While systemic mastocytosis (SM) is believed to impact men and women at relatively equal rates, how a patient experiences SM can vary widely by sex.
In SM, immune, hormonal and genetic changes interact with one another to amplify mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis. and symptom flares. Understanding how these changes can lead to differences in women and men may help you to better anticipate the course of the disease and work with your doctors to design more personalized care.
Men face a worse prognosis
Overall, males with SM tend to experience a poorer prognosis. Men present more frequently with high-risk mutations in certain genes, including:
- SRSF2.
- ASXL1.
- RUNX1.
Men are also more likely to develop more severe forms of SM, such as SM with an associated hematological neoplasmSM with an associated hematological neoplasm A form of advanced SM and the second-most common subtype of SM overall. In this subtype, SM occurs alongside another blood disorder. Also called SM with an associated myeloid neoplasm. (SM-AHN). Even within a particular subtype of SM, men generally have worse survival outcomes than women.
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Hormonal differences shape the disease course
Mast cells contain receptors that allow estrogen to directly bind to them. When this happens, mast cells become activated, releasing histamineHistamine A chemical released by mast cells when they are activated. Histamine causes many of the allergy-type symptoms in mastocytosis, including flushing, itching and hives. and other chemicals into the body that cause the symptoms of SM.
Although men face a worse prognosis, women with SM are more likely to experience anaphylaxis, especially during the reproductive years. This may in part be driven by increased levels of estrogen during these decades of life.
In addition to directly activating mast cells, estrogen increases levels of nitric oxide synthase, a family of enzymes that make nitric oxide. In the bloodstream, nitric oxide tells the blood vessels to relax, which worsens low blood pressure during episodes of anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis..
Other symptom differences in systemic mastocytosis
Aside from anaphylaxis, many other clinical features of SM vary by sex.
Skin symptoms: Women with SM report skin involvement more often than men. This might include itching, flushing or skin lesions.
Gastrointestinal symptoms: Digestive issues, such as abdominal cramping and diarrhea, are more common in women with SM.
Enlarged organs: Male patients with SM have a higher frequency of organomegaly (enlarged internal organs), a known complication of more advanced forms of SM.
Neurological symptoms: Women with SM are more likely to report headaches than males.
Bone symptoms: Both men and women with SM are susceptible to bone pain and osteoporosis. However, some studies show that younger men with SM may be at a greater risk of fracture than premenopausal women.
Implications for treatment and care
The available treatment options for SM don’t differ by sex. However, when you meet with your care team, you can discuss whether sex-specific disease monitoring may be right for you. Tracking hormonal shifts and changes in bone health, for example, can help you to better plan for future complications and comorbidities.
Read a patient’s firsthand account about living with bone disease: “What it’s like to live with systemic mastocytosis and osteoporosis”
