A literature review published in the Journal of Pre-Clinical and Clinical Research describes recent advancements in our understanding of the causes, diagnosis and care of systemic mastocytosis (SM).
SM and other forms of mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. are often caused by mutations in the KIT gene, which codes for the CD117 protein. The most common mutation, occurring in more than 90% of people with SM, is the KIT D816V mutation. Patients experience constant activation of CD117, which activates several downstream signaling pathways such as MAPK, JAK-STAT and PI3K-AKT. Activation of these pathways results in mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. proliferation throughout the body.
In addition to the KIT gene, individuals with SM may also harbor mutations in the TET2, RUNX1, ASXL1 and SRSF2 genes, which may lead to more severe symptoms.
Many people with mastocytosis present with a characteristic rash known as maculopapular lesions, alongside the Darier’s sign, which describes how rashes respond to pressure. The authors note that cutaneous mastocytosis is more common in children, while SM occurs more frequently in adults; this knowledge may help expedite the diagnostic process. Diagnosis of SM is based on the World Health Organization guidelines, which have a list of major and minor criteria that must be met.
Read more about SM testing and diagnosis
Treating SM is highly dependent on symptom presentation and severity. The European Competence Network on Mastocytosis and the National Comprehensive Cancer Network advise that physicians treat patients using a stepwise approach.
Anti-mediator therapies are typically the standard of care for treating SM. Therapeutic options include H1/H2 antihistaminesAntihistamines Medications that block the effects of histamine, the chemical found in mast cells that is responsible for many of the symptoms of SM, as well as many allergic reactions., mast cell stabilizers, leukotriene drugs and anti-immunoglobulin E (IgE) therapy. In addition, psoralen plus ultraviolet A (PUVA) therapy may help to address skin symptoms, while proton pump inhibitors can treat gastrointestinal distress.
Tyrosine kinase inhibitors are a targeted treatment method that can reduce mast cell proliferation. Multiple tyrosine kinase inhibitors are approved for use in SM, with more being investigated in clinical trials. Bezuclastinib, for example, was found to reduce mast cell burden by more than half in 93% of participants with advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. in the APEX trial. The SUMMIT trial of bezuclastinib in non-advanced SM similarly showed promising results.
For those facing severe disease and a poor prognosis, cytoreductive therapies such as interferon-alpha, cladribine or polychemotherapy may help to reduce mast cell burden. Allogenic hematopoietic stem cell transplantation can be used to treat highly aggressive forms of SM that do not respond to other treatments, too.
The therapeutic landscape for SM is wide and continues to grow. Tailored disease management and communication between doctors and patients, therefore, will remain essential to optimizing outcomes.
“A precision medicine approach integrating clinical features with molecular profiling is critical to further improving survival and quality of life in patients with mastocytosis,” the authors concluded. “Nevertheless, there is a need to further develop research in this area.”
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