease activity IgG desmoglein 1 and desmoglein 3 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 IgG desmoglein 3 and desmoglein 1 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 – penicillins, ciprofloxacin, furosemide, angiotensin converting enzyme inhibitors (captopril, enalapril), chloroquine, sulfasalazine, phenacetin, nifedipine, terbinafine	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 presentation	Serum autoantibodies	Perilesional biopsy staining
Variable skin lesions ranging from urticarial to vesicles to tense blisters on skin with pronounced pruritus; onset during or after pregnancy	IgG complement-fixing BMZ antibodies and IgG BP180 antibodies	C3 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 DISEASE (Linear IgA bullous dermatosis and chronic bullous disease of childhood)
Clinical presentation	Serum autoantibodies	Perilesional 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; however, some are drug induced – vancomycin, amiodarone, captopril, benazepril, ceftriaxone, cefamandole, cyclosporin, furosemide, lithium, diclofenac, atorvastatin, interleukin-2, interferon-gamma, piroxicam, penicillins, rifampin, trimethoprim and sulfamethoxazole, phenytoin, somatostatin, gemcitabine, vigabatrin, glibenclamide, diethylcarbamazine	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 presentation	Serum autoantibodies	Perilesional 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 diet	Granular BMZ IgA with stippling in dermal papillae; occasionally fibrillar IgA staining
BULLOUS LUPUS ERYTHEMATOSUS
Clinical presentation	Serum autoantibodies	Perilesional biopsy staining
Tense bullae, photodistributed	IgG BMZ, dermal or combined	Linear BMZ IgG; also may show granular IgM and C3 BMZ as in lupus band
LICHEN PLANUS
Clinical presentation	Serum autoantibodies	Perilesional 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 antibodies	Cytoid bodies staining with IgM and/or IgG, IgA, C3, and fibrinogen; prominent shaggy fibrinogen BMZ staining
CHRONIC ULCERATIVE STOMATITIS
Clinical presentation	Serum autoantibodies	Perilesional 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 palate	IgG stratified epithelial specific antinuclear antibodies on specific esophagus substrates	IgG 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

Further testing recommendations available for individual immunobullous diseases

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

Bullous lupus erythematosus
Chronic ulcerative stomatitis
Dermatitis herpetiformis
Epidermolysis bullosa acquisita
Linear IgA bullous dermatosis/linear IgA disease
Pemphigoid gestationis
Pemphigoid subtypes
- Bullous pemphigoid
- Mucous membrane pemphigoid/cicatricial pemphigoid
Pemphigus subtypes
- Pemphigus vulgaris
- Pemphigus foliaceus
- Pemphigus vegetans
- Pemphigus erythematosus (Senear-Usher disease)
- IgA pemphigus
- Paraneoplastic pemphigus

Epidemiology

Incidence – 1-2/1,000,000
- Pemphigoid – 10-13/1,000,000
Age – usually occurs in 40s-50s; can occur in childhood
- Linear IgA disease occurs during childhood 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; 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 Panel - Epithelial Basement Membrane Zone IgG & IgA, BP180 & BP230 IgG Antibodies 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 Panel - IgG Epithelial Cell Surface Antibodies and Levels of IgG Desmoglein 1 and Desmoglein 3 Antibodies, Serum 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, IgG desmoglein 1 and IgG desmoglein 3 antibodies by ELISAs 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 basement membrane zone (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 and the 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 (IgG Complement-Fixing Basement Membrane Zone Antibody) 0092283 Method: Quantitative Indirect Immunofluorescence	Test includes complement-fixing basement membrane zone antibodies, IgG basement membrane zone antibodies, and IgG BP180 antibody level Use along with perilesional skin biopsy for direct immunofluorescence 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 direct immunofluorescence 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 basement membrane zone 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 IgA Antibodies 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 basement membrane zone antibodies found in linear IgA disease and will not detect IgG basement membrane zone antibodies found in pemphigoid and epidermolysis bullosa acquisita or cell surface antibodies found in pemphigus	Use epithelial IgA basement membrane zone 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 Number	Comments
Epithelial Basement Membrane Zone IgG Antibodies 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 basement membrane zone 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 basement membrane zone IgG antibodies test to follow patients with pemphigoid, particularly those with normal BP 180 and BP 230 IgG antibody tests; use relevant tests to monitor other immunobullous disease activity
Bullous Pemphigoid (180 kDa and 230 kDa) Antigens, 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 basement membrane zone 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 basement membrane zone 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 BP 180 and/or IgG BP 230 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
IgG Desmoglein 1 & Desmoglein 3 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 IgG desmoglein 1 and desmoglein 3 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
IgG Epithelial Cell Surface Antibodies 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 or IgG epithelial cell surface antibodies and/or IgG desmoglein 1 and desmoglein 3 antibody 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 IgG desmoglein 1 and desmoglein 3 antibody 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 IgA Antibodies 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 IgG desmoglein 1 and desmoglein 3 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