Abstract
Objective To provide evidence that idiopathic inflammatory myopathy (IM) with myasthenia gravis (MG) frequently shows thymoma association and polymyositis (PM) pathology and shares clinicopathologic characteristics with IM induced by immune checkpoint inhibitors (ICIs).
Methods We analyzed the clinicopathologic features of 10 patients with idiopathic IM and MG identified in 970 consecutive patients with biopsy-proven IM.
Results Seven patients (70%) had thymoma. IM and MG were diagnosed with more than 5-year time difference in 6 thymomatous patients and within 1 year in 1 thymomatous and 3 nonthymomatous patients. Seven thymomatous patients showed rhabdomyolysis-like features with respiratory failure (4/7), dropped head (3/7), cardiac involvement (2/7), and positive anti–acetylcholine receptor (anti-AChR) and anti-titin antibodies (7/7 and 4/6, respectively) but rarely showed ocular symptoms (2/7) or decremental repetitive nerve stimulation (RNS) responses (1/7) at IM diagnosis. Three nonthymomatous patients showed acute cardiorespiratory failure with rhabdomyolysis-like features (1/3), positive anti-AChR and anti-titin antibodies (3/2 and 2/2, respectively), and fluctuating weakness of the skeletal muscle without ocular symptoms (3/3). Muscle pathology showed a PM pathology with infiltration of CD8-positive CD45RA-negative T-lymphocytes (9/9), scattered endomysial programmed cell death 1 (PD-1)–positive cells (9/9), and overexpression of programmed cell death ligand 1 (PD-L1) on the sarcolemma of muscle fibers around the infiltrating PD-1–positive cells (7/9).
Conclusion Rhabdomyolysis-like features, positive anti-AChR antibody without decremental RNS responses, and PD-L1 overexpression are possible characteristics shared by ICI-induced IM. Frequent thymoma association in patients with idiopathic IM and MG may suggest thymoma-related immunopathogenic mechanisms, including dysregulation of the immune checkpoint pathway.
Glossary
- anti-AChR=
- anti–acetylcholine receptor;
- CK=
- creatine kinase;
- CTLA-4=
- cytotoxic T-lymphocyte–associated protein 4;
- IBM=
- inclusion body myositis;
- ICI=
- immune checkpoint inhibitor;
- IM=
- inflammatory myopathy;
- MG=
- myasthenia gravis;
- MHC=
- major histocompatibility complex;
- MSA=
- myositis-specific autoantibody;
- PD-1=
- programmed cell death 1;
- PD-L1=
- programmed cell death ligand 1;
- PM=
- polymyositis;
- PSL=
- prednisolone;
- RNS=
- repetitive nerve stimulation;
- SFEMG=
- single-fiber electromyogram
Footnotes
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.
The Article Processing Charge was funded by the authors.
- Received September 4, 2018.
- Accepted in final form October 24, 2018.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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