Epidermolysis Bullosa Acquisita

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Immunobullous Skin Diseases Testing Algorithm

Clinical Background

Epidermolysis bullosa acquisita is a rare chronic autoimmune blistering disease.

Epidemiology

Incidence - 0.25 cases per million
Age of onset - all ages, peak onset age 40-50
Sex - M:F equal distribution

Pathophysiology

Subepidermal blister formation

Clinical Presentation

Blistering lesions of skin on areas of trauma and/or oral mucosa, with an acral distribution that heal with scarring
- Tense blisters with serous or hemorrhagic fluid
May have loss of hair and nail dystrophy

Treatment

Challenging to put into remission
Variety of agents currently in use, including colchicine and cyclosporine

See Also

Dermatitis Herpetiformis

Immunobullous Skin Diseases Screening

Linear IgA Disease

Paraneoplastic Pemphigus

Pemphigoid

Pemphigus

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Immunobullous Skin Diseases Testing Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Cutaneous Direct Immunofluorescence, Biopsy

ARUP #: 0092572

Methodology: Direct Immunofluorescence

Use:

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 epidermolysis bullosa acquisita

Limitations:

Test may be inaccurate if tissue not taken from correct location; type and age of lesion may also be important; specimen must have epidermis/epithelium and basement membrane zone

Tissue must be submitted in Michel’s or Zeus medium; this test cannot be performed on formalin-fixed tissue

Follow-up:

Concurrent serum testing for epidermolysis bullosa acquisita is most specific and sensitive for diagnosis with Pemphigoid Panel, Epithelial Skin Antibody, or Epithelial Basement Membrane Zone IgG Antibodies

Test name: Pemphigoid Panel - Epithelial Basement Membrane Zone IgG & IgA, BP180 & BP230 IgG Antibodies

ARUP #: 0092001

Methodology: Enzyme-Linked Immunosorbent Assay/Indirect Immunofluorescence

Use:

For diagnosis of epidermolysis bullosa acquisita, linear IgA disease (including linear IgA bullous dermatosis and childhood immunobullous disease) and most types of pemphigoid

Panel includes epithelial basement membrane zone IgG & IgA on human split skin and monkey esophagus substrates by IFA, BP 180 & BP 230 IgG antibodies by ELISAs

Useful to distinguish these immunobullous diseases from each other, such as pemphigoid, pemphigus and dermatitis herpetiformis

Use along with Pemphigus Panel and endomysial antibody, IgA, and testing to differentiate among the various immunobullous skin diseases in patients suspected or known to have any type of these disorders

Limitations:

Clinical correlation necessary since 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 direct immunofluorescence is helpful in diagnosis (>90% of pemphigoid and epidermolysis bullosa acquisita cases are positive)

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:

Use along with Pemphigoid Panel test and endomysial IgA antibody test, or Epithelial Skin Antibody testing to differentiate among the various immunobullous skin diseases in patients suspected or known to have any type of these disorders

For diagnosis of most types of pemphigus and for monitoring disease activity and response to therapy

Panel tests for IgG epithelial cell surface antibodies on intact human skin and monkey esophagus substrates by IFA and IgG desmoglein 1 and desmoglein 3 antibodies by ELISAs

Limitations:

Clinical correlation is necessary since cell surface antibodies by IFA, usually in low titers, may be found in normal individuals because of blood group reactivity or in patients with fungal infections, burns, drug reactions and other dermatoses

Testing for IgG pemphigus antibody types (most common) also may be confused with IgA pemphigus testing (rare)

Follow-up:

A concurrent perilesional skin biopsy for direct immunofluorescence is helpful for diagnosis because of increased sensitivity (>90% of epidermolysis bullosa acquisita, pemphigus, pemphigoid, linear IgA disease, and dermatitis herpetiformis cases are positive), although it is not possible to reliably distinguish pemphigus subtypes based on direct immunofluorescence

Monitor pemphigus disease activity and response to therapy with Pemphigus Panel

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:

Use along with Pemphigoid and Pemphigus Panel tests, or with Epithelial Skin Antibody testing to differentiate among the various immunobullous skin diseases in patients suspected or known to have any type of these disorders

Limitations:

This test alone is insufficient to diagnose immunobullous disease

Follow-up:

Perilesional skin biopsy by direct immunofluorescence is helpful in diagnosis (>90% of pemphigoid, pemphigus, linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa acquisita cases are positive)

Test name: Epithelial Skin Antibody

ARUP #: 0090299

Methodology: Indirect Immunofluorescence

Use:

Use along with endomysial antibody, IgA, test to differentiate among the various immunobullous skin diseases in patients suspected or known to have any type of these disorders

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

Limitations:

Does not include testing for antibodies to target antigens, BP180 & BP230 for pemphigoid and desmoglein 1 & 3 for pemphigus that may be more sensitive and the levels of which correlate with disease activity and response to therapy

Follow-up:

Test name: Epithelial Basement Membrane Zone IgG Antibodies

ARUP #: 0092056

Methodology: Indirect Immunofluorescence (IFA)

Use:

Establish diagnosis in patients suspected of having or known to have epidermolysis bullosa acquisita or any type of pemphigoid.

Distinguish these diseases from each other and other immunobullous disease, such as pemphigus and dermatitis herpetiformis

Limitations:

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

Note that this test does NOT include IgA basement membrane zone antibody determination; linear IgA disease may be missed

IgG BP180 and BP230 antibody levels are NOT included in this test which may increase sensitivity in diagnosing pemphigoid

Follow-up:

Perilesional skin biopsy by direct immunofluorescence is helpful in diagnosis (>90% of epidermolysis bullosa acquisita and pemphigoid cases are positive)