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Predictive Value of Immunodermatology Tests | ||
Disease | Serology | Histology |
| Pemphigus | 70-80% of patients demonstrate IgG antibodies to epithelial cell surface components by indirect immunofluorescence (IFA); 90% or more have IgG desmoglein 1 and/or IgG desmoglein 3 antibodies by enzyme-linked immunosorbent assay (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 | Approximately 50% of patients demonstrate IgG antibodies to BMZ components, 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) Disorder is sufficiently rare that predictive values are not available | Linear and/or dense granular IgG, IgM and often IgA staining along BMZ in perilesional skin; as the immunohistological findings are often used to make the diagnosis (>95% likely have these findings) Disorder is sufficiently rare that predictive values are not available |
| Chronic ulcerative stomatitis | IgG stratified epithelial specific-antinuclear antibodies on specific esophagus substrates Newly described entity; predictive values are not available | 100% have IgG antibodies to nuclei of basal and lower 1/3 keratinocyte cell layers with stratified epithelial-specific antinuclear antibody pattern A 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 antibody in dermal blood vessels in early lesion (24-48 hours old) |
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
Tests generally appear in the order most useful for common clinical situations
| Test name: Cutaneous Direct Immunofluorescence, Biopsy |
| ARUP #: 0092572 |
| Methodology: Direct Immunofluorescence (Direct Fluorescent Antibody Stain) |
| Use: Initial test along with serum tests to screen for immunobullous skin disease Determine presence and staining pattern of immunoglobulins (IgG, IgM, IgA), third component of complement (C3) and fibrinogen in perilesional skin or mucosal biopsy specimens from patients suspected of having pemphigus; perform this test with serum pemphigus panel |
| Limitations: May be inaccurate if tissue not taken from correct perilesional location (attached/intact epithelium or epidermis is needed) Not possible to reliably distinguish pemphigus subtypes based on direct immunofluorescence (DIF); serum testing helpful for subtyping Tissue must be submitted in Michel’s or Zeus medium; this test cannot be performed on formalin-fixed tissue |
| Follow-up: Concurrent serum testing with pemphigoid panel is the most sensitive for diagnosis and for determining subtype of subepidermal blistering disease Patients with indeterminate results should have repeat biopsy for by DIF and antibody levels monitored for disease activity |
| Test name: Pemphigoid Panel - Epithelial Basement Membrane Zone IgG & IgA, BP180 & BP230 IgG Antibodies |
| ARUP #: 0092001 |
| Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody |
| Use: Diagnose most types of pemphigoid, epidermolysis bullosa acquisita, linear IgA disease (including linear IgA bullous dermatosis and childhood immunobullous disease) Panel includes epithelial BMZ IgG & IgA antibodies by IFA on split human skin and monkey esophagus substrates, BP180 & BP230 IgG antibodies by ELISA Use in conjunction with pemphigus panel and endomysial antibody IgA testing to differentiate among the immunobullous skin diseases in patients suspected or known to have any type of immunobullous disease IgG BP180 and BP230 antibody levels may be useful in monitoring disease activity and response to therapy |
| Limitations: Clinical correlation necessary because incidence of false positives, although rare, increases with age Because of clinical overlap among immunobullous diseases and similar names, testing for pemphigoid may be confused with testing for pemphigus and misordered |
| Follow-up: Perilesional skin biopsy by DIF is helpful in diagnosis (>90% of pemphigoid and epidermolysis bullosa acquisita cases are positive) Use pemphigoid panel to monitor pemphigoid disease activity and response to therapy |
| Test name: Pemphigus Panel - IgG Epithelial Cell Surface Antibodies and Levels of IgG Desmoglein 1 and Desmoglein 3 Antibodies, Serum |
| ARUP #: 0090650 |
| Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody |
| Use: Diagnose most types of pemphigus and monitor disease activity and response to therapy Panel tests for IgG epithelial cell surface antibodies by indirect immunofluorescence (IFA) on intact human skin and monkey esophagus substrates and IgG desmoglein 1 and IgG desmoglein 3 antibodies by ELISA Use along with pemphigoid panel and endomysial IgA antibody testing, or epithelial skin antibody testing to distinguish the various disorders in patients suspected or known to have any type of immunobullous disease |
| Limitations: 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 Because of clinical overlap among immunobullous diseases and similar names, testing for pemphigus may be confused with testing for pemphigoid and misordered; testing for IgG pemphigus antibody types (most common) also may be confused with IgA pemphigus testing (rare disorder) |
