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Disease Profile

Systemic mastocytosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

All ages

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ICD-10

C96.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Systemic mast cell disease; SMCD

Categories

Blood Diseases

Summary

Systemic mastocytosis (SM) is a form of mastocytosis in which mast cells accumulate in internal tissues and organs such as the liver, spleen, bone marrow, and small intestines. It is typically diagnosed in adults. Signs and symptoms vary based on which parts of the body are affected. The disorder is usually caused by somatic changes (mutations) in the KIT gene.[1][2] Most cases are sporadic and not inherited, but familial cases rarely have been reported.[3] 

Systemic mastocytosis can be divided into 4 main categories which are distinguished by various features:[4]

Once a person is diagnosed, the category of SM must be determined, as treatment and prognosis differ for each.[4]

Symptoms

In systemic mastocytosis (SM), mast cells accumulate in internal organs such as the liver, spleen, bone marrow, and small intestines. The signs and symptoms vary based on which parts of the body are affected but may include:[1][2]

  • Anemia and bleeding disorders
  • Gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, and/or vomiting
  • Itching, hives, and/or flushing of the skin
  • Anaphylactoid reactions
  • Enlarged liver (hepatomegaly), spleen (splenomegaly), and lymph nodes (lymphadenopathy)

There are four main types of systemic mastocytosis which vary in severity. They include:[4]

  • Indolent systemic mastocytosis the most common form of SM with a slowly progressive (worsening over time) clinical course
  • Systemic mastocytosis with an associated hematologic nonmast cell lineage disorder a form of SM associated with other blood disorders (such as myeloproliferative or myelodysplastic conditions)
  • Aggressive systemic mastocytosis a severe form of SM usually characterized by organ impairment or organ failure due to aggressive mast cell infiltration
  • Mast cell leukemia a very rare and aggressive form of SM that is associated with greater than 10% immature mast cells in the peripheral blood or greater than 20% immature mast cells in bone marrow cultures

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Abnormal eosinophil morphology
0001879
Headache
Headaches
0002315
Malabsorption
Intestinal malabsorption
0002024
Mastocytosis
0100495
Nausea and vomiting
0002017
Urticaria
Hives
0001025
30%-79% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
Generalized osteosclerosis
0005789
Impaired temperature sensation
Abnormality of temperature sensation
Loss of temperature sensation

[ more ]

0010829
Leukopenia
Decreased blood leukocyte number
Low white blood cell count

[ more ]

0001882
Osteoporosis
0000939
Skin rash
0000988
Thrombocytopenia
Low platelet count
0001873
5%-29% of people have these symptoms
Abnormality of the gastric mucosa
Abnormality of the mucous membrane layer of stomach
0004295
Acute leukemia
0002488
Arthralgia
Joint pain
0002829
Ascites
Accumulation of fluid in the abdomen
0001541
Asthma
0002099
Bone marrow hypocellularity
Bone marrow failure
0005528
Bone pain
0002653
Chronic leukemia
0005558
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Hepatomegaly
Enlarged liver
0002240
Lymphadenopathy
Swollen lymph nodes
0002716
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Osteolysis
Breakdown of bone
0002797
Portal hypertension
0001409
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Splenomegaly
Increased spleen size
0001744
Sudden cardiac death
Premature sudden cardiac death
0001645
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Cutaneous mastocytosis
0200151
Edema
Fluid retention
Water retention

[ more ]

0000969
Erythema
0010783
Hypermelanotic macule
Hyperpigmented spots
0001034
Telangiectasia macularis eruptiva perstans
0007583

Cause

Most cases of systemic mastocytosis are caused by somatic mutations in the KIT gene. This gene encodes a protein that helps control many important cellular processes such as cell growth and division; survival; and movement. This protein is also important for the development of certain types of cells, including mast cells (immune cells that are important for the inflammatory response). Mutations in the KIT gene can leads to an overproduction of mast cells, which then accumulate in internal organs and lead to the symptoms of this condition.[5][2]

Diagnosis

A diagnosis of systemic mastocytosis (SM) is often suspected based on the presence of characteristic signs and symptoms. Additional testing can then be ordered to rule out other conditions with similar features; confirm the diagnosis; determine the type; and assess the severity. These tests may include:[2]

  • Bone marrow biopsy the most useful test used to diagnose the condition
  • Blood studies may show anemia, elevated histamine levels, thrombocytopenia, high white blood cell count (leukocytosis), low blood albumin levels (hypoalbuminemia), or high serum tryptase levels
  • Imaging studies may help to identify the extent and stage of the disease
  • Biopsies of affected organs (such as the liver and/or skin)
  • Genetic testing

More information about studies used to diagnose SM can be viewed here on the Medscape Reference website.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for systemic mastocytosis (SM) is based on the signs and symptoms present in each person. For example, the following medications may used to treat various symptoms associated with SM:[2][6]

    • Antihistamines to treat or prevent skin and gastrointestinal symptoms
    • Proton pump inhibitors to treat increased stomach acid
    • Epinephrine to treat anaphylaxis
    • Steroids to treat malabsorption (impaired ability to take in nutrients)
    • Mastcell stabilizers such as ketotifen to treat some of the skin symptoms
    • Cromolyn sodium to treat gastrointestinal symptoms, bone pain, headaches, and some of the skin manifestations

    If systemic mastocytosis is cancerous (mast cell leukemia) or associated with a blood disorder, steroids and/or chemotherapy may be necessary.[7]

    More specific information about treatment options can be accessed through the Treatment and Medication sections of the Medscape Reference website.

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • Midostaurin(Brand name: Rydapt) Manufactured by Novartis Oncology
      FDA-approved indication: Treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
      National Library of Medicine Drug Information Portal

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

      • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Merck Manual for health care professionals provides information on Systemic mastocytosis.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Systemic mastocytosis. Click on the link to view a sample search on this topic.

            References

            1. Bundra K and Akin C. Mastocytosis. National Organization for Rare Disorders. 2017; https://rarediseases.org/rare-diseases/mastocytosis/.
            2. Koyamangalath Krishnan. Systemic Mastocytosis. Medscape Reference. April 22, 2016; https://emedicine.medscape.com/article/203948-workup#showall.
            3. de Melo Campos P, Machado-Neto JA, Scopim-Ribeiro R, Visconte V, Tabarroki A, Duarte AS, Barra FF, Vassalo J, Rogers HJ, Lorand-Metze I, Tiu RV, Costa FF, Olalla Saad ST, and Traina F. Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412. Leuk Res. October 2014; 38(10):1245-1251. https://www.ncbi.nlm.nih.gov/pubmed/25139846.
            4. Mariana C Castells and Cem Akin. Systemic mastocytosis: Determining the category of disease. UpToDate. Waltham, MA: UpToDate; August, 2016;
            5. KIT. Genetics Home Reference. September 2014; https://ghr.nlm.nih.gov/gene/KIT.
            6. Castells MC and Akin C. Systemic mastocytosis: Treatment and prognosis. UpToDate. October 21 2016; https://www.uptodate.com/contents/systemic-mastocytosis-treatment-and-prognosis.
            7. Mastocytosis. National Institute of Allergy and Infectious Diseases (NIAID). October 2013; https://www.niaid.nih.gov/topics/mastocytosis/Pages/Treatment.aspx.

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