title: LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar cardiomyopathy: a study of 3 cases.
abstract: Autophagic vacuolar cardiomyopathy is an underrecognized, 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-induced and colchicine-induced autophagic vacuolar skeletal myopathies. In the current study, we use 3 cases of CQ-induced or HCQ-induced cardiomyopathy and 1 HCQ-treated control case to show that the same two markers can be used to diagnose autophagic vacuolar cardiomyopathies by light microscopy. CQ-induced 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 misdiagnosed patients, thus increasing the likelihood of favorable clinical outcomes.
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Brianne H
authors.initials: BH
authors.lastname: Daniels
authors.forename: Rodney D
authors.initials: RD
authors.lastname: McComb
authors.forename: Bret C
authors.initials: BC
authors.lastname: Mobley
authors.forename: Sakir Humayun
authors.initials: SH
authors.lastname: Gultekin
authors.forename: Han S
authors.initials: HS
authors.lastname: Lee
authors.forename: Marta
authors.initials: M
authors.lastname: Margeta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000009:adverse effects*; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism; D002738:Chloroquine / Q000009:adverse effects; D003951:Diagnostic Errors / Q000517:prevention & control; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D000071456:Sequestosome-1 Protein; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000962:Antimalarials; D015415:Biomarkers; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D006886:Hydroxychloroquine; D002738:Chloroquine