What is it?

Macrophage activation syndrome (MAS) is a potentially life-threatening rare complication of certain rheumatological conditions. In MAS, for reasons we don’t fully understand, there is over activation and unregulated production of certain cells of the immune system. The immune system is there to protect us against bugs and help fight infection. However in MAS, the cells that normally eat up and help get rid of bugs (macrophages) go into over drive and start eating up blood producing cells in the bone marrow. Other immune cells (T cells) start producing excess inflammatory chemical messengers (cytokines), which causes uncontrolled inflammation affecting different parts of the body.

What causes it?

We don’t fully understand what causes MAS or why some patients are at risk of developing MAS while others never do. MAS may occur where there is very active inflammation of the underlying rheumatological condition. It may also be triggered by infection (e.g. certain viruses) and at times by some medications. In some patients there may be an underlying genetic link (yet unknown), as it closely resembles an inherited condition called haemophagocytic lymphohistiocytosis (HLH).

What conditions may be affected by it?

  • Systemic Juvenile Idiopathic Arthritis (JIA) (most commonly)
  • Polyarticular JIA (rarely)
  • Other rheumatic conditions (e.g. Systemic Lupus Erythematosis, Juvenile Dermatomyositis, Systemic vasculitis, Mixed Connective Tissue Disease, other auto inflammatory conditions)

What problems does it cause?

The signs and symptoms of early MAS can be difficult to distinguish from infection or a flare up of the underlying rheumatological condition. The over active macrophages eat up the cells that produce blood cells which causes anaemia, infection risk and clotting (bleeding) problems. Other features may include:

  • High temperature
  • Enlarged liver and spleen
  • Enlarged lymph nodes
  • Headaches, Confusion, Irritability, Seizure, Coma
  • Rashes – bruises
  • Kidney involvement

In some children this settles very rapidly with a small increase in treatment. In others they may become very sick very quickly. Despite treatment there is a reported risk of death between 8-22% of cases.

How is it recognized?

If you have a child with a condition, which is known to put them at risk of MAS e.g. some children with systemic JIA, and they seem less well than you would expect with a ‘normal’ virus then you should contact your local rheumatology team for advice. If they seem particularly unwell they should be seen in your local A+E department where the staff can contact the rheumatology team for advice if necessary. There is no single test to diagnose MAS, and differentiating infection or a flare of the underlying rheumatological condition can be really difficult. For example, abnormalities may be seen in a sample of the bone marrow, but these abnormalities may be also seen with infection or a flare of the underlying condition. In addition, depending on when the sample is taken, in early MAS or the effect of some medications, the bone marrow may actually look normal. Regular blood tests are required to look for abnormal patterns, which may help your doctor to make the diagnosis (these include for example).

  • Full Blood Count
  • Ferritin
  • ESR
  • CRP
  • Clotting screen
  • Liver and Kidney function tests

Early suspicion and recognition is important to initiate treatment.

How is it treated?

Patients who develop MAS will require admission to hospital. Treatment consists of medication to try and turn off the uncontrolled inflammation as well as supportive treatment for any of the complications that may arise. These include:

  • High dose steroids via a drip. This may be required for several days, followed by oral or drip steroids depending on the patient’s condition.
  • Depending on progress or the extent of other organs that may be affected other combinations of drugs may be required for example ciclosporin, anakinra, immunoglobulin or etoposide.
  • Support for any other organs affected e.g., antibiotics, blood and platelet transfusions, kidney support.

Your rheumatology team would be happy to discuss any worries or anxieties that you may have about MAS at any time. Please remember this is an extremely rare complication of JIA.