Linear IgA bullous dermatosis

Linear IgA bullous dermatosis (LABD) is group of heterogeneous autoimmune subepidermal blistering diseases characterized by exclusively IgA autoantibodies targeting a component of the epidermal basement membrane zone. The laminina-lucida-type LABD, also known as chronic bullous dermatosis of childhood, is a rare disease, yet the most common autoimmune blistering disease among childeren with a peak incidence at 4-5 years of age. The major target antigens in laminina-lucida-type LABD are 120 kDa LAD-1 antigen, and its carboxyterminal proteolysed form 97 kDa LABD antigen 1 (LABD97). Both proteins are produced by cleavage of the extracellular domain of BP180, one of the main structural components of the hemidesmosome. The autoantigen targeted by IgA in the sublamina densa-type LABD, also known as IgA epidermolysis bullosa acquisita, is type VII collagen. In adults, LABD may also be drug-induced.</p

Dermatological examination of bullous diseases

Physical examination in bullous diseases always comprises looking at skin and mucous membranes. Examine the skin not only for the presence of vesicles or bullae but also for other efflorescence's and typical distribution pattern. Nikolsky sign tests the resilience of the healthy-lookig skin. The mucous membranes of mouth, nose, eyes and genitals need to be examined systematically. Disease activity and extent of skin and mucous membranes can be assessed using disease activity outcome measures that are validated for pemphigus, bullous pemphigoid and mucous membrane pemphigoid.</p

Dermatitis herpetiformis

Dermatitis herpetiformis (DH) is the specific skin manifestation of coeliac disease (CD) caused by the digestion of gluten in HLA-DQ2 or HLA-DQ8 individuals. DH is characterized by intensely pruritic polymorphic papulovesicular eruption on the extensor surfaces of the body. Both diseases are characterized by circulating IgA autoantibodies against tissue transglutaminase (tTG), which bind to the smooth muscle layer of the monkey esophagus causing the so-called EMA positivity. Additionally DH patient have another autoantibody population targeting the epidermal transglutaminase (eTG), the autoantigen of DH, which protein is highly homologous to tTG.</p

IgA pemphigus

IgA pemphigus (IGAP) is a rare variant of pemphigus characterized by tissue-bound and circulating autoantibodies exclusively from the IgA class against desmosomal and non-desmosomal proteins of the epidermis. Based on the clinics, histology, direct immunofluorescence and autoantibody profile it is classified in two types: the subcorneal pustulosis dermatosis (SPD) type and the intraepidermal neutrophilic IgA dermatosis (IEN) type. The first line therapy is dapsone.</p

Epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is a subtype of pemphigoid that may present with scarring similar to hereditary dystrophic epidermolysis bullosa, of which the naming of EBA was derived. The clinical subtype of EBA with scarring is named mechanobullous EBA, because blisters are evoked by sudden mechanical trauma to the skin. The other subtype of EBA with erythematous lesions without scarring is named inflammatory EBA, and may look like bullous pemphigoid. The mucous membranes can be involved in both subtypes. The pathogenesis is mediated by IgG or IgA against type VII collagen, which is the component of anchoring fibrils below the lamina densa. Diagnosis is confirmed by detection of a u-serrated linear pattern of immune depositions by direct immunofluorescence microscopy of a skin biopsy. The pathogenesis of both clinical subtypes is unknown, and is not related to binding of a particular epitope of the auto-antigen. EBA is associated with systemic lupus erythematosus and colitis ulcerosa. The disease is relative refractory to treatment.</p

Bullous systemic lupus erythematosus

Bullous systemic lupus erythematosus (BSLE) is rare heterogeneous cutaneous manifestation in patient with systemic lupus erythematosus (SLE). BSLE encompasses a subepidermal autoimmune bullous disease with type VII collagen autoantibodies, leading to epidermolysis bullosa acquisita in patients with SLE. Alternatively, an acute generalized hemorrhagic vesiculo-bullous eruption may also occur in patients with SLE caused by the extensive inflammatory reaction without the presence of type VII collagen. Vesicular eruptions can also be seen in subacute cutaneous lupus erythematosus due to severe inflammatory reaction with subepidermal clefting, which in extreme cases may resemble erythema multiforme (Rowell syndrome) or toxic epidermal necrolysis.</p

Bullous dermatitis artefacta

Bullous dermatitis artefacta is a psychodermatologic disorder in patients who mimic skin disease by inflicting themselves blisters. The diagnosis is often apparent at first visit. The diagnosis should never be immediately revealed to the patient. Instead a serious, yet limited, workup is advised, while developing a trustful patient-doctor relation. The strategy is to give the patient the impression you know it was self-inflicted, but leaving an escape for clearance by trivial causes imagined by the patient such as avoiding drinking coffee (narrow escape). In refractory cases, when confrontation becomes unavoidable, dual approach by dermatologist and psychiatrist is necessary.</p

Structure of hemidesmosomes and the epidermal basement membrane zone

Hemidesmosomes are complex, multiprotein structures that mediate the attachment of epithelial cells to the underlying basement membrane. While providing mechanical attachment, these adhesion units are extremely dynamic. They play a significant role in signaling pathways involved in various important cell functions, such as differentiation, wound healing, and survival. Structurally, hemidesmosomes contain the following molecules: plectin (over 500 kDa protein), BP230 (230 kDa antigen, also known as BPAG1), integrin A6B4, BP180 (180 kDa protein, also known as BPAG2 or type XVII collagen, laminin 332 and CD151 (protein of tetraspan superfamily). The epidermal basement membrane zone can be viewed as a thin sheet of matrix underlying the basal epithelial cells. It consists of lamina lucida and lamina densa, mainly containing laminin and type IV collagen networks. Type VII collagen which enters the composition of semicircular anchoring fibrils provide the attachment to the papillary dermis underneath the lamina densa of the basement membrane. When molecules in hemidesmosomes or in the basement membrane zone become target of autoantibodies a particular acquired subepidermal autoimmune blistering disease (sAIBD) will develop.</p