Paraneoplastic dermatomyositis appearing after nivolumab therapy for gastric cancer: a case report

Abstract

Background While dermatomyositis is often associated with malignancy, several autoimmune diseases like myositis can be caused by immune checkpoint inhibitors. Differentially diagnosing malignancy-associated dermatomyositis or myositis caused by immune checkpoint inhibitors is sometimes difficult, particularly when a patient with malignancy shows the symptoms of myositis after checkpoint inhibitor administration. We experienced such a case in which we had difficulties in diagnosing paraneoplastic dermatomyositis or drug-associated myositis. In this case, all of our team initially assumed that the diagnosis was myositis caused by immune checkpoint inhibitors. However, it turned out finally that the diagnosis was paraneoplastic dermatomyositis. Because the diagnosis was unexpected, we report here. Case presentation We report the case of a 71-year-old Japanese man who developed clinical symptoms of myositis, such as muscle aches and weakness, after initiation of nivolumab therapy for his gastric cancer. He was initially diagnosed with nivolumab-induced myositis, because the myositis symptoms appeared after nivolumab administration, and nivolumab is known to trigger various drug-associated autoimmune diseases. However, according to his characteristic skin lesions, the type of muscle weakness, his serum marker profiles, electromyography of his deltoid muscle, and magnetic resonance imaging, he was finally diagnosed as having paraneoplastic dermatomyositis. Accordingly, treatment with intravenously administered corticosteroid pulse treatment, immunoglobulin injection, and tacrolimus was applied; his symptoms subsequently improved. However, to our regret, at day 142 after administration, he died due to rapid worsening of his gastric cancer. Conclusion Differentially diagnosing paraneoplastic dermatomyositis or drug-associated myositis caused by immune checkpoint inhibitors is difficult in some cases. The differential diagnosis is crucial because it influences the decision regarding the appropriateness of the use of immunosuppressive treatment against the autoimmune diseases as well as the decision regarding the appropriateness of the continuous use of immune checkpoint inhibitors against the primary cancers. Because subclinical autoimmune disease may become overt after administering immune checkpoint inhibitors, non-apparent autoimmune diseases, which have already existed, should also be considered to avoid the delay of appropriate treatment, when symptoms of autoimmune diseases are recognized.

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

“…On the other hand, a de novo condition with features of myopathy/myositis has been described in recent years following ICI therapy in cancer patients [6,9,13]. The differentiation between paraneoplastic and ICI-induced myositis can be sometimes difficult [35]. Prospective studies [10][11][12] report only few cases of ICI-induced myositis, indicating a low prevalence of this condition.…”

Refractory Immune Checkpoint Inhibitor-Induced Colitis Improved by Tacrolimus: A Case Report

“…However, when IFX and VDZ prove ineffective, as in this case, the next course of action remains unclear for the most part. Regarding the effectiveness of immunosuppressants (e.g., tacrolimus used for this study) against irAEs, there have been reports of remission reached by tacrolimus against skin toxicity [ 23 ] or improvement in PSL/IFX-resistant nivolumab-induced colitis by oral administration of cyclosporine [ 24 ]. For the patient described herein, refractory ICI-related colitis was improved using tacrolimus.…”

Anti-transcription intermediary factor 1 gamma (TIF1γ) antibody-positive dermatomyositis associated with ascending colon cancer: a case report and review of the literature

“…The treatment for cancer in the case reports included surgical resection and chemoradiotherapy. Immune checkpoint inhibitors such as nivolumab and ipilimumab were reported in three cases [ 22 , 23 , 26 ]. One report noted that only surgical removal of the tumor resulted in the disappearance of the skin rash of DM [ 15 ].…”

“…Table 2 demonstrates this relationship. First, dysphagia is a major complication of DM because it leads to oral feeding difficulties and malnutrition [ 22 ]. Table 2 (a) shows the relationship between dysphagia and outcome; no significant difference ( P = 0.12; Pearson’s chi-square test) was noted between them, although the presence of dysphagia tended to be associated with a worse outcome.…”

“…In fact, patients with early-stage disease could firstly undergo surgery according to the cancer stage in Table 1 . Conversely, the patients with initial internal treatment include unresectable cancers, in which surgical resection itself is not applicable at the point of diagnosis [ 9 , 13 , 20 , 22 , 24 , 26 ]. Table 2 (c) shows the relationship between the maximum creatine kinase level and outcome.…”