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Case Challenges in Systemic Mastocytosis: Expert Answers to Your Questions

Released: May 06, 2026

Benjamin Ungar
Benjamin Ungar, MD
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Key Takeaways
  • HCPs should measure tryptase and test for KIT D816V mutations in patients presenting with maculopapular lesions.
  • Those with cutaneous mastocytosis in childhood rarely see their disease progress into SM in adulthood.
  • Patients with B and C findings require closer follow-up to ensure their disease does not progress.

In this commentary, Benjamin Ungar, MD, answers questions posed by healthcare professionals (HCPs) during 2 live webinars titled “Case Challenges in Systemic Mastocytosis: Clinical Insights From the Expert Roundtable” held in April 2026. Learn best practices for identifying patients with systemic mastocytosis (SM), including the symptoms and red flags that warrant referral to other specialties, and specific considerations for integrating targeted therapies in personalized treatment plans. 

For patients with maculopapular lesions, what features should prompt HCPs to evaluate them for SM?
Simply seeing maculopapular red-brown lesions on patients may be consistent with mastocytosis and should raise consideration for biopsy to evaluate for SM. Most patients with adult-onset cutaneous mastocytosis actually have SM, so if the biopsy is consistent with cutaneous mastocytosis, further evaluation for SM is needed. But there is some variability, particularly among those with lower-than-normal serum tryptase levels who are largely asymptomatic. These patients often have minimal bone marrow involvement or subdiagnostic findings; therefore, not everybody needs to be evaluated for SM. At a minimum, HCPs should measure baseline tryptase levels and test for KIT D816V mutations in peripheral blood for all patients with cutaneous lesions that are consistent with mastocytosis or, of more importance, in patients with a biopsy showing mast cell infiltrates. Then you can refer them to allergy/immunology or hematology/oncology, where a specialist can determine if further evaluation is warranted. 

Are there any special considerations that HCPs should keep top of mind when diagnosing and treating pediatric patients?
For pediatric patients, HCPs generally do not need to complete additional workup in terms of bone marrow biopsy or looking for systemic disease, as the vast majority of pediatric mastocytosis is limited to the skin. The primary exception to this is if they present with severe disease, in which case SM may be a consideration, and the cutaneous findings in these patients typically are monomorphic maculopapular lesions. If their tryptase level is elevated initially, it should taper down as their disease resolves. Although HCPs should monitor high tryptase levels in pediatric patients, they likely will not require a referral for additional workup.

Are there any pitfalls HCPs should be aware of when interpreting tryptase levels or KIT mutation testing?
KIT mutation testing is straightforward, and KIT D816V is the specific mutation that HCPs should look for. It is either positive or negative, with the variant allele fraction defining the burden of the mutation. In contrast, interpreting tryptase is much less straightforward because of a genetic trait called hereditary alpha tryptasemia (or HαT). Patients with HαT comprise approximately 5% of the population and present with elevated tryptase levels that are usually greater than 8 mg/mL. Therefore, approximately 5% of humans—at least in the United States and Western Europe—have elevated tryptase levels at baseline. This can confuse HCPs and patients alike, especially if tryptase levels are higher than 20 mg/mL, which is 1 of the minor criteria in the WHO diagnostic criteria for SM. So when HCPs check tryptase levels, it is important to keep in mind that HαT could be a cause of high levels.

If patients suspected of having SM present with B or C findings, how does that shape their prognosis or follow-up?
If any patients have B or C findings, they should be referred to hematology/oncology and allergy/immunology for appropriate workup and to begin treatment. It is also important for HCPs to have these patients follow up to evaluate their skin-related symptoms, because the skin can sometimes take longer to respond to treatment than other systems/domains (eg, gastrointestinal symptoms). Even though there are treatments that can help, patients' skin symptoms may not improve the way they hope for, so patients with B and C findings require closer follow-up to ensure their disease does not progress.

How early should HCPs refer patients with SM to assess their bone health?
The short answer to this question is immediately. Patients with SM are at increased risk for bone disease, such as osteopenia, osteoporosis, and fractures, so there is no benefit to pushing off their bone health assessment. Even if patients have a normal bone density, they can be connected with endocrinology, which can help them with preventative approaches. Otherwise, patients with low bone density need to be treated as soon as possible.

What characteristic(s) make patients good candidates for avapritinib?
It depends on the patient, but avapritinib is generally used in those who remain symptomatic despite achieving disease control or using maximally tolerated treatment with at least a handful of antimediator therapies. Many patients are on antihistamines (ie, cetirizine or famotidine), omalizumab, and/or montelukast and are still symptomatic despite our best efforts. In these patients, particularly when their tryptase levels are elevated, avapritinib can improve their quality of life enormously. Another group of patients who are good candidates for avapritinib is those with more aggressive or advanced disease. These patients generally have a high mast cell burden, increased serum tryptase levels, significant bone marrow involvement, and/or a high KIT D816V variant allele fraction. When patients present with these disease characteristics, HCPs should recognize that there is a higher risk involved. Therefore, avapritinib may be used in these patients sooner, even if they are moderately symptomatic.

How long can patients be on avapritinib?
A downside to treating SM with avapritinib is the current lack of evidence and guidance on stopping therapy. In general, the approach should be that avapritinib is a long-term/ongoing treatment. This may change in the future as more potent, targeted tyrosine kinase inhibitors appear that allow patients to achieve deeper remission. But for now, this is an open-ended question, and most patients with SM will be on therapy for the long term.

If patients are undergoing a liver transplant, can they use avapritinib at the same time?
Because patients are at risk of bleeding, including intracranial hemorrhage, with avapritinib, it should not be taken when undergoing a liver transplant. It may depend on the reason they are anticipating hepatic transplant, but avapritinib should be stopped 3-5 days before surgery in most cases. One possible exception might include those with aggressive SM and portal hypertension, in which it’s their disease that may be causing the liver failure. In that case, avapritinib may lead to cytoreduction, but that is a very specific case in which the primary cause of liver failure is SM. In all other situations, the answer is no.

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