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LC3 and p62 as Diagnostic Markers of Drug-induced Autophagic Vacuolar Cardiomyopathy

  • Author(s): Daniels, Brianne H
  • McComb, Rodney D
  • Mobley, Bret C
  • Gultekin, Sakir Humayun
  • Lee, Han S
  • Margeta, Marta
  • et al.
Abstract

Autophagic vacuolar cardiomyopathy is an under recognized, but potentially fatal, complication of treatment with chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), which are used as therapy for  malaria and common connective tissue disorders. Currently, the diagnosis of autophagic vacuolar cardiomyopathy is established through an endomyocardial biopsy and requires electron microscopy, which is not widely available and has a significant potential for sampling error. Recently, we have reported that immunohistochemistry for autophagic  markers LC3 and p62 can replace electron microscopy in the diagnosis of HCQ- and  colchicine-induced autophagic vacuolar skeletal myopathies. In the current study, we use three cases of CQ- or HCQ-induced cardiomyopathy and one HCQ-treated control case to show that the same twomarkers can be used to diagnose autophagic vacuolar cardiomyopathies by light microscopy. CQ- or HCQ-induced autophagic vacuolar cardiomyopathy is not universally fatal, but successful treatment requires early detection. By lowering the barriers to diagnosis, the application of these immunohistochemical markers will decrease the number of misdiagnosedpatients, thus increasing the likelihood of favorable clinical outcomes.

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