IgA Pemphigus

Updated: Jun 18, 2021
  • Author: Jose A Plaza, MD; Chief Editor: Dirk M Elston, MD  more...
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Immunoglobulin A (IgA) pemphigus is a group of newly characterized immune-mediated intraepidermal blistering skin diseases. Unlike typical immunoglobulin G (IgG)–mediated pemphigus, IgA pemphigus is characterized by tissue-bound and circulating IgA autoantibodies that target the desmosomal proteins of the epidermis. [1, 2, 3, 4, 5]

Histopathologically, epidermal acantholysis and neutrophil infiltration predominate, hence the synonyms intraepidermal neutrophilic (IEN) IgA dermatosis, intraepidermal IgA pustulosis, IgA herpetiform pemphigus, and intercellular IgA vesiculopustular dermatosis have been used to describe this group of diseases. However, no consensus has been reached concerning the nomenclature.

Two subtypes of IgA pemphigus have been identified: subcorneal pustular dermatosis (SPD)–type IgA pemphigus and IEN-type IgA dermatosis. Although clinical presentation is similar, these variants have distinct autoantibody target proteins. Several studies have also suggested the possibility that IgG/IgA pemphigus represents an additional subtype of IgA pemphigus; however, a consensus is not yet determined. [6, 7, 8, 9] Nonetheless, in a systematic review, Kridin et al showed that if IgG/IgA pemphigus was a unique subtype of IgA pemphigus it would be the third most common subtype behind SPD and IEN types. [7]

Hashimoto et al described an alternative classification for IgA pemphigus, terming the disease “intracellular IgA dermatosis”. [10] In addition to the SPD and IEN types, four disease subtypes have been described. Patients with vegetating lesions and pemphigus vegetans–like histology are classified as IgA pemphigus vegetans (IgA-PVeg). Those with desmoglein-1 or desmoglein-3 target antigens are diagnosed with having IgA pemphigus foliaceus (IgA-PF) or IgA pemphigus vulgaris (IgA-PV), respectively. All other cases not meeting these criteria are diagnosed as unclassified or atypical IgA dermatosis.

Exact classification of IgA pemphigus is not always straightforward, with cases often showing multiple overlapping immunological profiles with regard to IgA reactivity against autoantigens of the epidermis or basement membrane zone. Geller et al conducted a literature review of multiple cases of atypical IgA pemphigus, wherein each case showed a heterogeneous immunological profile, such that they did not fit into the conventional classification schemes based on their autoantibodies against various adhesion molecules. [11, 12] After this review, Geller et al suggested the reclassification of these atypical variants of IgA pemphigus under the general term “IgA pemphigus spectrum” in an effort to combat the limitations of the current classification scheme.

IgA pemphigus has not been described in animals. Although the term IgA pemphigus has not been established in the veterinary literature, IgA deposition around epidermal cells has been detected by direct immunofluorescence in animals affected with pemphigus foliaceus.

Medscape articles on other variants of pemphigus include Pemphigus Erythematosus, Pemphigus Foliaceus, Pemphigus Herpetiformis, Pemphigus Vulgaris, Drug-Induced Pemphigus, and Paraneoplastic Pemphigus.



The exact pathomechanism of IgA pemphigus is not well defined. According to currently available data, IgA autoantibodies clearly bind to desmosomal components of the epidermis, desmogleins, or desmocollins. The SPD-type variant exhibits IgA autoantibodies targeting the transmembrane glycoprotein desmocollin 1 present within keratinocyte desmosomes. In contrast, heterogenous target antigens are seen in the IEN IgA dermatosis subtype. IgA autoantibodies in these patients have been shown to bind to desmogleins 1 and 3 in addition to an unspecified nondesmosomal transmembrane protein. [13] The hallmark finding in IgA pemphigus is autoantibodies binding to sites containing the monocyte/granulocyte IgA-Fc receptor (CD89), causing intraepidermal neutrophilic pustules. [14, 15, 16] The direct pathogenic effects of the IgA autoantibodies and exact mechanism of blister formation have not been established.

In a systematic review of 137 cases, Kridin et al found that only 20.5% of cases diagnosed as a specific subtype of IgA pemphigus (either IEN or SPD) had supporting data regarding immunoreactivity. The available data in the review support the currently accepted association of SPD type with desmocollin 1, as well as the association of heterogenous antigens with regard to IEN-type. [7]



The exact pathomechanism of IgA pemphigus is not well defined at the present time. Clearly, IgA autoantibodies are initiated to target desmosomal components, although the initiating mechanism is unknown. At least three desmosomal components, including desmoglein 3 (in IEN-type IgA pemphigus), desmoglein 1, and desmocollin 1 (in SPD-type IgA pemphigus foliaceus), have been identified as target antigens in IgA pemphigus. [17, 18, 19, 20, 13, 21, 22] Other unidentified target antigens also may be involved.

A possible role for a specific cytokine has been postulated in IgA pemphigus. Interleukin 5, a TH2-secreted cytokine that preferentially induces B cells to produce IgA class antibodies, may be activated preferentially in patients with IgA pemphigus.

