APPROACH TO THE

DIAGNOSIS OF
BLISTERING
DISEASES
Pathologists Perspective
CLINICAL FINDINGS
• Age and Gender
• Location & distribution
• Gross blister characteristics
• Arrangement of blisters
• Medical history
HISTOLOGIC FEATURES
• Mechanism of tissue split
• (acantholysis vs spongiosis)
• Microanatomic plane of blister
• (intraepidermal vs subepidermal)
• Assessment of an associated inflammatory infiltrate
• (neutrophils, eosinophils, or both versus lymphocytes versus mast
cells).
• Distribution pattern
• (papillary dermal abscesses versus diffuse bandlike).
ANCILLARY STUDIES
• Direct immunofluorescence (DIF)
• Required for most cases of
• histology per se is often not specific
• Best to biopsy perilesional skin
• within 1 cm of a blister if the skin appears normal or
• immediately adjacent to erythema if the skin is inflamed
• specimen should be placed in a transport medium (Michel’smedium)
• snap frozen in liquid nitrogen, or
• sent in saline-soaked gauze
LABORATORY TESTS
• Circulating autoantibodies
• Against epidermal transglutaminase: Highly specific
HISTOLOGY & DIF
Histology and IF remain the gold standard for diagnosing
autoimmune blistering disease.
Pattern-Based Approach

1) Nearly normal skin

2) Epidermocentric change
3) Adnexocentric change
4) Cystic change
5) Bullous and pustular dermatosis
6) Dermocentric change
7) Panniculocentric change
Key Features
Papillary neutrophilic microabscesses / Subepidermal blisters
with neutrophils
 Clinical Findings
Linear IgA bullous
Dermatitis herpetiformis
dermatosis
• 2nd to 4th decade (rare in • 3rd decade of life or older
Age and Gender elderly, infants, or children) (can affect children)
• M>F • F>M
• 90% - elbows, knees,
Location & • Trunk and extremities
buttocks, scapula, & scalp
distribution • Mucosa
• Oral lesions are absent
• papulovesicles, bullae,
Gross blister • papules, papulovesicles, or
and/or
characteristics urticarial plaques
urticarial plaques
• Annular, polycyclic, and
Arrangement of • grouped or herpetiform
targetoid lesions
blisters • pattern
• “cluster of jewels”
Medical history • gluten-sensitive enteropathy • Drug intake
Histologic Findings
Dermatitis
herpetiformis
• Subepidermal vesiculation
• Neutrophilic abscesses in tips
of dermal papillae
• Slight fibrin deposition in the
tips of dermal papillae at
points of vesiculation
Linear IgA bullous
dermatosis
• Subepidermal vesiculation
• Neutrophils are the
predominant inflammatory cell
• Some cases may demonstrate
scattered eosinophils and a
mild perivascular lymphocytic
inflammatory infiltrate
DIF Findings
Dermatitis
herpetiformis
• Granular deposition of IgA
within dermal papillae ± along
dermal–epidermal junction.
• Granules have a vertical
“picket fence” appearance.
Linear IgA bullous
dermatosis
• Linear deposition of IgA
along the dermoepidermal
junction (the only
immunoreactant present in 80-
100% of cases)
References
• Patterson, J. W. (2013). Practical Skin Pathology: A Diagnostic
Approach. Elsevier.
• Patterson, J. W., & Weedon, D. (2016). Weedons skin pathology.
Edinburgh: Churchill Livingstone Elsevier.
• Elder, D. E. (2013). Atlas and synopsis of Levers histopathology of
the skin. Philadelphia: Wolters Kluwer/Lippincott Williams &
Wilkins Health.
• Busam, K. J. (2016). Dermatopathology (A Volume in the Series
Foundations in Diagnostic Pathology), Second Edition. Elsevier.
• Elston, D. M., & Ferringer, T. (2014). Dermatopathology.
Edinburgh: Saunders Elsevier.
• Goldblum, J. R., Lamps, L. W., McKenney, J. K., Myers, J. L., &
Ackerman, L. V. (2018). Rosai and Ackermans surgical pathology.
Philadelphia, PA: Elsevier.