What are other Names for this Condition? (Also known as/Synonyms)

• SM (Systemic Mastocytosis)

What is Systemic Mastocytosis? (Definition/Background Information)

• Mastocytosis is a rare disorder that results from often abnormal and excessive numbers of mast cells in the skin and, rarely, in the organs. It is generally caused by a mutation in a protein termed C-KIT receptor, which resides on the surface of cells and binds to a factor (stem cell factor) that helps certain types of cells to grow
• Mast cells, which reside in the connective tissue, store chemicals important to initializing the inflammatory and allergic responses. They also have important immune functions (ingesting disease-causing microbes). Once activated, mast cells release chemicals including heparin, histamine, and serotonin that stimulate the body’s inflammatory response
• Systemic Mastocytosis (SM) is an uncommon form of mastocytosis affecting several tissues and organs in the body, including the skin. Middle-aged and older adults are generally susceptible to this type of mastocytosis. The condition causes fatigue, joint problems, pain in the abdomen, headaches, night sweats, breathing difficulties, and elevated heart rates
• According to the updated World Health Organization (WHO) classification (2016), the following subtypes of Systemic Mastocytosis are noted:
  • Indolent Systemic Mastocytosis (ISM)
  • Smouldering Systemic Mastocytosis (SSM)
  • Systemic Mastocytosis with Associated Clonal Hematologic Non-Mast Cell Lineage Disease (AHNMD)
  • Aggressive Systemic Mastocytosis (ASM)
  • Mast Cell Leukemia (MCL)
• A diagnosis of Systemic Mastocytosis involves satisfying a set of major and minor criteria outlined by medical experts. The tests may include general physical examinations, blood tests, imaging studies, skin and bone marrow biopsies, and genetic testing to detect KIT gene mutations. Systemic Mastocytosis may lead to several complications, including rarely, the formation of malignancies
• Presently, there are no standard treatment options available for mastocytosis. Generally, a management of the symptoms and controlling the inflammatory response is needed; this may involve anti-histamine treatment. Surgically removing severely affected tissues may be a treatment option as well. The prognosis of individuals with Systemic Mastocytosis varies depending on the type and severity of the condition

Who gets Systemic Mastocytosis? (Age and Sex Distribution)

• Systemic Mastocytosis constitute only about 10% of all mastocytosis
• Most cases are diagnosed in adults, particularly in the 50-80 years age group
• Children are also known to develop the condition but to a much lesser extent
• Both males and females are equally susceptible to the condition
• Worldwide, it can affect all racial and ethnic groups

What are the Risk Factors for Systemic Mastocytosis? (Predisposing Factors)

• A majority of Systemic Mastocytosis cases are observed in middle-aged and elderly adults
• A positive family history is rarely observed in mastocytosis; and, no other specific risk factors have been identified

However, in general, the following are believed to increase one’s susceptibility to mastocytosis:

• Smoking
• Exposure to radiation and industrial chemicals
• Chemotherapy
• In rare cases, viral infections

There are also a host of factors that may trigger histamine release further aggravating the skin signs and symptoms in mastocytosis. Some of these include:

• Medications such as opioid painkillers, non-steroidal anti-inflammatory drugs (NSAIDs), vitamin supplements, antibiotics, anticholinergics, etc.
• Venom injection from snake bites and bee stings
• Emotional stress
• Lack of sleep
• Hot or cold weather, and temperature changes
• Certain viral and bacterial infections
• Iatrogenic factors such as application of local anesthetic, vaccines, administration of contrast media, and even certain invasive procedures

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Systemic Mastocytosis? (Etiology)

The cause of formation of Systemic Mastocytosis is mostly due to mutations in the KIT gene. In some cases, it is caused by unknown factors.

• Specifically, it is a small change (mutation) in the region of DNA of a receptor called C-KIT. This receptor is responsible for stimulating mast cells to grow and divide (proliferate)
• Mast cells that have defective C-KIT receptors are unable to respond to signals from their environment. Thus, they proliferate independently of external signals
• The overabundance of abnormal mast cells in skin causes the inappropriate stimulation of the inflammatory response. This leads to the signs and symptoms of Systemic Mastocytosis

In a vast majority of cases, the condition occurs sporadically. Occasionally, when Systemic Mastocytosis is inherited, an autosomal dominant pattern of inheritance is noted.

What are the Signs and Symptoms of Systemic Mastocytosis?

The signs and symptoms of Systemic Mastocytosis may vary from one individual to another. It may be mild or severe, and also depend on the specific form of mastocytosis.

