The Development of Mastocytosis
What are mast cells? / What is mastocytosis?
Mast cells are cells of the immune system found in numerous tissues throughout the body. They contain various signaling molecules — including histamine and tryptase — and play a central role in inflammatory responses, immune defense, and allergic reactions. Particularly high concentrations of mast cells are found in the skin, in the mucous membranes of the mouth and throat, the lungs, and the gastrointestinal tract.
Mastocytosis involves an abnormal proliferation of mast cells. This increases the risk that the signaling molecules stored in the mast cells will be released in large quantities. These can cause a variety of symptoms, such as itching or gastrointestinal problems. Many affected individuals also exhibit typical skin changes. In rare cases, a marked increase in mast cells in the bone marrow – the site of blood formation – also leads to changes in the blood count.
What causes mastocytosis?
In the vast majority of cases, mastocytosis is caused by an acquired change in the KIT gene, known as a KIT mutation. This mutation causes mast cells to grow uncontrollably and become activated more easily. Why this genetic change occurs is not yet fully understood; in most cases it probably occurs spontaneously.
Is mastocytosis hereditary?
Mastocytosis is generally not inherited. The KIT mutation responsible for the disease arises during a person’s lifetime (a so-called somatic mutation) and is not passed on to children. A clustered occurrence within families has been observed only very rarely. The risk of passing on mastocytosis to one’s children is therefore extremely low.
Clinical Presentation
What types of mastocytosis are there?
Mastocytosis is a condition in which mast cells proliferate abnormally and accumulate in various tissues of the body. Two main types are generally distinguished:
In cutaneous mastocytosis, mast cells proliferate exclusively in the skin. This type occurs predominantly in childhood and resolves on its own in most cases.
In adults, however, systemic mastocytosis is usually present. In this case, internal organs are affected, such as the bone marrow, liver, or gastrointestinal tract, sometimes accompanied by additional proliferation of mast cells in the skin. Systemic mastocytosis is typically chronic and can vary greatly in severity. Depending on the severity and course of the disease, a distinction is made between non-advanced and advanced forms. Advanced systemic mastocytosis can also occur in conjunction with other blood disorders.
What are the typical symptoms of mastocytosis?
Typical symptoms of cutaneous mastocytosis include brownish-red skin lesions that often appear on the thighs and on the abdomen and back. In adults, these skin lesions are usually only a few millimeters in size, whereas in children they tend to be several centimeters. When scratched or rubbed, the skin lesions become red, swell, and start to itch – this is known as Darier’s sign. This reaction can also be triggered by changes in temperature or, occasionally, by infections. Less commonly, hives may appear all over the body.
In addition to skin lesions, affected individuals may experience a wide variety of symptoms. These include gastrointestinal symptoms such as abdominal pain, nausea, vomiting, and diarrhea. Headaches, dizziness, and difficulty concentrating may also occur. Additionally, joint and bone pain – often affecting the forearms and lower legs – as well as fatigue and exhaustion may be present.
About half of the adults with systemic mastocytosis suffer from allergies, which can also be severe (anaphylaxis). This can lead to a sudden rise in body temperature, shortness of breath, and circulatory collapse. The most common triggers are bee and wasp stings.
In the advanced form of systemic mastocytosis, symptoms depend on which organs are affected. These may include, for example, severe anemia or bone marrow dysfunction, liver dysfunction, intestinal dysfunction, etc. Nonspecific symptoms in these cases often include fever, general malaise, and loss of appetite and weight.
What are the possible disease courses?
The course of mastocytosis can vary greatly. In children, a cutaneous form of mastocytosis is common, which may partially or completely resolve over time. In adults, the course ranges from mild symptoms to severe forms. The most common form in adults is indolent systemic mastocytosis, which usually has a stable course and is generally associated with a normal life expectancy. Rare aggressive forms or those in combination with other blood disorders require more intensive and specialized treatment. The individual course depends on the type of disease, organ involvement, and response to therapy.
