Iatrogenic Pharmaceutical Amyloidosis Associated with Insulin and Enfuvirtide Administration

Abstract

Drug-induced amyloidosis is a rare form of iatrogenic amyloidosis and represents a localized process. Insulin and Enfuvirtide are two peptide drugs which may cause localized amyloidosis after prolonged use (i.e., AIns and AEnf, respectively) commonly identified as abdominal subcutaneous masses at the injection site. In particular, self-assembled aggregation process of insulin is known to occur at certain conditions leading to impaired systemic absorption through the amyloid plaques and, in some cases, severe insulin resistance. Moreover, AIns can be misdiagnosed as systemic immunoglobulin-derived amyloidosis especially when the clinical context is unknown or the patient presents a monoclonal gammopathy. Enfuvirtide is a new antiretroviral agent termed “fusion inhibitor” and used for the treatment of HIV-1 infection. The injection site reactions to Enfuvirtide are frequent. Therefore, precise amyloid typing by immunohistochemistry (IHC) and/or mass spectrometry-based proteomics is required for diagnosis of iatrogenic amyloidosis and bears clinical significance.