Search

Dermatomyositis (DM) is associated with interstitial lung disease (ILD) and malignancy. However, the coexistence of ILD and malignancy (DM-ILD-malignancy) is rare, and limited information exists regarding its management. Herein, we report the case of a 70-year-old man who developed DM with rapidly progressive ILD and advanced gastric cancer and provide a literature review of managing DM-ILD-malignancy. The patient presented with typical DM skin rashes and shortness of breath, which worsened within 1 month, without muscular symptoms. Additionally, the patient tested negative for myositis-specific autoantibodies (MSAs). Computed tomography revealed ILD and advanced gastric cancer, which was confirmed on endoscopic examination to be a poorly differentiated adenocarcinoma. Although the patient's ILD progressed rapidly, surgical treatment of the cancer was prioritized. Prednisolone (PSL) 0.5 mg/kg was initiated 3 days before surgery and increased to 1 mg/kg at 7 days postoperative. Remarkable improvement in the skin rash and ILD was observed, and the PSL dose was tapered without immunosuppressants. A literature review revealed that anti-melanoma differentiation-associated gene 5 and anti-aminoacyl transfer RNA synthetase antibodies are the predominant MSAs in DM-ILD-malignancy, and the optimal treatment should be determined based on several factors, including ILD patterns, and malignancy type and stage. In particular, lung cancer may be a risk factor for the acute exacerbation of ILD, and preceding immunosuppression would be useful. Furthermore, prioritizing surgery for gastric cancer is effective because of its paraneoplastic nature., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The induction of autoimmune diseases during tumour necrosis factor-alpha inhibitor (TNFi) usage has been described. Herein, we report a rare case of a 49-year-old woman with antimelanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM), which developed 5 weeks after the introduction of an etanercept biosimilar to rheumatoid arthritis (RA). Four of the five known cases, including ours, of anti-MDA5Ab-positive DM complicated with RA revealed anti-MDA5Ab-positive DM following TNFi usage. When patients with RA are diagnosed with interstitial lung disease during TNFi usage, anti-MDA5 Ab-positive DM could be a differential diagnosis., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: To evaluate the efficacy and safety of ustekinumab (UST) in a multicentre, randomised, double-blind, placebo-controlled trial in adult Japanese patients with active polymyositis (PM) and dermatomyositis (DM)., Methods: Fifty-one Japanese adults diagnosed with active PM/DM who did not respond adequately to one or more standard-of-care treatments were randomised 1:1 to receive UST (n=25) or placebo (n=26). Participants received body weight-range based intravenous administration of UST (6 mg/kg) or placebo at week 0 followed by 90 mg subcutaneous (SC) administration of UST or placebo every 8 weeks from week 8 to week 24. At week 24, placebo group crossed over to receive body weight-range based intravenous administration of UST, and thereafter, all participants received/were to receive SC administration of UST 90 mg every 8 weeks (week 32 through to week 72). The primary efficacy endpoint was the proportion of participants who achieved minimal improvement (≥20) in the International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at week 24., Results: No statistically significant difference was seen in the proportion of participants who achieved minimal improvement (≥20) in IMACS TIS at week 24 between the treatment groups (UST 64.0% vs placebo 61.5%, p=0.94) based on the primary estimand of the primary endpoint analysis., Conclusions: UST was safe and well tolerated but did not meet the primary efficacy endpoint in adult Japanese participants with active PM/DM based on the primary analysis at week 24 in the study., Trial Registration Number: NCT03981744., Competing Interests: Competing interests: KK has received consulting fee as medical advisor, honoraria/ speaking fees and support for conducting clinical studies (paid to the hospital) from Janssen. TI has received honoraria/ speaking fees from Asahi Kasei, Astellas, Boehringer Ingelheim, Janssen, and Ono Pharmaceuticals and support for conducting clinical studies (paid to the hospital) from Janssen. TG has received honoraria/speaking fee from Asahi Kasei, Astellas, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eisai, Janssen, MBL, Nippon Shinyaku, Pfizer, and Ono Pharmaceuticals and support for conducting clinical studies (paid to the hospital) from Janssen. YT, HO, RZ, MA and KN are employees of Janssen Pharmaceuticals. HO and KY are Janssen Pharmaceuticals employees and shareholders of Johnson & Johnson., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Anti-melanoma differentiation-associated protein-5 (MDA5) autoantibodies (Abs) are associated with rapidly progressive interstitial lung disease (RP-ILD) in dermatomyositis (DM). Because the addition of plasma exchange (PE) and rituximab (RTX) to triple therapy is inadequate in severe cases, we treat such cases with intensive induction therapy (IIT) combining all these options with tofacitinib (TOF). In this study, we investigated the poor prognostic factors and the efficacy and safety of IIT., Methods: Thirty-three patients diagnosed with anti-MDA5 Ab-positive DM in our institution between 2014 and 2021 were included. The clinical characteristics of poor prognosis were retrospectively analysed using principal component analysis (PCA), and the outcomes of IIT were analysed in terms of survival, assessed using the Kaplan-Meier test, and adverse events., Results: Although triple therapy with RTX, PE, or intravenous immunoglobulin was administered before the introduction of IIT, eight of 12 RP-ILD cases with a ferritin level >400 ng/mL (mean, 2,342) died within a median of 2.5 months. PCA revealed distinct clusters for prognosis, and age and serum ferritin were leading predictors of the prognosis. IIT, consisting of combinations of triple therapy with higher doses of methylprednisolone, PE, RTX, and TOF, was applied to eight patients (mean ferritin, 3,558). Although two patients died even with these regimens, a significant improvement in survival was documented. Several IIT-related adverse events were observed, including viral and fungal infections and cytopenia., Conclusions: IIT significantly improved the survival of patients with severe anti-MDA5 Ab-positive RP-ILD. Although infections are noted, their benefits outweigh the risks in younger patients with high serum ferritin levels.

