Posted July 21, 2009
Alan E. Siroy, MD, MPH
Autoimmune blistering diseases are a rare group of mucocutaneous disorders that can result in irreversible sequelae
and death if accurate diagnosis and treatment are not rendered promptly.1, 2 Two of the most common diseases in this
group are pemphigus vulgaris and bullous pemphigoid, which are disorders characterized by the production of autoantibodies
that target structural proteins important to the maintenance of intercellular and cell-to-basement membrane adhesion.3, 4
Diagnosis of these disorders requires the integration of clinical findings, histopathologic characteristics, immunofluorescent
analysis, and further immunologic laboratory testing (eg enzyme-linked immunosorbent assay) if necessary.
Pemphigus vulgaris is the most common subtype of the pemphigus group of disorders, which presents as flaccid mucocutaneous
blisters that have a tendency to rupture
easily.5, 6 If left untreated, progression of the disease may lead to death within
five years of onset in some cases, due to secondary bacterial infection and sepsis.1 Bullous pemphigoid is the most common
autoimmune blistering skin disease and presents with large, tense, cutaneous blisters.1, 3Ruptured bullae may lead to erosions
that are susceptible to bacterial infection. Current treatment for pemphigus vulgaris and bullous pemphigoid involves
immunosuppressive therapy, which may include both topical and systemic application of steroids, depending on the severity of disease.
Surgical pathologists and dermatologists who are trained in dermatopathology
and/or immunodermatology play an important role in the diagnosis of pemphigus
vulgaris and bullous pemphigoid. As mentioned earlier, histopathologic characteristics,
immunofluorescent analysis, and further immunologic laboratory testing must
be integrated with the clinical findings in order to establish an accurate diagnosis.
Histopathologically, pemphigus vulgaris displays acantholysis, suprabasal separation
of the epithelium, and sparse inflammatory infiltrate.1, 2, 6 These
findings occur due to IgG autoantibodies targeting the desmosomal protein desmoglein
3, which serves an important role in intercellular adhesion of the epidermis
and mucosal epithelium.7, 8 Direct
immunofluorescence on a perilesional mucocutaneous biopsy displays intercellular
deposition of IgG antibody and/or C3 complement along the epithelial cell surfaces.1,
6 Indirect immunofluorescence shows the presence of circulating serum
IgG autoantibodiesthrough intercellular deposition on substrates such as human
skin or monkey esophagus.1,6 Enzyme-linked immunosorbent assay (ELISA)
allows for further specificity in the detection of circulating IgG autoantibodies
that target desmoglein 3 and in the measurement of antibody titers that correlate
with disease activity.9 Histopathologic examination of a cutaneous
biopsy of bullous pemphigoid shows subepidermal blistering with an inflammatory
infiltrate consisting of eosinophils and neutrophils.1, 2 These findings
are the result of IgG autoantibodies targeting the hemidesmosomal proteins
BP230 and BP180, which serve an important role in anchoring epidermal basal
cells to the basement membrane.10, 11 Direct immunofluorescence on perilesional
biopsy demonstrates a linear deposition of IgG and C3 along the basement membrane.1,
2 Indirect immunofluorescence on human skin or monkey
esophagus substrates displays serum antibody deposition in a linear fashion
along the basement membrane as well.1, 2 ELISA
may be utilized to detect circulating autoantibodies to BP180 as well as to
monitor disease activity through the measurement of antibody titers.12
In summary, pemphigus vulgaris and bullous pemphigoid are autoimmune blistering disorders, that require the integration of clinical,
histopathologic, and immunopathologic findings for diagnosis. Communication between the clinician and the
dermatopathologist/immunodermatologist is essential for prompt and accurate diagnosis, allowing for the immediate initiation of
immunosuppressive therapy in order to significantly reduce morbidity and mortality.
- Nousari HC, Anhalt GJ. Pemphigus and bullous pemphigoid. Lancet. 1999;354(9179):667-672.
- Yeh SW, Ahmed B, Sami N, Razzaque Ahmed A. Blistering disorders: diagnosis and treatment. Dermatol Ther. 2003;16(3):214-223.
- Mihai S, Sitaru C. Immunopathology and molecular diagnosis of autoimmune bullous diseases. J Cell Mol Med. 2007;11(3):462-481.
- Burgeson RE, Christiano AM. The dermal-epidermal junction. Curr Opin Cell Biol. 1997;9:651-658.
- Ahmed AR. Clinical features of pemphigus. Clin Dermatol. 1983;1(2):13-21.
- Korman N. Pemphigus. J Am Acad Dermatol. 1988;18(6):1219-1238.
- Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion.
- Koch PJ, Mahoney MG, Ishikawa H, et al. Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss
of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris. J Cell Biol. 1997;137(5):1091-1102.
- Ishii K, Amagai M, Hall RP, et al. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent
assays with baculovirus-expressed recombinant desmogleins. J Immunol. 1997;159(4):2010-2017.
- Giudice GJ, Emery DJ, Diaz LA. Cloning and primary structural analysis of the bullous pemphigoid autoantigen BP180.
J Invest Dermatol. 1992;99(3):243-250.
- Mueller S, Klaus-Kovtun V, Stanley JR. A 230-kD basic protein is the major bullous pemphigoid antigen.
J Invest Dermatol. 1989;92(1):33-38.
- Kobayashi M, Amagai M, Kuroda-Kinoshita K, et al. BP180 ELISA using bacterial recombinant NC16a protein as a diagnostic and monitoring
tool for bullous pemphigoid. J Dermatol Sci. 2002;30(3):224-232.
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