Pathogenesis, disease course, and prognosis of adult-onset Still's disease: an update and review

Abstract

Objective: Adult-onset Still's disease (AOSD) is a rare but clinically well-known polygenic systemic autoinflammatory disease. In this review, we aim to present frontiers in the pathogenesis, clinical features, diagnosis, biomarkers, disease course, prognosis, and treatment in AOSD. Data sources: We retrieved information from the PubMed database up to July 2019, using various search terms and relevant words, including AOSD and Still's disease. Study selection: We included data from peer-reviewed journals. Both basic and clinical studies were selected. Results: Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of macrophages and neutrophils followed by a cytokine storm. Diagnosis and prognosis evaluation of AOSD is still challenging; therefore, there is an urgent need to identify better biomarkers. Biologic agents, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α antagonists in the treatment of AOSD, have good prospect. Conclusion: This review highlights the advances in pathogenesis, potential biomarkers, disease course, and treatment in AOSD.

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

“…The increased urinary proteins in AOSD were enriched in pathways of the innate immune system and neutrophil degranulation. Hyperactivation of innate immune cells, especially monocytes/macrophages and neutrophils, is the hallmark of AOSD (1,3). Additionally, the levels of neutrophil granular protein myeloperoxidase and elastase-combined DNA were elevated in patients with AOSD (22).…”

“…Adult-onset Still’s disease (AOSD) is a systemic, multigenic autoinflammatory disease characterized by cardinal manifestations of fever, arthritis and/or arthralgia, skin rash, sore throat, leukocytosis, and excessive neutrophil proportion, in combination with other symptoms, such as myalgia, pericarditis, pleuritis, and elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and ferritin levels ( 1 – 3 ). The disease may cause life-threatening complications such as fulminant hepatic failure, pulmonary arterial hypertension, disseminated intravascular coagulation, acute respiratory distress syndrome, and macrophage activation syndrome ( 1 ).…”

Circulating Neutrophil Extracellular Traps Signature for Identifying Organ Involvement and Response to Glucocorticoid in Adult-Onset Still’s Disease: A Machine Learning Study

“…AOSD is a systemic autoinflammatory disorder of unknown etiology, commonly manifested with fever of unknown origin ( 1 ). Routine inflammatory markers, cytokines, and several molecules reflecting innate immune activation are increased in patients with AOSD and used in clinical practice ( 20 ).…”

“…Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease, typically characterized by fever of unknown origin, evanescent rash, polyarthralgia, and even life-threatening complications, such as macrophage activation syndrome (MAS), fulminant hepatitis, and cardiopulmonary system involvement (1). Cardiopulmonary involvement was defined as pericarditis, pneumonia, pleuritic, and pulmonary arterial hypertension (PAH) as well as any cardiac or pulmonary disorder related to the AOSD (2).…”

Case of Adult-Onset Still’s Disease in 65-year-old man

“…These genes and its mutations in combination with other triggers cause macrophages activation, that secrete cytokines (IL-6, IL-8, TNF-α). That leads to cytokine storm and intensive inflammatory response with high serum ferritin [20], procalcitonin, CRP and ESR levels, leukocytosis, neutrophilia, anemia and thrombocytosis [21,22,23,24]. Because of liver abnormalities that can occur in AOSD the level of liver enzymes can be increased [14].…”