Indolent Systemic Mastocytosis: What It Is and What It Means for You

Indolent systemic mastocytosis, usually shortened to ISM, is a rare immune condition affecting an estimated 1 in 10,000 to 20,000 people worldwide. If you have ISM, here is what it can mean for your daily life.¹

What is indolent systemic mastocytosis?

Mast cells are immune cells that help protect you. They live in your skin, gut, bone marrow, and the tissue around your organs. When activated, a mast cell releases chemicals called mediators, such as histamine and tryptase. These cause the swelling, itching, and flushing of an allergic reaction.^1,2

The “indolent” in ISM means slow-moving. In ISM, your body makes too many abnormal mast cells, and over time, they build up in your tissues.^1,2

“Systemic” means the condition can impact multiple organs in the body. Mast cells can gather in your bone marrow, digestive tract, liver, and spleen as well as your skin.^1,2

How ISM is different from other types of systemic mastocytosis

The World Health Organization (WHO) recognizes 6 types of systemic mastocytosis. The 3 mildest and most common types are:^1-4

• Bone marrow mastocytosis – Mast cells build up in the bone marrow, causing brittle and weakened bones but no skin symptoms.
• Indolent systemic mastocytosis – The most common type in adults, and one of the milder forms, but it can worsen over time. Skin symptoms are common.
• Smoldering systemic mastocytosis – Symptoms can be more serious than indolent systemic mastocytosis, affecting organs like the spleen. It worsens over time and includes more pronounced skin symptoms.

Advanced, more severe types of systemic mastocytosis are rare and include:^1-4

• Aggressive systemic mastocytosis – Mast cells severely impair organ function.
• Systemic mastocytosis with another blood disorder – Occurs alongside a blood or bone marrow condition, such as cancer.
• Mast cell leukemia – The rarest and most serious type.

What causes indolent systemic mastocytosis

About 80 percent of people with systemic mastocytosis have a variant, or a change, in a gene called a KIT gene. That gene makes a protein that signals mast cells to grow and divide. When it changes, the signal sticks in the “on” position, and your body makes too many mast cells.^1,2,5,6

This change almost always happens on its own during your life, in your own cells, rather than being inherited. It is generally not passed down to children, and it affects men and women equally.^1,2,5,6

How indolent systemic mastocytosis is treated

There is no cure for ISM. Treatment aims to control your symptoms and lower your risk of a severe allergic reaction.^6,7

Two drugs carry US Food and Drug Administration (FDA) approval for the treatment of ISM:^8,9

• Avapritinib (Ayvakit®) – A KIT inhibitor, approved for adults with indolent systemic mastocytosis (ISM).
• Cromolyn sodium (Gastrocrom®) – A mast cell stabilizer, approved for the management of people with mastocytosis.

According to the FDA, some versions of cromolyn oral concentrate have “limited availability” due to shortages. Some versions of medications may be available while others are not. Your doctor will be able to help you decide what is right for you.^10,11

Many people also use supportive treatments aimed at specific symptoms, including:^2,4,6,7

• Avoiding your triggers – The foundation of daily control.
• H1 antihistamines – For itching, flushing, headaches, and stomach pain.
• H2 antihistamines – For stomach and reflux symptoms.
• Leukotriene inhibitors – For flushing, cramping, and breathing symptoms.
• Drugs that lower stomach acid – Proton pump inhibitors, for reflux and ulcers.
• Bone-protecting drugs – Used when a bone density scan shows thinning.

It is also recommended people who have systemic mastocytosis carry epinephrine. It comes as an auto-injector (EpiPen®) or a nasal spray. Always carry 1-2 doses with you so that you are prepared to administer treatment in the event of anaphylactic shock, a severe, life-threatening allergic reaction.^5-7

The antihistamines, leukotriene inhibitors, acid-lowering drugs, and bone-protecting drugs listed above are not approved by the US Food and Drug Administration to treat indolent systemic mastocytosis specifically. They may be approved for other conditions. A doctor may prescribe them “off-label” when evidence suggests they help. Talk to your doctor about what is right for you.

What to expect over time

Prognosis depends on the aggressiveness of the type of systemic mastocytosis that a person has. Because ISM moves slowly and is a milder type, people with ISM tend to have a life expectancy that is similar to the general population.^4,6

Talk to your doctor

ISM looks different for everyone. Some people manage their symptoms with daily medication, and others need more support.

It is recommended that ISM patients have their bone health regularly monitored. A bone density scan is recommended at diagnosis and again during follow-up to check for signs of osteoporosis.^6,7

Bring your questions to appointments, and speak up when something changes. It is important to have regular conversations with your doctor about your symptoms and treatment to find what works for you.