Track topics on Twitter Track topics that are important to you
Macrophage activation syndrome(MAS) is a complication of bone marrow suppression, coagulopathy and CNS dysfunction which occurs in rheumatic diseases. Normally the (Hemophagocytic Lympho-Histiocytosis) HLH-2004 criteria is used to diagnose patients with MAS. However this criteria is probably not sensitive and would probably be fulfilled quite late into the disease. Thus there would be an unacceptable delay. Ravelli et al came up with a different set of criteria based on data of patients reported in literature.
Systemic onset juvenile idiopathic arthritis (SoJIA) is the most common cause of MAS. MAS in other rheumatic illnesses occurs in the setting on unbridled inflammation. In both SoJIA and uncontrolled rheumatic disease the patient is liable to have high WBC counts and high platelet counts. Bone marrow suppression which is one of the pathognomic features of MAS would be picked up very late if absolute cut off values were utilized. Kelly et al used the same arguments in their review to suggest that in MAS/Reactive hemophagocytic lymphohistiocytosis(ReHLH), the trend of change in laboratory parameters would be more useful than absolute cut offs. Hence the investigators propose new candidate criteria which are based on trends of laboratory parameters and seek to determine their utility in comparison to absolute cut offs of HLH or Ravelli criteria. The investigators also wanted to determine that among the Ravelli criteria and HLH-2004 criteria, which were fulfilled earlier in patients diagnosed as having MAS.
Study hypothesis:-Criteria which measure serial trend of laboratory parameters would be fulfilled earlier than absolute cut offs when diagnosing MAS in patients with rheumatic illness.
Abbreviations:- ANC:- Absolute neutrophil count DIC:- Disseminated intra-vascular coagulation HLH:- Hemophagocytic lymphohistocytosis IAHS:- Infection associated hemophagocytic syndrome MAS:- Macrophage activation syndrome MODS:- Multi-organ dysfunction syndrome NK cell:- Natural Killer cells ReHLH:- reactive HLH SoJIA:- Systemic onset juvenile idiopathic arthritis SLE:- Systemic lupu erythematosus WBC:- white blood cell count
Background and Introduction:- The first appearance in literature of description of patients with what was later to be known as macrophage activation syndrome (MAS) is probably the description of SoJIA patients who had a fulminant course with hepatic failure by Boone et al1 and those with coagulopathy by Silverman et al2. However the term "macrophage activation syndrome" (and Syndromes of inappropriate macrophage activation in childhood) was first used in medical literature by French pediatricians and hemat-oncologists3-5. The credit for the same is wrongly attributed to Stephen et al, who were actually the first to use the term in "rheumatology" literature in their description of 4 SoJIA patients with this complication6. It is evident from the quoted literature that MAS at the time of it's intial recognition as a symptom complex or complication of rheumatic illness, was a universally fatal illness. Since then our understanding of it's pathology and it's treatment has grown considerably.
The main defect in MAS is deficient NK cell activity. Hence a trigger which stimulates the immune system leads to unchecked CD8+ T cell proliferation which persists even after elimination of the trigger. These T cells secrete IFN-gamma which leads to macrophage overstimulation. This in turn activates a cytokine storm production (TNF a, IL 1 and IL 6) and phagocytosis of marrow elements by the marcophages, ultimately leading to MODS7. MAS usually occurs in the setting of an untreated or inadequately controlled rheumatic disease with severe systemic inflammation. The diagnosis is difficult particularly against this background and therefore a high clinical suspicion is paramount.
Among the many rheumatic diseases MAS has been predominantly described associated with SoJIA. The next most common rheumatic illness described has been SLE. The hallmarks of this complication are Bone marrow suppression, DIC with abnormal bleeding, encephalopathy/ seizures, and hepatitis. MAS has been increasing been recognized to have similarities with Class II histiocytic disorders or hemophagocytic lymphohistiocytosis (HLH). In the most recent classification of these disorders Class II disorders have been further subdivided into primary (due to a genetic defect), secondary (due to infections, malignancies, immunodeficiency) and reactive (due to rheumatic diseases)8. The last category alludes to MAS.
Rationale and justification:-The HLH disorders are diagnosed using the HLH criteria. However as pointed out by Kelly et al9 and Ravelli et al10 use of this criteria to diagnose patients with MAS (i.e. Reactive HLH) would lead to a unacceptable loss of sensitivity and significant delay. Some components of the HLH criteria such as Soluble NK cell activity, CD-25 values above normal for age, and molecular diagnosis consistent with HLH are neither practical nor feasible in most clinical settings for a majority of rheumatology patients.
