Macrophage Activation Syndrome

Macrophage Activation Syndrome – General Information

Macrophage Activation Syndrome or MAS is a rare but often fatal complication of several chronic rheumatic diseases of childhood, which can be characterized acutely with no remitting high fever, lymphadenopathy, hepatosplenomegaly, hepatocellular injury, pancytopenia, liver dysfunction, hypertriglyceridemia, and hyperferritinemia. These are usually followed by the dysfunctions of the nervous system and coagulopathy, and very rare they can be associated with lungs, kidneys or cardiac tissues. It usually appears with systematic-onset juvenile idiopathic arthritis that is also named “Still’s disease” and in association with systemic lupus erythematosus (SLE) and Kawasky disease. It is believed to be related to reactive hemaphagocytic lymphohistiocytosis (HLH) and it is similar to it in pathophysiology. The diagnosis relies on the symptoms outlined below and also on an analyze of the NK (natural killer) cell function, which are cells involved in the innate immune responses like the macrophages, dendritic cells, mast cells, neutrophils and eosinophils.

This medical condition usually appears due to excessive activation and proliferation of the T lymphocytes and macrophages and in association with many rheumatic diseases, but usually in systematic juvenile rheumatoid arthritis (SJRA). In the acute phase of the Macrophage Activation Syndrome it is commonly found in the lymph nodes, spleen or bone marrow a lymphohistiocytic infiltrate and an increased circulation of the T-cells cytokines and monokines. Macrophage Activation Syndrome is the name applied to HLH associated with diverse rheumatic diseases. HLH is a heterogeneous autosomal recessive disease and hereditary which is prevalent with the parental consanguinity (consanguinity means to be from the same genetic lineage as another person like parents, grandparents and so on, relatives in general).

Macrophage Activation Syndrome – Symptoms

In the majority of cases what causes Macrophage Activation Syndrome is a viral infection or a medication that is not adequate for the organism. The activation and proliferation of macrophages and T lymphocytes is incontrollable and that is why the reason for the development of this disease is unclear and is the subject of many researches.

The common symptoms of the Macrophage Activation Syndrome are:

• High fever.
• Abnormal levels of perforin, which is a cytolytic protein.
• Hepatosplenomegaly is the concomitant enlargement of both liver and spleen.
• Lymphadenopathy is a disease of the lymph nodes.
• Pancytopenia is a reduction of the figurate elements of the blood.
• Liver dysfunctions.
• Hepatocellular injury
• Disseminated intravascular coagulation.
• Coagulopathy
• Low concentrations of serum albumin
• High levels of liver enzymes
• Hypofibrinogenemia, which is a reduction of fibrinogen in the blood and can be hereditary.
• Hyperferritinemia.
• Hypertriglyceridemia, which is an excess of triglycerides in the blood.
• Deranged renal function
• Depression caused by the low levels of fibrinogen, which is a protein involved in the clotting of the blood.
• Swollen lymph glands
• A drop of varying extent in white blood cells and hemoglobin
• An early drastic drop in platelet count
• Hemophagocytosis is an unusual syndrome that is characterized by: fever, splenomegaly, jaundice (is also known as “icteric” and is a yellowing of the skin, conjunctiva of the eye and mucous membranes) and has an immunogenetic basis.

Macrophage Activation Syndrome – Treatment

The diagnosis of the Macrophage Activation Syndrome can be done on clinical and biochemical grounds, and this diagnosis can be sustained by the finding of differentiated macrophages phagocytosing hematopoietic cells in the bone marrow which is a sponge-like tissue located in the center of certain bones and contains stem cells. But unfortunately the bone marrow does not always reveal the infection. Another way to diagnose this disease is performing biopsies of the target organs (besides the bone marrow, such as the liver), but the frequent appearance of coagulopathy in acute Macrophage Activation Syndrome is a huge risk. But in the case in which there is no other solution of getting conclusive evidence of the existence of MAS and excluding the other pathologies a liver biopsy is justified.

There has not been established a treatment for the Macrophage Activation Syndrome, but the usually treatment include a high dose of glucocorticoids (which are a class of steroid hormones, that can be characterized by their ability to connect with the cortisol) and cyclosporine (which is a immunosuppressant drug, used in immunosuppressant therapy to inhibit or prevent the activity of the immune system), and in some cases the treatment used is the same as in hemaphagocytic lymphohistiocytosis. In the treatment of this medical condition, children have used corticosteroids (which are steroid hormones produced in the adrenal cortex), but the bad part is that the prolonged use of this corticosteroids can result in death. Another way of treatment was the use of intravenous methylprednisolone (which is also a corticosteroid) pulse therapy, but as it did not help the patience it was replaced by Etanrecept.

A recent report has outlined the fact that Etanrecept may be a useful drug in the treatment of Macrophage Activation Syndrome. Etanrecept is a recombinant (meaning a form of the DNA) soluble tumor necrosis factor-alpha receptor fusion protein (which is a cytokine –a group of protein and peptides- that is involved in systematic inflammation such as: autoimmune diseases, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis). Also another drug, Enbrel, reduces the actions of chemicals in one’s organism, chemicals that are involved in inflammatory diseases and immune responses.

A study made on ten patients that suffered from Macrophage Activation Syndrome has shown that the patients best responded to the treatment based on cyclosporines and glucocorticoids, and this outlines that as there has not been discovered other treatments for this disease this are the best alternatives to at least slow down the its evolution. Another study made on a boy who suffered from this disease has shown that administration of corticosteroids was not effective, at all, but his organism responded prompt to cyclosporines, this is way we can affirm that the treatment differs from a patient to another, it has an equal distribution to both male and female patients, the maximum age of developing Macrophage Activation Syndrome is 18 months of age and it does not have any predilection for a specific race.