Medically reviewed by Archana Sharma, DO
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- Indolent systemic mastocytosis (ISM) is a rare blood disorder that happens when the body makes too many mast cells, a type of white blood cell involved in allergic reactions.
- Potential complications of ISM include anaphylaxis, bone health problems, gastrointestinal symptoms, and more.
- Working with your healthcare team to develop an ISM treatment and management plan can lower the risk of complications.
For people with indolent systemic mastocytosis (ISM), their bodies make too many mast cells—these cells are part of the immune system, so people with ISM often experience severe reactions (anaphylaxis) in response to a number of different triggers. But this overproduction of mast cells can also lead to other complications throughout the body, including stomach problems, rashes, brain fog, and more.
1. Anaphylaxis
Anaphylaxis, a life-threatening allergic reaction, is one of the most commonly reported complications of ISM. In fact, some estimates show that around 50% of people with ISM or related systemic mastocytosis (SM) sub-types experience anaphylaxis.
People with ISM have a higher number of mast cells, which are immune system cells responsible for allergic reactions. When mast cells come into contact with allergens like food or pollen, they release histamines and other chemicals that produce an allergic response. Sometimes these reactions can be severe, leading to symptoms such as:
- Throat tightness
- Trouble breathing
- Itchy, red welts
- Low blood pressure
- Fast heart rate
- Nausea and vomiting
- Dizziness
- Fainting
- A feeling of doom
Anaphylaxis is a medical emergency that can be fatal if it's not treated. People with ISM should plan to carry two epinephrine auto-injectors (EpiPens) with them in case of a serious allergic reaction.
2. Loss of Bone Density
Mast cells are produced in the bone marrow, or the soft tissue found inside the bone. Since people with ISM experience an overproduction of mast cells, they often have high concentrations of these cells in their bone marrow.
This can lead to a number of bone health issues, including low bone mineral density and osteoporosis. These conditions raise the risk of bone breaks and fractures and may cause pain, reducing the quality of life of people with ISM.
Research suggests that 30–60% of patients with systemic mastocytosis (SM), the umbrella term for ISM and closely related diseases, have osteoporosis.
3. Gastrointestinal Distress
In ISM, mast cells can accumulate in the gastrointestinal tract and cause symptoms, including:
- Abdominal pain and cramps
- Nausea
- Bloating
- Diarrhea
- Acid reflux
- Vomiting
- Flatulence
These symptoms usually start slowly and may be mistaken for other chronic health conditions, such as irritable bowel syndrome.
4. Skin Problems
People with ISM commonly experience skin symptoms, including skin flushing or itchiness. Other common concerns include urticaria pigmentosa or maculopapular rash—these both refer to raised, discolored bumps or patches of skin that are sometimes painful or itchy.
Skin lesions may appear purple, gray, or black on people with darker skin tones, while they may look red, pink, or brown on those with lighter skin tones.
5. Anemia
The overproduction of mast cells in ISM can affect blood health and raise the risk of anemia, a shortage of functional red blood cells. When this happens, people may struggle to get enough oxygen, which can lead to weakness, dizziness, heart rhythm issues, and more.
Anemia may be more common in people who have more aggressive forms of SM, rather than ISM.
6. Enlarged Spleen or Liver
In people with ISM, mast cells can accumulate in organs, including the gastrointestinal tract, the bone marrow, and sometimes the liver and spleen.
When mast cells build up in the spleen or liver, these organs can become enlarged. An enlarged liver (hepatomegaly) may not be able to function as well, while an enlarged spleen (splenomegaly) may rupture more easily.
Severe complications that involve the spleen and liver are usually found in more advanced types of SM.
7. Brain Fog and Mood Symptoms
It's common for people with ISM to experience cognitive symptoms, including brain fog, memory issues, or difficulty focusing. In addition, patients' mental health is often affected—some people may experience depression, mood changes, tiredness, or irritability.
These symptoms likely happen when high numbers of mast cells (or the chemicals they produce) infiltrate the nervous system.
Treating Complications and Lowering Your Risk
The keys to managing ISM are taking steps to limit mast cell activity in your body and treating any symptoms or complications that arise from the disease.
To limit reactions from mast cells in the body, your care team will likely set you up with a treatment plan that may include:
- Skin care: Topical creams keep your skin moisturized and reduce the risk of reactions.
- Antihistamines: Common antihistamines can help block mast cells from releasing too much histamine in your organs and tissues, limiting allergic reaction symptoms.
- Tyrosine kinase inhibitors: New medications, such as midostaurin (Rydapt) and avapritinib (Ayvakit), target the genetic mutation that causes the overproduction of mast cells in ISM.
It's also important for people with ISM to avoid anything that triggers mast cells (and an allergic reaction) in the first place. Common triggers include insect bites, sudden temperature changes, certain drugs, pollen, pet dander, and certain foods.
If you do develop complications from ISM, your team of doctors can help you find treatments to mitigate symptoms:
- Epinephrine auto-injectors (EpiPens) help you avoid anaphylaxis.
- Bisphosphonates or other drugs to treat osteoporosis can reduce your risk of bone fractures.
- Blood transfusions or medications can replace red blood cells in people with severe anemia.
- Proton pump inhibitors (such as Prevacid) or oral corticosteroids ease stomach symptoms.
- Individualized plans from mental health professionals can help you manage depression or brain fog.
- Ultraviolet therapy paired with certain oral medications can reduce skin flare-ups.
