Epidermolysis Bullosa Acquista (EBA)

  • Rarest subepidermal bullous disease: annual incidence of 0.25 cases per million in Western Europe (may be more common in Asians and African-Americans)
  • Any age
  • HLA associations:
    • DRB1*1501 and DR5 in Caucasians and African-Americans
    • DRB1*13 in Koreans

  • IgG auto-antibodies to type VII collagen (Col7) (major component of anchoring fibrils located in lamina densa and sublamina densa)
  • Specifically targets NC1 >>> NC2 domain of Col7

Proposed role of antibodies: 

  • leukocyte infiltration – Interference with the assembly of Col7
  • Inability of Col7 to bind matrix proteins 
  • Correlation of auto-antibody titers with disease severity

Antibodies can cross placenta

Non-inflammatory mechanobullous disease (mimics dystrophic EB) – classic presentation 

  • Acral or trauma prone non inflammatory ±hemorrhagic skin blisters that heal with atrophic scarring, milia and dyspigmentation ± pseudosyndactyly, nail dystrophy, complete nail loss
  • Mucosal involvement (50%) – vesicles and erosions in mouth, larynx and esophagus which may lead to dysphagia and laryngeal stenosis  
  • Scalp involvement (20% of patients) – non-healing erosions and scarring alopecia

Inflammatory subtypes –can convert from one variant to another or exhibit clinical overlap

  • BP-like (most common)
  • MMP-like
  • LABD-like 

Childhood EBA: overlaps with childhood BP and LABD

Histopathology: 

  • Subepidermal blister 
  • Non-inflammatory 
  • BP-like or MMP-like variants: variable dermal inflammatory infiltrate with predominant neutrophils, some eosinophils and lymphocytes 

Electron microscopy: 

  • split within sublamina densa with reduction of anchoring fibrils 
  • Rarely at lamina lucida 

DIF of perilesional skin:

  • Linear IgG >> C3, IgA, IgM along basement membrane zone
  • Salt-split  – IgG dermal side of blister 
  • U-serration

IIF: 

  • Circulating IgG > IgA auto-antibodies detected in 50% of patients 
  • Salt-split – dermal side

Immunoelectron microscopy: 

  • “Gold-standard” for EBA diagnosis
  • Auto-antibody binding to anchoring fibrils and lamina densa 

Other immunochemical studies: Western immunoblotting, ELISA

  • Dystrophic epidermolysis bullosa (mild dominant dystrophic), bullous pemphigoid, mucous membrane pemphigoid (including Brunsting-Perry variant), anti-laminin γ1 pemphigoid, porphyria cutanea tarda, pseudoporphyria or rare porphyrias (porphyria variegata), bullous systemic lupus erythematosus

  • Often refractory to treatment – anecdotal reports due to rarity of disease
  • BP-like EBA: Systemic corticosteroids with immunosuppressants such as azathioprine, methotrexate, mycophenolate mofetil, cyclophosphamide or rituxumab
  • Reported benefit with colchicine, dapsone, gold, cyclosporine, IVIg (severe unresponsive disease)
  • Childhood disease: Dapsone and prednisolone