Ravelli et al came up with a different set of criteria for patients with MAS based on data of patients reported in literature10. A comparison of the 2 criteria in a retrospective longitudinal study11 (albeit with a very small sample size) showed that the Ravelli et al criteria to be much more sensitive and enabled patients to be diagnosed much earlier than when the HLH-2004 criteria was used. In both SoJIA and uncontrolled rheumatic disease the patient is liable to have high WBC counts and high platelet counts. Bone marrow suppression which is one of the pathognomic features of MAS would be picked up very late if absolute cut off values were utilized. Kelly et al used the same arguments in their review to suggest that in MAS/ReHLH, the trend of change in laboratory parameters would be more useful than absolute cut offs.
Hence we propose new candidate criteria which are based on trends of laboratory parameters which would probably be able to predict MAS earlier than absolute cut offs of laboratory parameters.MAS has now undergone a name change (to Reactive HLH) and an image change (from an universally terminal illness to a dreaded but treatable complication). Hence the need for recognition and early diagnosis is more important today than ever before. In this era of potent and novel immuno-modulatory medications, a sensitive criteria which would pick up patients prone to develop MAS or in the process of developing MAS would give us the edge to finally help us rein in this terrifying disease.
Observational Model: Case-Only, Time Perspective: Retrospective
Macrophage Activation Syndrome
Amrita Institute of Medical Sciences
Enrolling by invitation
Amrita Institute of Medical Sciences & Research Center
Published on BioPortfolio: 2014-08-27T03:14:53-0400
The investigators evaluate the effectiveness and safeness of low-dose Recombinant Human Interleukin-2 （rhIL-2） for MAS.
A Study to Investigate the Safety and Efficacy of an Anti-IFN-gamma mAb in Children With Systemic Juvenile Idiopathic Arthritis (sJIA) Developing Macrophage Activation Syndrome/ Secondary Hemophagocytic Lymphohistiocytosis (MAS/sHLH)
Macrophage Activation Syndrome (MAS) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of systemic Juvenile Idiopath...
RAGE (the receptor for advanced glycation end-products) is a marker of alveolar type I cell injury and a pivotal mediator of acute inflammation and innate immunity. RAGE pathway is highly ...
The primary purpose of this study is to determine whether giving injections of anakinra is a safe and well tolerated treatment to give as an adjunct to standard prescribed treatment for pa...
The study is a prospective observational study focused on monitoring the effects of various treatment options for acute coronary syndrome (ACS) patients by measuring serum neopterin levels...
The past decade has seen substantial progress in defining the cause and pathogenesis of the chronic childhood arthropathy systemic juvenile idiopathic arthritis (SJIA) and its related complication mac...
To validate whether the 2016 ACR/EULAR classification criteria of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA) is practical in the real world.
Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (SJIA), and has pathologic similarity to hemophagocytic lymphohistiocytosis (HLH). Int...
In this issue of , Zhang et al. (https://doi.org/10.1084/jem.20171417) show that the suppressive epigenetic enzyme Ezh2 is an important regulator of macrophage activation. The absence of Ezh2 leads to...
Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome, which if not promptly treated, can lead rapidly to critical illness and death. HLH is termed macrophage activation syndrome (...
The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.
A serious complication of childhood systemic inflammatory disorders that is thought to be caused by excessive activation and proliferation of T-LYMPHOCYTES and MACROPHAGES. It is seen predominantly in children with systemic onset JUVENILE IDIOPATHIC ARTHRITIS.
A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (RECEPTOR, MACROPHAGE COLONY-STIMULATING FACTOR).
Particles of any solid substance, generally under 30 microns in size, often noted as PM30. There is special concern with PM1 which can get down to PULMONARY ALVEOLI and induce MACROPHAGE ACTIVATION and PHAGOCYTOSIS leading to FOREIGN BODY REACTION and LUNG DISEASES.
Factors secreted by stimulated lymphocytes that prime macrophages to become nonspecifically cytotoxic to tumors. They also modulate the expression of macrophage cell surface Ia antigens. One MAF is INTERFERON-GAMMA. Other factors antigenically distinct from IFN-gamma have also been identified.
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...
Benign Prostatic Hyperplasia (BPH) Erectile Dysfunction Urology Urology is the branch of medicine concerned with the urinary tract and diseases that affect it. Examples include urethritis, urethrostenosis and incontinence. Urology is a su...