U‐serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases

Summary Background  Epidermolysis bullosa acquisita (EBA) can be differentiated from other subepidermal bullous diseases by sophisticated techniques such as immunoelectron microscopy, salt‐split skin antigen mapping, fluorescence overlay antigen mapping, immunoblot and enzyme‐linked immunosorbent assay. Objectives  To determine whether the diagnosis can also be made by routine direct immunofluorescence microscopy. Methods  We studied frozen skin biopsies from 157 patients with various subepidermal immunobullous diseases. Results  We found three distinct ‘linear’ fluorescence patterns at the basement membrane zone: true linear, n‐serrated and u‐serrated. The true linear pattern, often seen in conjunction with either the n‐ or the u‐serrated pattern, was found in any subepidermal immunobullous disease with nongranular depositions. In bullous pemphigoid, mucous membrane pemphigoid, antiepiligrin cicatricial pemphigoid, p200 pemphigoid and linear IgA disease the n‐serrated pattern was found, corresponding with depositions located in hemidesmosomes, lamina lucida or lamina densa. However, in EBA and bullous systemic lupus erythematosus the u‐serrated staining pattern was seen, corresponding with the ultralocalization of type VII collagen in the sublamina densa zone. The diagnosis of EBA with IgG or IgA autoantibodies directed against type VII collagen was confirmed by immunoelectron microscopy, salt‐split skin antigen mapping, fluorescence overlay antigen mapping or immunoblotting. Conclusions  Using this pattern recognition by direct immunofluorescence microscopy we discovered several cases of EBA which would otherwise have been erroneously diagnosed as a form of pemphigoid or linear IgA disease.