A paraneoplastic mixed bullous skin disease: breakdown in tolerance to multiple epidermal antigens

We report a new type of paraneoplastic mixed bullous skin disease in a patient with a B-cell lymphoma associated with monoclonal IgM kappa paraproteinaemia. The patient's clinical and histological features were reminiscent of bullous pemphigoid. Characterization of antiepidermal antibodies by immunoblotting and indirect immunoelectron microscopy demonstrated a novel pattern of reactivity: IgG antibodies were directed against desmoplakins I-II and BPAG2, and were associated with antidesmoglein 3 polyclonal IgM antibodies. Such an autoreactive pattern involving antidesmoplakins, anti-BPAG2 and antidesmoglein 3 antibodies has not been previously reported. It reflects the breakdown of tolerance to multiple epidermal antigens observed in some patients with malignancy.