No Disease Too Small - Patient Guide

No Disease Too Small is a campaign that offers information and guidance for patients and their loved ones as they search for answers about symptoms and the disease. An educated patient and physician can work together as partners throughout the diagnosis and treatment journey.

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A guide to systemic mastocytosis (SM)

Systemic mastocytosis (SM) is a group of rare blood diseases where too many abnormal mast cells, which are specialized immune cells, collect in more than one body tissue. Mast cells can accumulate in the skin and internal organs, including the liver, spleen, bone marrow, and tissues of the gastrointestinal tract, which can lead to inflammatory and allergic reactions and other symptoms1,2,3.

What is the clinical definition of mastocytosis?
  • Mastocytosis is a rare disease where the body makes abnormal mast cells that accumulate in various organ systems2,4.
  • A “mast” cell is a type of white blood cell in the immune system2.
    • Mast cells help heal wounds and protect the body from infection. Mast cells also are specialized to release multiple chemical mediators, including histamine, tryptase, heparin and others, which can contribute to inflammatory and allergic reactions and other clinical symptoms5,6.
  • “Cytosis” is a suffix that means an increase in the number of cells7.
  • There are two types of mastocytosis: systemic and cutaneous2*.
  • In SM, the accumulation of mast cells can affect both the skin and internal organs, resulting in systemic symptoms, and may cause organ damage1,3.

*Cutaneous mastocytosis is more common in children, and is outside the scope of this document2.

How common is SM?
  • SM is very rare, and people who have SM may have difficulty finding support1,4.
  • Around the world, SM affects between 1 in 20,000 and 1 in 40,000 people1.
  • The median age at SM diagnosis in adults is 55 years8.
  • SM is not usually linked to family history; the risk of getting SM is greater if there is a change in a particular gene3.
  • Blood tests that measure levels of tryptase, as well as bone marrow tests, are necessary to diagnose SM3.
Why is SM so difficult to diagnose?
  • Symptoms may initially be minor and progress over time.
  • SM is underdiagnosed for several reasons:
    • Symptoms frequently seen in SM are often the same as those seen in many other illnesses, frequently leading to incorrect diagnosis8.
    • Physicians are not accustomed to seeing the disease. Patients may cycle between many different physicians and specialists before receiving a correct diagnosis4.
  • An SM diagnosis can take 2 to 10 years4.
What impact does SM have on the body?
  • There are different kinds of SM, and some are more serious than others. Very serious cases can lead to organ damage or even organ failure3.
  • When the body produces too many mast cells, the increased number of chemical mediators released can result in symptoms, including, but not limited to, flushing, itching, nausea, diarrhea, low blood pressure and anaphylaxis2,3,6.
  • The organs SM affects are usually the bone marrow, skin, liver, spleen, lymph nodes, and those of the gastrointestinal tract3.
  • Symptoms may depend on which organ is being affected:
    • Bone involvement can result in bone pain6.
    • Nausea, vomiting, abdominal pain, and diarrhea are seen when cells in the gastrointestinal (GI) tract are affected9.
    • When mast cells begin to accumulate in body tissues, the lymph nodes, liver, and spleen may swell3,6.
    • When the skin is affected, symptoms including severe itching and flushing (which can be triggered by temperature changes), fever, exercise and friction6.
  • Physicians should work to develop a treatment plan best suited to manage patient symptoms10.
What are the symptoms of SM?
  • SM symptoms can vary significantly from one person to another.
  • If the following symptoms are present, the patient should talk to a health care provider2,3,9,11.
    • Skin rash
    • Itching or pruritus
    • Flushing of the skin
    • Anemia
    • Digestive problems such as stomach pain, diarrhea, malabsorption, weight loss, nausea, or vomiting
    • Extreme allergic-like reactions called anaphylaxis that can occur after a bee or insect sting that can cause swelling of the face, tongue, or eyes; trouble breathing, or dizziness
    • Swelling in liver, spleen, or lymph nodes
    • Headache
    • Fatigue
    • Osteoporosis
    • Bone pain
    • Extreme reactions to heat, cold, or other physical triggers
Misdiagnoses of other diseases
  • People with SM are often diagnosed with other, more common illnesses because they have the same symptoms as SM, including8.
    • Irritable bowel syndrome
    • Malabsorption syndrome
    • Urticaria
    • Carcinoid syndrome
    • VIPoma
    • Zollinger-Ellison syndrome
    • Leukemia
    • Other myeloproliferative disorders

How does SM impact someone’s everyday life?

Like many other long-term or chronic diseases, SM can dramatically affect a person’s daily quality of life11.

  • Living with a chronic illness, especially one so difficult to diagnose, can impact the mental health of the patient11.
  • Some of the feelings a patient with SM may feel during their diagnosis and treatment are11: 
    • Increased stress
    • Fear and/or anxiety
    • Poor motivation
    • Sadness and/or depression
    • Isolation
  • If a patient with SM is experiencing physical or emotional health problems, he or she should talk with a health care professional. It is important to seek support and counseling to help cope with these feelings.
Living with Systemic Mastocytosis

Meet Andrew, patient from the UK living with systemic mastocytosis (SM), a rare blood disorder that can affect many different body systems, including internal tissues and organs, such as the liver, spleen, bone marrow and small intestines.

If a patient is concerned about SM, what should he or she do?
  • An informed conversation with a physician is the first step. Patients with symptoms common in SM should not hesitate to ask questions about the disease.  
  • It is important to know about the different types of SM10 – there are five – and to ask specific questions about testing that can help a physician make an SM diagnosis, so treatment can begin.
  • For a list of key questions to help both patients and health care providers, visit No Disease Too Small (www.nodiseasetoosmall.com).
The five types of SM

SM is categorized into five subtypes, determined by the affected organs10. They differ in severity, treatment approach, and life expectancy3,10,12. 