A possible role for specific T-cell receptors has also been suggested in IgA pemphigus. Gamma/delta T-cell receptor–containing T cells, which have been found to be important in influencing mucosal IgA production, may be involved in the IgA pemphigus process. [23]

Additionally, a possible role for the binding site for monocyte/granulocyte IgA-Fc receptor (CD89) in human IgA1 has been suggested for IgA pemphigus. Human IgA1 antibody has a binding site for the monocyte/granulocyte IgA-Fc receptor (CD89) that is located distally to the hinge region, thus providing a stronger resistance to protease digestion. The protease-resistant property of IgA1 may provide efficient binding of neutrophils, thus allowing the intraepidermal neutrophil infiltration that may contribute to the blistering process. [16]

Postembedding immunoelectron microscopy has localized the target antigen of SPD-type IgA pemphigus to the extracellular domain of desmocollin, whereas the target antigen of IEN-type IgA pemphigus was found to be in an intercellular space outside the desmosomal areas. These findings suggest that the pathomechanism of IgA pemphigus involves the weakening of extracellular components of cell-to-cell adhesion molecules.

An association of IgA pemphigus and IgA gammopathy and lung cancer has been reported. [24] Additionally, an association of peripheral T-cell lymphoma complicated by IgA pemphigus has been reported. [25]

Historically, numerous studies have hypothesized various disease correlations with IgA pemphigus, including IgA gammopathy, multiple myeloma, and ulcerative colitis. In their systemic review, Kridin et al found that IgA pemphigus was associated with IgA gammopathy in 9.5% of cases and ulcerative colitis in 6.6% of cases. [7] Only two of the 137 patients examined presented with IgA-type multiple myeloma in conjunction with the IgA pemphigus. Other possible hematologic associations include peripheral T-cell lymphoma, chronic myeloid leukemia, and diffuse large B-cell lymphoma. [7] Ultimately, given the possible correlations with IgA pemphigus, screening for associated comorbidities is recommended at the time of presentation.

The 2005 report of cases of pemphigus characterized by the presence of both IgA and IgG classes of autoantibodies raises the question of whether this IgA/IgG pemphigus is a subset of IgA pemphigus or a novel disease entity. [26] There is currently no consensus regarding the validation of IgA/IgG pemphigus as a unique subtype of IgA pemphigus.

In some cases of IgA pemphigus, IgA autoantibodies from a single patient were detected against all three desmocollin proteins (desmocollins 1, 2, and 3), [27] and, in some patients, IgA autoantibodies from an individual patient were found to recognize both desmocollin and desmoglein proteins. [28] These cases of multiple target antigens identified by patient IgA autoantibodies support the occurrence of epitope spreading, an interesting autoimmune phenomenon in which the inflammatory event "releases" a new target antigen (or antigens) to be recognized by the immune system, leading to a subsequent autoimmunity to the new target antigen (or antigens). [29]




IgA pemphigus is a group of newly characterized diseases, and its frequency is unknown. It has been reported in the United States. IgA pemphigus also has been reported in Asia (including Japan and India [30] ), South America (including Brazil [31] ), and Europe (including Scandinavian countries [32] ). A 2004 article surveying patients affected by autoimmune blistering diseases in Kuwait suggested that IgA pemphigus may be extremely rare in that part of the world. [33] A systematic review by Kridin et al shows that IgA pemphigus has been reported in 26 different countries as of 2019. [7]


IgA pemphigus is a rare disease and is newly characterized; therefore, the race distribution is unknown. IgA pemphigus has been reported in American, European, South American, and Asian patients.


The sex distribution of IgA pemphigus is unknown. Kridin et al performed a systematic review of IgA pemphigus in 2019. [7] They looked at 119 studies spanning 137 patients with IgA pemphigus and found a slight female to male preponderance of 1.1 : 1.


The systematic review by Kridin et al shows that IgA pemphigus has been reported in persons ranging in age from 1 month to 94 years in a review of 137 cases reported from 1983-2019. [7] This review determined the average to be 51.5 years.



Unlike IgG-mediated pemphigus, as a group of diseases, IgA pemphigus usually exhibits a milder clinical phenotype. The prognosis usually is good according to the limited clinical data available.

IgA pemphigus is a pruritic superficial blistering disease and usually heals without scarring if treated properly.

Mortality directly resulting from IgA pemphigus has not been reported. In general, the clinical course of IgA pemphigus is less severe than that of IgG-mediated pemphigus, and no significant morbidity exists. In some patients with IgA pemphigus, pruritus is a significant symptom and may interfere with the patient's daily life. Some authors have suggested that the most severe symptoms of the disease actually arise from the adverse effects of the immunosuppressive treatments, including corticosteroids. [34, 35]


Patient Education

Instruct patients with IgA pemphigus regarding the potential adverse effects of immunosuppressive treatment (eg, prednisone use). Adverse effects may include infection, malignancies, adrenal insufficiency, and osteoporosis.

Teach patients to recognize the symptoms and signs of adverse effects and to report them to the physician if noted. Patients may be inclined to scratch lesions as pruritus may be a prominent symptom. Scratching may cause excoriations, increasing the risk of secondary infection.