Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.
Systemic mastocytosis (SM) is a rare disease in which mast cells accumulate in the skin, bone marrow, and organs such as the spleen and liver.1,2 The 4 main types of SM are characterized by different features and range from an indolent form (indolent SM) to more aggressive types, such as SM with an associated non-mast cell lineage clonal hematological disease (SM-AHNMD), aggressive SM (ASM), and mast cell leukemia (MCL).1,3,4
The feature mainly responsible for the development of SM is mutation of the oncogene KIT, which codes for the stem cell factor receptor KIT, a transmembrane tyrosine kinase involved in regulating the proliferation and survival of mast cells and in cytokine production.3 Symptoms associated with SM result from the accumulation of mast cells in tissues and organs and the discharge of vasoactive mediators from mast cells.5 The signs and symptoms reported by patients with SM vary according to the organ in which mast cells have accumulated. Bleeding disorders and anemia, gastrointestinal symptoms (eg, abdominal pain, nausea, vomiting and diarrhea), and other signs and symptoms (eg, flushing, itching, hives, splenomegaly, hepatomegaly, lymphadenopathy) may develop. Anaphylactoid reactions may also occur.1
Both the diagnosis and treatment of SM can be challenging because the symptoms affect many organs and diverse pharmacological approaches can be used.4,5 A primary care physician should record the patient’s medical history and conduct a physical examination.5 When a diagnosis of SM is suspected, patients are ideally referred to specialized centers where a multidisciplinary team of specialists will confirm the diagnosis and provide follow-up. The medical team of a patient with SM often includes a hematologist, a dermatologist, an immunologist, and other specialized physicians who can help manage the disease and its symptoms, with the goal of preventing severe manifestations of SM.4,5
SM is a neoplastic proliferation of mast cells; therefore, a hematologist, who specializes in the treatment of blood diseases and cancer, will be part of the multidisciplinary care team.6,7 In addition to treating SM, the hematologist will evaluate and monitor the patient for any associated hematological disorder.8
The accumulation of mast cells in the skin and subsequent release of chemical mediators typically results in symptoms similar to those of an allergic reaction. Typical chemical mediators released by mast cells include histamine, leukotriene C4, prostaglandin D2, chemokines, cytokines, and heparin.8 Patients who have cutaneous mastocytosis or SM with skin involvement may have urticaria, in which patches of skin are often itchy and irritated.8 The care team of a patient with SM will therefore include a dermatologist, who specializes in the diagnosis and treatment of conditions of the skin, hair, and nails, including diseases such as eczema and skin cancer.9
Various substances, including allergens such as pollen, can trigger the release of mast cell mediators and cause an allergic reaction.10 A severe allergic reaction, anaphylaxis, may develop in a patient with SM and lead to cardiovascular collapse and death.10 Patients with SM are frequently followed by specialists in the diagnosis and treatment of allergic diseases, such as immunologists and allergists.5,6,11
A gastroenterologist specializes in the diagnosis and treatment of diseases of the gastrointestinal tract and liver.12 Patients with SM can benefit from the inclusion of a gastroenterologist in their care team because several gastrointestinal issues, such as nausea and vomiting and liver enlargement, may develop.1
In addition to hematologists, dermatologists, immunologists, and gastroenterologists, other medical specialists, such as nurses and pharmacists, are part of the care team. They are crucial in identifying and managing an allergic response, such as anaphylaxis, and reporting these events to the team coordinator. Pharmacists should educate patients about the use and administration of epinephrine when needed.5
Questions for the Care Team
Patients can find a specialist in mast cell disease through referral, by searching various networks, or by joining and consulting online support communities.13 Once a consult is scheduled, preparing for the appointment can ensure a successful visit. Patients may find it useful to keep a daily record of their symptoms and to write down what appears to have triggered any allergic reactions; the record can later be shown to their physician. It may be also useful to prepare in advance a list of questions to ask the specialist during the visit.14
1. Systemic mastocytosis. Genetic and Rare Diseases Information Center (GARD). Accessed April 18, 2022.
2. Systemic mastocytosis. Mayo Clinic. Accessed April 18, 2022.
3. Piris-Villaespesa M, Alvarez-Twose I. Systemic mastocytosis: following the tyrosine kinase inhibition roadmap. Front Pharmacol. 2020;11:443. doi:10.3389/fphar.2020.00443
4. Zanotti R, Tanasi I, Crosera L, et al. Systemic mastocytosis: multidisciplinary approach. Mediterr J Hematol Infect Dis. 2021;13(1):e2021068. doi:10.4084/MJHID.2021.068
5. Gangireddy M, Ciofoaia GA. Systemic mastocytosis. StatPearls [Internet]. Updated July 21, 2021. Accessed April 18, 2022.
6. Systemic mastocytosis. NCCN Guidelines for Patients® 2022. National Comprehensive Cancer Network. Accessed April 18, 2022.
7. Duckworth CB, Zhang L, Li S. Systemic mastocytosis with associated myeloproliferative neoplasm with t(8;19)(p12;q13.1) and abnormality of FGFR1: report of a unique case. Int J Clin Exp Pathol. 2014;7(2):801-807.
8. Mastocytosis. National Organization for Rare Disorders (NORD). Accessed April 18, 2022.
9. What is a dermatologist? American Academy of Dermatology Association. Accessed April 18, 2022.
10. Systemic mastocytosis. American Academy of Allergy Asthma & Immunology. Accessed April 18, 2022.
11. About allergists / immunologists. American Academy of Allergy Asthma & Immunology. Accessed April 18, 2022.
12. What is a gastroenterologist? American College of Gastroenterology. Accessed April 18, 2022.
13. Finding a physician. The Mast Cell Disease Society. Accessed April 18, 2022.
14. Preparing for doctor’s visit. Mastocytosis Society Canada. Accessed April 18, 2022.
Reviewed by Hasan Avcu, MD, on 4/28/2022.