  • Indolent SM (ISM) is the most common and mild type of SM3. Symptoms may include itching skin, fainting, headaches, vomiting, or diarrhea13. Those with ISM have a low risk of progression to a more advanced form6.  
    • Prognosis: Typically favorable6.
  • Smoldering SM (SSM) is usually characterized by a high volume of mast cells in the bone marrow. Those with SSM may have a higher likelihood of progressing to an advanced disease category6.
    • Prognosis: May indicate tendency to progress to a more advanced form6.
  • SM with an associated hematologic neoplasm (SM-AHN) is a type of SM where the patient has an additional blood disorder, most often myeloproliferative disorders or a myelodysplastic syndrome6. 
    • Prognosis: Depends on associated hematological neoplasm6.
  • Aggressive SM (ASM) is a severe type of SM. Mast cells will collect in different organs and can cause organ damage or failure3.
    • Prognosis: Less favorable6.
  • Mast cell leukemia (MCL) is a rare and serious type of SM. There are many more mast cells circulated in the bone marrow with MCL. The outcome with MCL is very poor6.
    • Prognosis: Life expectancy may be limited6.

SM-AHN, ASM, and MCL are all defined as advanced SM and have lower survival rates compared to ISM and SSM14.
 

Which tests can diagnose SM?
  • Because SM symptoms are commonly found in other diseases (such as a skin rash), it can be difficult to diagnose8. 
  • There are, however, several specific tests that can more precisely determine if SM is present:
    • Blood tests frequently used to diagnose SM: 
      • Blood serum tryptase test: Serum tryptase is an enzyme, or chemical, produced by the mast cells5. A person with SM is likely to have higher levels of tryptase in the bloodstream3. 
      • Other blood tests to evaluate organ damage:
        • Blood serum albumin test: A serum albumin test is a simple blood test that measures the amount of albumin in the patient’s blood. Low levels of albumin are often associated with inflammation in the liver, kidney disease and malnutrition15.
        • Alkaline phosphatase (ALP) test: The test measures the amount of ALP enzyme in the bloodstream. If ALP levels are elevated, it indicates a problem with the liver or bones16. 
        • Hemoglobin test: Anemia, a condition in which the blood has fewer red blood cells than normal, can be a sign of SM3,17. A hemoglobin test is used to check for anemia18.
        • Complete Blood Count (CBC): Low blood platelet count (thrombocytopenia), and high white blood cell count (leukocytosis) can be signs of advanced variants of SM3,20. CBC tests measure many different parts of the blood, including the overall number of white blood cells and platelets18.
      • Genetic mutation testing: Learning if a genetic mutation is present can help a physician diagnose SM3. A mutation is a change in a gene’s structure6. In SM, changes in a gene called KIT make mast cells keep growing20. About 9 out of 10 patients with SM have a KIT mutation called KIT D816V21. Detecting the genetic mutation is an important part of identifying SM3.
      • CT Scanning and other imaging: Infiltration of abdominal organs and lymph nodes can be seen best by a variety of CT and other scans22.
    • Biopsies 
      • Bone marrow biopsy: Mast cells form in the bone marrow5. Physicians can test a patient’s bone marrow to see if it contains abnormal mast cells, meeting specific criteria. In addition to determining the presence of SM, the test can help physicians understand which type of SM is present3. A bone marrow biopsy is a procedure performed using a biopsy needle to extract organ samples23. 

For more information and resources, visit No Disease Too Small (www.nodiseasetoosmall.com).

The Mastocytosis Society* may be another source of information for you: www.tmsforacure.org
 

*The Mastocytosis Society is a not-for-profit group, independent from Novartis. Novartis has no financial interest in this organization, but may provide occasional funding support. Novartis is not responsible for the organization’s information content or actions.

1. Systemic mastocytosis. Orpha.net. 2018.
2. Mastocytosis. GARD. 2018.
3. Systemic mastocytosis. GARD. 2018.
4. Sev’er A, et al. Women’s Health Urban Life. 2009; 8(2):84-112.
5. Krystel-Whittemore M, et al. Frontiers in Immunology. 2015;6:620.
6. Bundra K, et al. Mastocytosis. NORD. 2018.
7. Cytosis. Mosby's Medical Dictionary. 8th ed. Elsevier Health Sciences; 2009.
8. Krishnan K, et al. Systemic Mastocytosis. Medscape. 2018.
9. König A, et al. EU survey and results about mastocytosis. May 2011:1-14. 2018.
10. Valent P, et al. Blood. 2016;129(11):1420-1427.
11. Moura D, et al. PLoS One. 2011; 6(10): e26375.
12. Lim K-H, et al. Blood. 2009;113(23):5727-5736.
13. Indolent systemic mastocytosis. Orpha.net. November 2018.
14. Gotlib J, et al. N Engl J Med. 2016;374(26):2530-2541.
15. Albumin Blood Test. MedlinePlus. 2018.
16. ALP - blood test. MedlinePlus. 2018.
17. Anemia of Inflammation or Chronic Disease. NIDDK. 2018.
18. Blood Tests. NHLBI. 2018.
19. Thrombocytopenia. NHLBI. 2018.
20. Pardanani A. Am J Hematol. 2016;91(11):1146-1159.
21. Garcia-Montero AC, et al. Blood. 2006; 108(7):2366-2372.
22. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Systemic Mastocytosis, V.2.2019 ©National Comprehensive Cancer Network, Inc., 2019. All rights reserved. Accessed Feb. 7, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
23. Bone marrow biopsy. MedlinePlus. 2018.
24. Deslypere G, et al. Belgian Journal of Hematology. 2013;4(3):85-89.

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