Immune checkpoint inhibitor-related myositis and myocarditis: diagnostic pitfalls and imaging contribution in a real-world, institutional case series

Alex Vicino; Andreas F Hottinger; Sofiya Latifyan; Sarah Boughdad; Fabio Becce; John O Prior; Thierry Kuntzer; Jean-Philippe Brouland; Vincent Dunet; Michel Obeid; Marie Théaudin

doi:10.1007/s00415-023-12134-x

Immune checkpoint inhibitor-related myositis and myocarditis: diagnostic pitfalls and imaging contribution in a real-world, institutional case series

J Neurol. 2024 Apr;271(4):1947-1958. doi: 10.1007/s00415-023-12134-x. Epub 2023 Dec 23.

Authors

Affiliations

¹ Nerve-Muscle Unit, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. alex.vicino@chuv.ch.
² Lundin Family Brain Tumor Center, Departments of Oncology and Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
³ Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵ Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶ Nerve-Muscle Unit, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁷ Pathology Institute, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁸ Immunology and Allergy Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

^# Contributed equally.

Abstract

Background: Immune checkpoint inhibitors (ICIs) are reshaping the prognosis of many cancers, but often cause immune-related adverse events (irAEs). Among neurological irAEs, myositis is the most frequently reported. Our aim is to describe clinical and non-clinical characteristics, treatment and outcome of all irMyositis (skeletal limb-girdle and/or ocular myositis) and irMyocarditis cases in our reference center.

Methods: We retrospectively enrolled all irMyositis/irMyocarditis patients seen between 2018 and 2022. We reviewed demographics, clinical characteristics, biological, neurophysiological, imaging workup, treatment and outcome.

Results: We included 14 consecutive patients. The most frequent treatments were pembrolizumab (35%) or ipilimumab-nivolumab combination (35%). Limb-girdle, ocular (non-fluctuating palpebral ptosis and/or diplopia with or without ophthalmoparesis) and cardiac phenotypes were equally distributed, overlapping in 40% of cases. Ocular involvement was frequently misdiagnosed; review of brain MRIs disclosed initially missed signs of skeletal myositis in one patient and ocular myositis in 3. Seven patients had other co-existing irAEs. When performed, myography showed a myogenic pattern. CK was elevated in 8/15 patients, troponin-T in 12/12 and troponin-I in 7/9 tested patients. ICI were discontinued in all cases, with further immunosuppressive treatment in nine patients. In most cases, neurological and cardiological outcome was good at last follow-up.

Conclusion: Myositis is a potentially severe irAE. Despite its heterogeneous presentation, some highly suggestive clinical symptoms, such as ocular involvement, or radiological signs should raise physicians' attention to avoid misdiagnosis. We thus recommend a multidisciplinary assessment (including complete neuromuscular evaluation) even in case of isolated myocarditis. Our series underlines the importance of an early diagnosis, since suspension of ICI and adequate treatment are usually associated with good functional outcome.

Keywords: Imaging; Immune-checkpoint-inhibitor; Immune-related-adverse-event; Myocarditis; Myositis.

Publication types

Review

MeSH terms

Antineoplastic Agents, Immunological* / adverse effects
Humans
Immune Checkpoint Inhibitors
Myocarditis* / chemically induced
Myocarditis* / complications
Myocarditis* / drug therapy
Myositis* / diagnosis
Retrospective Studies

Substances

Immune Checkpoint Inhibitors
Antineoplastic Agents, Immunological