Mastocytosis

Mastocytosis

Article
Bone, Muscle, & Joint
Digestive Health
+5
Contributed byLester Fahrner, MD+1 moreApr 18, 2021

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

  • Mast Cell Disease

What is 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
  • There are two main forms of Mastocytosis, namely cutaneous Mastocytosis (CM) and systemic Mastocytosis (SM):
    • Cutaneous Mastocytosis is the most common form of Mastocytosis affecting the skin. In this type, there is an increase in mast cells in skin. Infants are generally susceptible to this type of Mastocytosis. The condition causes skin redness, itching, and swelling in the affected area
    • Systemic Mastocytosis 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 Mastocytosis are noted:

  • Cutaneous Mastocytosis:
    • Maculopapular Cutaneous Mastocytosis (previously termed Urticaria Pigmentosa)
    • Diffuse Cutaneous Mastocytosis (DCM)
    • Mastocytoma of Skin (or Solitary Mastocytoma)
    • Telangiectasia Macularis Eruptiva Perstans (TMEP)
  • Systemic Mastocytosis:
    • 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)
  • The tests to diagnose cutaneous Mastocytosis include general physical examinations, blood tests, skin biopsies, and genetic testing to detect KIT gene mutations. A diagnosis of systemic Mastocytosis involves satisfying a set of major and minor criteria outlined by medical experts. Uncontrollable inflammatory responses, tissue scarring, and organ dysfunction are some complications that could arise from Mastocytosis
  • 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. Addressing potential organ impairment to prevent complications is important. The prognosis of individuals with systemic Mastocytosis varies depending on the type and severity of the condition. Children with cutaneous Mastocytosis are generally known to recover over time, and the outcomes are typically good

Who gets Mastocytosis? (Age and Sex Distribution)

  • Mastocytosis is a relatively rare disorder, with an estimated global prevalence of 1 in 20, 000 to 1 in 40,000
    • Cutaneous Mastocytosis constitute nearly 90% of all Mastocytosis
    • While, systemic Mastocytosis constitute the remaining 10%
  • Children aged less than 12-24 months can develop Cutaneous Mastocytosis
  • Individuals aged 50-80 years usually develop Systemic Mastocytosis
  • Both men and women are equally susceptible to the condition
  • All racial and ethnic groups are prone to the disorder

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

  • A majority of cutaneous Mastocytosis cases are observed during infancy and early childhood
  • 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

These factors are presumably not in play with childhood-onset mastocytosis.

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 Mastocytosis? (Etiology)

The cause of Mastocytosis is usually genetic. 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 these abnormal mast cells causes the inappropriate stimulation of the inflammatory response. This leads to the signs and symptoms of Mastocytosis

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 Mastocytosis?

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

  • Skin signs and symptoms may include: 
    • Blisters and hives (urticaria)
    • Discolored spots, especially in clusters
    • Thickened spots with an orange-peel texture
    • Severe itching (pruritus)
  • Systemic signs and symptoms may include:
    • Abdominal pain
    • Difficulty breathing
    • Rapid heart rate (tachycardia)
    • Headache 
  • Bone, joint, and muscle signs and symptoms may include:
    • Bone pain (ostealgia)
    • Joint pain (arthralgia)
    • Muscle pain (myalgia)
  • Nonspecific (constitutional) presentations may include: 
    • Fatigue
    • Weight loss
    • Fever
    • Night sweats

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 Mastocytosis Diagnosed?

The following are some tests and exams that may be used in the diagnosis of 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 from mast cells which are a minor criterion for diagnosis
    • Elevated lactate dehydrogenase which can be a prognostic indicator
    • Elevated alkaline phosphatase levels showing possible bone involvement
  • Imaging studies of the affected region
  • 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

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 Mastocytosis?

Following are complications that may arise from Mastocytosis:

  • Emotional stress
  • Uncontrollable inflammatory and allergic reactions; severe reactions may result in anaphylaxis that can be life-threatening
  • Permanent tissue scarring
  • Severe discomfort
  • Multiple organ damage and dysfunction such as the liver and spleen
  • Treatment-related complications
  • Progression of cutaneous Mastocytosis to systemic Mastocytosis
  • Progression of systemic Mastocytosis to malignancies
  • A mixed organic brain disorder with headache, irritability, fatigue, poor attention span, poor work capacity, and difficulty with personal interactions

How is Mastocytosis Treated?

At the present time, there are no standard treatments available for Mastocytosis. The treatment options are dependent on the severity of the condition, as well as the patient’s health, and are usually geared towards symptom relief.

  • Cutaneous Mastocytosis that is confined/localized to a region and is “symptomless” may not require any treatment
  • Avoiding and/or controlling the triggers that worsen the condition is important
  • Antihistamine therapy may be recommended in some individuals
  • Localized forms of symptomatic Cutaneous Mastocytosis may be treated with phototherapy (PUVA or UVB)
  • In case of anaphylaxis, subcutaneous epinephrine or adrenaline may be administered
  • Chemotherapy, radiation therapy, surgery including bone marrow/stem cell transplantation may be considered
  • 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 Mastocytosis be Prevented?

Presently, it may be difficult to avoid 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 Mastocytosis
  • Limit exposure to radiation and industrial chemicals 
  • Cessation of smoking

Other home care tips include:

  • Always keeping skin clean and healthy
  • Wearing gloves while applying ointment on the blisters is advised
  • Children’s nails should be cut short so that infection from scratching the blisters can be avoided
  • Frequent washing of hands is recommended
  • The affected child or adult is best advised to stay indoors in case of any “flare ups”
  • 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 Mastocytosis? (Outcomes/Resolutions)

The prognosis of 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.

  • Cutaneous Mastocytosis in children is usually not life-threatening and the condition generally resolves before puberty
  • Systemic Mastocytosis can be aggressive and may progress to advanced stages such as cancer. In such cases, the prognosis may be guarded to poor

Additional and Relevant Useful Information for 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.

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On the Article

Krish Tangella MD, MBA picture
Approved by

Krish Tangella MD, MBA

Pathology, Medical Editorial Board, DoveMed Team
Lester Fahrner, MD picture
Reviewed by

Lester Fahrner, MD

Chief Medical Officer, DoveMed Team

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