Macrophage activation syndrome in the era of biologic therapy. Evidencebased diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis. In pediatric rheumatology, the term macrophage activation syndrome mas refers to a condition caused by excessive activation and expansion of t lymphocytes and macrophagic histiocytes that exhibit hemophagocytic activity. Macrophage activation syndrome mas is the term used to describe a potentially lifethreatening complication of systemic inflammatory disorders, which occurs most commonly in systemic juvenile idiopathic arthritis jia and in its adult equivalent, adultonset stills disease 14, although its occurrence in patients. Macrophage activation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood. Kawasaki disease kd is an acute systemic vasculitis of unknown etiology. Emapalumab treats glucocorticoidrefractory macrophage activation syndrome mas in patients with sjia. Pdf use of infliximab in the treatment of macrophage. Macrophage activation syndrome mas mas is present in up to 50% of children with systemic juvenile idiopathic arthritis sjia in a subclinical or overt 10% form. Activation syndrome an overview sciencedirect topics. The goal in treating mas is to reduce bodywide inflammation as quickly as possible and prevent organ damage. Macrophage activation syndrome macrophage activation syndrome new criteria.
It belongs to the hemophagocytic lymphohistiocytosis group of diseases. Macrophage activation syndrome mas is a clinical disorder associated with systemic symptoms caused by overwhelming inflammation caused by immune dysregulation often in the setting of rheumatologic disease with marked increases in circulating cytokines. The genetics, clinical features, and diagnosis of hlh are presented separately. Pdf tumor lysis syndrome occurring during treatment of. Drugs used to treat macrophage activation syndrome. Kd can be complicated with macrophage activation syndrome. Macrophage activation syndrome mas is a potentially fatal complication of rheumatic disease, most notably systemic juvenile idiopathic arthritis. Macrophage activation syndrome mas is a rare but lifethreatening condition that can affect children with rheumatic disease, particularly those with systemic onset juvenile idiopathic arthritis. The following list of medications are in some way related to, or used in the treatment of this condition. Highdose anakinra as treatment for macrophage activation. Apart from these inflammatory disorders, different autoinflammatory dysfunctions like kawasaki disease, systemic lupus erythematosus, and periodic fever syndromes can trigger the onset of adult and childhood macrophage activation syndrome. May 23, 2016 macrophage activation syndrome mas is a disorder whereby the immune system generates very high levels of substances cytokines that promote inflammation to the extent dysfunction occurs in multiple organ systems which if unchecked, is frequently fatal to the affected individual.
We assessed the clinical features and outcomes based on therapeutic options adopted during hospital stay for adult patients with macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis masshlh. In adults, macrophage activation syndrome develops due to the complication of stills disease. Use of infliximab in the treatment of macrophage activation. Apr 19, 2019 macrophage activation syndrome is a condition in which the bodys immune system activates excessively, leading to tissue and organ damage. Standardized diagnostic and treatment guidelines for mas in sjia are currently lacking. Macrophage activation syndrome mas is a term used by rheumatologists to describe a potentially lifethreatening complication of systemic inflammatory disorders, most commonly systemic juvenile idiopathic arthritis sjia and its adult equivalent adult onset still disease and systemic lupus erythematosus sle 1. Etoposide is usually prescribed along with first or second line treatment option. Macrophage activation syndrome mas is a lifethreatening condition, and it is a subset of hemophagocytic lymphohistiocytosis hlh. This treatment significantly improved the condition of the child and in our opinion prevented a fatal outcome. The mainstay of mas treatment is glucocorticoid therapy. It is sometimes difficult to establish the diagnosis of hemophagocytic lymphohistiocytosis hlh, and the combination of the physical symptoms and certain laboratory tests is required.
Macrophage activation syndrome mac is a form of hemophagocytic lymphohistiocytosis hlh in patients with juvenile idiopathic arthritis and other rheumatologic conditions. To identify macrophage activation syndrome mas in patients with systemic juvenile idiopathic arthritis sjia undergoing tocilizumab tcz treatment, and to confirm laboratory marker changes and responses to treatment. Mar 19, 2020 atlantamacrophage activation syndrome mas, a subset of hemophagocytic lymphohistiocytosis hlh disease, can be a fatal result of rheumatic disease. Reginas daughters participation resulted in significant health improvement and a better quality of life for her daughter after participating in the fourweek treatment. The clinical features include a persistent highgrade fever, hepatosplenomegaly, lymphadenopathy, hemorrhagic manifestations, and a sepsislike condition. Mar 24, 2016 macrophage activation syndrome mas is a potentially fatal complication of rheumatic disease, most notably systemic juvenile idiopathic arthritis. Macrophage activation syndrome mas is a pathological systemic. It occurs most commonly with systemiconset juvenile idiopathic arthritis sojia. Macrophage activation syndrome mas is a severe and potentially lethal complication of several inflammatory diseases but seems particularly linked to systemic juvenile idiopathic arthritis sjia. Within 48 hours of anakinra treatment, blood count increased and fever abated.
