Why is systemic mastocytosis so hard to diagnose?

The journey to a systemic mastocytosis (SM) diagnosis is often a long one: Studies have found that on average, it takes six years after symptoms appear for a patient to finally be diagnosed.

Here are some of the reasons why the road to diagnosis is so winding.

Symptoms can seem unrelated and unpredictable

SM is characterized by a buildup of abnormal mast cells in organs beyond the skin. (When mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. buildup is limited to the skin, it’s called cutaneous mastocytosis.)

Mast cells are one of the many types of cells that form the immune system. They help defend the body against pathogens that can cause infections. When they sense a threat, they release chemical mediators, such as histamineHistamine A chemical released by mast cells when they are activated. Histamine causes many of the allergy-type symptoms in mastocytosis, including flushing, itching and hives.. These substances tell the body to help move immune cells in to fight the threat — a reaction that causes symptoms.

In most people, this might mean itching, hives, flushing and sinus congestion. But in people with SM, the excess mast cells can lead to many more symptoms, such as:

• Fatigue or weakness.
• Abdominal pain, bloating, nausea, vomiting or diarrhea.
• Acid reflux.
• Dizziness or fainting.
• Heart palpitations.
• Bone, muscle or joint pain.
• Headaches.
• Brain fog, difficulty concentrating or memory problems.
• Mood changes, including anxiety or depression.
• Wheezing or shortness of breath.

In people with SM, mast cells can also release their mediators more easily than in other people. Sometimes they react to classic allergic triggers, like pollen or mold. But they may also react to uncommon triggers, like hot water, perfumes and even the sun.

To add another complication, mast cells are present in many areas throughout the body. That means SM symptoms can affect many different organs and systems. Many of these symptoms are also what doctors call nonspecific. This means they can occur in many different conditions, making it harder to identify SM as their cause.

All this means SM symptoms can affect several different parts of the body, sometimes without an obvious trigger. A person with SM might wake up feeling heart palpitations one day, have abdominal pain another day and sinus congestion a week later. Connecting the dots is no easy task.

Symptoms can resemble other conditions

Doctors tend to think of the most common diseases associated with a patient’s symptoms — not the rare ones. This can be a problem when a patient’s SM symptoms match those of another disease. If a patient has abdominal pain and diarrhea, their doctor will assume they have a digestive condition. If a patient has itching and nasal congestion, their doctor will suspect they have allergies.

The reasoning makes sense: In most patients, common conditions are the cause of symptoms. But it also means that a rare disease like SM may not be considered right away. 

The result is often that a person with SM spends years going from one appointment to another, trying to figure out what is going on.

Read more about how SM affects the body: “Systemic mastocytosis and organ damage: How and why it occurs“

Diagnosis requires specialized testing

Another reason SM is hard to identify is that the disease cannot be diagnosed through the most common blood tests. Diagnosing systemic mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. actually requires a combination of lab test results — but patients with SM can often have normal findings in some tests, meaning that even if SM is on a doctor’s radar they might rule out the condition.

For example, one indicator of SM is high levels of tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM., which is a substance produced by mast cells. However, many people with mastocytosis have normal tryptase levels, without the high numbers that indicate SM.

Another example is genetic testing to look for changes in the KIT gene. The KIT D816V mutation — the most common cause of SM — is often present in only a tiny fraction of the genetic material being tested, especially when peripheral blood is used for the test. This makes it easy to miss. A bone marrow biopsyBone marrow biopsy A procedure to collect a sample of bone marrow using a needle. Often used to examine the characteristics of mast cells and diagnose SM. is often needed to look for abnormal mast cells and help confirm the diagnosis, but this testing is more involved.

Raising awareness of systemic mastocytosis

Before a doctor can order any of these tests, they have to consider SM as a possible explanation. This shows the importance of raising awareness. 

Patients, advocacy groups and health care professionals can work together to improve understanding of the disease, share reliable information and draw attention to the challenges people face before getting a diagnosis.

Read about SM Ambassador Tara Keith’s long road to an ISM diagnosis: “My 25+ year journey to diagnosis of indolent systemic mastocytosis“