Macrophage Activation Syndrome: different mechanisms leading to a one clinical syndrome

Abstract

BackgroundMacrophage activation syndrome (MAS) is a severe complication of rheumatic disease in childhood, particularly in systemic Juvenile Idiopathic Arthritis (sJIA). It is characterize by an uncontrolled activation and proliferation of T lymphocytes and macrophages.Main contentMAS is currently classified among the secondary or acquired forms of haemophagocytic lymphohistiocytosis (sHLH). The reason is that MAS shares clinical and laboratory features with primary genetic HLH (pHLH). In this context is conceivable that some of the pathogenic mechanisms of pHLH may be involved in other forms of HLH. Heterozygosity for mutations of genes involved in pHLH may lead to a cytotoxic defect and to a development of clinical overt disease. But other different contributors might be involved to the development of MAS such as infections or underlying inflammation. In MAS, the inflammatory status of the patient is a major contributor of the disease. Indeed, the majority of the MAS episodes occurs during active disease phases or at disease onset. In addition, recent evidence in animals and humans suggest that genetics may also play a major role in contributing to hyperinflammation and particularly to macrophages hyper-responses.ConclusionsWe hypothesize that HLH may be one unique clinical syndrome, to whose generation different mechanisms may contribute, and maintained by one final effector mechanism.

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

“…Cytokine storm syndromes (CSS) are a group of disorders representing a variety of inflammatory etiologies with the final result of overwhelming systemic inflammation, hemodynamic instability, multiple organ dysfunction, and potentially death [208,209]. Specifically, macrophage activation syndrome [210] and hemophagocytic lymphohistiocytosis (HLH) [211] represent two clinically similar CSS with an unknown degree of etiopathogenic overlap [208]. The interaction between endothelial and immune cells could play a crucial role in COVID-19, especially in severe cases and in the late stages of the disease [212].…”

Adjunctive vitamin D for the treatment of active juvenile idiopathic arthritis: An open‑label, prospective, randomized controlled trial

“…As a result of chronic inflammation, patients with JIA suffer from joint pain, swelling, restricted range of motion and joint deformity (1). Severe extra-articular abnormalities may also accompany this disease, including uveitis, which occurs more frequently in antinuclear antibody (ANA)-positive patients and can lead to blindness, and macrophage activation syndrome (MAS), a complication of sJIA that can lead to multi-organ insufficiency and even mortality (3,4) Previous studies indicated that vitamin D played an important role in maintaining both the skeletal and immune systems (5,6). Vitamin D regulates the innate and adaptive immune systems by activating the vitamin D receptor, which is distributed widely on immune cells (7,8).…”

Application of MS score in macrophage activation syndrome patients associated with adult onset Still’s disease

“…MAS is a life-threatening complication of rheumatic disorders, including sJIA, adult-onset Still's disease (AOSD) and lupus. [1][2][3][4] Timely diagnosis and appropriate treatment of MAS are particularly important to improve the prognosis of MAS patients. At present, hemophagocytic lymphohistiocytosis (HLH)-2004 and HLH-2009 criteria are widely used to identify MAS associated with AOSD.…”