| Follow-up: Concurrent perilesional skin biopsy evaluated by 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) Use pemphigus panel to monitor disease activity and response to therapy |
| Test name: Epithelial Skin Antibody |
| ARUP #: 0090299 |
| Methodology: Indirect Immunofluorescence (Indirect Fluorescent Antibody) |
| Use: Discriminate among clinically similar immune-mediated skin diseases such as 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 Panel includes epithelial BMZ IgG & IgA antibodies by IFA and IgG & IgA cell surface antibodies by IFA on split human skin, intact human skin and monkey esophagus substrates |
| Limitations: Although helpful in screening for immunobullous disease, not as sensitive as combination of pemphigus and pemphigoid panels |
| Follow-up: Perilesional skin biopsy by DIF is helpful in diagnosis (>90% of pemphigus, pemphigoid, epidermolysis bullosa acquisita, linear IgA disease, dermatitis herpetiformis cases are positive) IgG desmoglein 1 and 3 antibodies and/or IgG BP180 and BP230 antibodies tests are helpful in determining immunobullous disease subtype and monitoring response to therapy |
| Test name: Herpes Gestationis Factor (IgG Complement-Fixing Basement Membrane Zone Antibodies) |
| ARUP #: 0092283 |
| Methodology: Indirect Immunofluorescence (Indirect Fluorescent Antibody) |
| Use: Order along with perilesional skin biopsy for diagnosis of pemphigoid (herpes) gestationis Follow persistent or recurrent disease activity with antibody titers |
| Follow-up: Perilesional biopsy for cutaneous DIF is important to establish diagnosis See Immunobullous Skin Diseases Testing algorithm |
| Test name: Paraneoplastic Pemphigus Antibody Screen |
| ARUP #: 0092107 |
| Methodology: Indirect Fluorescent Antibody |
| Use: Order along with perilesional skin biopsy to aid in diagnosis of paraneoplastic pemphigus Follow persistent or recurrent disease activity with antibody titers |
| Follow-up: Perilesional biopsy for cutaneous direct immunofluorescence is important to establish diagnosis See Immunobullous Skin Diseases Testing algorithm |
| Test name: Tissue Transglutaminase (tTG) Antibody, IgA with Reflex to Endomysial Antibody, IgA by IFA |
| ARUP #: 0050734 |
| Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody |
| Use: Use along with pemphigoid and pemphigus panel tests, or epithelial skin antibody testing to differentiate among the immunobullous skin diseases in patients suspected or known to have any type of immunobullous disease |
| Limitations: Will not detect IgA or other BMZ antibodies that characterize linear IgA disease |
| Follow-up: Perilesional skin biopsy by DIF is helpful in diagnosis (>90% of dermatitis herpetiformis cases are positive) |
| Test name: Epithelial Basement Membrane Zone IgA Antibodies |
| ARUP #: 0092057 |
| Methodology: Indirect Immunofluorescence (Indirect Fluorescent Antibody) |
| Use: Order along with the pemphigus panel, endomysial antibodies test and perilesional skin biopsy to screen for immunobullous skin disease (preferred screening test combination) Follow persistent or recurrent disease activity with antibody titers and levels |
| Limitations: Clinical correlation necessary because incidence of false positives, although rare, increases with age Test is specific for IgA BMZ antibodies found in linear IgA disease and will not detect IgG BMZ antibodies found in pemphigoid or epidermolysis bullosa acquisita or cell surface antibodies found in pemphigus |
| Follow-up: Perilesional skin biopsy by DIF may be necessary for final clinical diagnosis See Immunobullous Skin Diseases Testing algorithm |
| Test name: Epithelial Basement Membrane Zone IgG Antibodies |
| ARUP #: 0092056 |
| Methodology: Indirect Immunofluorescence (Indirect Fluorescent Antibody) |
| Comments: Component of pemphigoid panel Test alone is not as useful as pemphigoid panel in initial diagnosis of immunobullous disease |
| Test name: Bullous Pemphigoid (180 kDa & 230 kDa) Antigens, IgG |
| ARUP #: 0092566 |
| Methodology: Enzyme-Linked Immunosorbent Assay |
| Comments: IgG BP180 and BP230 by ELISA are also components of pemphigoid panel; panel test may be more useful for initial diagnosis of pemphigoid and in monitoring response to therapy; normal results do not rule out pemphigoid |
| Test name: IgG Desmoglein 1 & Desmoglein 3 |
| ARUP #: 0090649 |
| Methodology: Enzyme-Linked Immunosorbent Assay |
| Comments: IgG desmoglein 1 and desmoglein 3 by ELISA are also components of pemphigus panel; panel test may be more useful for initial diagnosis of pemphigus and in monitoring response to therapy |
| Test name: IgG Epithelial Cell Surface Antibodies |
| ARUP #: 0090266 |
| Methodology: Indirect Fluorescent Antibody |
| Comments: Component of pemphigoid panel Test alone is not as useful as pemphigus panel in initial diagnosis of immunobullous disease |
| Test name: Pemphigus IgA Antibodies |
| ARUP #: 0092106 |
| Methodology: Indirect Fluorescent Antibody |
| Comments: Order along with IgG cell surface antibody test in initial diagnosis of immunobullous disease because of rarity of IgA pemphigus |