Successful Treatment of Intravenous Immunoglobulins in a Patient with Intractable Epidermolysis Bullosa Acquisita with Autoantibodies to Type VII Collagen and Laminin Alpha-3

Abstract

Case Reportprogressive blistering skin lesions on the face, trunk, and extremities, which were treated with topical corticosteroids and antihistamines but showed no clinical improvement. On physical examination, severely pruritic erythemas and vesicles were diffusely distributed all over the body, most of which were eroded because of scratching ( Figure 1a). The erythematous rashes showed a variety of morphological patterns, erosions, flaccid bullae, and concentric erythemas with a wood-grainlike appearance (Figures 1b and 1c). Oral and conjunctival mucosal lesions were absent. The patient had no medical history, and the results of laboratory examinations were within normal ranges, except for mild hypercholesterolemia. Enzyme-linked immunosorbent assays showed negative results for all desmoglein 1 (Dsg1), Dsg3, bullous pemphigoid 180 (BP180) and BP 230.A skin biopsy specimen from an erythematous legion on the chest containing a vesicle showed subepidermal blistering and dense infiltration of neutrophils, eosinophils, and histiocytes in the superficial dermis (Figure 2a). The infiltrated cells were condensed in the papillary layer of the dermis (Figure 2b). Direct immunofluorescence (DIF) revealed linear deposition of IgG and C3 along the epidermal basement membrane zone (BMZ; Figure 2c). Indirect immunofluorescence (IIF) demonstrated circulating IgG anti-BMZ antibodies at a titer of 1:160, which bound to the dermal side of 1M NaCl-split normal human skin (data not shown).Immunoblot (IB) analysis of normal human dermal extracts revealed that IgG antibodies in the patient serum reacted with a 290-kDa protein band with the same mobility as an epidermolysis bullosa acquisita (EBA) antigen (type VII collagen; Figure 2d). IB of purified human laminin-332 (epiligrin or laminin-5) also detected IgG reactivity with the 165-kDa and 145-kDa forms of the alpha-3 subunit of laminin-332, which were also recognized by a positive control serum from a patient with anti-laminin-332-type mucous membrane pemphigoid (MMP) (Figure 2e). Other IB analyses of normal human epidermal extracts, the recombinant proteins of NC16a and the C-terminal domains of BP180, and a concentrated HaCaT cell culture supernatant showed no positive reactivity (data not shown).The patient was initially treated with dapsone (50 mg/day), which dramatically improved his pruritus, but failed to suppress the development of the erythemas and vesicles. Gradual increase in levels of liver transglutaminases led to cessation of dapsone. Because both pruritus and skin lesions were refractory to subsequent oral prednisolone (40 mg/day) or betamethasone (6 mg/day), double filtration plasmapheresis (DFPP) was performed. However, after 3 cycles of DFPP, the patient abruptly developed a high fever, showed deterioration of liver function, and showed increase in levels of white blood cells (12,800 cells/µL, normal<9,000 µL) and C-reactive protein (15.7 mg/dL, normal<0.3 mg/dL). Methicillin-resistant staphylococcal aureus (MRSA) was detected from a blood specimen and from a c...

Therapeutic Applications of Human and Bovine Colostrum in the Treatment of Gastrointestinal Diseases and Distinctive Cancer Types: The Current Evidence

“…Whereas in adults, colostrum promotes healing of the GI tract and protects against gut pathogens (bacteria, viruses, fungi, yeast, mold, etc. ), and leaky gut syndrome ( Shah, 2000 ; Hurley and Theil, 2011 ; Osada et al., 2014 ; Wu Xiaoyun and Xiong Lin, 2015 ). The major bioactive components of bovine colostrum and their functions in children and adults are summarized in Table 1 .…”