Dermatitis Herpetiformis

Algorithm(s)

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

Immunobullous Skin Diseases Testing Algorithm

Clinical Background

Dermatitis herpetiformis is a chronic, pruritic skin disease that is usually associated with intestinal gluten sensitivity (celiac disease).

Epidemiology

Incidence - 10-39 per 100,000
Age of onset - childhood to older years; peak onset 20-40 year olds
Sex - M:F, nearly equal, slight male predominance
Ethnicity - most common in northern European descendants but occurs in all ethnic groups

Risk Factors

Gluten-sensitive enteropathy (celiac disease)
Lymphoma
Autoimmune diseases including lupus, thyroid, diabetes
Oral aphthae

Pathology and Immunopathology

Granular and/or fibrillar deposition of IgA in dermal papillae and, less commonly, in blood vessels
Neutrophilic microabscesses in the dermal papillae
Dermal infiltration of neutrophils and eosinophils

Clinical Presentation

Intense pruritus with excoriations
Papulovesicular lesions and urticarial wheals located on extensor surfaces (elbows and knees) in a symmetrical distribution - classically involves extensor surfaces of arms, knees and buttocks
Chronic eczematoid skin changes

Treatment

Dietary modification to eliminate gluten ingestion
Dapsone

See Also

Celiac Disease

Epidermolysis Bullosa Acquisita

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 biopsy specimen(s) from patients suspected of having dermatitis herpetiformis

Limitations:

Immunopathologic findings may rarely show similarities to lupus erythematosus

Granular and fibrillar IgA immune deposits may be sparse in dermatitis herpetiformis

Perilesional skin biopsy or biopsies are best to detect characteristic findings, which may not be present in lesional skin

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

Follow-up:

This test is best performed together with serum testing for IgA endomysial and tissue transglutaminase antibodies and followed with IgA endomysial antibodies to monitor disease activity and response to therapy

Patients with indeterminate results should be monitored with antibody levels and for disease activity

Test name: Celiac Disease Panel with Reflex to Titer

ARUP #: 0051060

Methodology: Nephelometry/Indirect Fluorescent Antibody/Enzyme-Linked Immunosorbent Assay

Use:

For diagnosis of celiac disease in association with suspected or known dermatitis herpetiformis

Limitations:

Patients on a gluten-free diet may be negative

Some patients with dermatitis herpetiformis will be negative

Because of overlapping clinical features among immunobullous diseases, recommend initial testing concurrently with Pemphigoid and Pemphigus Panels

Follow-up:

Monitor increased IgA endomysial and tissue transglutaminase 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:

Use along with endomysial antibody, IgA/Celiac Disease Panel, and Pemphigus Panel to differentiate various immunobullous skin diseases in patients suspected to have any type of such disorders

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

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 dermatitis herpetiformis, pemphigoid, epidermolysis bullosa acquisita, linear IgA disease, and pemphigus 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 endomysial antibody, IgA, and Pemphigoid Panel tests to differentiate immunobullous skin diseases in patients suspected to have any type of such disorders

Follow-up:

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:

Test or follow patient suspected of having dermatitis herpetiformis and/or celiac disease

Limitations:

May be negative if patient is following a gluten-free diet

False-positive IgA tissue transglutaminase antibody levels may occur in other inflammatory bowel diseases

Follow-up:

Can be used to monitor disease activity and response to therapy

Patients with borderline/indeterminate results should be monitored for disease activity

Additional Information

Endomysial antibody testing (IgA and IgG) and tissue transglutaminase antibody testing (IgA and IgG) can also be ordered through the Immunodermatology Laboratory with serum sent along with biopsy; both IFA and ELISA are performed and correlated with direct immunofluorescence.