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Mastocytosis: Overview, Diagnosis, and Treatment

About Mastocytosis

Mastocytosis, or mast cell activation disorder, is a disorder that is characterized by an increased number of mast cells in the gastrointestinal (GI) tract, skin, bone marrow, spleen, liver, and lymph nodes.1 Mast cells play a central role in inflammatory processes and in severe reactions such as anaphylaxis.2 There are two common forms of mastocytosis—systemic mastocytosis and cutaneous mastocytosis.

  • Systemic mastocytosis (SM) is the more severe form of mastocytosis and is more common in adults than children. The symptoms vary, as do the organs affected, and can include skin lesions, pain in inner organs, bone pain, diarrhea and vomiting, weight loss, and cardiovascular symptoms. Tryptase levels are increased in the majority of various kinds of SM.3
  • Cutaneous mastocytosis (CM) is the more benign form of mastocytosis, affecting only the skin. Urticaria pigmentosa is the most common presentation of cutaneous mastocytosis in children and represents 70 to 90 percent of the cases. CM is more common in children than adults, and is often outgrown.4,5

It is not known how many people are suffering from mastocytosis, but the incidence has been conservatively proposed to be from three to seven new patients per million per year.6 Most cases of mastocytosis have a benign cause over a lifetime. Some cases occur during infancy and early childhood and others appear in adulthood.6 Mastocytosis in childhood may resolve spontaneously and usually only involves the skin; whereas the course in patients with adult-onset disease is normally chronic and includes not only the skin but also systemic symptoms from other organ systems.6

3 to 7 new patients per million per year6

The incidence of mastocytosis has
been conservatively proposed to be
from three to seven new patients
per million per year.6

Patients that have mastocytosis may also have acute systemic symptoms, including:6

  • Flushing
  • Shortness of breath
  • Palpitations
  • Nausea
  • Diarrhea
  • Hypotension
  • Syncope
  • Lethargy
  • Fatigue lasting several hours

The most common physical symptoms of mastocytosis involve the skin, liver, spleen, and cardiovascular system. In the case of some chronic systemic symptoms, the gastrointestinal tract and nervous system
may also be involved.6

Mastocytosis: Refining differential diagnosis through testing

The most common physical symptoms of mastocytosis involve the skin, liver, spleen, and cardiovascular system. In the case of some chronic systemic symptoms, the gastrointestinal tract and nervous system may also be involved.6 Most patients with this disease will have itchy lesions on their skin.

The World Health Organization (WHO) has a consensus on definitions of various forms of mastocytosis and on diagnostic criteria.7

MAJOR CRITERIA

  • Histological/immunohistochemical alterations: Mast cell aggregates containing more than 15 mast cells in bone marrow sections

MINOR CRITERIA

  • Cytological alterations: >25% of morphologically abnormal mast cells
  • Detection of c-kit mutations on codon 816
  • Immunophenotypic alterations: Expression of CD25 (± CD2) in mast cells from bone marrow, peripheral blood, or other organs
  • Total serum tryptase levels persistently >20ng/mL (not applicable if there is a comorbid blood disorder or evidence of acute mast cell release)


DIAGNOSIS OF SYSTEMIC MASTOCYTOSIS

  • At least one major criterion plus one minor criterion
  • At least three minor criteria
Try Symptom Selector

Not sure which allergy or autoimmune disease could be behind your patient’s symptoms? Use this interactive tool to take the next step in making your differential diagnosis. 

Mastocytosis and anaphylaxis

Tryptase testing can measure the total level of tryptase released by mast cells into the circulation. This enables a healthcare provider to evaluate a person’s baseline tryptase level or any transient increases in the level of tryptase after a suspected allergic reaction. In healthy individuals, the tryptase baseline levels have been reported to range approximately between 1–15 μg/l.3,8

The prevalence of anaphylaxis in adults with the diagnosis of mastocytosis is reportedly as high as 49 percent, significantly higher than expected in the general population.6 In children, the risk to develop anaphylaxis is restricted to those with extensive skin symptoms and also a high baseline serum level of tryptase.6 The robustness of tryptase makes it a useful tool for confirming mast cell involvement.Together with clinical findings, tryptase test results can help you rule in systemic mastocytosis.

