Case Reports in Hematology published a new report describing a woman whose repeated, severe anaphylactic episodes ultimately led to a diagnosis of indolent systemic mastocytosis (SM). Her lengthy course of therapy was complicated by initially inconclusive testing and the absence of the typical signs used to diagnose SM.
Although SM is defined by specific diagnostic criteria, this case illustrates how difficult it can be to meet those criteria in practice. Diagnosis often requires a combination of blood tests, bone marrow evaluation and genetic testing. However, patients without the classic signs of mast cell disease may undergo years of evaluation before reaching a clear diagnosis.
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The report describes a 35-year-old woman who first presented to an emergency department in 2017 after a wasp sting triggered cardiac arrest and required intensive care. In the months that followed, she developed unpredictable flushing episodes and allergic reactions to multiple triggers, including specific foods, perfumes and soaps. Laboratory testing showed elevated serum tryptase, a marker sometimes associated with mast cell activation.
She was initially treated using multiple medications aimed at stabilizing mast cells and reducing allergic reactions. Early bone marrow biopsies suggested abnormal mast cell activity but did not meet the World Health Organization (WHO) criteria required to diagnose SM. Allergy-directed therapy, including antihistamines, leukotriene inhibitors, cromolyn and omalizumab provided only partial relief.
As symptoms worsened, the patient began experiencing anaphylaxis every two to three weeks, often requiring emergency care and multiple doses of epinephrine. A highly sensitive polymerase chain reaction (PCR) test eventually detected the KIT D816V mutation, and a later bone marrow biopsy revealed more than 25% atypical mast cells. Together, these findings fulfilled the diagnostic criteria for SM.
“The diagnosis of systemic mastocytosis was made only after three minor criteria were fulfilled, highlighting the need for sensitive testing and repeated assessment,” the authors wrote.
Treatment with midostaurin, a multikinase inhibitor with activity against KIT D816V, reduced the frequency and severity of her reactions for several months. However, as symptoms returned, she transitioned to interferon therapy while awaiting clinical trial enrollment.
In September 2021, the patient started avapritinib through a clinical trial for indolent SM (ISM). Over the following year, she reported fewer anaphylactic episodes, improved gastrointestinal and skin symptoms and better day-to-day functioning. By late 2022, she had experienced no further severe anaphylaxis and had significantly reduced her need for supportive medications.
The authors noted that the case highlights the diagnostic difficulties faced by patients with ISM, particularly those without early skin involvement or with initially negative genetic testing. They added that highly sensitive testing methods and emerging targeted therapies may improve outcomes for individuals with persistent symptoms.
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