**5. Epidermolysis bullosa acquisita (EBA)**

Epidermolysis bullosa acquisita (EBA) is a rare, acquired subepidermal blistering disease of skin and mucous membranes, which is characterized by autoantibodies to collagen VII [47]. The disease occurs at similar rates in males and females and is common in the fourth and fifth decades, but 4.6% of patients are younger than 17 years of age [48].

The disease is divided into two types mechanobullous (non-inflammatory) and inflammatory type. Mechanobullous EBA is the most common type of EBA [49]. Skin fragility, tense bullae, erosions, milium, and scar formation can be observed in areas exposed to trauma, especially the extensor surfaces of the acral regions, in the mechanobullous type [50, 51]. Although mucosal involvement is less common than the inflammatory type, esophageal stenosis may develop. Milia, atrophic scars, hyper and hypopigmentation, nail dystrophy and loss, cicatricial alopecia, and digital contractures can be seen due to scar formation during healing [47]. This type should be distinguished from porphyria cutanea tarda in particular. While bullous lesions and erosions in acral areas seen in both are similar; In porphyria, hirsutism, photosensitivity, scleroderma-like skin changes, and high porphyrin in the urine are expected [52].

In the inflammatory type, the lesions can be seen in not only trauma-prone areas but also all skin, involving the trunk, central body, extremities and skin folds, and mucous membranes, so it is different from the mechanobullous type. It shows clinical findings similar to other subepidermal bullous diseases and is divided into subtypes named according to the diseases they resemble; BP-like EBA, cicatricial pemphigoidlike EBA, linear IgA bullous dermatosis (LABD)-like EBA and Brunsting-Perry pemphigoid-like EBA [47, 48].

Among inflammatory subtypes, BP-like EBA is the most common [47, 49]. Significant itching is observed in patients with BP-like EBA. It is usually present with tense bullae and erosions on urticarial or erythematous skin, which can occur in any part of the skin, including the face, and may affect the oral mucosa. In addition, lesions surrounded by intact skin can also be seen at trauma sites. Formation of cicatrice or millium is rare during healing [49]. Histopathology reveals a subepidermal blister with eosinophilic-rich infiltrate, and u-serrated pattern linear deposition of C3 and IgG in the basement membrane zone is detected in DIF examination [18, 47].

LABD-like EBA (IgA-EBA) patients present with tense bullae with annular or polycyclic array are seen on urticarial plaques with or without oral mucosal involvement. Milia and scar development are not expected. Subepidermal blisters are characterized by linear IgA deposits in the BMZ on direct immunofluorescence (DIF) [47, 53, 54].

MMP-like EBA mainly affects mucous membranes such as mouth, pharynx, esophagus, conjunctiva, anus, genital area, and respiratory tract and heals with scarring. As in MMP, organ-specific complications may occur due to scar formation in the mucous membranes [54, 55].

Brunsting-Perry pemphigoid-like EBA; subepidermal blisters located on the head and neck with atrophic scars with minimal or no mucosal involvement [56].

It is not clinically and histopathologically possible to distinguish all these inflammatory and non-inflammatory EBA forms from other subepidermal bullous diseases. As with most other subepidermal bullous dermatoses; linear deposits of IgG and C3 in BMZ can be demonstrated in perilesional skin. Diagnosis requires a demonstration of the presence of in situ and/or circulating IgG autoantibodies against collagen VII. At this point, the salt-split skin immunofluorescence test is can be used. EBA sera react on the dermal side of the salt-split skin, while BP sera react on the epidermal side [47, 55].

EBA may be associated with cancer as well as infectious, cardiovascular, metabolic, neurological, and chronic inflammatory diseases, such as inflammatory bowel disease, thyroiditis, rheumatoid arthritis, and psoriasis [48].

The choice of treatment for EBA depends on the severity of the disease. Although there are various methods to determine the severity of the disease, in recent research, patients with body surface area < 10%, without functional loss and severe mucosal involvement, are classified as non-severe. Patients with body surface area involvement > 10%, functional loss, and severe mucosal involvement are classified as severe [37, 47].

First of all, it is important to be protected from local traumas and infections. Topical corticosteroids are the first choice in mild and localized diseases. Depending on the condition of the disease, firstly colchicine(0.5–2 mg/day) or dapsone(50–100 mg/day) should be added to the treatment as an adjuvant in non-severe disease. If there is a partial response, oral prednisone (0.5–1 mg/kg/day) can be added to the treatment. In severe disease or resistance to other treatments, first-line treatment is intravenous immunoglobulin(IVIG) (2 g/kg over 5 days) and oral prednisone (1–1.5 mg/kg/day) or pulse therapy with methylprednisolone (1 g IV for 3 days). In case of partial response or unresponsiveness to previous treatments, mycophenolate mofetil (2–3 g/day) or cyclosporine (5 mg/kg/day), or azathioprine (100–200 mg/ day) can be added to the treatment. If there is still no response to treatment, rituximab (1 g IV on D0 and D14 or 375 mg/m2 weekly for 4 weeks) is used every 6 months. Methotrexate, cyclosporine, cyclophosphamide, and plasma exchange are other treatment methods that can be used [37, 38, 47].
