Subcorneal Pustular Dermatosis–Type IgA Pemphigus With Autoantibodies to Desmocollins 1, 2, and 3

Abstract

Background: IgA pemphigus is a rare neutrophilic acantholytic autoimmune disease that is characterized by IgA deposits on keratinocyte cell surfaces. Clinically and histologically, IgA pemphigus is divided into 2 major subtypes: subcorneal pustular dermatosis and intraepidermal neutrophilic IgA dermatosis. We report the first case of subcorneal pustular dermatosis-type IgA pemphigus that showed reactivity to all 3 isoforms of the desmocollin family by indirect immunofluorescence microscopy of COS7 cells transfected with desmocollin 1, 2, or 3. Observations: We describe a 94-year-old woman with IgA pemphigus with a unique immunopathologic pattern. Direct immunofluorescence microscopy revealed IgA deposits throughout the entire epidermis, with stronger staining in the upper epidermis. The autoantibodies from this patient did not show IgA or IgG reactivity with desmogleins via immunoblotting or enzyme-linked immunosorbent assay. By indirect immunofluorescence by the use of COS7 cells transfected with desmocollin 1, 2, or 3, IgA autoantibodies in a serum sample from our patient clearly reacted with all of them. Conclusions: The pathophysiology and autoantigen profile of bullous autoimmune diseases, especially pemphigus and its subforms, are more complex than previously believed. Because pemphigus seems to be a heterogeneous disorder, further studies are needed to evaluate the complexity of the disease.

IgA pemphigus associated with diffuse large B-cell lymphoma showing unique reactivity with desmocollins: unusual clinical and histopathological features

“…Some previous cases of IgA pemphigus showed IgA reactivity with the entire epidermis, despite the presence of subcorneal pustules. IgA antibodies in one case reacted to Dsc1–3, 2 while another case reacted to Dsc1 and Dsg1 3 . The findings in these cases are different from the unique clinical and histopathological features seen in our case, which showed small pustules in the mid‐epidermis, as well as prominent subcorneal pustules.…”

“…Our case may be classified as a novel subtype of IgA pemphigus with a unique and previously undescribed autoantibody profile. Immunofluorescence represented the combined staining pattern of Dsc2 and Dsc3, as Dsc1 and Dsc2 are expressed strongly in the upper epidermis and weakly in the lower epidermis, while Dsc3 is most strongly expressed in the basal layers and weaker in the suprabasal layers 2 . The failure to detect IgA anti‐Dsc antibodies in the cDNA transfection method is probably due to a lower sensitivity than the novel ELISA.…”

IgA/IgG Pemphigus with Infiltration of Neutrophils and Eosinophils in an Ulcerative Colitis Patient

“…In some IgA pemphigus patients, multiple target antigens have been identified (10)(11)(12). Multiple autoantibodies in our patient might be produced via epitope spreading phenomenon.…”

IgG Autoantibody Response against Keratinocyte Cadherins in Endemic Pemphigus Foliaceus (Fogo Selvagem)

“…While anti-Dsg1 IgG and IgG4 autoantibodies have been shown to be pathogenic in PF and FS (Rock et al , 1989), there have been reports of autoantibody responses to other members of the cadherin family of proteins in certain pemphigus phenotypes. Dsg3 is diagnostic and pathogenically relevant in pemphigus vulgaris (PV) (Amagai et al , 1991), while Dsc antigens may be relevant in IgA pemphigus (Duker et al , 2009) and certain forms of PV (Mao et al , 2010). Autoantibodies against Dsg4 (Nagasaka et al , 2004) and E-cadherin (Evangelista et al , 2008) have also been described in PV and PF, respectively.…”