ImmunoGlobulin Antibody (IgA) Mediated Epidermolysis Bullosa Aquisita
The Presentation and symptoms of IgA Mediated Epidermolysis Bullosa Aquisita, is the same as LAD in the early stages, because it actually mimics LAD, but lesions become much deeper, and closer together, sometimes causing quite large areas to become devoid of epidermis. It is a much more severe, and rarer disease. (see abstract below)
J Am Acad Dermatol 2002 Dec ;47(6):919-25
Abstract quote:-We describe 2 adult patients with a subepidermal bullous dermatosis with exclusively linear IgA depositions along the epidermal basement membrane zone that were deposited in the sublamina densa zone as witnessed by direct immunoelectron microscopy.Indirect immunofluorescence microscopy of patients' sera revealed circulating IgA autoantibodies that bound exclusively to the dermal site of salt-split skin substrate. Immunoblot analysis using dermal and keratinocyte extracts were negative. Indirect immunofluorescence microscopy using type VII collagen-deficient skin ("knockout" substrate) showed no IgA binding, whereas linear IgA binding was seen at the epidermal basement membrane zone in normal human skin. The autoantigen in the patients was thus type VII collagen. A diagnosis of IgA-mediated epidermolysis bullosa acquisita (IgA-EBA) was made. We systematically reviewed the literature of this subset of patients with linear IgA dermatosis on the basis of the following criteria: exclusive binding of serum-IgA to the dermal side of salt-split skin or IgA depositions in the sublamina densa zone by indirect or direct immunoelectron microscopy. We learned that IgA-EBA is clinically indistinguishable from the classic "lamina-lucida type" linear IgA dermatosis or from the inflammatory type of IgG-mediated epidermolysis bullosa acquisita (IgG-EBA).
In the case of IgA mediated Epidermolysis Bullosa Aquisita, there is a defect in the genes that normally promote the formation of anchoring filaments, or Hemidesmosomes. An area directly below the Lamina Lucida Area of the BMZThese structures anchor the epidermis, to the dermis, and the gene defect leads to the tissues blistering, and seperating from one another. The pathogenic result of which, is equal to and treated as third degree burns.
The mechanobullous, noninflammatory form of epidermolysis bullosa acquisita,was defined in 1971 and is characterized by extreme skin fragility, trauma-induced blisters and erosions localized to the extensor skin surface, healing with scars and milia.
In addition to the mechanobullous variant, several inflammatory subtypes of epidermolysis bullosa acquisita were also defined, clinically mimicking bullous pemphigoid, linear IgA disease, or mucous membrane pemphigoid. Certain epidermolysis bullosa acquisita patients present with inflammatory phenotype at the onset of the disease with overlapping or later evolving mechanobullous features .
From The Brit.Assoc. Dermatol. (IMPORTANT! Please note in red)
Epidermolysis bullosa acquisita (EBA) IgG is an autoimmune bullous disease with frequent ocular involvement, but visual loss is rare.
In contrast, EBA patients with predominant IgA autoantibodies more frequently develop severe ocular involvement, which tends to be refractory to therapy.
NB. Proving yet again, that patients who have a bullous disease with predominant IgA autoantibodies are more difficult and less responsive to treatmant than Bullous disease with predominant IgG Autoantibodies, when affecting mucous membranes. The resulting scarring of these tissues is what creates permenant and potentially serious damage, such as blindness, deafness etc.
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(Personal note:- Which proves the point that Iga mediated bullous disease is more likely to affect the eyes and prove refractory to treatment.)
This is an article presented to the B.J.D UK concerning myself, written and presented by my own specialists. However it is copyrighted and must be paid for... (no direct link available)
British Journal of Dermatology 156 (4), 775–777. doi:10.1111/j.1365-2133.2006.07739.N.H. Cox, M.A. Bearn, J. Herold, G. Ainsworth, C. Liu (2007) Blindness due to the IgA variant of epidermolysis bullosa acquisita, and treatment with osteo-odonto-keratoprosthesis.
http://www.ingentaconnect.com/content/bsc/bjd/2007/00000156/00000004/art00040;jsessionid=3hc6044sxvoao.victoria
http://openurl.ingenta.com/content?genre=article&issn=0007-0963&volume=156&issue=4&spage=775&epage=777
http://dx.doi.org/10.1111/j.1365-2133.2006.07739.x
Br J Dermatol 1997 Aug;137(2):270-5 Abstract quote:-
Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen, the major component of anchoring fibrils. The classical phenotype of EBA is a non-inflammatory, mechanobullous disease resembling the dystrophic forms of inherited epidermolysis bullosa.Mucous membrane involvement is frequent but usually mild. (personal note :-the above refers to the usual classic IgG (inherited) EBA)
We report a one-year-old girl suffering from IgA-EBA, who presented with an initial eruption of disseminated urticarial lesions and tense blisters of the skin but subsequently developed severe oral and ocular lesions reminiscent of cicatricial pemphigoid. Direct immunofluorescence of the skin and buccal mucosa revealed linear IgA and C3 at the basement membrane zone (BMZ). IgA anti-BMZ autoantibodies stained the dermal side of salt-split skin by indirect immunofluorescence and recognized a dermal protein of 290 kDa co-migrating with type VII collagen by immunoblotting.Direct and indirect immunoelectron microscopy revealed IgA deposits overlying the anchoring fibrils. The ocular involvement led to total blindness in spite of intense treatment. This case of childhood IgA-EBA is particularly striking because of the cicatricial pemphigoid phenotype with severe ocular involvement which resulted in blindness. It reinforces the necessity to use modern immunological methods to classify autoimmune bullous diseases in order to allow early and appropriate treatment.
http://www.ncbi.nlm.nih.gov/pubmed/9292080?dopt=abstractplus
We report two patients with 'IgA-EBA' with ocular involvement. Both initially presented with a generalized bullous disease, and direct immunofluorescence microscopy demonstrated IgA in the basement membrane zone of the skin, and in the conjunctiva and cornea of patient 1. On salt-split patient skin, IgA was found predominantly on the dermal side of the artificial split in both patients.Direct immunoelectron microscopy demonstrated IgA below the lamina densa in close association with the anchoring fibrils in both patients. In patient 1, who had a prolonged course of the disease, the skin disorder responded well to treatment with cyclosporin, but the ocular involvement ended in bilateral blindness despite repeated surgical treatment. In patient 2, the blister formation and scarring conjunctivitis was stopped by a combination of prednisolone and colchicine.These patients show that in subepithelial blistering diseases, early delineation of disease nosology is critical to detect subtypes with severe ocular involvement such as 'IgA-EBA'.
