Epidermolysis bullosa acquisita, classical variant L12.-

The classic variant of epidermolysis bullosa acquisita is a rare, acquired, traumatically induced, blistering autoimmune disease with IgG antibodies against type VII collagen (NC1 domain), the main component of the "anchoring fibrils" in the dermoepidermal junction zone.

On the basis of their clinical appearance, two main subgroups of epidemolysiosis acquisita diseases can be distinguished:

• classical or mechanobullous (non-inflammatory) type and
• non-classical inflammatory or non-mechanobullous type which is subdivided as follows:
  • BP-like EBA (45%) - tight blisters on erythematous or urticarial skin, mainly trunk and extremities.
  • MM (mucosal membrane)-EBA (7%)- lesions and scarring on the mucous membranes of the mouth. Oesophagus, trachea, conjunctiva
  • EBA type Brusnting-Perry (7%) - variant under the picture of a localized scarring pemphigoid; chronic recurrent bullous dermatosis on the head and neck, sometimes with hair loss, usually no mucosal involvement
  • IgA-EBA(3%) - variant under the picture of a linear IgA dermatosis of childhood. Linear IgA deposits in the basement membrane zone

Little data is available on the pathogenesis of classic mechano-bullous, non-inflammatory EBA. Various mechanisms have been discussed, such as autoantibodies bound to COLVII affecting it by interfering with interactions with extracellular matrix proteins in the BMZ, such as type IV collagen and fibronectin. Another possibility is that autoantibodies directly interfere with the formation of the antiparallel dimer of COLVII and destabilize the anchoring fibrils.

Mechanobullous/classical/non-inflammatory EBA: In the mechanobullous form of EBA, skin fragility and vesiculobullous lesions occur in areas that are exposed to greater pressure and trauma, especially on the extensor sides of the acra (hands, feet, elbows, knees, shin area). The lesions occur mainly on normal skin, without edema or erythema. They occur a few hours after traumatization of the skin, although this can also be minimal. Mucosal lesions are common. Another clinical feature of this form is that milia, atrophic scars, hyper- or hypopigmentation, nail dystrophy and loss, cicatricial alopecia, digital contractures and oesophageal stenosis may develop during the course of the disease (Prost-Squarcioni C et al. 2018).

The histopathological findings in EBA vary depending on the type and duration of the lesion. In classic or mechanobullous EBA, subepidermal clefting with papillary edema and sparse inflammatory infiltration is observed.

Linear IgG and C3 deposition in the basement membrane zone. Pattern corresponding to the localization of collagen VII in the sublamina densa zone of the skin.

At high magnification, a typical pattern of IgG deposits can be observed, which is typical for EBA: the so-called "U-serrated pattern" (Br J Dermatol 2004). This is an important diagnostic criterion, as circulating autoantibodies can only be detected in approx. 50-60% of EBA patients. The diagnosis of EBA is clearly established with the determination of the "U-serrated pattern" in direct IF.

Immunoelectron microscopy shows IgG deposits below the lamina densa, sometimes also on the anchoring fibrils. However, this method is only used by very few centers and is reserved for special cases.

In approx. 50-60% of patients, IgG and/or IgA autoantibodies against type VII collagen can be detected serologically. Detection is initially carried out using indirect IF with salt-split skin as a substrate. In EBA, the autoantibodies bind to the bottom of the artificial blister. However, this is not conclusive for EBA, as the p200 antigen and laminin-332 are also expressed at the bottom of the bladder.

ELISA (NC1/NC2) or immunochip (with COL7-expressing cells) can be used to detect collagen 7-specific antibodies. It is also possible to detect a band at 290 kD using a Western blot on a dermal extract.

Porphyria cutanea tarda: Mechanical bullous EBA cannot be clinically differentiated from porphyria cutanea tarda (PCT) as both diseases show skin fragility with blistering and scarring in traumatic areas. Hypertrichosis, liver dysfunction and elevated ferritin and porphyrin levels can occur in PCT and contribute to the diagnosis.

Differentiation from hereditary epidermolysis bullosa

Bullous medicinal exanthema: medical history; blistering on the trunk, possibly mucous membranes, not on mechanically altered areas such as hands, elbows, feet, knees

Dermatitis herpetiformis: small burning blisters. Not caused by trauma. IF: granular IgA deposits in the tips of the papillae.

Pemphigus vulgaris: flaccid blisters, not traumatically triggered, detection of specific antibodies

Pemphigoid, bullous: Detection of specific antibodies, no traumatic triggering

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