 

Mastocytosis and insect-sting hypersensitivity

In patients with a known sensitivity to Hymenoptera (bees, yellow jackets, wasps, and hornets) venom and a history of allergic reaction, venom immunotherapy given for 3 to 5 years may induce long-term protection in most patients.10

Testing Confidence

Testing Increases Diagnostic Confidence

Adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis to 90 percent.i,ii Conventionally, a diagnosis of allergic or autoimmune disease relies on the case history and a physical examination. However, adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis.i,ii Diagnostic testing can also help to improve the patient’s quality of life and productivity, reduce costs associated with absenteeism, and optimize use of medication, in addition to decreasing unscheduled healthcare visits.iii,iv 

i. Duran-Tauleria E, Vignati G, Guedan MJ, et al. The utility of specific immunoglobulin E measurements in primary care. Allergy. 2004;59 (Suppl78):35-41.
ii. NiggemannB, Nilsson M, Friedrichs F. Paediatric allergy diagnosis in primary care is improved by in vitro allergen specific IgE testing. Pediatr Allergy Immunol. 2008;19:325-331
iii. Welsh N, et al. The Benefits of Specific Immunoglobulin E Testing in the Primary Care Setting. J Am Pharm Assoc. 2006;46:627.
iv. Szeinbach SL, Williams B, Muntendam P, et al. Identification of allergic disease among users of antihistamines. J Manag Care Pharm. 2004; 10 (3): 234-238

Learn about allergies.

Learn more about testing.

Management and care of patients with mastocytosis

Unfortunately for healthcare providers and patients, there is no one single treatment that can be used to address mastocytosis. The main strategy is avoidance of identified triggers and allergens, such as insect stings, temperature extremes, irritation, alcohol, or medications (e.g., aspirin, radiocontrast agents, certain anesthetic agents).9

Clinical guidelines have been developed to help guide the management and treatment of patients with mastocytosis. Across practice parameters and guidelines, re-evaluation is recommended for mastocytosis, especially in young children.11 Practice parameters for the usage of allergen immunotherapy may also be a relevant resource.

Even with a specific management plan in place, symptoms may recur. Patients with a history of anaphylaxis require the most vigilant maintenance. If anaphylaxis is initiated by a known allergen, especially that of Hymenoptera venom, you will likely want to consider immunotherapy and discuss the possibility with your patients during subsequent follow-up visits.10 If symptoms persist, or if you suspect additional allergies have developed, it may be helpful to conduct further testing.

Practice Parameters

Practice parameters and guidelines

for mastocytosis:

References
  1. Valent P, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007;37. 435-53. 
  2. Valent P, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-225.
  3. Schwartz, LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin N Am. 2006; 26(3):451-463. 
  4. Hartmann K, et al. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol. 2016 Jan;137(1):35-45 
  5. Castells M et al. Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations. Am J Clin Dermatol. 2011 Aug 1; 12(4): 259–270. 
  6. Brockow K, Metcalfe DD. Mastocytosis. Chem Immunol Allergy. 2010;95:110–24. 
  7. Valent P, Akin C, Metcalffe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017 Mar 16;129(11):1420-1427  
  8. Komarow et al. Serum tryptase levels in atopic and nonatopic children. J Allergy Clin Immunol. 2009(124): 845-47.  
  9. Molderings GJ, Brettner S, Homann J, et al. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J Hematol Oncol. 2011;4:10.
  10. González de Olano D, Alvarez-Twose I, Esteban-López MI, et al. Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis presenting with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol. 2008;121(2):519-526.
  11. Castells, M, Metcalfe DD, and Escribano L. Guidelines for the Diagnosis and Treatment of Cutaneous Mastocytosis in Children. Am J Clin Dermatol. 2011;12(4):259-270.