Background The use of immune checkpoint inhibitors (ICIs) against programmed cell death protein -1 (PD-1), its ligand (PD-L1) and cytotoxic T- lymphocyte associated protein 4 (CTLA4) have been increasing. Immune induced myocarditis, myositis and myasthenia gravis are rare but potentially severe complications from these agents. Here we report 3 cases of ICI induced myocarditis, myositis, myasthenia gravis and transaminitis as a cluster, and highlights early diagnosis, prompt initiation of steroid sparing immunosuppressive therapy and multidisciplinary management.
Methods Three patients received anti-PD-1 ICIs developed cardiac, neuromuscular complications and transaminitis within 4 weeks after initiation. Clinical data were retrospectively reviewed from medical records.
Results All patients had elevated cardiac enzymes, developed complete heart block and underwent coronary catheterisation and pacemaker insertion. All patients developed myositis and myasthenia gravis (table 1) and were managed by multi-disciplinary team involving oncology, cardiology and neurology. Single-fibre electromyography was performed to confirm presence of myositis. One of three patients had positive acetylcholinesterase antibody, anti- muscle specific kinase antibody was negative in all cases. All patients developed grade 2–3 transaminitis with normal bilirubin. All patients received high-dose steroids. Steroid sparing therapy including intravenous immunoglobulin and mycophenolate mofetil were used early in 2 cases and was associated with rapid recovery of toxicities.
Conclusions ICI induced myocarditis can be associated with myositis, myasthenia gravis and transaminitis. A high index of suspicion, comprehensive investigations and early involvement of multi-disciplinary teams are key to early accurate diagnosis. In steroid refractory cases, we propose early initiation of steroid sparing immunosuppressive therapy after 3 days.
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