Systemic Mastocytosis (SM)

Mastocytosis is a heterogeneous disorder characterized by the excessive growth and accumulation of morphologically and immunophenotypically abnormal mast cells (MCs) in one or more organs. The systemic form of the disease, systemic mastocytosis (SM), is characterized by the diffuse and/or focal infiltration of neoplastic mast cells in various organs, including the bone marrow, spleen, liver, and gastrointestinal tract. The clinical presentation of SM is variable; common features are a lengthy history of urticaria pigmentosa (see below), the insidious onset of flushing, cramping abdominal pain, diarrhea, bone pain, and hepatosplenomegaly.¹ Symptoms in SM can be attributed to the release of mediators or to MC infiltration of cutaneous and extracutaneous tissue.² 

Cutaneous Findings

Both the cutaneous and systemic forms of mastocytosis are characterized by involvement of the skin. The skin is the only organ affected in the cutaneous type. A maculopapular rash gradually develops in which small, brown, flat or elevated spots are surrounded by erythematous and pruritic skin. This finding is referred to as urticaria pigmentosa or maculopapular cutaneous mastocytosis.³ The lesions of urticaria pigmentosa typically appear at a young age and increase over several years; the condition is diagnosed with a skin biopsy.⁴

Darier’s sign, a form of dermatographism that is associated with SM, is due to the presence of mast cells in affected skin. In patients with cutaneous involvement, such as urticaria pigmentosa, urticaria and/or erythema may develop over a region that has been lightly scratched (Darier’s sign).⁵ Urticaria pigmentosa lesions may also sting or itch with changes in temperature.⁶ Unlike other forms of dermatographism, Darier’s sign is urtication following stimulation that is limited to involved areas of the skin; uninvolved areas are spared.⁵ 

Mediator-Related Symptoms 

The release of mediators such as histamine, leukotriene C4, prostaglandin D2, chemokines, cytokines, and heparin may manifest as allergic events, fluid extravasation leading to hypotension, hypersecretion of stomach acid, and increased tone of bronchiolar smooth muscle manifesting as wheezing. Headache, dizziness/lightheadedness, syncope/presyncope, and hypotension may also result. The release of histamine results primarily in flushing and the hypersecretion of gastric acid, which may cause gastroesophageal reflux disease, abdominal pain, bloating, and diarrhea.^1,3 

The massive degranulation of MCs may lead to life-threatening episodes of anaphylaxis in response to certain triggers, such as Hymenoptera venom, physical and emotional stress, alcohol, spicy food, and medications. Common medications that may trigger anaphylaxis are aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics, muscle relaxants, and radiocontrast material.³

Symptoms Arising From Extracutaneous Organ Infiltration

The infiltration of various organs by MCs in SM, including bone, liver, spleen, and lymph nodes, gives rise to a variety of features.³ 

Bone marrow infiltration by MCs can result in cytopenias and osteolysis.³ Musculoskeletal symptoms, including bone pain, arthralgias, and myalgias, are present in 31% of patients.¹ Osteopenia or osteoporosis may develop in patients with bone involvement, predisposing them to pathologic bone fractures.⁶ 

Liver infiltration can result in hepatomegaly in 27% of patients who have SM, associated with elevated liver enzymes, impaired hepatic function, and portal hypertension.^1,3 Splenomegaly is present in 37% and hepatosplenomegaly in 21% of patients.¹ MC infiltration of lymph nodes leads to lymphadenopathy, which is found in 21% of patients.^1,3 

References

1. 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

2. Nallamilli S, O’Neill A, Wilson A, Sekhar M, Lambert J. Systemic mastocytosis: variable manifestations can lead to a challenging diagnostic process. BMJ Case Rep. 2019;12(8):e229967. doi:10.1136/bcr-2019-229967

3. Mastocytosis. NORD (National Organization for Rare Disorders). Accessed April 12, 2022.

4. Caplan RM. The natural course of urticaria pigmentosa. Analysis and follow-up of 112 cases. Arch Dermatol. 1963;87:146-157. doi:10.1001/archderm.1963.01590140008002

5. Galen BT, Rose MG. Darier’s sign in mastocytosis. Blood. 2014;123(8):1127. doi:10.1182/blood-2013-11-538355

6. Systemic mastocytosis. MedlinePlus Genetics. Accessed April 12, 2022.

Reviewed by Harshi Dhingra, MD, on 4/16/2022.

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Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.