Diagnostic Measures
How is mastocytosis diagnosed?
The diagnosis of mastocytosis is made through an interdisciplinary approach. Clinical symptoms, skin findings, blood test results, microscopic changes in tissue (most commonly skin or bone marrow, occasionally the gastrointestinal tract), and genetic analyses of blood and/or tissue are all considered to establish the diagnosis and assess the extent of the disease.
Is a bone marrow aspiration necessary to definitively diagnose mastocytosis? / When is it appropriate to perform a bone marrow aspiration?
In adults with a well-founded clinical or laboratory suspicion of mastocytosis, a bone marrow aspiration is generally appropriate and recommended. The test allows for a definitive diagnosis, provides important information regarding the prognosis, and reveals whether there is an additional hematopoietic disorder present. In addition, highly sensitive genetic analyses can be performed on bone marrow, which are often not sufficiently informative when performed on blood.
What is tryptase, and what role does it play in the diagnosis of mastocytosis?
Tryptase is an enzyme stored in mast cells that is released upon activation. Unlike other mediators such as histamine, tryptase can be reliably measured in the blood. In mastocytosis, the number of mast cells is elevated, leading to an increase in the continuous release of tryptase. For this reason, tryptase can be used as a marker for mastocytosis. Measuring tryptase is therefore part of the diagnostic process and can also be used to monitor the progression of the disease.
However, there are also other reasons for elevated tryptase in the blood, including advanced age, renal insufficiency, and a genetic mutation causing increased tryptase production (familial/hereditary alpha-tryptasemia; see next question).
What is HaT and what role does it play in the diagnosis of mastocytosis?
Hereditary alpha-tryptasemia (HaT) is a congenital genetic condition in which the body continuously produces higher levels of the enzyme tryptase. This is not a disease in itself, but it can exacerbate symptoms caused by mast cells, e.g., skin problems, gastrointestinal symptoms, or cardiovascular disorders. HaT can also occur alongside mastocytosis and influence symptoms. Therefore, testing for HaT can be helpful when the causes of symptoms (see Clinical presentation) are unclear or tryptase levels are elevated. Since mastocytosis can occur with or without associated HaT, the HaT test is not decisive for the diagnosis of mastocytosis. However, it can be helpful in explaining certain symptoms.
What is the KIT D816V VAF, and what role does it play in the diagnosis of mastocytosis?
The KIT gene is specifically mutated at the position encoding the 816th amino acid of the corresponding protein in >90% of mastocytosis cases (D816V, the negatively charged amino acid aspartate is replaced by the fat-soluble amino acid valine in the mutated protein, which changes the functions of the protein). Since few other diseases exhibit such mutations, the detection of this mutation in blood or tissue is considered diagnostically helpful. In addition, the ratio of mutated KIT genes to non-mutated genes (from other cells in the blood or tissue), known as the variant allele frequency (VAF), allows for certain prognostic assessments and should be determined using sensitive methods at the onset of the disease and throughout its course.
Is there a specific center in Switzerland for tissue-based (biopsy) diagnosis of systemic mastocytosis, and how can I send my samples there?
The SAKK Reference Center for Malignant Lymphomas at the Institute of Medical Genetics and Pathology of the University Hospital Basel hosts the internationally leading experts in the field Prof. Alexandar Tzankov and Prof. Stefan Dirnhofer, and it provides access to state-of-the-art molecular techniques for the primary and second-opinion diagnosis of systemic mastocytosis. This requires standard formalin-fixed biopsies (primary diagnosis) or paraffin-embedded biopsies from the archives of the primary diagnostic institutes (second-opinion diagnosis); see also: https://www.unispital-basel.ch/pathologie.
SAKK-Referenzzentrum für maligne Lymphome
Institut für Medizinische Genetik und Pathologie
Universitätsspital Basel
Schönbeinstrasse 40
4031 Basel
Tel. +41 61 265 27 57
Treatment
What treatment options are recommended for the various types of mastocytosis?
