Julia Lehman, M.D.
Professor of Dermatology
Professor of Laboratory Medicine and Pathology
Department of Dermatology
Mayo Clinic, Rochester, Minnesota
Hi, I’m Dr. Julia Lehman, and I’m a professor of dermatology and laboratory medicine and pathology at Mayo Clinic and I also serve as the lab director of the Mayo Clinic Immunodermatology Lab. It is my pleasure today to talk to you today about subepidermal autoimmune blistering diseases that are mediated by collagen VII autoantibodies.
I have no disclosures to report.
Autoimmune bullous dermatoses comprise a rare category of blistering skin disease that is caused by the development of autoantibodies against various constitutive parts of the dermal-epidermal junction.
What this category of diseases has in common is that patients tend to develop tense blisters on the skin or mucosa. 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 immunobullous diseases.
So, let’s start by reviewing the prototypical subepidermal autoimmune blistering disease.
Bullous pemphigoid is a clinically and immunologically heterogeneous subepithelial blistering condition that is generally due to the presence of circulating IgG autoantibodies directed against the NC16A domain of BP180. Most affected patients are elderly, and they develop tense, inflammatory blisters on the skin and mucosa. Affected patients have a statistically higher rate of pre-existing neurodegenerative diseases than age-matched unaffected patients.
Diagnosis is supported by skin biopsy, which generally shows an eosinophil-rich subepidermal blister as shown here. Direct immunofluorescence from perilesional inflamed skin shows linear deposition with IgG and C3.
Serum studies can also support the diagnosis. Indirect immunofluorescence shows epidermal deposition of IgG on human salt-split skin, as well as linear deposition on monkey esophagus substrate. ELISA for BP180 and BP230 antibodies is often positive.
However, not all subepidermal autoimmune blistering eruptions are pemphigoid. For the remainder of the talk, we’ll discuss subepidermal autoimmune blistering eruptions with different pathogenic mechanisms, clinical presentations, histopathologic features, laboratory findings, and clinical course.
Epidermolysis bullosa acquisita (EBA) is a much rarer subepidermal autoimmune blistering disease that, like pemphigoid, presents with tense blisters. Often, the blisters are not quite as inflammatory as those seen in pemphigoid, and blisters may be located in areas prone to trauma.
Because the micro-anatomic level of the split is lower in the basement membrane zone than that of pemphigoid, the skin tends to heal with scarring. Unlike pemphigoid, epidermolysis bullosa acquisita is more likely to affect younger patients. Inflammatory bowel disease is a known association with EBA, possibly due to the presence of collagen VII in both the GI mucosa and the skin. While most patients with pemphigoid respond to medical therapies, those with EBA may have a more refractory course and may require heavier doses of immunosuppression to achieve disease control.
Skin biopsy shows a subepidermal split, which is usually pauciinflammatory but may be neutrophil-rich. Direct immunofluorescence of perilesional erythema can show linear IgG and C3, which is identical to the pattern seen in bullous pemphigoid.
Serum studies can be used to help differentiate pemphigoid from epidermolysis bullosa acquisita. Specifically, indirect immunofluorescence shows dermal deposition of IgG on human salt-split skin, as well as linear deposition on monkey esophagus substrate. ELISA for BP180 and BP230 antibodies is usually negative, or if it is positive, the results are almost they are almost always very low positive.
Bullous lupus erythematosus is also extremely rare and, like epidermolysis bullosa acquisita, is also mediated by collagen VII autoantibodies. It can also present with tense subepidermal blisters, which can heal with scarring. These patients tend to have concomitant systemic lupus, often with serious kidney disease. Patients may also have photosensitivity and other clinical stigmata of lupus erythematosus.
Skin biopsy also shows a subepidermal split, which is usually pauciinflammatory just like epidermolysis bullosa acquisita, but in some cases can be neutrophil-rich as we see in this case. Direct immunofluorescence of perilesional erythema can show linear IgG and C3, which again is indistinguishable from pemphigoid or EBA.
Serum studies can also help support the diagnosis. Indirect immunofluorescence shows dermal deposition of IgG on human salt-split skin, as well as linear deposition on monkey esophagus substrate. A serum ANA is almost always positive, given the patients’ concomitant systemic lupus erythematosus. ELISA for BP180 and BP230 antibodies are often negative, or if they are positive, they are almost always low positive.
Today we’d like to introduce a new diagnostic test available at Mayo Clinic, the collagen VII autoantibody ELISA. This test can detect circulating autoantibodies against collagen VII, and specifically, the NC-1 domain. Identification of these antibodies circulating in patients with tense subepidermal blistering conditions would be highly suggestive of epidermolysis bullosa acquisita, or in the appropriate clinical setting, bullous lupus erythematosus.
There may be other potential uses for the test as well. Specifically, some researchers have shown that the presence of collagen VII autoantibodies may correlate with relapse in bullous pemphigoid. However, this observation requires validation.
So why is it important to accurately diagnose epidermolysis bullosa acquisita or bullous lupus? Number one would be prediction of the clinical course. As we discussed, epidermolysis bullosa acquisita can have a refractory clinical course and often requires intense immunosuppression. The second reason would be selection of appropriate treatment. Both of these conditions require tailored therapy to target the precise disease. And finally, identification of associated systemic disorders, which in the case of epidermolysis bullosa acquisita could be inflammatory bowel disease, or in the case of bullous lupus erythematosus, would be systemic manifestations of systemic lupus erythematosus.
Ultimately, a diagnosis of subepidermal autoimmune blistering diseases requires careful clinico-immuno-pathologic correlation.
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 very much.
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