Macrophage activation syndrome in children with rheumatic. Soon afterward, her fever ceased and high levels of both ferritin and creactive. Mas manifests as fever, liver dysfunction, pancytopenia, central nervous system disturbance, hyperferritinemia, hemophagocytosis, and coagulopathy. Gietka p, wieteskaklimczak a, smorczewskakiljan a, rutkowskasak l. Standardized diagnostic and treatment guidelines for. Rheumaknowledgy macrophage activation syndrome mas. When is patient transfer required for the treatment of.
Hemophagocytic syndrome, hemophagocytic lymphohistiocytosis hlh, histiocytic erythrophagocytosis. Macrophage activation syndrome angelo ravelli, md macrophage activation syndrome mas is a serious complication of childhood systemic inflammatory disorders that is thought to be caused by excessive activation and proliferation of t lymphocytes and macrophages. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with juvenile idiopathic arthritis and other rheumatologic. Mas is a severe, potentially fatal disease characterized by severe systemic inflammation.
New options emerge for treating macrophage activation. Objective to described the clinical and laboratory features and outcome of 67 macrophage activation syndrome mas. To describe the features and treatment of macrophage activation syndrome mas in a single. The treatment of macrophage activation syndrome mas is traditionally based on the parenteral administration of high doses of corticosteroids. New therapeutic options for refractory mas targeting individual cytokines are emerging. People with macrophage activation syndrome that are very sick should be treated with medications to suppress the immune system. Macrophage activation syndrome mas is a clinical syndrome caused by excessive activation and proliferation of well differentiated macrophages. Aug 31, 2018 macrophage activation syndrome mas is a lifethreatening condition, and it is a subset of hemophagocytic lymphohistiocytosis hlh. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with juvenile idiopathic arthritis and other rheumatologic conditions, will be discussed here. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with juvenile idiopathic arthritis and other rheumatologic clinical. New targeted treatment for macrophage activation syndrome. Macrophage activation syndrome mas aboutkidshealth. Anakinra 100 mg subcutaneously daily was initiated, along with pulse methylprednisolone 1 gday for 3 days, then prednisone 25 mg twice daily. Macrophage activation syndrome in the era of biologic.
The medications that are typically used are a combination of the intravenous steroid dexamethasone decadron and a chemotherapy medication called etoposide toposar. Anakinra is a commercially available product kineret approved for the treatment of rheumatoid arthritis. The optimal treatment for this kd complication has not been. Macrophage activation syndrome as onset of systemic lupus. Macrophage activation syndrome mas is a potentially fatal condition.
Macrophage activation syndrome clinical presentation. Macrophage activation syndrome in adults with rheumatic disease. Macrophage activation syndrome treated with anakinra the. Macrophage activation syndrome mas is the term used to describe a potentially lifethreatening complication of systemic inflammatory disorders, which occurs most commonly in systemic juvenile. In refractory cases treatment regimens are used similar. Macrophage activation syndrome mas or hemophagocytic lymphohistiocytosis hlh is a life.
Macrophage activation syndrome mas is a clinical syndrome caused by excessive activation. In individuals with macrophage activation syndrome mas, the immune system is uncontrolled and works in overdrive, leading to too much inflammation in the entire body. Macrophage activation syndrome treatment, symptoms, life. The treatment and prognosis of patients with hlh and the macrophage activation syndrome mas, a form of hlh in patients with juvenile idiopathic arthritis and other rheumatologic conditions, will be.
A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for macrophage activation syndrome. Chronic nk cell lymphoproliferative disorder can be differentiated from nk cell leukemia based on the absence of chronic ebv infection. Most commonly used treatments include highdose glucocorticoids, and cyclosporine. A diagnosis of macrophage activation syndrome mas was made.
List of macrophage activation syndrome medications 1. Treatment of macrophage activation syndrome mas with anakinra mas the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Despite its success in treating acute sjia, patients with sjia treated with tocilizumab remain at risk for mas, arguing that il6 blockade alone is. Jan 17, 2018 macrophage activation syndrome mas is a potentially life.
