Immunobullous skin diseases are a group of autoimmune blistering diseases that affect skin and mucous membranes and are caused by or associated with the deposition of specific antibodies on cutaneous structures.
Epidemiology
- Incidence - rare disorders
- Age - most occur during the ages of 40 to 60
- Linear IgA disease can occur during childhood
- Herpes Gestationis occurs in females during childbearing years
Clinical Presentation
- Although the various immunobullous skin diseases have certain clinical and histological features that characterize them, often their presentation is atypical and/or shows overlap with each other and other diseases including common skin diseases such as eczema and urticaria
- Most common feature is the presence of a blistering lesion
Diagnosis
- Indications for testing - blistering disease without obvious etiology
- See Immunobullous Skin Diseases Testing algorithm
- Laboratory testing
- Serum antibody tests
- Autoantibodies may be present in normal individuals, usually in low titers and/or levels; clinical correlation is needed
- Serum antibody tests
- Histology
- Perilesional skin biopsy for direct immunofluorescence along with appropriate serum antibody tests are very helpful for the initial diagnosis of immunobullous skin diseases because of increased sensitivity with tissue studies and ability to distinguish diseases by serum studies
Predictive Value of Immunodermatology Tests | ||
Disease | Serum Studies - | Tissue Studies- |
Bullous pemphigoid | 70-80% of patients demonstrate IgG antibodies to BMZ components by indirect immunofluorescence, with epidermal staining on split skin 80% or more have BP230 (BPAg1) and/or BP180 (BPAg2) IgG antibodies by ELISA which correlate with disease activity | >90% of patients have characteristic linear deposition of IgG and C3 (also IgA) along the BMZ in perilesional skin |
Dermatitis herpetiformis | Approximately 85% of patients demonstrate IgA endomysial antibodies by indirect immunofluorescence which is 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 |
Epidermolysis bullosa acquisita | Approximately 50% of patients demonstrate IgG antibodies to BMZ components, dermal staining on split skin by indirect immunofluorescence | >95% of patients show strong IgG and C3 in a thick linear BMZ band in perilesional skin; other immunoglobulins may also be present |
Herpes gestationis | Approximately 85% of patients demonstrate HG factor (HG IgG) by complement fixing indirect immunofluorescence and BP180 (BPAg2) antibodies by ELISA Approximately 25% have IgG at the BMZ | >95% of patients have intense linear C3 at BMZ; 25% show linear IgG BMZ in perilesional skin |
Pemphigus | 70-80% of patients demonstrate IgG antibodies to epithelial cell surface components by indirect immunofluorescence, 90% or more have IgG desmoglein-1 and/or 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 cell surface IgG and/or C3 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 |
Refer to Immunobullous Skin Disease Screening topic at www.arupconsult.com for a chart of Clinical Presentation and DiagnositicTesting for Immunobullous Skin Diseases
| Tests |
| Test name: Herpes Gestationis Factor (IgG Complement-Fixing Basement Membrane Zone Antibodies) |
| ARUP #: 0092283 |
| Methodology: Indirect Immunofluorescence |
| Use: Order along with perilesional skin biopsy for diagnosis of herpes gestationis Follow persistent or recurrent disease activity with antibody titers |
| Limitations: |
| Follow-up: Perilesional biopsy for cutaneous direct immunofluorescence is recommended
See Immunobullous Skin Diseases Testing algorithm
|
| Test name: Paraneoplastic Pemphigus Antibody Screen |
| ARUP #: 0092107 |
| Methodology: Indirect Immunofluorescence |
| Use: Order along with perilesional skin biopsy to help in the diagnosis of paraneoplastic pemphigus Follow persistent or recurrent disease activity with antibody titers |
| Limitations: |
| Follow-up: Perilesional biopsy for cutaneous direct immunofluorescence is recommended
See Immunobullous Skin Diseases Testing algorithm
|
| Test name: Pemphigoid Panel - Epithelial Basement Membrane Zone IgG & IgA, BP180 & BP230 IgG Antibodies |
| ARUP #: 0092001 |
| Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Immunofluorescence |
| 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 |
| Follow-up:
Perilesional biopsy for cutaneous direct immunofluorescence is recommended See Immunobullous Skin Diseases Testing algorithm |
| 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 Immunofluorescence |
| Use: Order along with the pemphigoid panel, endomysial antibodies test and perilesional skin biopsy to screen for immunobullous skin disease (preferred screening test combination) Follow disease activity and therapeutic response with antibody titers and levels |
| Limitations: Clinical correlation necessary because cell surface antibodies may be found in normal individuals and in patients with burns, fungal infections, drug reactions and other dermatoses |
| Follow-up: Perilesional biopsy for cutaneous direct immunofluorescence is recommended
See Immunobullous Skin Diseases Testing algorithm
|
| Test name: Epithelial Skin Antibody |
| ARUP #: 0090299 |
| Methodology: Indirect Immunofluorescence |
| Use: Order along with endomysial antibody test and perilesional skin biopsy to screen for immunobullous skin disease Follow persistent or recurrent disease activity with disease specific antibody titers and levels |
| Follow-up: Perilesional biopsy for cutaneous direct immunofluorescence is recommended See Immunobullous Skin Diseases Testing algorithm |
| Test name: Cutaneous Direct Immunofluorescence, Biopsy |
| ARUP #: 0092572 |
| Methodology: Direct Immunofluorescence |
| Use: Order along with serum tests to screen for immunobullous skin disease |
| Limitations: |
| Follow-up:
See Immunobullous Skin Diseases Testing algorithm
|
| Test name: Tissue Transglutaminase Antibody, IgA with Reflex to Endomysial Antibody, IgA Titer by IFA |
| ARUP #: 0050734 |
| Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody |
| Use: Order along with IgA tissue transglutaminase antibody test and perilesional skin biopsy to screen for presence of immunobullous skin disease Follow disease activity with antibody titers and levels |
| Follow-up: Perilesional biopsy for cutaneous direct immunofluorescence is recommended See Immunobullous Skin Diseases Testing algorithm |
| Test name: Epithelial Basement Membrane Zone IgG Antibodies |
| ARUP #: 0092056 |
| Methodology: Indirect Immunofluorescence (IFA) |
| Comments: |
| Test name: Epithelial Basement Membrane Zone IgA Antibodies |
| ARUP #: 0092057 |
| Methodology: Indirect Immunofluorescence |
| Comments: |
| Test name: Bullous Pemphigoid (180 kDa & 230 kDa) Antigens, IgG |
| ARUP #: 0092566 |
| Methodology: Enzyme Linked Immunosorbent Assay |
| Comments: |
| Test name: IgG Desmoglein 1 & Desmoglein 3 |
| ARUP #: 0090649 |
| Methodology: Enzyme-Linked Immunosorbent Assay |
| Comments: |
| Test name: IgG Epithelial Cell Surface Antibodies |
| ARUP #: 0090266 |
| Methodology: Indirect Immunofluorescence |
| Comments: |
| Test name: Pemphigus IgA Antibodies |
| ARUP #: 0092106 |
| Methodology: Indirect Immunofluorescence |
| Comments: |
General References
Comprehensive Review: September 2008
Last Update: September 2008
