IgA Pemphigus

Updated: Apr 19, 2017
  • Author: Neil Sandhu, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

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]

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

Two subtypes of IgA pemphigus have been identified: subcorneal pustular dermatosis (SPD)–type IgA pemphigus and intraepidermal neutrophilic (IEN)–type IgA dermatosis. Although clinical presentation is similar, these variants have distinct autoantibody target proteins.

Hashimoto et al described an alternative classification for IgA pemphigus, terming the disease “intracellular IgA dermatosis (IAD)”. [5] 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 IAD.

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.

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Pathophysiology

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 subcorneal pustular dermatosis-type variant exhibits IgA autoantibodies targeting the transmembrane glycoprotein desmocollin 1 present within keratinocyte desmosomes. In contrast, heterogenous target antigens are seen in the intraepidermal neutrophilic 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. [6] The hallmark finding in IgA pemphigus is autoantibodies binding to sites containing the monocyte/granulocyte IgA-Fc receptor (CD89), causing intraepidermal neutrophilic pustules. [7, 8, 9] The direct pathogenic effects of the IgA autoantibodies and exact mechanism of blister formation have not been established.

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Epidemiology

Frequency

United States

IgA pemphigus is a group of newly characterized diseases, and its frequency is unknown, although IgA pemphigus has been reported in the United States.

International

IgA pemphigus is a group of newly characterized diseases, and its frequency is not yet defined. IgA pemphigus has been reported in Asia (including Japan and India [10] ), South America (including Brazil [11] ), and Europe (including Scandinavian countries [12] ). 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. [13]

Race

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.

Sex

The sex distribution of IgA pemphigus is unknown. A review of 28 cases reported from 1982-1997 revealed a male-to-female ratio of 1:1.33.

Age

IgA pemphigus has been reported to occur in persons aged 1 month [14] to 85 years. A review of 28 cases reported from 1982-1997 determined the average age of onset to be 53 years.

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Prognosis

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 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.

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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.

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