IgA Pemphigus Workup

Updated: Apr 18, 2017
  • Author: Blanca Anais Estupiñan; Chief Editor: Dirk M Elston, MD  more...
  • Print
Workup

Laboratory Studies

Skin biopsy is performed in IgA pemphigus (see Procedures).

Next:

Other Tests

Perform other tests, if available, to document the diagnosis of IgA pemphigus, including immunoblotting, enzyme-linked immunosorbent assay (ELISA), and special immunofluorescence studies.

Immunoblotting in IgA pemphigus

Immunoblotting documents the specific skin antigen recognized by the patient's IgA autoantibodies. Immunoblotting has documented IgA autoantibodies (from 1 patient with IEN-type IgA pemphigus) that target desmosomal component desmoglein 3, which is located at the lower part of epidermis. However, other investigators were unable to detect IgA immunoreactivity to this protein in patient sera; therefore, the significance of the antigen remains unknown.

Enzyme-linked immunosorbent assay in IgA pemphigus

In theory, ELISA should be a good methodology for documenting the specific desmosomal antigen(s) recognized by patient IgA autoantibodies, since it uses native protein and increases detection sensitivity. In 2001, ELISA detected IgA autoantibodies recognizing desmoglein 3 and desmoglein 1 in a small percentage of patients with IgA pemphigus. [5] In many patients, no antigens are detected, suggesting the presence of alternative unidentified target proteins.

Special immunofluorescence tests in IgA pemphigus

Special immunofluorescence tests using cultured cells that express recombinant desmosomal component (desmocollin 1) document the presence of circulating IgA autoantibodies that recognize desmosomal component. Special immunofluorescence tests have documented IgA autoantibodies from patients with SPD-type IgA pemphigus. The tests detected desmosomal component desmocollin 1; however, this test is not generally available.

Previous
Next:

Procedures

Skin biopsy is performed and specimens analyzed to establish the diagnosis using histopathology and direct and indirect immunofluorescence. In contrast to classic IgG-mediated pemphigus, acantholysis may be minimal or absent in IgA pemphigus. In the case of patients presenting with extensive pustular eruptions, some authors recommend direct immunofluorescence of perilesional skin as an early screening test, owing to its high detection rate of IgA deposition in the epidermis. [30, 31]

Histopathology is performed on specimens of blistered skin. Histopathology demonstrates an intraepidermal blister, which may be located subcorneally (SPD-type IgA pemphigus), suprabasally, or at mid epidermis (IEN-type IgA pemphigus). Histopathology demonstrates silent or absent acantholysis and is not characteristically observed as in classic pemphigus. A mixed inflammatory infiltrate is observed, including intraepidermal neutrophil infiltration forming a neutrophilic microabscess, which is the hallmark of IgA pemphigus (see the image below).

Histopathologic examination of a blister lesion ob Histopathologic examination of a blister lesion obtained from a patient with immunoglobulin A pemphigus shows a suprabasal blistering process, acantholysis, and an inflammatory cell infiltrate containing numerous neutrophils (hematoxylin and eosin, original magnification X50).

Direct immunofluorescence performed on perilesional skin sections is considered the criterion standard test. Direct immunofluorescence documents the immune-mediated disease process. Direct immunofluorescence predominantly detects IgA and, sometimes, to a lesser extent, IgG and complement component C3 deposited at the cell surfaces of the epidermis. Since acantholysis in IgA pemphigus is minimal and sometimes even absent, it can be argued that immunofluorescence should be used as an early screening test for the diagnosis of patients with widespread pustular eruptions.

Indirect immunofluorescence is performed using patient serum on monkey esophagus or other epithelial substrates. Indirect immunofluorescence documents the presence of IgA circulating autoantibodies in patient serum that recognize skin epidermal cell surface components (see the image below). Indirect immunofluorescence with monkey esophagus usually detects IgA circulating autoantibodies in serum that bind to epithelial cell surfaces in approximately half the patients. Intercellular antibody deposition is detected more frequently using human skin for indirect immunofluorescence. Using this method, studies have found intercellular antibody deposition in up to 65% of patients with IgA pemphigus. Titers of IgA pemphigus autoantibodies are much lower than the titers of IgG autoantibodies observed in IgG-mediated pemphigus.

Indirect immunofluorescence microscopy performed o Indirect immunofluorescence microscopy performed on monkey esophagus substrate (with serum from a patient with immunoglobulin A pemphigus) detects the immunoglobulin A1 subclass of circulating autoantibodies that label the epithelial cell surfaces of the substrate.
Previous