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Introduction

Hello, I’m Dr. Julia Lehman, director of the Mayo Clinic Immunodermatology Laboratory and I’m a dermatopathologist and dermatologist at Mayo Clinic. I’d like to talk to you today about IgA-mediated autoimmune bullous dermatoses.

Disclosures

I have no disclosures to report.

Autoimmune bullous dermatoses

Autoimmune bullous dermatoses comprise a rare category of blistering skin diseases that are caused by the development of autoantibodies against various constitutive parts of the epidermis or dermal-epidermal junction. For example, pemphigus develops when autoantibodies are directed against desmogleins, the proteins that glue keratinocytes of the epidermis or the mucosal epithelium to one another, while pemphigoid develops when autoantibodies are directed against bullous pemphigoid antigens, which can help hold the basement membrane zone together. In either case, autoantibodies can lead to the loss of adhesion and cause erosions or ulcerations clinically.

Accurate diagnosis of diseases in this category is essential to assure appropriate therapeutic decisions, as well as to recognize systemic diseases known to be associated with the autoimmune bullous dermatosis.

Specific autoimmune blistering diseases

So let’s start by reviewing specific autoimmune blistering diseases. 

Pemphigoid is a clinically and immunologically heterogeneous collection of subepidermal blistering conditions that have in common the presence of autoantibodies targeted towards components of the basement membrane zone that are usually of the IgG subtype and that usually fix complement. In some cases, IgA antibodies are also detected using either direct or indirect immunofluorescence methods. When present in pemphigoid, IgA antibodies are associated with the development of mucosal involvement and typically portend a more severe or treatment-refractory clinical course.

Autoimmune bullous dermatoses

Pemphigus is a collection of intraepidermal blistering conditions that have in common the presence of autoantibodies targeted towards desmogleins, proteins that contribute to intercellular adhesion of epidermal or mucosal epithelial keratinocytes. These autoantibodies are usually of the IgG4 subclass. When IgA is detected in an intercellular pattern in conventional pemphigus, either using direct immunofluorescence or indirect immunofluorescence with the IgA conjugate, patients may be more likely to respond to therapies such as dapsone.

IgA-mediated autoimmune bullous dermatoses

Linear IgA bullous dermatosis is a subepidermal autoimmune blistering disorder that presents with tense blisters, often arranged in an annular configuration. Biopsy shows a neutrophil-rich subepidermal blister, and direct immunofluorescence shows strong linear IgA deposition along the basement membrane zone. Linear IgA bullous dermatosis is important to recognize clinically, as it is most often triggered by medications (in particular vancomycin) or an underlying medical condition such as a carcinoma.  

Dermatitis herpetiformis is a gluten-sensitive dermopathy that presents with pruritic grouped papules, classically on the elbows, knees, upper back, and sacrum. Biopsy shows neutrophils in the dermal papillae, and direct immunofluorescence shows granular deposition along the basement membrane zone and in the dermal papillae. Accurate recognition of this entity is essential to assure screening for gluten-sensitive enteropathy, maintenance of a gluten-free diet, and appropriate medication selection.

IgA pemphigus is a very rare intraepidermal blistering condition characterized by pustules clinically. Acantholysis with neutrophils can be seen on biopsy, and direct immunofluorescence demonstrates IgA cell-surface deposition. Treatment often includes dapsone or other agents that target neutrophils.

When to suspect IgA-mediated disease

There are a few clinical clues that might suggest involvement by an IgA-mediated autoimmune bullous dermatosis, including the presence of pustules, lesions arranged in an annular configuration, mucosal involvement, known IgA monoclonal gammopathy, or neutrophils on skin biopsy. However, these clues are neither entirely specific nor sensitive, so advanced testing is required for a definitive diagnosis.

Indirect immunofluorescence with IgA conjugate

The various patterns that can be seen with indirect immunofluorescence with IgA conjugate include epidermal pattern on salt-split skin, which correlates either with linear IgA bullous dermatosis or the presence of IgA in pemphigoid; the mixed or dermal pattern on salt-split skin, which correlates with “dermal” linear IgA bullous dermatosis or epidermolysis bullosa acquisita with IgA involvement; or cell-surface deposition on monkey esophagus substrate, which correlates with IgA pemphigus or IgG/IgA pemphigus.

Laboratory detection of AIBD with IgA component

In order to accurately diagnose IgA-mediated autoimmune bullous dermatoses, both tissue and serum testing are typically required. Specifically, patients should undergo biopsy of perilesional erythema for standard biopsy and direct immunofluorescence. The exception is dermatitis herpetiformis, for which the direct immunofluorescence specimen should be derived from intact, normal skin approximately 1 cm away from active lesions.  

Serum-based testing includes indirect immunofluorescence with IgG and IgA conjugate, and ELISA for BP and desmoglein autoantibodies. If dermatitis herpetiformis is in the clinical differential diagnosis, then the Celiac cascade can be ordered. 

Clinico-immuno-pathologic correlation

Ultimately, as there is no single pathognomonic feature of IgA-mediated autoimmune bullous dermatosis, accurate diagnosis requires careful correlation of clinical information, histopathologic findings, direct immunofluorescence features, and results of serum studies. Our immunodermatologists would be happy to discuss cases with you, if you are uncertain about a patient’s diagnosis.

Why is accurate recognition of IgA-mediated AIBD important?

In summary, accurate recognition of IgA-mediated autoimmune bullous dermatoses is important to aid in prediction of clinical course, selection of appropriate treatment, and identification of associated systemic disorders.

Thank you

Thank you so much for your attention. If you have questions or requests relating to this talk, please send an email to the address listed here or for more information, visit our website at www.mayocliniclabs.com. Thank you.

Questions?

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