Macrophage activation syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at November 19, 2016
StartDiseasesMacrophage activation syndrome

Macrophage activation syndrome occurs when macrophages and T lymphocytes are activated and then grow uncontrollably which can cause life-threatening consequences. It is most often seen in children with rheumatic diseases such as juvenile lupus and juvenile arthritis, and is triggered by several events including nonsteroidal anti-inflammatory drug (NSAID) toxicity; disease flare-ups; and reactions to methotrexate and to some of the biologic medicines used to treat underlying rheumatic disease. Treatment consists of administering high doses of corticosteroids; cyclosporin A is used when the symptoms do not respond well to the use of corticosteroids.

Contents

Definition & Facts

Macrophage activation syndrome is a relatively rare complication of rheumatic diseases that occurs most often in children. It is considered to be a dangerous immune response to triggers such as NSAIDs or methotrexate, viral infections, and flare-ups of the rheumatic disease itself. The abnormal response of the immune system can quickly become a life-threatening situation.

Its onset is typically sudden with a persistent high grade fever, depression, enlarged spleen (splenomegaly), and very low levels of blood cells (red blood cells, white blood cells, and platelets). Those affected by MAS may also suffer seizures and coma.

Symptoms & Complaints

Patients with macrophage activation syndrome have the following symptoms:

Macrophage activation syndrome affects the central nervous system as well, and those with the syndrome may complain of headaches, irritability, and lethargy. More serious central nervous system involvement includes disorientation, seizures, and coma.

Causes

On a cellular level, the body produces a protein called perforin which is supposed to help disintegrate those cells that are destructive; instead, in people suffering from macrophage activation syndrome, this protein fails to perform its intended purpose.

There is no single factor responsible for cases of macrophage activation syndrome. Since MAS occurs in people with certain autoimmune diseases, it may be precipitated by several different triggers: flare-ups of the disease itself, viral infections, toxic responses to NSAIDs, and toxic responses to methotrexate and injections of gold salts.

MAS has also happened in some cases in which a person has undergone treatment with newer biologic medications. Whether the newer medications are solely responsible for these instances of MAS is still a matter of some debate. Other patients who have undergone autologous bone marrow transplants have also suffered incidences of the syndrome; these cases were determined to originate from the serious depletion of T-cells coupled with an infection.

Newer research into cytokines may be useful, as only certain ones seem to be released during MAS. Cytokines are so-called “signaling” molecules that facilitate communication between cells and direct them to injured or traumatized areas of the body. However, during MAS, this communication becomes chaotic.

Diagnosis & Tests

Macrophage activation syndrome can mimic several other serious medical issues, as there is no one factor or characteristic that differentiates it from other conditions. MAS can mimic a serious infection, even sepsis, or appear as a side effect of a medication or a flare-up of the known disease or condition.

Diagnosis via biopsy is no longer recommended for MAS, as the diminished clotting ability precludes obtaining necessary tissue samples. Instead, more specific criteria have been developed of late to be more specific to MAS itself.

In addition to the listed symptoms, patients should have tests done to look for elevated levels of ferritin in the blood. Ferritin is a protein common to almost all living animals and plants, and is responsible for storing and releasing iron. It is commonly used to detect anemia and iron overload in the body; with MAS, ferritin levels are also used to determine the body’s response to treatment.

Treatment & Therapy

Since macrophage activation syndrome can rapidly become fatal, it is crucial that a correct diagnosis be made early. Even so, treatment options vary. Some patients are treated with corticosteroids; other patients receive cyclosporin. This is the usual treatment regimen. Those patients who normally receive the drug anakinra (an immunosuppressant drug used to treat rheumatoid arthritis) may have an episode of MAS; on the other hand, there are some patients who receive anakinra as a treatment for MAS.

The latter set have shown a rather dramatic improvement in their MAS symptoms and this remains a paradox, since treatment for arthritis with biologics has been known to be a factor in causing macrophage activation syndrome in the first place. Due to the potentially fatal nature of MAS, treatment in an intensive care unit is strongly recommended and the patient should also be monitored for sepsis.

Prevention & Prophylaxis

Even though macrophage activation syndrome may affect anyone with a rheumatic disease, it most often affects children with juvenile arthritis. Many of the characteristics of MAS are still unknown, such as why children with juvenile arthritis are affected, why some of the biologic medicines help certain patients yet hinder others, which pathways are used at the onset of MAS, etc.

As the exact causes of the syndrome are not yet fully understood, there is no one type of prevention. Current strategies that may be undertaken by a patient with a rheumatic disease and by their support network include controlling the rheumatic disease, trying to avoid infections, and generally trying to remain as healthy as possible (via regular exercise and healthy diet).

Research into the involvement of cytokines may prove useful in future treatment; today the standard treatment remains corticosteroids (such as prednisone) and cyclosporin. Early detection of MAS is also important in reducing the likelihood of complications.