Learn The BasicsSystemic mastocytosis (SM) is a rare disease that is usually caused by a sporadic mutation in the KIT gene. This gene codes for a protein called CD117 transmembrane tyrosine kinase, which is involved in the growth, survival and migration of mast cells.
The most common KIT mutation associated with the disease is the D816V mutation, which is a point mutation and a single letter change at position 816. This results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
More than 90% of patients with SM have the KIT D816V mutation.
This mutation leads to mast cells becoming more sensitive to the effects of a signaling protein called stem cell factor (SCF), which stimulates their production and survival.
These mast cells then accumulate in different tissues and organs throughout the body and release substances such as histamine, leukotrienes and cytokines, which lead to inflammation and the development of the disease’s symptoms.
Mutations in the KIT gene are usually not inherited and occur sporadically by themselves. In very rare cases, SM can be passed down in families.
In rare cases, SM has been associated with mutation in other genes such as the TET2, IgE, JAK2 and RAS genes.
Environmental triggers of SM
There are many environmental triggers that could lead to the development of an SM attack.
These environmental triggers include:
- Consuming alcoholic drinks.
- Eating spicy foods.
- Taking certain medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants and anesthetics.
- Experiencing sudden changes in temperature like jumping in cold water.
- Exercise and physical activity.
- Insect venom such as being stung by a bee, wasp or ant.
- Physical or emotional stress.
Prevention
Identifying and avoiding environmental triggers may help prevent SM attacks. For example, not consuming spicy foods and alcohol, avoiding insect bites, exposure to hot or cold, strenuous activity, anesthesia, surgery, endoscopy and stress and not taking certain medications can help prevent SM attacks.
Patients with SM may consider wearing a medical alert bracelet listing the medications that are known to trigger an SM attack. These medications can be different for each individual patient.
Patients with a diagnosis of SM should also carry a self-injectable syringe of epinephrine (also known as an EpiPen) to treat SM attacks that could otherwise lead to anaphylactic shock, which can be life-threatening.
It is important to note that these prevention methods can only reduce the risk of allergic reactions and cannot prevent SM, which is caused by a genetic mutation in most cases.
Populations most at risk
The risk of SM is the same among men and women.
The disease is usually more commonly seen in adults but can also develop during childhood. The risk of developing SM increases as a person gets older.
SM is more often seen in people of Caucasian descent and has an estimated prevalence of one in 7,700 to 10,400 people in Europe.
