Mast cells play an important role in our health. These tissue-based immune cells live in every organ in our body. Mast cells act as sentinels for the immune system. They are armed to recognize and respond to foreign invaders, such as a virus or an allergen. The sentinels counterattack with powerful chemical mediators that seek to repair tissue after the harm is contained.
When these mast cells start to increase in number or release chemical mediators at the wrong time, it can result in mast cell disease.
Mast cell diseases are caused by abnormal and/or overly active mast cells. Some people are born with a mast cell disease. Others may get it in childhood or adulthood. Mast cell diseases are rare, but they are increasingly recognized and diagnosed by doctors. The most common are mastocytosis, mast cell activation syndrome (MCAS) and hereditary alpha-tryptasemia syndrome (HαT).
Common symptoms of mast cell diseases include skin rashes, unexplained flushing, stomach pain, gastrointestinal tract problems, nausea, bloating and bone or joint pain. People with mast cell diseases might suddenly feel hot, even in a normal-temperature room. They may have a severe reaction to certain foods, medicines or an insect sting. They may struggle with life-threatening symptoms.
Symptoms might suggest an allergic reaction. But what to do if allergy testing is inconclusive? In this case, your doctor may evaluate you for a mast cell disease.
What are mast cells?
Mast cells are white blood cells in our immune system. They reside in body tissue and help protect us from viruses, germs, allergens, irritants and toxins. When mast cells detect one of these invaders, they help fight it off by releasing chemical mediators. But in the process of doing so, they trigger inflammation that can lead to symptoms in multiple body organs.
In people with mast cell diseases, the mast cells don’t work right. They may multiply too fast or over-react, sometimes in response to certain triggers such as allergens. When this happens, it can disrupt the function of the body organs. Mast cells are responsible for allergic reactions, including anaphylaxis (a severe allergic reaction).
What are the symptoms of mast cell disease?
Some people with mast cell diseases may have occasional symptoms. Others may have daily symptoms. Everyone’s symptoms are different but may involve multiple organ systems, including:
- Skin: a rash, skin lesions, flushing, swelling
- Stomach: Abdominal pain, nausea, vomiting, diarrhea, heartburn
- Brain: Feeling confused, trouble thinking, feeling anxious or sad, shaking, headaches
- Bones: Weak bones, bone pain
- Heart: Blood pressure changes, heart racing, fainting
- Breathing: Shortness of breath
- Anaphylaxis (a life-threatening allergic reaction)
Symptom triggers can include:
- Heat, cold or temperature change
- Friction or vibration on the skin
- Stress
- Pain
- Exercise
- Bug bites or stings
- Alcohol
- Contrast dyes that you might receive during a medical test
- Certain foods or medicines
- Infections
Patients may have many symptoms and triggers. They may visit many doctors seeking treatment. It can be difficult for some to find a doctor who connects the dots to a mast cell disease.
How are mast cell diseases diagnosed?
If you think you may have a mast cell disease, consider seeing a specialist. A board-certified allergist and immunologist can help with the diagnosis. Other specialists that can help with diagnosis include a gastroenterologist, dermatologist, endocrinologist and hematologist.
Mast cell disease signs and symptoms may vary in different people since mast cells can cause problems in any part of the body. Doctors will examine the skin for lesions. If lesions are found, the doctor will stroke the lesion to see if hives develop. This is called Darier’s sign and it usually indicates a mast cell disease is present. (If there are no lesions but stroking the skin still causes hives, then the diagnosis may be non-clonal or secondary mast cell disease.)
Blood and urine tests are common diagnostic tools. In a blood test, doctors look for serum tryptase – a marker of mast cell burden or activation – both at the baseline level and during a mast cell reaction. Urine tests examine for rises in histamine, leukotriene C4 or prostaglandin D.
Doctors may conduct a biopsy. In a biopsy, the doctor removes a small part of the skin or bone marrow and look at it under a microscope. This can confirm a mast cell disease diagnosis.
Doctors might order CT scans to see how your mast cells are affecting your body. Some patients may undergo genetic tests as well to confirm a diagnosis.
Diagnosing Mast Cell Disease in Skin of Color
Diagnostic criteria may differ between people with light skin and darker skin. Mast cell disease often involves skin symptoms: spots or rashes. For people with light skin, there is redness on the skin. For people of color, the affected skin may appear purple, brown, tan or gray. Reddish-brown spots, called urticaria pigmentosa, may be less noticeable on darker skin. Rashes may be less noticeable or visible on darker skin than in people with lighter skin.