• Some of the systemic signs and symptoms include:
  • Abdominal pain
  • Difficulty breathing
  • Rapid heart rate (tachycardia)
  • Headache
  • Anemia
  • Ulcers in the gastrointestinal tract, mostly affecting the stomach and small intestine
• Bone, joint, and muscle signs and symptoms include:
  • Bone pain (ostealgia)
  • Joint pain (arthralgia)
  • Muscle pain (myalgia)
• Skin signs and symptoms may include: 
  • Blisters and hives (urticaria)
  • Discolored spots, especially in clusters
  • Severe itching (pruritus)
• Nonspecific (constitutional) signs and symptoms include: 
  • Fatigue
  • Weight loss
  • Fever
  • Night sweats
  • Dizziness

Systemic Mastocytosis may take place as “attacks” when several signs and symptoms are noted simultaneously. Also, the presence of triggers, such as certain medications, sunlight, or medical procedures, may cause a flare up (inflammatory response) of the signs and symptoms.

How is Systemic Mastocytosis Diagnosed?

The following are some tests and exams that may be used in the diagnosis of Systemic Mastocytosis:

• Physical exam to detect skin abnormalities and comprehensive medical history evaluation
• Blood smear to detect:
  • Increased numbers of mast cells
  • Abnormally-shaped mast cells
  • Reduced numbers of red blood cells (anemia)
  • Reduced numbers of platelets (thrombocytopenia)
• Blood tests to detect:
  • Elevated total tryptase levels which are a minor criterion for diagnosis of systemic disease
  • Elevated lactate dehydrogenase levels which have prognostic ramifications
  • Elevated alkaline phosphatase levels as a sign of bone involvement
• Radiographic tests to detect bone deficiencies
• Bone marrow biopsy to detect increased cell numbers (hypercellularity)
• Skin biopsy to detect:
  • Clusters of mast cells
  • Abnormally-shaped mast cells
• Genetic tests to detect a KIT mutation, if necessary

In order to diagnose Systemic Mastocytosis, one major and one minor, or three minor criteria, from the following list, must be satisfied:

• Major criterion: Dense infiltrates of more than 15 mast cells in multiple areas, such as in the bone marrow or an extracutaneous organ
• Minor criteria:
  • Aberrant phenotype on the mast cells (pos. for CD2 and/or CD25)
  • Aberrant mast cell morphology (spindle-shaped)
  • Finding of mutation in KIT(D816V)
  • Serum tryptase is over 20 ng/ml

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Systemic Mastocytosis?

Following are some of the complications that may arise from Systemic Mastocytosis:

• Emotional stress
• Uncontrollable inflammatory and allergic reactions; severe reactions may result in anaphylaxis that can be life-threatening
• Permanent tissue scarring
• Severe discomfort
• Treatment-related complications
• Progression of Systemic Mastocytosis to malignancies

How is Systemic Mastocytosis Treated?

Systemic Mastocytosis treatment depends on the severity and type of the condition, and on the age and health status of the individual. However, there is no cure for the condition.

• Avoiding and/or controlling the triggers that worsen the condition is important
• Antihistamine therapy may be recommended in some individuals
• Symptomatic skin mastocytosis may be treated with phototherapy (PUVA or UVB)
• In case of anaphylaxis, subcutaneous epinephrine or adrenaline may be administered
• In cases where the exact genetic cause is unknown or is not associated with C-KIT mutation, cytoreductive chemotherapy may be recommended. This is the treatment of mastocytosis with US FDA-recommended chemotherapy drugs
• Cytoreductive surgery may be an option for those with systemic forms of the condition. While surgery on the skin is considered relatively straightforward, this type of surgery for internal organs should be carefully considered and only performed by an experienced surgeon

Periodic monitoring or follow-up of the condition with the healthcare provider is recommended.

Note: Caution should be exercised while using non-steroidal anti-inflammatory medications (NSAIDs) such as Ibuprofen or naproxen. These medicines could cause upset stomach, as well as release of histamines, which could cause severe and adverse reactions.

How can Systemic Mastocytosis be Prevented?

Presently, it may be difficult to avoid Systemic Mastocytosis. However, some of the following factors may be considered:

• If there is a family history of the condition, then genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• Identify, avoid, or control the triggers for Systemic Mastocytosis
• Limit exposure to radiation and industrial chemicals 
• Cessation of smoking
• Patients may be advised to carry injectable epinephrine to overcome serious allergic reactions

Some narcotics used in general anesthesia can cause mast cells to release their chemicals, including histamine, leading to shock. Patients must be told to inform all physicians of their mast cell disease to protect them from this. A ‘permanent’ passive reminder such as a MedicAlert device is strongly recommended.

What is the Prognosis of Systemic Mastocytosis? (Outcomes/Resolutions)

• The prognosis of Systemic Mastocytosis depends on the severity and type of the condition, and on the age and health status of the individual. The prognosis may vary on a case-by-case basis
• In some cases, the condition can be aggressive and even progress to advanced stages such as cancer. In such cases, the prognosis may be guarded. The risk for developing into malignancies is 7% and 30% in children and adults respectively

Additional and Relevant Useful Information for Systemic Mastocytosis:

Recently, it has been shown that the chemicals released by mast cells also affect the activities of the bone cells. These include bone-building osteoblasts and bone-digesting osteoclasts. Mast cells have been linked to stimulation of osteoclasts and inhibition of osteoblasts, resulting in bone deficiencies.