Adult Still’s disease fatal evolution complicated with Macrophagic activation syndrome

Background:The coronavirus disease 2019 (COVID-19), caused by a novel corona virus named SARS-CoV-2, has emerged as a global pandemic. Severe inflammatory process is one of main pathogenesis of COVID-19 and this involves cytokine storm along with overactivation of macrophage. On another front, cytokine storm with macrophage activation is frequently observed in various connective tissue diseases including dermatomyositis with positive antimelanoma differentiation-associated protein 5 (anti-MDA5) autoantibodies and adult Still’s disease. Macrophage activation during inflammatory states is partially characterized by an increased serum ferritin levels and hyperferritinaemia and characteristics shared by the three diseases are a topic of interest to rheumatologists, however, no study has evaluated anti-MDA5-positive dermatomyositis and adult Still’s disease in comparison to COVID-19.Objectives:The aim of this study was to highlight the homology and heterogeneity of COVID-19, anti-MDA5 dermatomyositis, and adult Still’s disease by comparing clinical pictures of each disease in order to discuss their respective pathogeneses.Methods:We reviewed consecutive, newly diagnosed, untreated patients with COVID-19, anti-MDA5 dermatomyositis, or adult Still’s disease. We compared their clinical, laboratory, and radiological characteristics, including the prevalence of macrophage activation syndrome and lung involvement in each disease.Results:The numbers of patients with COVID-19, anti-MDA5 dermatomyositis, and adult-onset Still’s disease with hyperferritinaemia (serum ferritin ≥ 500ng/dL) who were included for main analysis were 22, 14, and 59, respectively. COVID-19 and adult Still’s disease both featured hyperinflammatory status, such as high fever and elevated serum C-reactive protein, whereas COVID-19 and anti-MDA5 dermatomyositis both presented with severe interstitial lung disease and hypoxaemia. While two-thirds of the patients in each group met the criteria for macrophage-activated syndrome that is used in systemic juvenile idiopathic arthritis, the HScore, an indicator of haemophagocytic lymphohistiocytosis, was low in anti-MDA5 dermatomyositis and COVID-19 even in severe or critical cases. The findings of chest computed tomography were similar between COVID-19 and anti-MDA5 dermatomyositis (Figure 1).Conclusion:COVID-19 shared clinical features with rheumatic diseases characterised by hyperferritinaemia, including anti-MDA5 dermatomyositis and adult Still’s disease. These findings should be investigated further in order to shed light on the pathogenesis of not only COVID-19 but also the aforementioned rheumatic diseases.References:[1]Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. (2020) 395: 1033-4.[2]Gono T, Sato S, Kawaguchi Y, et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford). 2012; 51(9):1563-70.Figure 1.Imaging characteristics of chest CT scans in patients with COVID-19, anti-MDA5 dermatomyositis, and adult Still’s disease A)Bilateral ground-glass and consolidative opacities with peripheral distribution in COVID-19. B)Bilateral ground-glass opacities with peripheral consolidations in anti-MDA5 dermatomyositis. C)Pleural effusion with pleural thickening on the left side in adult Still’s disease.Disclosure of Interests:Yasushi Kondo: None declared., Yuko Kaneko: None declared., Hisoshi Takei: None declared., Hiroya Tamai: None declared., Tsutomu Takeuchi Grant/research support from: received research grants outside the submitted work from Abbvie, Astra Zeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Novartis, Takeda Pharmaceutical, Abbott Japan Co., Ltd., Astellas Pharma, Ltd., Daiichi Sankyo, Pfizer, Sanofi–Aventis, Santen Pharmaceutical, Teijin Pharma Ltd., Asahikasei Pharma Corp., SymBio Pharmaceuticals Ltd., Celtrion, Nipponkayaku Co. Ltd., Eli Lilly Japan, and Taisho Toyama Pharmaceutical.

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FRI0505 TOCILIZUMAB DISCONTINUATION AFTER REMISSION ACHIEVEMENT IN PATIENTS WITH ADULT STILL’S DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3491 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 851.2-851

Author(s):

H. Tamai ◽

Y. Kaneko ◽

T. Takeuchi

Keyword(s):

Laboratory Data ◽

Good Control ◽

Still’S Disease ◽

Median Dose ◽

Chugai Pharmaceutical ◽

Still's Disease ◽

Adult Still's Disease ◽

The Mean ◽

Recurrence Group ◽

Observation Period

Background:The efficacy of tocilizumab, an interleukin (IL)-6 receptor inhibitor, has been proved in patients with adult Still’s disease on suppressing systemic inflammation and decreasing glucocorticoid dose. However, whether tocilizumab can be discontinued after remission achievement is unclear.Objectives:To clarify the possibility of tocilizumab discontinuation in patients with adult Still’s disease who achieved remission with tocilizumab.Methods:Consecutive patients with adult Still’s disease diagnosed according to the Yamaguchi’s criteria in our hospital from April 2012 until September 2019 were retrospectively reviewed. Patients who were in good control with tocilizumab were included in the analysis, and their clinical courses were collected from their medical charts. Patients were divided according to the presence of recurrence after tocilizumab discontinuation and compared.Results:Among 42 patients with adult Still’s disease who had a history of intravenous tocilizumab of 8mg/kg use, 13 patients discontinued tocilizumab following a good disease control. During the mean observation period of 26.4 months, six patients (46%) remained in remission while seven patients (54%) developed recurrence after tocilizumab discontinuation. The sex and the mean observation period were not different between the patients with recurrence and those without (71% vs 50%, p=0.43; 27.3 months vs 25.4 months, p=0.93, respectively), but the age at tocilizumab discontinuation tended to be higher in the recurrence group than the non-recurrence group (64.0 years vs 46.5 years, p=0.08). The disease activity including swollen joint counts and laboratory data at tocilizumab discontinuation were comparable between the two groups (serum ferritin levels, 88 ng/mL vs 122 ng/mL, p=0.67). While the duration of tocilizumab use was not different between the two groups (29.4 months vs 39.5 months, p=0.40), the mean interval of tocilizumab infusion at tocilizumab discontinuation in the recurrence group was 3.6 weeks, shorter than the 6.7 weeks in the non-recurrence group (p=0.03). The median dose of prednisolone at tocilizumab discontinuation was 5.0 mg/day in the recurrence group and 0.0 mg/day in the non-recurrence group (p=0.06). In the recurrence group, the duration from the last tocilizumab administration to recurrence was 7.8 months, and the median dose of prednisolone at recurrence was 5.0 mg/day.Conclusion:Patients with adult Still’s disease remaining in remission with a longer interval of tocilizumab administration and a lower dose of prednisolone was likely to succeed in withdrawal of tocilizumab.Disclosure of Interests:Hiroya Tamai: None declared, Yuko Kaneko Speakers bureau: Dr. Kaneko reports personal fees from AbbVie, personal fees from Astellas, personal fees from Ayumi, personal fees from Bristol-Myers Squibb, personal fees from Chugai, personal fees from Eisai, personal fees from Eli Lilly, personal fees from Hisamitsu, personal fees from Jansen, personal fees from Kissei, personal fees from Pfizer, personal fees from Sanofi, personal fees from Takeda, personal fees from Tanabe-Mitsubishi, personal fees from UCB, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.

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