Misdiagnosis and delayed diagnosis of mast cell disease are common in people of color. Medical training has improved in recent years. But more research on mast cell disease in people of color is needed.
How are mast cell diseases treated?
Mast cell disease treatment first involves addressing severe symptoms from anaphylaxis. Managing mast cell disease may include using medications that reduce the mast cell action.
Anaphylaxis treatment
Some people with mast cell disease may experience anaphylaxis, a severe reaction. It results from a sudden, rapid release of the mediators from mast cells. Epinephrine is the first line of treatment for anaphylaxis. Give epinephrine at the first sign of severe symptoms. It is the only medication that can reverse anaphylaxis. Epinephrine can cause side effects such as anxiety, dizziness, shakiness, headache, and nausea, but these are usually mild and not life-threatening.
Keep epinephrine with you at all times. Carry two devices of epinephrine in case symptoms return after the first dose.
If your symptoms improve after one dose of epinephrine and you’re feeling better, you do not need to go the hospital or emergency department. However, you should administer a second dose and seek emergency medical help if…
- symptoms return or worsen after the first dose of epinephrine;
- you have severe anaphylaxis;
- symptoms do not go away promptly or completely after the first dose of epinephrine.
If you do not have epinephrine readily available, call 911, or go to the hospital, emergency department or urgent care clinic right away for treatment. Do not delay!
Medications
Medications are available to make mast cells less reactive. They also block the effects of mast cell mediators. These medications include:
- H1 and H2 antihistamines – blocks the effects of histamine and reduce symptoms
- Mast cell stabilizers (cromolyn sodium, ketotifen) – prevents mast cells from releasing histamine and leukotrienes
- Leukotriene inhibitors such as montelukast – blocks leukotrienes, inflammatory chemicals released by mast cells
- Aspirin (only under direct physician’s supervision)
- Omalizumab (brand name Xolair®) – targets the protein antibody Immunoglobulin E (IgE) to limit the release of histamine from mast cells
- Tyrosine kinase inhibitors for systemic mastocytosis
Tyrosine kinase inhibitors are medications that can help stop symptoms before they start. They work by inhibiting the proteins that lead to a buildup of mast cells. They can also stop or limit histamine release. Three tyrosine kinase inhibitors are available to treat mastocytosis. They are avapritinib (brand name Ayvakit®), imatinib (brand name Gleevec®) and midostaurin (brand names Rydapt® and Tauritmo®). Tyrosine kinase inhibitors are taken orally as a pill. They are typically prescribed for people with advanced disease.
Severe mast cell diseases may require treatment with chemotherapy. This does not mean the patient has cancer. However, people with mast cell diseases are at increased risk for certain cancers.
Talk with your doctor about what medication or treatment is right for you.
What are different types of mast cell disorders?
There are three main types of mast cell disease. These include mastocytosis, mast cell activation syndrome and hereditary alpha tryptasemia syndrome.
Mastocytosis
Mastocytosis is a disorder in which abnormal mast cells build up in the body. These mast cells develop a mutation that allows them to evade mechanisms that control their growth. This unchecked growth disrupts the tissue it’s designed to protect. They transfer into organs including the skin, bone marrow, digestive system and respiratory system. Symptoms can include flushing, skin rashes, stomach pain, diarrhea, hypertension or hypotension, syncope and musculoskeletal pain.
People with systemic mastocytosis are at higher risk for developing anaphylaxis. Severe cases are rare, but they can lead to organ failure or certain types of cancer.
Mast cell activation syndrome (MCAS)
People with mast cell activation syndrome have overactive mast cells. The mast cells release chemical mediators such as histamine too frequently. It can occur with or without exposure to an allergen trigger. People with MCAS are at higher risk for anaphylaxis. It can lead to symptoms such as hives, swelling, difficulty breathing, low blood pressure and severe diarrhea. People with MCAS also are at risk for severe allergic reactions, or anaphylaxis.
Sometimes the cause of symptoms is unknown – this is called idiopathic MCAS.
Hereditary alpha-tryptasemia syndrome
Hereditary alpha-tryptasemia (HαT) is a genetic trait. It affects 4-8% of the general population. People with this trait have high levels of the protein alpha tryptase. This protein is found around blood vessels and in mast cells. The tryptase levels become more elevated during an allergic reaction.