Treatment for mastocytosis depends on the form of the disease and the severity of the symptoms. It is always important to avoid known triggers such as insect bites, certain medications, or alcohol, to prevent flare-ups. In cutaneous mastocytosis (when only the skin is affected), the focus is on symptom relief, and antihistamines are often used to alleviate itching, redness, and swelling. In systemic mastocytosis (when internal organs are involved), additional medications such as cromoglicic acid can help reduce or block the release or effects of mast cell mediators. In severe cases, targeted therapy, e.g. with tyrosine kinase inhibitors/KIT inhibitors, may be necessary to control the disease. If a further type of blood cancer is present in addition to systemic mastocytosis, specific hematological therapies, some of which may be intensive, are used.
What treatment options are available if I have had anaphylaxis following a bee or wasp sting?
A severe allergic reaction to an insect sting may indicate the possible presence of mastocytosis and should be investigated for this condition once the symptoms have subsided. Following an allergic reaction (anaphylaxis) to a bee or wasp sting, specific immunotherapy (hyposensitization) is the most important treatment for preventing future reactions. This therapy is administered under careful medical supervision and can be particularly effective for people with mastocytosis, but it is also associated with certain risks.
In addition, it is very important to always carry an emergency kit with you. This should contain an epinephrine auto-injector, an antihistamine, and a corticosteroid. Thorough training in the proper use of the emergency kit as well as regular check-ups with a specialist in allergology are strongly recommended.
Do I always have to carry an emergency kit and an epinephrine auto-injector with me? How many?
Ja, als Patientin oder Patient mit Mastozytose und einem erhöhten Risiko für Yes, as a patient with mastocytosis and an increased risk of severe allergic reactions (anaphylaxis) upon contact with triggers (e.g., insect stings, certain medications), it is strongly recommended that you carry an epinephrine auto-injector (EpiPen® or Jext®) with you.
Useful tips:
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You should always have at least one epinephrine auto-injector within reach.
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Better yet, two: It is often recommended to carry two auto-injectors, as a second dose of epinephrine is required in about 20% of cases, especially if:
- you are far from medical facilities
- you have had severe reactions in the past
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Talk to your treating physician (e.g., an allergist or hematologist) about your individual situation and ask for clear instructions on what to do.
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Carry an emergency card or wear a bracelet that indicates your mastocytosis and risk of anaphylaxis.
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Make sure your auto-injectors have not expired and are stored correctly (at room temperature, not in direct sunlight or extreme cold).
Can mastocytosis be cured?
In children, the condition often presents as a cutaneous form of mastocytosis, which may partially or completely resolve over time.
The most common form in adults is non-advanced systemic mastocytosis, which is usually chronic, i.e. it persists over a longer period of time. With targeted treatment, symptoms can often be well controlled and quality of life significantly improved. Regular medical check-ups, avoiding triggers, and a personalized treatment plan are essential. In cases of severe symptoms, so-called tyrosine kinase inhibitors (medications that specifically inhibit the altered KIT receptor) may also be considered as a treatment option. These can help achieve a long-lasting symptom-free period.
In cases of advanced systemic mastocytosis requiring an intensive treatment approach, a cure can sometimes be achieved through a bone marrow transplant.
Living with the Disease
Are there any activities that are not recommended for people with mastocytosis?
Yes, there are certain activities and situations that people with mastocytosis should avoid or approach with caution due to the risk of mast cell activation and a potential anaphylactic reaction. This depends heavily on the individual’s specific condition, potential triggers, and overall health. Here are the most important guidelines:
1. Saunas and exposure to heat or cold
Extreme heat and sudden temperature changes (e.g., when moving from a sauna to a cold plunge pool) can activate mast cells and trigger symptoms such as circulatory problems or even anaphylactic reactions.
