Immune myopathy with large histiocyte-related myofiber necrosis

Neurology. 2019 Apr 9;92(15):e1763-e1772. doi: 10.1212/WNL.0000000000007260. Epub 2019 Mar 20.


Objective: To describe the features of a new, pathologically distinctive, acquired myopathy with an unusual pattern of scattered necrotic muscle fibers that are neighbored, surrounded, or invaded, by large, often multinucleated, histiocytic cells.

Methods: Retrospective review of records and muscle pathology of 4 patients.

Results: Clinical features common to our patients included muscle pain and proximal, symmetric, moderate to severe, weakness in the arms and legs progressing over 1-4 weeks. Patients had other associated systemic disorders, including anemia in all, and hemophagocytic lymphohistiocytosis, hepatic disease, Raynaud phenomenon, metastatic cancer, and cardiomyopathy, in 1 patient each. Serum creatine kinase (CK) levels at presentation were very high, ranging from 10,000 to 102,000 U/L. Three patients improved within 3 months after treatment. Muscle pathology included scattered necrotic muscle fibers with cytoplasm that stained for C5b-9 complement, especially around fiber peripheries, pale on nicotinamide adenine dinucleotide and often dark on hematoxylin & eosin. Large, often multinucleated, cells with features of histiocytes, including anatomical features on electron microscopy and immunostaining for major histocompatibility complex Class I and histiocyte markers (HAM56, CD68, CD163, and S100), were usually closely apposed to the surface of, or invaded, necrotic myofibers.

Conclusions: Patients with large-histiocyte-associated myopathy (LHIM) had a subacute onset of proximal predominant weakness, associated systemic disorders, very high serum CK, and a pathologically distinctive pattern of large histiocyte-associated muscle fiber necrosis. LHIM may be caused by an autoimmune, histiocyte-mediated attack directed against muscle fibers.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Creatine Kinase / blood
  • Disease Progression
  • Female
  • Histiocytes / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / pathology*
  • Muscle Weakness / etiology
  • Muscular Diseases / immunology*
  • Muscular Diseases / pathology*
  • Musculoskeletal Pain / etiology
  • Necrosis
  • Retrospective Studies


  • Biomarkers
  • Creatine Kinase