Having the trait does not mean you will have mast cell disease symptoms. About one-third of people with HaT don’t have mast cell disease symptoms. Those who do, however, are at higher risk for having systemic mastocytosis and anaphylaxis.
Living with Mast Cell Disease
Living with a mast cell disease can be hard. Avoiding triggers is a challenge because there are so many. They can range from sudden changes in temperatures to certain foods. Also, symptoms can vary from person to person. They can affect multiple organ systems, including the skin, heart, lungs, gut and bones. When symptoms are severe, it can lead to life-threatening anaphylaxis.
Medications are usually a key part of living with mast cell diseases. These can block the reactivity of mast cells. Managing the condition successfully is also key. You may have to adjust your diet if foods are a trigger. You may have to wear extra layers to protect yourself from sudden changes in weather.
Once you find a doctor knowledgeable in mast cell diseases, discuss your triggers and ways to manage your condition. With planning and preparation, you can live an active life with a mast cell disease.
Mental Health and Mast Cell Disease
The link between mental health and mast cell diseases is a combination of factors. Mast cell diseases can cause neurologic or psychiatric disorders. The stress of living with a chronic illness that make take years to properly diagnose is a risk factor for mental health problems. Treatment side effects may also contribute to mental health concerns.
Ask your doctor for a referral to a mental health specialist if you don’t already have one. providers.
Questions & Answers (Q&A) on Mast Cell Diseases
You may have specific questions about mast cell diseases. Here’s a Q&A with some common questions. If there’s something you’d like to see covered, please email the editor with more questions.
Patient Story: Mastocytosis and Anaphylaxis
Gail Barbera is a past Board of Directors member of The Mast Cell Disease Society.
My husband and I had just arrived at a restaurant for dinner with his family. When we were seated, I suddenly began to feel a familiar pain in my stomach. It was like a rock poking my mid-torso. I felt flushed. I knew then I had less than a minute before anaphylaxis struck.
My head began to buzz and my vision “grayed.” I managed to get my epinephrine and put it in front of my sister-in-law, who is a nurse. Then … down I went, unconscious on the floor.
I have systemic mastocytosis. It is mast cell disease that involves abnormal mast cells building up in my organs. Due to this, I have experienced anaphylaxis more than a dozen times. It has happened at work, in a store, on the side of the road.
My sister-in-law injected the epinephrine. She called out my name, but I was not able to respond. I felt disoriented, confused, and sleepy. I eventually opened my eyes and heard someone say the ambulance was coming. My husband asked if we could be sent to the hospital where my mastocytosis specialist would be able to provide treatment.
When the ambulance arrived, the EMT put an oxygen mask on me, but I still struggled to get air. The stomach pain was terrible by that point. I had a prescription protocol signed by my doctor just for this type of situation. But the EMTs said they couldn’t give me pain medicine until I had seen a doctor.
At the hospital, the ER staff contacted my mastocytosis specialist. The doctors started an IV, adding antihistamines and morphine. Slowly the pain subsided.
Since the episode, my doctor adjusted my treatment plan to help slow the progression of mastocytosis-related anaphylaxis should it occur again. And I always carry my epinephrine and the prescription protocol with me wherever I go.
For support and further information about mast cell diseases, please visit The Mast Cell Disease Society.
Mast Cell Disease Podcasts
‘Mast Cell Diseases & Systemic Mastocytosis: The Basic Science’
‘Symptoms and Triggers of Mast Cell Disease’ Podcast
How to Diagnose Mast Cell Disease
How are Mast Cell Diseases Treated?
How Do Stress and Low Histamine Diets Impact Mast Cell Disease?
Living with Systemic Mastocytosis
Mast Cell Disease, the Hematologist and New Treatments on the Horizon
What to Know About Advanced Systemic Mastocytosis
Reviewed by:
Anne Maitland, MD, FACAAI, is director of Allergy & Immunology Services at the Metrodora Institute. She previously served as assistant professor in the Department of Medicine, Allergy & Clinical Immunology, at Icahn School of Medicine at Mount Sinai in New York City. Dr. Maitland is very active in increasing awareness of immune-mediated disorders. She is also involved with research to continually improve the treatment of allergies, asthma and recurrent infections.
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