Use saunas and steam rooms only after consulting your doctor. Avoid extreme temperatures and abrupt changes. Monitor your individual response. The same applies to cold exposure (e.g., cold chambers).
2. Swimming Pools and Chlorinated Water
Chemicals like chlorine can irritate the skin and activate mast cells. Cold or very warm water can also trigger reactions. Therefore, approach swimming with caution. Avoid pools with high chlorine levels. Caution is also advised when swimming in cold water (e.g., lakes in winter).
3. Exercise and physical exertion
Strenuous exercise can activate mast cells through physical stress, especially in hot weather or when dehydrated. Moderate exercise is often unproblematic and can even be helpful. Make sure to stay well-hydrated and take regular breaks. Opt for activities with steady exertion (e.g., yoga, swimming in moderate temperatures).
4. Workplace
Certain environments or activities may expose you to triggers, e.g., chemicals (such as those found in industrial settings), heat, cold, or certain fragrances. Similarly, severe stress or irregular work hours can worsen the symptoms of mastocytosis. If necessary, inform relevant parties about your condition to receive support.
5. Stress and Emotional Distress
Stress is a common trigger for mast cell activation. Try stress management strategies such as meditation, breathing exercises, or psychological support
6. Medications and Substances
Some medications (e.g., pain relievers such as opioids) or substances (e.g., alcohol, caffeine) can activate mast cells. Discuss any medication with your doctor and keep a list of safe medications and a list of those you have had adverse reactions to.
However, it is important that you do not restrict yourself completely but rather remain active within safe limits to maintain your quality of life. An experienced doctor (specializing in mastocytosis) can provide you with personalized advice.
Are there medications I should avoid as a mastocytosis patient?
Some medications can trigger or worsen symptoms in people with mastocytosis. These include certain pain relievers (e.g., opioids, aspirin, and ibuprofen), some anesthetics, and certain contrast agents. Similarly, alcohol can activate mast cells.
Which substances are problematic varies from person to person. Therefore, any new medication should be discussed with your treating physician beforehand. It is advisable to keep a personal list of medications you tolerate well and those you do not.
What preparations do I need to make before a dental procedure (under local anesthesia)?
Before a dental procedure is carried out, it is important that your dentist is aware of your mastocytosis. Discuss with them which local anesthetics are safe for you - adrenaline-free formulations are generally better tolerated. It is often recommended to take antihistamines or other preventive medications before the procedure. Bring your emergency medications (e.g., epinephrine auto-injector) with you to the appointment. The procedure should only be scheduled if you feel stable and have no acute symptoms.
What preparations do I need to make for a procedure under general anesthesia?
Before a procedure under general anesthesia is carried out, you should inform your anesthesia team about your mastocytosis well in advance. Discuss together which anesthetics are safest for you, as some medications can trigger allergic reactions. It is often recommended to take antihistamines or cortisone as a preventive measure. Bring your emergency medications (e.g., epinephrine auto-injector) with you and keep them ready or hand them to the anesthesia team. The procedure should only take place if you have no acute symptoms or infections.
Is there a way to easily exchange information with others affected by the condition?
Yes, in Switzerland, people affected by mastocytosis can exchange experiences with one another. A central point of contact is the SELMAS association (Swiss Association for Mastocytosis Patients, Family Members, and Supporters). SELMAS offers patients and their families a platform for sharing experiences and information. SELMAS regularly organizes events that provide opportunities to meet other people with the condition and share experiences on how to cope with it.
Contact SELMAS:
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Website: mastozytose.ch
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E-Mail: info@mastozytose.ch
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Phone: 079 206 75 18
In addition, SELMAS works closely with the Swiss Mastocytosis Network (Swiss Mastocytosis), an initiative of physicians and scientists with a special interest in mastocytosis. This network is committed to providing the best possible care for those affected in Switzerland and maintains regular communication with SELMAS. Physicians from Swiss Mastocytosis regularly participate in clinical trials of new medications for mastocytosis.