Methods a total of 67 mas patients from three centers from january 2007 to. Macrophage activation syndrome in patients with systemic. Most of the physicians start with an intravenous methylprednisolone 30 mgkgdose. Haemophagocytic lymphohistiocytosis hlh is a hyperinflammatory syndrome, which if not promptly treated, can lead rapidly to. Evidencebased diagnosis and treatment of macrophage. Actemra can mask macrophage activation syndrome in.
The diagnosis can be challenging due to frequent lack of a unique clonal marker. Macrophage activation syndrome is the dysregulation of macrophage lymphocyte interactions leading to uncontrolled proliferation and activation of macrophages and t cells. Synonymous with secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome mas is a term used by rheumatologists to describe a potentially lifethreatening complication of. Apr 15, 2020 boom v, anton j, lahdenne p, quartier p, ravelli a, wulffraat nm, et al. Although macrophage disorders are usually a consequence of a decrease in function, an increase in macrophage activity can also have adverse consequences for individuals.
However, some fatalities have been reported, even among patients treated with massive doses of corticosteroids. A personalized diagnostic and treatment approach for. Further, there was a high suspicion for macrophage activation syndrome given his ferritin of 7,358ngml, triglycerides of 290mgdl and interleukin2 receptor of 7,250pgml. We report the case of a 71yearold japanese woman with adultonset stills disease aosd in whom macrophage activation syndrome mas developed despite therapy with oral highdose prednisolone. Successful tocilizumab therapy for macrophage activation.
The best treatment for mas has not been firmly established. Oct 06, 2015 lowdose il2 interleukin2 treatment in macrophage activation syndromemas the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. First line treatment for macrophage activation syndrome is. Macrophages are a type of immune cell in the body that eats infectious organisms and damaged cells. Treatment of macrophage activation syndrome mas with anakinra. All drug classes antirheumatics 1 tnf alfa inhibitors 1. Tumor lysis syndrome occurring during treatment of macrophage. Macrophage activation syndrome symptoms, treatments. Macrophage activation syndrome genetic and rare diseases. Drugs used to treat macrophage activation syndrome the following list of medications are in some way related to, or used in the treatment of this condition. The resources below provide information about treatment options for this condition.
Nov 21, 2018 macrophage activation syndrome mas is a lifethreatening complication of rheumatic disease that, for unknown reasons, occurs much more frequently in individuals with systemic juvenile idiopathic arthritis sjia and in those with adultonset still disease. Lowdose il2 interleukin2 treatment in macrophage activation syndrome mas the safety and scientific validity of this study is the responsibility of the study sponsor and. Tcell blocking agent, such as cyclosporine a also showed efficacy. Diagnostic criteria for macrophage activation syndrome.
Recent findings in hemophagocytic lymphohistiocytosis, a disease that. Macrophage activation syndrome causes, symptoms, diagnosis. Features, treatment, and outcomes of macrophage activation. Treatment with actemra can complicate the diagnosis of macrophage activation syndrome in patients with systemic jia by masking symptoms, a study reports. Macrophage activation syndrome an overview sciencedirect. Treatment of macrophage activation syndrome mas with. Diagnosis is a challenge, treatment has to be started early and be aggressive to reduce the. Successful treatment of severe paediatric rheumatic diseaseassociated macrophage activation syndrome with interleukin1 inhibition following. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome mas, adult onset stills disease aosd, catastrophic antiphospholipid syndrome caps and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments. Haemophagocytic lymphohistiocytosis hlh is a hyperinflammatory syndrome, which if not promptly treated, can lead rapidly to critical. Successful treatment of severe paediatric rheumatic diseaseassociated macrophage activation syndrome with interleukin1 inhibition following conventional immunosuppressive therapy. In macrophage activation syndrome, macrophages are excessively activated and cant be shut down. In adults, mas is rarely associated with systemic lupus.
Common symptoms reported by people with macrophage activation syndrome. Treating systemic juvenile idiopathic arthritis sjia with actemra tocilizumab can modify the clinical and laboratory features of macrophage activation syndrome. Evidencebased diagnosis and treatment of macrophage activation. Successful treatment of macrophage activation syndrome in. Listing a study does not mean it has been evaluated by the u. Normally, when the immune system is activated, it fights the infection in a coordinated and controlled manner. Macrophage activation syndrome mas can occur in the setting of hematologic malignancies. Dec 03, 2015 macrophage activation syndrome mas is a severe and potentially lethal complication of several inflammatory diseases but seems particularly linked to systemic juvenile idiopathic arthritis sjia. Clinical characteristics and treatment outcomes of.