Epidermolysis bullosa acquisitaL12.30

Rare, acquired, blistering autoimmune disease with antibodies against type VII collagen, the main component of the "anchoring fibrils" in the dermoepidermal junction zone. The disease can occur after viral infections, as a paraneoplastic syndrome, also after autoimmunological reactions (e.g. after autologous stem cell transplantation).

A distinction is made between 3 clinical variants:

• Classic, acral, mechano-bullous form (blistering only in mechanically stressed areas).
• Generalized, inflammatory form, clinically corresponding to bullous pemphigoid (blistering ubiquitous).
• Localized form under the picture of scarring pemphigoid.

Incidence in Western Europe: 0.25-1.0/1.0 million inhabitants/year. No ethnic clustering.

Blister-forming autoimmune disease; autoantigen is collagen type VII, which is the main component of the anchoring fibrils of the papillary dermis. The antibodies bind to the NC1 domain of collagen type VII.

Occurrence is possible at any age, usually between the 40th and 60th year of life. Rarely also occurring in children. m:w=1:1;

Integument:

• In the classic form of the disease, tight, non-inflammatory blisters of various sizes are found, predominantly on mechanically traumatized skin regions (especially hands, elbows, feet, knees) and, in rare cases, on the oral mucosa. Occasionally, the affected areas heal with skin atrophy or milia, hyper- and hypopigmentation.
• A second clinical variant (30% of cases) presents as a generalized, pruritic, inflammatory disease with the appearance of bullous pemphigoid.
• A third variant presents as localized Brunsting-Perry scarring pemphigoid.
• A fourth variant has been described under the picture of a linear IgA dermatosis, with blistering of the face, partly under the picture of impetigo contagiosa.

Extracutaneous manifestations: In rare cases, formation of esophageal or urethral strictures.

Reviews have identified an association between epidermolysis bullosa acquisita (EBA) and inflammatory bowel disease (IBD). In 42 coincident cases, Crohn's disease (K50.9) was detected 35x and ulcerative colitis (K51.9) 7x. In most cases, inflammatory bowel disease preceded the skin lesions (Reddy H et al 2013). Note: The antigen of EBA (collagen type VII) is also expressed in the intestinal mucosa between epithelium and stratum proprium.

Subepidermal blistering. Edema of the dermis. Bulky, diffusely arranged, predominantly neutrophil infiltrates in the upper dermis, in the case of gaping blood and lymph vessels. Diagnosis: Diffuse, superficial, predominantly neutrophil dermatitis with subepidermal blistering.

Electron microscopy: fissure formation in the dermo-epidermal junction zone in the area of the sublamina densa zone. Reduction of the number of anchoring fibrils.

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 detected, which is typical for EBA: the so-called "U-serrated pattern" (Br J Dermatol 2004). This is an important diagnostic criterion, since circulating autoantibodies can be detected in only about 50-60% of EBA patients. With the detection of the "U-serrated pattern" in direct IF, the diagnosis of EBA is unequivocal.

In immunoelectron microscopy IgG deposits below the lamina densa, partly also at the anchoring fibrils. However, this method is only used by very few centers and is reserved for special cases.

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

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

Clinic and detection of a u-serrated pattern in direct IF confirm the diagnosis.

If the pattern does not present in the direct IF, the diagnosis can be made in the case of linear Ig/C3 deposits in the direct IF as follows:

1. Serological detection of type VII collagen specific autoantibodies.
2. Immunoelectron microscopy

Systemic therapy is indicated in cases of generalization or mucosal involvement. Only some patients (especially with a strong inflammatory component) respond well to monotherapy with systemic glucocorticoids, medium dosage (60-80 mg/day prednisone equivalent). Therefore, the combination of glucocorticoids with the following immunosuppressants should be sought:

• Azathioprine (e.g. Imurek) 1-2 mg/kg bw/day.
• Cyclophosphamide (e.g. Endoxan) 50 mg/day
• DADPS (e.g. dapsone fatol) 100-150 mg/day
• Ciclosporin A (e.g. Sandimmun) 5-7 mg/kg bw/day
• Colchicine (e.g. Colchicine Dispert Drg.) 0.5-2 mg/day.

Therapy trial is also possible with vitamin E (e.g. Evit Kps.) high dose 600-1200 mg/day. Under this therapy complete healing is described in individual cases, but the improvement occurs only over a long period of time.

Newer therapeutic approaches:

• IVIG: Immunoglobulins (e.g. Pentaglobin) 5 ml/kg bw/day i.v. for 3-7 consecutive days in combination with e.g. Prednisolon or Ciclosporin A treatment should lead to better results. According to literature, intravenous immunoglobulins seem to have a therapeutic effect only initially. Long-term improvements have not been described among them.
• Plasmapheresis may reduce the maintenance dose of glucocorticoids and immunosuppressants as an adjunctive measure.

Preventive; if possible, no exceptional mechanical stress on the skin.

In individual cases the simultaneous occurrence of malignancies has been described (cervical carcinoma, multiple myeloma, pancreatic carcinoma).

Associations with other autoimmune diseases have been described frequently: autoimmune thyroiditis, systemic lupus erythematosus, Crohn's disease.

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