The presence of intra-lamina lucida blister formation in epidermolysis bullosa acquisita: possible role of leukocytes

Abstract

In evaluating patients we have noted disparity between the locations of bound immunoreactants and the level of blistering in epidermolysis bullosa acquisita (EBA). We examined 10 consecutive EBA patients by routine histology, direct (DIF) and indirect (IIF; intact and NaCl-split skin) immunofluorescence, immunofluorescence mapping (IM), and/or direct immunoelectron microscopy (DIEM). DIF was positive in each. IIF was positive in 3/8 and 6/7 patients when intact and split skin were used as substrates. DIEM revealed immunoreactants within the lamina densa (LD) in 6/10, sub-LD in 1/10, and both LD and sub-LD in 3/10 patients. In contrast, by DIEM and IM, blister formation was noted within the lamina lucida (LL) in 7/9 and 8/10, sub-LD in 1/9 and 1/10, and within both LL and sub-LD in 1/9 and 1/10, respectively. In the presence of neutrophils within the upper dermis (n = 6), cleavage occurred within the LL in 5 specimens; in one additional specimen containing predominantly neutrophils, cleavage occurred within both LL and sub-LD. In the presence of mononuclear cells (n = 2), intra-LL cleavage occurred. In the presence of eosinophils, cleavage occurred within both LL and sub-LD. In the one specimen lacking any infiltrate, the cleavage plane was exclusively sub-LD. Intra-LL cleavage planes are more common than sub-LD ones in at least early cases of EBA. These findings likely represent the intra-LL-separating effect of leukocyte-derived proteolytic enzymes, when such cells are chemoattracted to the dermoepidermal junction by bound immuno-reactants.