Tocilizumab and rituximab for anti-MDA-5 positive amyopathic dermatomyositis complicated with macrophage activation syndrome and progressive fibrosing interstitial lung disease

Background:Adult-onset still’s disease (AOSD) is a systemic inflammatory condition characterized by fevers, polyarthritis, skin rashes and increased leukocyte and neutrophil counts [1]. Sometimes life-threatening complications such as macrophage activation syndrome (MAS), disseminated intravascular coagulopathy (DIC) can be occurred without response to glucocorticoid and disease-modifying antirheumatic drugs (DMARDs).Objectives:To describe an AOSD patient with life-threatening interstitial lung disease (ILD) and MAS response to tocilizumab.Methods:This is a case report at our medical practice.Results:A 43-year-old man was hospitalized for a 2-week history of fever accompanying skin rashes, polyarthritis, sore throat, leukocytosis (the maximum leukocyte count 37.25×109/L with 89.9% neutrophils), elevated levels of C-reactive protein (190.9mg/L) and ferritin level was very high (>15000ng/ml), Several antibiotics were consequently used, but fever was on going. Chest CT displayed diffuse interstitial lung disease. Infectious diseases and lymphoma were excluded and AOSD with ILD was diagnosed. However, MAS occurred the 20 days later after the pulse of intravenous MP (MP 500mg×3days) following MP 40 mg/day, which cannot stop the situation deteriorating. The minimum total white blood cells, hemoglobin and platelets went down to 0.25×109/l, 53g/l and 18×109/l. Finally, tocilizumab rescued this patient from desperation.Conclusion:Tocilizumab was effective in AOSD with life-threatening ILD and MAS.References:[1]E. Feist, S. Mitrovic, and B. Fautrel, Mechanisms, biomarkers and targets for adult-onset Still’s disease. Nat Rev Rheumatol 14 (2018) 603-618.Disclosure of Interests:None declared

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Serum proteome analysis of systemic JIA and related pulmonary alveolar proteinosis identifies distinct inflammatory programs

10.1101/2021.01.20.21250141 ◽

2021 ◽

Author(s):

Guangbo Chen ◽

Gail Deutsch ◽

Grant Schulert ◽

Hong Zheng ◽

SoRi Jang ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Lung Disease ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Pulmonary Alveolar Proteinosis ◽

Systemic Juvenile Idiopathic Arthritis ◽

List Type ◽

New Findings ◽

Alveolar Proteinosis ◽

Activation Syndrome

AbstractObjectivesRecent observations in systemic Juvenile Idiopathic Arthritis (sJIA) suggest an increasing incidence of high-mortality interstitial lung disease (ILD), characterized pathologically by a variant of pulmonary alveolar proteinosis (PAP). The co-occurrence of macrophage activation syndrome (MAS) and PAP in sJIA suggested a shared pathology, but features of drug reaction such as anaphylaxis, rashes, and eosinophilia are also common in these patients. We sought to investigate immunopathology and identify biomarkers of this lung disease.MethodsWe used SOMAscan to measure >1300 analytes in serum samples from healthy controls and patients with sJIA-PAP, sJIA, sJIA-MAS, and other associated diseases, and verified selected findings by ELISA and lung immunostaining. Because a sample’s proteome may reflect multiple states (SJIA, MAS, SJIA-PAP), we used linear regression modeling to identify subsets of altered proteins associated with each state.ResultsMarkers identified for sJIA, including SAA, S100A9, and S100A12, were consistent with previous reports. Proteome alterations in sJIA and MAS overlapped substantially, including new findings of heat shock proteins and glycolytic enzymes. sJIA, MAS, and sJIA-PAP shared elevation of IL-18. Importantly, we identified a unique sJIA-PAP signature whose expression was independent of sJIA-MAS activity. Key proteins were ICAM5 and MMP7, previously observed markers of fibrotic ILD. Immunohistochemistry showed expression of these proteins in sJIA-PAP lung, supporting a pulmonary source. The eosinophil chemoattractant CCL11 was elevated in sJIA-PAP, but not sJIA/MAS or other PAP.ConclusionsWe found novel circulating proteins associated specifically with sJIA, sJIA/MAS and sJIA-PAP. Select biomarkers, such as ICAM5, could aid in early detection and management of sJIA-PAP.Key MessagesPulmonary Alveolar Proteinosis (PAP) occurring in the setting of Systemic Juvenile Idiopathic Arthritis (sJIA) is an increasingly-noted, dangerous condition that has been associated with Macrophage Activation Syndrome (MAS).We evaluated >1300 serum proteins by aptamer array, verifying and localizing key proteins, and identified novel pathways associated with MAS (HSPs, glycolysis), candidate pathways/proteins associated with PAP in sJIA (e.g., ICAM5, MMP7, and type 2 chemokines), and divergence of the sJIA/MAS and sJIA-PAP proteomes.This analysis supports the evaluation of novel pathways in MAS, the validation of screening/monitoring biomarkers in sJIA-PAP, and the management of PAP as a disease process enmeshed with, but distinct from, sJIA and MAS.

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