Pembrolizumab-induced Ocular Myasthenia Gravis with Anti-titin Antibody and Necrotizing Myopathy

Onda, Asako; Miyagawa, Shuji; Takahashi, Naoko; Gochi, Mina; Takagi, Masamichi; Nishino, Ichizo; Suzuki, Shigeaki; Oishi, Chizuko; Yaguchi, Hiroshi

doi:10.2169/internalmedicine.1956-18

Cited by 27 publications

(13 citation statements)

References 11 publications

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“…It is also common with concomitant myositis and myocarditis and high levels of serum CK along with ICI-induced MG [3, 7]. Positivity for anti-titin has previously been reported for pembrolizumab-induced MG combined with necrotizing myositis [11]. Clinical signs of MG were difficult to identify in the predominant clinical picture of polymyositis in our patient.…”

Section: Discussionmentioning

confidence: 69%

Immune Checkpoint Inhibitor-Induced Polymyositis and Myasthenia Gravis with Fatal Outcome

et al. 2020

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We here report on a 74-year-old man diagnosed with a pT3cN0 <i>BRAF</i>-mutated and mismatch repair-deficient adenocarcinoma in the colon ascendens and 3 liver metastases. After hemicolectomy, the patient received treatment with the PD-1 inhibitor pembrolizumab. Three weeks later (on day 22), laboratory tests showed leukocytosis and an increase in transaminases; immune checkpoint inhibitor (ICI)-induced hepatitis was suspected and prednisolone therapy was initiated. On day 29, the patient was acutely hospitalized due to dyspnea, somnolence and walking difficulties. Dysarthria, hoarseness, muscle pain and weakness had developed and the dose of prednisolone was increased. Serum levels of lactate dehydrogenase, creatine kinase and myoglobin were increased and ICI-induced myositis was suspected. Antibodies against acetylcholine receptor and titin were present, indicating myasthenia gravis. Eventually, bulbar myopathy developed, including dysarthria and dysphagia, and the patient could no longer attain saturation without oxygen. The patient was transferred to the intensive care unit, intubated and given methylprednisolone, intravenous immunoglobulins and infliximab. The patient developed carbon dioxide retention and died on day 39. Microscopical examination of the intercostal musculature, diaphragm, cervical musculature and tongue showed inflammatory infiltration and fibrosis consistent with a pronounced myositis. In the liver, microscopical examination did not show metastases from colorectal cancer but instead a hepatocellular cancer. The cause of death was determined as respiratory insufficiency due to polymyositis. In conclusion, ICIs may induce myositis combined with neurological immune-related adverse events. In patients developing muscle weakness and pain under ICI therapy, myositis should be suspected.

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Section: Discussionmentioning

confidence: 69%

Immune Checkpoint Inhibitor-Induced Polymyositis and Myasthenia Gravis with Fatal Outcome

et al. 2020

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“…[29] Extraocular muscle involvement in IRAE can be due to inflammatory myopathies [30,31] that sometimes mimic thyroid orbitopathy [32] or may present as autoimmune antibody-mediated ocular myasthenia gravis. [33] Reported IRAE autoimmune antibodies related to myasthenia gravis include antiacetylcholine receptor and antititin receptor antibodies. [33] Discontinuation of the TCT along with steroids and intravenous immunoglobulin may be considered.…”

Section: Immune Checkpoint Inhibitors (Icis)mentioning

confidence: 99%

“…[33] Reported IRAE autoimmune antibodies related to myasthenia gravis include antiacetylcholine receptor and antititin receptor antibodies. [33] Discontinuation of the TCT along with steroids and intravenous immunoglobulin may be considered. [34] Other reported IRAE include uveitis related ocular hypotony with secondary steroid-induced cataracts, [35] uveitis and papillitis, [36] bilateral bird shot chorioretinopathy, [37] paraneoplastic retinopathy, [38] enophthalmos, [39] Miller Fisher syndrome.…”

Section: Immune Checkpoint Inhibitors (Icis)mentioning

confidence: 99%

Targeted Cancer Therapy and Its Ophthalmic Side Effects: A Review

Bindiganavile

Bhat

Lee

et al. 2021

Journal of Immunotherapy and Precision Oncology

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“…Additionally, MG very rarely may manifest with symptomatology exclusive to the ocular muscles, known as ocular myasthenia gravis (OMG). Although there have been multiple post-surveillance case reports of patients receiving anti-PD-1 therapy presenting with new or exacerbated MG, to date, there have only been eight reported cases of anti-PD-1 associated OMG; five of which were a direct result of pembrolizumab [ 4 - 9 ]. A case of pembrolizumab-induced OMG is described.…”

Section: Introductionmentioning

confidence: 99%

Pembrolizumab-Induced Ocular Myasthenic Crisis

Lorenzo¹,

Fitzpatrick²,

Campdesuner³

et al. 2020

Cureus

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Pembrolizumab, one of many novel immune checkpoint inhibitors (ICPi), is a monoclonal antibody that enhances immunity against cancer cells. Extensive escalation in immune activity predisposes to unsought immune-related adverse events. Due to progressive mesothelioma, a 67-year-old man was referred to the research unit and enrolled in a clinical trial with a cluster of differentiation (CD) 27 chemotherapeutic agent. He began crossover treatment and received just two doses of pembrolizumab, 33 and 16 days prior to admission. He subsequently presented to the emergency department with three days of acute onset severe diplopia and a drooping left eye. Acetylcholine receptor (AChR) antibodies returned positive at 13.9 nmol/L, and a diagnosis of ocular myasthenia gravis (OMG) was made. During his hospitalization, the patient was managed with methylprednisolone 80 mg intravenously daily, with conversion to prednisone 60 mg by mouth daily at time of discharge. Neuro-ophthalmology consultation was sought in the outpatient setting, and the patient was started on pyridostigmine. He was readmitted two weeks later with symptoms of progressive diffuse weakness, unsteady gait, and dysphagia, all in the setting of persistent diplopia. Intravenous immunoglobulin (IVIG) was promptly initiated, in addition to the pyridostigmine previously initiated in the outpatient setting. Unfortunately, after three IVIG treatments, the patient had experienced little improvement in his symptoms, and therefore elected hospice care. Although ICPis have revolutionized the management of a multitude of malignancies, recognition of immune-related adverse events is of critical importance.

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Pembrolizumab-induced Ocular Myasthenia Gravis with Anti-titin Antibody and Necrotizing Myopathy

Cited by 27 publications

References 11 publications

Immune Checkpoint Inhibitor-Induced Polymyositis and Myasthenia Gravis with Fatal Outcome

Immune Checkpoint Inhibitor-Induced Polymyositis and Myasthenia Gravis with Fatal Outcome

Targeted Cancer Therapy and Its Ophthalmic Side Effects: A Review

Pembrolizumab-Induced Ocular Myasthenic Crisis

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