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

• ISM (Indolent Systemic Mastocytosis)

What is Indolent 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. When the skin is affected, it is known as cutaneous mastocytosis; when the skin and other organs are affected, it is known as systemic mastocytosis
• Mast cells, which reside in the connective tissue, store chemicals important to initializing the inflammatory and allergic responses. Once activated, mast cells release chemicals including heparin, histamine, and serotonin that stimulate the body’s inflammatory response
• Indolent Systemic Mastocytosis (ISM) is the most common form of systemic mastocytosis that typically involves the skin and presents few other systemic symptoms. It is reportedly the mildest form of systemic mastocytosis with good outcomes, due to low mast cell count/burden
• The tests and procedures to diagnose Indolent Systemic Mastocytosis may include general physical examinations, blood tests, imaging studies, skin and bone marrow biopsies, and genetic testing to detect KIT gene mutations
• Presently, there are no standard treatment options for mastocytosis. Generally, management of the symptoms and controlling the inflammatory response is needed; this may involve anti-histamine treatment. The prognosis of individuals with Indolent Systemic Mastocytosis varies depending on the severity of the condition but is mostly good

Who gets Indolent Systemic Mastocytosis? (Age and Sex Distribution)

• Indolent Systemic Mastocytosis constitute nearly 90% of all systemic mastocytosis cases
• Most cases are diagnosed in adults. 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 Indolent Systemic Mastocytosis? (Predisposing Factors)

• A majority of Indolent 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 Indolent Systemic Mastocytosis? (Etiology)

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

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

What are the Signs and Symptoms of Indolent Systemic Mastocytosis?

The signs and symptoms of Indolent Systemic Mastocytosis (ISM) may vary from one individual to another. It may be mild or severe. The signs and symptoms of ISM may include:

• Maculopapular lesions - multiple red brown to tan brown spots on skin
• Itching may be noted
• Darier sign: It is the activation of mast cells by rubbing an area of the affected skin, which results in reddish skin that is itchy and swollen. This is usually seen in young children, within a few minutes of rubbing/scratching the skin
• Face and body may appear flushed
• Diarrhea
• Fatigue

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 Indolent Systemic Mastocytosis Diagnosed?

The following are some tests that may be used in the diagnosis of Indolent 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 can indicate mast cell elevation in systemic disease
  • Elevated lactate dehydrogenase which is a prognostic aid in systemic disease
  • Elevated alkaline phosphatase levels which can indicate bone involvement in systemic disease
• 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 Indolent Systemic Mastocytosis?

Significant complications are not usually seen with Indolent Systemic Mastocytosis. However, in some cases, the following may be noted:

• 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

How is Indolent Systemic Mastocytosis Treated?

The treatment of Indolent Systemic Mastocytosis treatment depends on the severity 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
• Localized forms of 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 Indolent Systemic Mastocytosis be Prevented?

Presently, it may be difficult to avoid Indolent 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 Indolent Systemic Mastocytosis? (Outcomes/Resolutions)

• The prognosis of Indolent Systemic Mastocytosis depends on the severity of the condition, and on the age and health status of the individual. The prognosis may vary on a case-by-case basis
• However, in a vast majority of cases, the condition presents mild symptoms and individuals are known to have good outcomes (normal life expectancy is noted)

Additional and Relevant Useful Information for Indolent 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.