Modern diagnosis of autoimmune blistering skin diseases

Abstract

The diagnostic gold standard of autoimmune bullous diseases is the detection of autoantibodies in skin or mucous membranes by direct immunofluorescence microscopy of a perilesional biopsy. The molecular characterisation of several target antigens within the last 10 years has, however, fostered the development of sensitive and specific diagnostic tools that allow the serological diagnosis in about 90% of patients. Based on the recombinant immunodominant portions of the target antigens, ELISA systems are commercially available for the detection of circulating antibodies against desmoglein 1, desmoglein 3, envoplakin, BP180, and BP230. Autoantibodies against the soluble ectodomain of BP180 (LAD-1), laminin 332, type VII collagen, and most recently, laminin γ1 can be detected by Western blotting with recombinant or cell-derived forms of these proteins. The definite differentiation between the various immunobullous disorders that comprise about a dozen entities is increasingly important since more diverse treatment options are employed. Exact diagnosis is also pivotal for the prognosis, since some autoimmune bullous diseases may indicate an underlying tumor. Association with a malignancy has been shown in paraneoplastic pemphigus (in 100%) and anti-laminin 332 mucous pemphigoid (in 25%) In pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, autoantibodies to desmoglein 3, desmoglein 1, and BP180, respectively, have been shown to correlate with the disease activity. The detection of serum autoantibodies during the course of the disease may thus be helpful in guiding treatment decisions in these patients.