Linear IgA Disease

Algorithm(s)

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

Immunobullous Skin Diseases Testing Algorithm

Clinical Background

Linear IgA disease is a blistering disorder of skin and mucous membranes

In adults, known as linear IgA bullous dermatosis
In children, known as chronic bullous disease of childhood

Epidemiology

Prevalence - rare disorder
Age of onset
- Adult form - 30-50 year olds
- Childhood form - birth-10 year olds
Sex - M:F, fairly equal distribution

Risk Factors

Certain drugs - antibiotics (vancomycin), lithium, nonsteroidal anti-inflammatory agents (diclofenac, piroxicam), cyclosporine, diuretics (furosemide) and others
Association with infections
Autoimmune diseases - ulcerative colitis, systemic lupus erythematous, rheumatoid arthritis
Malignancies - lymphoma, chronic lymphocytic leukemia (rare in both)

Pathophysiology

Neutrophil involvement in linear IgA disease is usually greater than in pemphigoid and epidermolysis bullosa acquisita in which eosinophil involvement is prominent
Serum IgA basement membrane zone antibodies bind to the epidermal, dermal or combined epidermal-dermal areas of split skin.
- 97 kD LABD and LAD-1 are cleavage products of BP180 and are major antigenic targets
- Type VII collagen may be antigen which accounts for dermal staining on split skin

Clinical Presentation

Similar to pemphigoid or epidermolysis bullosa acquisita
Papulovesicles, bullae or urticarial plaques on extensor, central or flexural sites with truncal involvement
Involvement of oral mucosa is common in adult disease, ocular involvement also occurs
May have severe pruritus
Classical presentation - “String of pearls” lesion consisting of grouped vesicles
Perineal and perioral involvement common in children

Treatment

Dapsone
Immunosuppressives, less responsive to prednisone than pemphigoid

See Also

Dermatitis Herpetiformis

Epidermolysis Bullosa Acquisita

Immunobullous Skin Diseases Screening

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 linear IgA disease

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 linear IgA disease is most specific for diagnosis or Pemphigoid Panel for more inclusive testing

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 linear IgA disease (including linear IgA bullous dermatosis and childhood immunobullous disease), epidermolysis bullosa acquisita, 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 immunobullous diseases from each other, such as linear IgA disease from other types of pemphigoid, pemphigus and dermatitis herpetiformis

Use along 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

Limitations:

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

Follow-up:

Perilesional skin biopsy by direct immunofluorescence is helpful in diagnosis (>90% of linear IgA disease, epidermolysis bullosa acquisita, pemphigoid, and dermatitis herpetiformis 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 and endomysial IgA antibody testing, 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

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

Follow-up:

A concurrent perilesional skin biopsy for direct immunofluorescence is helpful for diagnosis because of increased sensitivity (>90% of pemphigus, pemphigoid, linear IgA disease, epidermolysis bullosa acquisita, 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: Epithelial Basement Membrane Zone IgA Antibodies

ARUP #: 0092057

Methodology: Indirect Immunofluorescence

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

Monitor treatment response

Limitations:

This 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 for direct immunofluorescence may be necessary for final clinical diagnosis

Test name: Epithelial Skin Antibody

ARUP #: 0090299

Methodology: Indirect Immunofluorescence

Use:

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

Panel includes epithelial basement membrane zone 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:

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:

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