Epidermolysis bullosa acquisita (EBA)

Dermolytic pemphigus; Acquired epidermolysis acquisita; Acquired epidermolysis bullosa; EBA.

EBA is an autoimmune disease characterised by the formation of blisters on the skin and mucous membranes. While it mainly affects adults, it can reach people of any age. Triggers can be viral infections, paraneoplastic syndromes and autoimmunological reactions, for example after autologous stem cell transplantation.

Although the incidence of MSDs in Western Europe is between 0.25-1.0 per 1.0 million population annually, it predominantly affects adults. There are reports of paediatric cases. So far, there is no clear evidence that gender, ethnicity or geographical location influence the risk of MSDs.

In 2018, the International Bullous Diseases Group identified several forms of MSDs, including:

• Classical/mechanobullous form
• Nonclassical/bullous pemphigoid-like form
• Mucosal form
• Brunsting-Perry form
• IgA form
• Generalised, inflammatory form (blistering ubiquitous).
• Localised form resembling the picture of scarring pemphigoid.
  

The pathogenesis of EBA (epidermolysis bullosa acquisita) is characterised by the formation of antibodies against collagen type VII, a major component of the anchoring fibrils in the basement membrane zones of skin and mucosa. This antibody formation leads to immune-mediated disruption of the anchoring fibrils, which contributes to cleavage within the basement membrane zone and subsequently to clinical blister formation. An underlying autoimmune process that promotes the production and deposition of these antibodies to type VII collagen appears to be a major contributor to the development of the clinical disease. It is important to emphasise that the autoantigen in this blistering autoimmune disease is collagen type VII, particularly in its NC1 domain, which is the major component of the anchoring fibrils of the papillary dermis.

The clinical manifestations of MSD vary. In addition to the classic, non-inflammatory form of MSD, MSD can also present as inflammatory blistering. Classic EBA shows skin fragility and the formation of non-inflammatory, tense vesicles and blisters. These may occur in areas repeatedly exposed to mild trauma. Blistering on the face, sometimes in the image of impetigo contagiosa. An association between MSDs and inflammatory bowel disease has been noted. Patients frequently report tension blisters, especially in trauma-prone areas. Some may have a history of other autoimmune diseases. In adults with consistent clinical features, such as skin fragility and trauma-induced tense blisters leading to milia and scarring, and without a family history of hereditary blistering, a diagnosis of classic MSD should be considered.

Diagnosis is based on clinical symptoms, biopsy results and serological tests. It is important to think of MSDs in patients with blistering symptoms. Direct immunofluorescence microscopy and immunoelectron microscopy can also contribute to the diagnosis. The presence of antibodies to type VII collagen distinguishes EBA from the true forms of other autoimmune diseases with blistering. Direct immunofluorescence shows a linear IgG and C3 deposition in the basement membrane zone. A "U-serrated pattern" can be detected at high magnification, which is diagnostic for EBA.

Depending on the form of MSD, lesions can be localised or widespread and affect different areas of the body, including mucous membranes.

A biopsy typically shows subepidermal blisters. Immunofluorescence tests can help confirm the diagnosis. In older lesions, skin fibrosis may be present, a finding that correlates with the clinical development of scars. Classic EBA is characterised by a sparse lymphocytic infiltrate in the superficial dermis. Inflammatory EBA variants show an intense infiltrate around blood vessels, hair follicles or in the interstitial space of the upper dermis. Electron microscopy reveals a separation in the zone between the dermis and epidermis, especially in the area of the dense sublayer. A reduced number of anchoring fibrils is evident.

In addition to skin symptoms, patients may also experience problems such as malnutrition, blindness or gum disease. In rare cases, formation of oesophageal or urethral strictures.

EBA has a chronic course. Some forms can lead to significant scarring and dysfunction.

Patients should avoid physical trauma and practice good skin and oral care.

• Kridin K, Kneiber D, Kowalski EH, Valdebran M, Amber KT. Epidermolysis bullosa acquisita: A comprehensive review. Autoimmune Rev. 2019 Aug;18(8):786-795.
• Kasperkiewicz M et al.(2016) Epidermolysis Bullosa Acquisita: From Pathophysiology to Novel Therapeutic Options. J Invest Dermatol 136:24-33.
• Schmidt E et al (2013) Pemphigoid diseases. Lancet 381:320-332.
• Reddy H et al (2013) Epidermolysis bullosa acquisita and inflammatory bowel disease: a review of the literature. Clin Exp Dermatol 38:225-229; quiz 229-30.
• Goebeler M, Zillikens D (2003) Blistering autoimmune diseases of childhood] Dermatologist 54: 14-24.
• Vodegel RM (2003) Anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita: differentiation by use of indirect immunofluorescence microscopy. J Am Acad Dermatol 48: 542-547.
• Hertl M, Schuler G (2002) Bullous autoimmune dermatoses. 1: Classification. Hautarzt 53: 207-219.
• Jappe U et al (2000) Epidermolysis bullosa acquisita with ultraviolet radiationsensitivity. Br J Dermatol 142: 517-520.
• Bauer JW (1999) Ocular involvement in IgA-epidermolysis bullosa acquisita. Br J Dermatol 141: 887-892.
• Busch JE et al (2007) Epidermolysis bullosa acquisita and pancreatic neuroendocrine carcinoma-coincidence or pathogenetic association. JDDG 10: 916-918.