What is Macrophage Activation Syndrome?
Macrophage Activation Syndrome (MAS) is a severe, potentially life-threatening inflammatory condition in which the immune system becomes dangerously overactive. It is considered a form of secondary hemophagocytic lymphohistiocytosis (HLH) and typically occurs in the setting of autoimmune or autoinflammatory diseases. In MAS, certain white blood cells (macrophages and T-cells) become excessively activated and start damaging the body’s own tissues and organs.
What causes Macrophage Activation Syndrome?
MAS is often triggered by an underlying autoimmune or autoinflammatory disease. Common causes include:
- Systemic Juvenile Idiopathic Arthritis (sJIA) – the most frequent associated condition in children
- Systemic lupus erythematosus (SLE)
- Adult-onset Still’s disease
- Viral or bacterial infections
- Certain cancers like lymphomas
- Genetic immune disorders, in rare cases
The syndrome may also be triggered by medications, especially those that affect immune regulation.
Who is at risk of developing MAS?
People most at risk include:
- Children with systemic juvenile idiopathic arthritis
- Adults with autoimmune diseases such as lupus or Still’s disease
- Individuals with immunodeficiencies or genetic HLH mutations
- People undergoing treatment with immunosuppressive drugs
- Those with a recent infection or flare-up of an autoimmune disease
What are the symptoms of Macrophage Activation Syndrome?
MAS symptoms can develop rapidly and resemble a severe infection or sepsis. Common signs include:
- Persistent high fever
- Enlarged liver or spleen (hepatosplenomegaly)
- Severe fatigue and weakness
- Low blood cell counts (anemia, low platelets, low white blood cells)
- Bleeding or bruising easily
- Abdominal pain
- Jaundice (yellowing of the skin or eyes)
- Confusion or neurological symptoms
- Organ failure in severe cases
Early recognition is critical, as MAS can progress rapidly without treatment.
How is Macrophage Activation Syndrome diagnosed?
Diagnosis is challenging and based on a combination of clinical findings and lab tests. Tests often include:
- Complete blood count (CBC) – shows low levels of red and white blood cells and platelets
- Elevated ferritin – very high levels are a key marker of MAS
- Liver function tests – often abnormal
- Coagulation tests – may show signs of clotting abnormalities
- Bone marrow biopsy – may show hemophagocytosis (immune cells eating other blood cells)
- Inflammatory markers – such as elevated ESR, CRP, and triglycerides
Is Macrophage Activation Syndrome treatable?
Yes, MAS is a medical emergency but can be treated if caught early. Treatment typically involves:
- High-dose corticosteroids – to suppress the immune response quickly
- Immunosuppressive medications – such as cyclosporine, anakinra (IL-1 inhibitor), or tocilizumab (IL-6 inhibitor)
- Biologic therapies – used in cases associated with autoimmune diseases
- Treatment of the underlying disease (e.g., lupus, Still’s disease)
- Supportive care – including blood transfusions and treatment for organ complications
- Hospitalization, often in an intensive care unit (ICU), may be required for severe cases
Can Macrophage Activation Syndrome be prevented?
There is no guaranteed way to prevent MAS, but early and consistent management of underlying autoimmune diseases can reduce the risk. Regular monitoring and prompt attention to symptoms like fever or fatigue are critical in high-risk patients.
What is the outlook for someone with MAS?
MAS can be fatal if not diagnosed and treated early. However, with prompt medical care, many people recover fully. The outcome depends on how quickly treatment is started and how well the underlying disease is managed. Some individuals may have recurrent episodes and require long-term follow-up with a rheumatologist or immunologist.