Myocarditis and myositis/myasthenia gravis overlap syndrome induced by immune checkpoint inhibitor followed by esophageal hiatal hernia: A case report and review of the literature

Abstract

Immunotherapy with programmed death 1 (PD-1) inhibitor has shown activity as first- or second-line treatment for various metastatic human malignancies. Immune-related adverse events (irAEs) are now well-described, and most organ sites are potentially influenced, but the prevalence of myocarditis and myositis/myasthenia gravis (MG) overlap syndrome following esophageal hiatal hernia induced by immunotherapy is rarely reported. Here, we describe a 71-year-old woman with a progressed unresectable extrahepatic cholangiocarcinoma and biliary obstruction. She had no prior history of muscle weakness and neuromuscular disease with a normal body mass index. She was treated with sintilimab as a rescue regimen of immunotherapy. After the first cycle of treatment, she experienced a grade 4 myopathy including simultaneous myositis, myalgia, and myocarditis due to multiple injuries in her cardiac, skeletal, and ocular muscles. She had elevated levels of creatine kinase (CK), cardiac troponin I, and myoglobin (MYO), but MG and myositis-specific and myositis-related antibodies were negative. Immunotherapy was discontinued and pulse high-dose methylprednisolone with a slow tapering and intravenous immunoglobulin (IVIG) was initiated. Two weeks later, the patient’s clinical presentation improved significantly. A subsequent cardiac magnetic resonance (MR) examination revealed an old myocardial injury that may be a result of immune-related cardiac toxicity. In the third month following the PD-1 inhibitor therapy, she restarted systemic chemotherapy in combination with an anti-angiogenic agent but without immunotherapy. Half a year later, she complained of repeated abdominal distension and radiographic examinations and endoscopy showed a clinically confirmed diagnosis of sliding hiatal hernia of the esophagus and gastroesophageal reflux disease. Due to mild symptoms associated with gastroesophageal reflux, she was suggested close monitoring with acid secretion blockade rather than immediate surgical intervention. The severity for patients with myositis and myocarditis accompanied without MG is similar to those with MG. Considering the use of PD-1 inhibitors is increasing in cancer patients, physicians should therefore pay more attention to immunotherapy-induced myocarditis with myositis/MG overlap syndrome. Since we hypothesize diaphragmatic hiatal hernia as a potential consequence of immunotherapy-induced myositis, reports on hiatal hernias subsequent to immunotherapy-induced myositis are needed.

Clinical characteristics and management of immune checkpoint inhibitor-related cardiotoxicity: A single-center experience

“…The subclinical type of cardiotoxicity manifests as a variety of abnormal biomarkers (mainly TnI, CK, BNP) with no symptoms. ICI-induced asymptomatic myocarditis can occur with concurrent myositis or myasthenia gravis in some cases ( 5 , 6 , 34 ). In the present study, the incidence of cardiac irAEs was as high as 2.46% (subclinical type 0.82%; severe type 1.64%) in the single center.…”

“…Due to the low frequency and subtle features of the initial clinical presentations of cardiac irAEs, these cases are usually missed on subsequent initial presentation, despite being obvious, or are underappreciated due to the nonspecific clinical manifestations ( 5 ). In addition, clinical risk factors associated with ICI-related cardiotoxicities have not been identified, although patients with the combination of CTLA-4 and PD-1 inhibition are prone to develop serious cardiotoxicities ( 6 ). Here, we presented a series of ICI-related cardiotoxicity cases at a single center.…”