Autoimmune basement membrane and subepidermal blistering diseases

Abstract

Autoimmune mucocutaneous blistering diseases (ABDs) represent a group of conditions that manifest with blisters on the skin and/or mucous membranes. Bullous pemphigoid (BP) is the most common autoimmune mucocutaneous blistering disease. In BP, the location of the blisters is subepidermal and the oral involvement is rare. Variants of BP have been described, including pemphigoid vegetans; however, this disease is not completely characterized. The majority of ABDs have blisters and/or vesicles, that are often pruritic, and manifest autoantibodies to diverse proteins. These proteins include 1) hemidesmosomal plaque proteins(ie, BP230, plectins), 2) transmembrane proteins such as BP180 and α6β4-integrin, which are connected via laminin 332 to type VII collagen and 3) currently uncharacterized 105 kDa and 200 kDa molecules. Other ABDs include drug-induced linear IgA disease, bullous systemic lupus erythematosus (BSLE), dermatitis herpetiformis (DH), cicatricial pemphigoid (CP; also termed mucous membrane pemphigoid), lichen planus pemphigoides (LPP), pemphigoid gestationis (PG), herpes gestationis(HG), chronic bullous dermatosis of childhood (CBDC) and the localized forms of CP, such as Brunsting-Perry pemphigoid. The diagnosis of ABDs requires clinical data; skin biopsies (in 10% buffered formalin) for hematoxylin and eosin (H&E) examination and skin biopsies(in Michel's transport medium) for direct immunofluorescence (DIF). In many ABDs, the histopathologic findings demonstrate a subepidermal vesicle or bulla with a luminal inflammatory infiltrate of neutrophils, eosinophils and/or lymphocytes. In many ABDs, an extensive perivascular and interstitial inflammatory infiltrate is also noted subjacent to the blister in the upper dermis. Normal skin adjacent to an ABD plaque is often excellent for DIF results. Many ABD biopsies reveal autoantibody deposition at the lesional basement membrane zone (BMZ); IgG, IgM, IgA, other immunoglobulins, complement components and fibrinogen may be detected. Indirect immunofluorescence (IIF) yields antibody titer data; the titers usually correlate with disease activity and with ELISA. Linear epitopes are commonly studied by using an immunoblotting (IB) assay. Topical and systemic corticosteroids remain as mainstays of therapy in ABDs; however, multiple other immunosupressors and/or " steroid sparing agents " such as azathioprine have been demonstrated to be of therapeutic value. In the IgA mediated dermatoses, dapsone is often helpful; in addition, liver and blood testing (including G6PD levels) is indicated. The prognosis depends on each case; rapid diagnosis avoids complications and assists in maintaining a good quality of life for each patient. Abbreviations and acronyms: Autoimmune mucocutaneous blistering diseases (ABDs), bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), chronic bullous dermatosis of childhood (CBDC), adult linear IgA bullous dermatosis (LAD), lichen planus pemphigoides (LPP), immunohistochemistry (IHC), direct and indirect immunofluorescence (DIF and IIF), hematoxylin and eosin (H&E), antibodies (Abs), basement membrane zone (BMZ), intercellular staining between epidermal keratinocytes (ICS), pemphigus vulgaris (PV), cicatricial pemphigo-id (CP), dermatitis herpetiformis (DH), sodium dodecyl sulfate (SDS), SDS-PAGE (SDS polyacrylamide gel electrophoresis), bullous systemic lupus erythematosus (BSLE); bullous pemphigoid antigens II(180 kDa) and I(230 kDa)(BP180 and BP230), epidermolysis bullosa simplex (EBS), intravenous immunoglobulin (IVIG).