Objectives: To assess the efficacy and safety of branched chain amino acids (BCAAs) in the treatment of PM/DM prior to official approval of their use in Japan., Methods: Treatment naïve adults with PM/DM were enrolled in a randomized, double-blind trial to receive either TK-98 (drug name of BCAAs) or placebo in addition to conventional treatment. After 12 weeks, patients with an average manual muscle test (MMT) score <9.5 were enrolled in an open label extension study for a further 12 weeks. The primary endpoint was the change of the MMT score at 12 weeks. The secondary endpoints were the clinical response and the change of functional index (FI)., Results: Forty-seven patients were randomized either to the TK-98 (n = 24) or placebo (n = 23) group. The changes of MMT scores at 12 weeks were 0.70 (0.19) [mean (s.e.m.)] and 0.69 (0.18), respectively (P = 0.98). Thirteen patients from the TK-98 group and 12 from the placebo group were enrolled in the extension study. The MMT scores in both groups improved similarly. The increase of the FI scores of the shoulder flexion at 12 weeks was significantly greater in the TK-98 group [27.9 (5.67) vs 12.8 (5.67) for the right shoulder flexion, and 27.0 (5.44) vs 13.4 (5.95) for the left shoulder; P < 0.05]. Frequencies of adverse events up to 12 weeks were similar., Conclusion: BCAAs showed no effect on the improvement of the muscle strength evaluated by MMT and the clinical response. However, they were partly effective for improving dynamic repetitive muscle functions., Trial Registration: UMIN-CTR Clinical Trial, https://center6.umin.ac.jp/, UMIN000016233., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Although pregnancy is an important risk factor for autoimmune rheumatic diseases, little is known regarding the association between pregnancy and dermatomyositis (DM) or polymyositis (PM). Herein, we present two patients with DM that developed during the perinatal period. The first patient was positive for anti-aminoacyl synthetase (ARS) antibody and developed DM in the 14th week of pregnancy. Despite treatment, her foetus died of intrauterine growth restriction in the 27th week. The second patient was positive for anti-melanoma differentiation-associated gene 5 (MDA-5) antibody and developed DM 1 week after miscarriage at 9 weeks of gestation. The patient developed severe interstitial pneumonia, and intensive therapy including tofacitinib and rituximab administration was required. Our cases and a literature review revealed that various myositis-specific autoantibodies, including anti-ARS, anti-Mi-2, anti-TIF-1γ, and anti-MDA-5, are associated with DM and PM triggered by pregnancy. We also found that delay in commencing treatment in case of active disease including myositis and interstitial pneumonia, and poor response to corticosteroids were related to poor foetal outcomes in DM and PM. Although rare in pregnant women, it is critical to consider the possibility of DM and PM in patients presenting with rash, fever, weakness, and cough, and testing for myositis-specific autoantibodies is recommended., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The aims of this study were to clarify the long-term outcome of patients with polymyositis and dermatomyositis (PM/DM) and to elucidate prognostic factors using statistical analysis., Methods: We enrolled patients with PM/DM who visited our department between 1990 and 2014. Diagnoses of PM/DM and clinically amyopathic DM were based on the definitions of Bohan and Peter, and Sontheimer, respectively. We also obtained clinical data, such as age of onset, sex, medications, and presence of interstitial lung disease and malignancies, as well as laboratory tests, including the values of creatine kinase, KL-6, and ferritin. The follow-up was conducted until June 2014., Results: A total of 124 patients (PM: 46, DM: 78) were enrolled. The mean age of onset was 53.5 years, and females were predominant (64.5%). Overall survival rates were 93%, 86%, and 78% for 1, 5, and 10 years, respectively. The survival rates were significantly lower in patients with higher age of onset, with malignancies, and with hyperferritinemia in univariate analysis; however, multivariate analysis identified age of onset and serum ferritin as the most significant prognostic factors., Conclusions: Our study indicates that when age of onset and serum ferritin are used in combination, we can predict prognosis of patients with PM/DM.