Systemic Mastocytosis (SM)

Systemic mastocytosis is a rare hematological disease characterized by the overproliferation of mast cells, which are white blood cells produced in the bone marrow, within the connective tissues throughout multiple organ systems, including the liver, spleen, skin, bones, lungs, joints, and digestive tract.1,2

Upon activation by an allergen, mast cells release inflammatory chemical mediators such as histamine, heparin, growth factors, and cytokines, which promote new blood vessel growth and vasodilation to assist the body’s immune system in fighting the perceived threat. Mediator release results in the common symptoms of skin flushing and itching, and the release of large amounts of mediators may lead to anaphylaxis, nausea, vomiting, diarrhea, abdominal cramping, and hypotension.1,3 


The reported prevalence of systemic mastocytosis in Europe is 1 in every 7,700 to 10,400 individuals.4 The global prevalence for all forms of mastocytosis (including cutaneous mastocytosis) is estimated to be 1 in 10,000 people, with the assumption of underdiagnosis.4,5


The true incidence rates are unknown because the underdiagnosis or misdiagnosis of systemic mastocytosis is suspected.6 Investigators in one study reported that of 140 patients, systemic mastocytosis was not diagnosed properly in 36%; 20% of cases were overlooked and 16% of the cases were misdiagnosed, although the misdiagnosis was the incorrect subtype of systemic mastocytosis.7


Because systemic mastocytosis is acquired or somatic, and very rarely congenital, the disease manifests predominantly in adults with an average age of 60 years at the time of diagnosis.4 

Systemic mastocytosis is very rare among pediatric patients, although it has been reported.4 For example, the report of the first documented case of systemic mastocytosis, by J. M. Ellis, detailed the autopsy results of a 1-year-old girl in which mast cell proliferation had occurred in multiple organs.8 

Typically, in 80% of pediatric cases, mastocytosis is diagnosed within the first year of life; however, most of these cases involve only the skin (cutaneous mastocytosis), so they do not meet the criteria for systemic mastocytosis.6 Therefore, systemic mastocytosis may occur at any age.4


Systemic mastocytosis affects men and women equally.4


Systemic mastocytosis occurs preferentially in people of Caucasian descent.4


The 5 subtypes of systemic mastocytosis include the following:

  • Indolent systemic mastocytosis, which includes the subvariant isolated bone marrow mastocytosis;
  • Smoldering systemic mastocytosis;
  • Aggressive systemic mastocytosis;
  • Systemic mastocytosis with an associated hematological non-mast cell lineage disease; 
  • Mast cell leukemia. 

Most studies confirm that the most prevalent form of systemic mastocytosis is the indolent systemic mastocytosis subtype, which has the best clinical outcomes regarding survival rates; the rarest subtype is mast cell leukemia, which has the worst survival rate.

In a study conducted in Denmark in 2014, the most common subtype in a cohort of 548 adults with a diagnosis of systemic mastocytosis was indolent systemic mastocytosis (82%), followed by unknown subtype (11%), systemic mastocytosis with an associated hematological non-mast cell lineage disease (4%), aggressive systemic mastocytosis (2%), and mast cell leukemia (1%). The cumulative incidence was 12.46 per 100,000 people. The prevalence within the 14-year duration of the study was 9.59 per 100,000 people in Denmark.9

Investigators at the Mayo Clinic, who in 2009 conducted a 14-year retrospective study of 342 adults with a diagnosis of systemic mastocytosis, reported that 46% had indolent systemic mastocytosis, 40% had systemic mastocytosis with an associated hematological non-mast cell lineage disease, 12% had aggressive systemic mastocytosis, and 1% had mast cell leukemia.10

In 2013, investigators who analyzed 42 Dutch patients with a diagnosis of systemic mastocytosis reported that 71% had indolent systemic mastocytosis, 2% had smoldering systemic mastocytosis, 5% had presumed indolent systemic mastocytosis, and 22% had a high risk for indolent systemic mastocytosis.11


  1. Systemic mastocytosis. MedlinePlus Genetics. Accessed April 17, 2022.
  2. Systemic mastocytosis. Symptoms and causes. Mayo Clinic. Accessed April 17, 2022.
  3. Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2016;6:620. doi:10.3389/fimmu.2015.00620
  4. Systemic mastocytosis. Orphanet. Accessed April 17, 2022.
  5. Brockow K. Epidemiology, prognosis, and risk factors in mastocytosis. Immunol Allergy Clin North Am. 2014;34(2):283-295. doi:10.1016/j.iac.2014.01.003
  6. Mastocytosis: statistics. Cancer.Net. Approved February 2022. Accessed April 17, 2022.
  7. Schwaab J, Hartmann NC do O, Naumann N, et al. Importance of adequate diagnostic workup for correct diagnosis of advanced systemic mastocytosis. J Allergy Clin Immunol Pract. 2020;8(9):3121-3127.e1. doi:10.1016/j.jaip.2020.05.005
  8. Ellis JM. Urticaria pigmentosa; a report of a case with autopsy. Arch Pathol (Chic). 1949;48(5):426-435.
  9. Cohen SS, Skovbo S, Vestergaard H, et al. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. 2014;166(4):521-528. doi:10.1111/bjh.12916
  10. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113(23):5727-5736. doi:10.1182/blood-2009-02-205237
  11. Doormaal JJ van, Arends S, Brunekreeft KL, et al. Prevalence of indolent systemic mastocytosis in a Dutch region. J Allergy Clin Immunol. 2013;131(5):1429-1431.e1. doi:10.1016/j.jaci.2012.10.015

Reviewed by Hasan Avcu, MD, on 4/27/2022.