Macrophage Activation Syndrome

What is macrophage activation syndrome?

Macrophage activation syndrome is a condition in which the body’s immune system activates excessively, leading to tissue and organ damage. Macrophages are a type of immune cell in the body that “eats” infectious organisms and damaged cells. In macrophage activation syndrome, macrophages are excessively activated and can’t be shut down. As a result, they eat the body’s own blood cells and release substances that cause widespread inflammation, leading to tissue and organ damage.

Symptoms include fever, a painful mass or masses in the abdomen, easy bruising or bleeding, swollen lymph nodes, a rash, headache, confusion, vision changes, seizures and/or coma as well as difficulty breathing.

Treatment of this potentially life-threatening condition includes addressing underlying autoimmune (rheumatic) conditions or infections, immunosuppressants or medications for neurological symptoms, as well as stem cell transplants.

Given the life-threatening nature of the disease, you should go to the ER immediately for blood tests and stabilization.

Macrophage activation syndrome symptoms

Main symptoms

Symptoms that affect the majority of people with macrophage activation syndrome include the following.

• Fever: The fever will usually persist over many days, unlike the fever seen in systemic juvenile idiopathic arthritis, which tends to occur intermittently.
• Painful mass or masses in the abdomen: There may be a mass in the upper right side of the abdomen. This is due to swelling of the liver, which becomes inflamed in macrophage activation syndrome. There may also be a mass in the upper left side of the abdomen. This is due to swelling of the spleen, which enlarges with inflammation.
• Easy bruising or bleeding: Many people with macrophage activation syndrome will develop easy bruising or bleeding, such as nosebleeds or bleeding gums. This occurs because macrophage activation syndrome causes low levels of blood cells and factors that are important for forming blood clots.

Other symptoms

Symptoms that affect some people with macrophage activation syndrome include the following.

• Swollen lymph nodes: About one-third of people with macrophage activation syndrome will develop swollen lymph nodes. These can be located in the neck, near the ears, in the groin area, or in other parts of the body.
• Rash: About one-third of people with macrophage activation syndrome will develop a rash. The specific type of rash can vary and may include red spots and bumps, dark red/purple spots, pinpoint red spots, or red skin all over the body.
• Headache, confusion, vision changes, seizures, and/or coma: About one-third of people with macrophage activation syndrome will develop these symptoms of the nervous system.
• Difficulty breathing: This can occur because high levels of inflammation cause blood vessels in the lungs to become leaky, causing fluid to build up in the lungs.

Macrophage activation syndrome causes

Macrophage activation syndrome is a specific type of a broader condition called hemophagocytic lymphohistiocytosis. Macrophage activation syndrome develops in people who have underlying rheumatic disorders, which are autoimmune disorders of the joints and connective tissues.

Macrophage activation syndrome more often affects children. Specific factors that lead to the development of macrophage activation syndrome are detailed below.

Genetic mutations

Many of the genetic mutations associated with macrophage activation syndrome involve genes that are important for certain cells of the immune system to kill abnormal cells, including overactive macrophages. Mutations in these genes prevent the immune system from killing overactive macrophages, leading to macrophage activation syndrome.

Autoimmune disorders

Macrophage activation syndrome, by definition, occurs in people who have an underlying rheumatic disorder, or an autoimmune disorder of the joints and connective tissues. The most common rheumatic disorder associated with macrophage activation syndrome is a condition called systemic juvenile idiopathic arthritis, which causes fever, rash, and joint pain in children. Less commonly, macrophage activation syndrome may be found in people with lupus, rheumatoid arthritis, Kawasaki disease, or other rheumatic diseases.

Infection

Getting an infection can trigger the development of macrophage activation syndrome in people with underlying genetic mutations and rheumatic disorders. Infections can trigger the body’s immune system to activate, and excessive activation of the immune system can then lead to macrophage activation syndrome. Macrophage activation syndrome is most often associated with viral infection such as herpes, the flu, HIV, or viruses that cause infectious mononucleosis, but can also develop after bacterial infections such as tuberculosis.

Starting a new medication

People with underlying rheumatic disease who start a new medication may develop macrophage activation syndrome. For example, this has been seen in people with systemic juvenile idiopathic arthritis who start a medication called tocilizumab (Actemra), which downregulates a part of the immune system.

Treatment options and prevention

Macrophage activation syndrome is a dangerous and potentially life-threatening disorder if not treated. Therefore, it is important to identify and treat macrophage activation syndrome as well as any organ damage that it may cause. People with macrophage activation syndrome due to any underlying rheumatic disorder or infection can sometimes improve from treating the underlying disorder alone. In other cases, more aggressive treatment may be needed. Specific treatment options for macrophage activation syndrome are detailed below.

Treatment of the underlying rheumatic disorder

People with macrophage activation syndrome due to an underlying rheumatic disorder who have mild symptoms may improve from treating the rheumatic disorder alone. The treatment will vary based on the specific rheumatic disorder but often will include a course of oral or intravenous steroids such as methylprednisolone (Medrol).

Treatment of any triggering infections

This treatment will vary depending on the specific infection. For example, people with HIV should be started on antiretroviral drugs for HIV.

Medications to suppress the immune system

People with macrophage activation syndrome who are very sick should be treated with medications to suppress the immune system. The medications that are typically used are a combination of the intravenous steroid dexamethasone (Decadron) and a chemotherapy medication called etoposide (Toposar). Some doctors may also add a third medication called cyclosporine (Sandimmune). These medications are usually continued for at least eight weeks.

Medications for neurological symptoms

People with macrophage activation syndrome who develop neurological symptoms such as headache, confusion, seizures, or coma may benefit from medications injected into the spinal canal. These may include a combination of a steroid called hydrocortisone (Cortef) and a medication called methotrexate (Trexall).

Stem cell transplant

People with macrophage activation syndrome who have severe symptoms and do not improve with other treatments may benefit from a stem cell transplant. In a stem cell transplant, your bone marrow is destroyed with chemotherapy or radiation, and stem cells from a healthy donor are given to you to re-populate the bone marrow.

When to seek further consultation

If you or your child develops any symptoms of macrophage activation syndrome, including a persistent fever, masses in the abdomen, swollen lymph nodes, easy bruising/bleeding, or neurological symptoms, you should go to your doctor right away. Your doctor can order tests to see if you or your child is developing macrophage activation syndrome and offer the appropriate treatment.