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Systemic mastocytosis FAQs
MASTer Class in Systemic Mastocytosis: Expert Answers to Your Questions

Released: February 19, 2026

Benjamin Ungar
Benjamin Ungar, MD
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Key Takeaways
  • Healthcare professionals must ensure patients with systemic mastocytosis understand the chronic nature of their disease, including the fact that maculopapular cutaneous lesions may persist throughout their lives.
  • Increased tryptase levels, confirmed KIT D816V mutations, and prior hymenoptera venom anaphylaxis are red flags that should prompt referral to allergy and immunology for evaluation.
  • Those with cutaneous mastocytosis in childhood rarely see their disease progress into systemic mastocytosis in adulthood.

In this commentary, review questions posed by healthcare professionals (HCPs) during several live symposia titled “MASTer Class in Systemic Mastocytosis: A Multidisciplinary Clinical Skills Curriculum to Improve Diagnosis and Management” that were held in January 2026. Take home best practices for counseling patients about the chronic nature of systemic mastocytosis (SM), learn the symptoms and red flags that warrant a referral to other specialties like allergy and immunology, and understand how SM is differentiated among other mast cell activation disorders in adult and pediatric patients.

What expectations should HCPs set with patients regarding the chronic nature of SM and the continuous manifestations they can experience even while on systemic therapy?

It is important for HPCs to counsel patients that SM is chronic in nature. This includes the maculopapular cutaneous lesions; patients can present with a few skin lesions initially, and more lesions can develop with time for many patients. For example, SM may first present on their thighs and then expand to their trunk, and some patients have widespread involvement over their whole body. That is why it is important for HCPs to set expectations with their patients, including considering the potential cosmetic impact. Conversely, when patients start to see their skin lesions improve, it can be a sign that the disease is moving more internally—which might not be a good sign. Others might see their skin lesions persist through treatment. Therefore, it is critical that HCPs counsel patients on what to expect with these skin lesions and follow up with them frequently to ensure they are not experiencing disease progression even when on systemic therapy.

Which SM-associated symptoms are red flags that should prompt HCPs to refer patients to allergy and immunology? 

SM-associated symptoms can be quite varied, involving multiple organ systems, including fatigue, abdominal pain, diarrhea, bone pain, hypotension, chest pain, headache, and brain fog among many others. When a patient has multiple symptoms like these, it should be a red flag for further evaluation of SM. When SM is being considered, there are 3 things HCPs should ideally do before referring patients to allergy and immunology. First, HCPs should complete a biopsy of any skin lesions suspicious of mastocytosis, measure tryptase levels, which is a helpful screening test, and complete genetic testing for KIT D816V mutation. Of note, the genetic test for the KIT D816V mutation should be done via PCR, not next-generation sequencing. Beyond these considerations, allergy and immunology can triage patients and help coordinate additional specialist referrals.

An important question that also can help assess for potential SM is whether patients have experienced hymenoptera venom anaphylaxis. Hymenoptera venom comes from the stings of various winged insect species like bees, hornets, and wasps, but not mosquitoes. When stung, patients with SM can experience serious anaphylaxis that is often characterized by hypotensive syncope, and hymenoptera venom anaphylaxis–related fatalities have been reported. HCPs should ask their patients if they have ever experienced anaphylaxis and specifically anaphylaxis with loss of consciousness. Any anaphylaxis with hypotensive syncope denotes a high-risk group of patients with SM. Determining which patients fall into this group and taking preventive measures can have a dramatic impact. 

What clinical information should HCPs include in their referral notes to facilitate a timely and accurate diagnosis?

It is important to document any skin biopsy and pathology results, as well as any signs or symptoms identified on a review of systems potentially indicating affected systems/organs. This often requires a long visit with patients, so there may not be time to characterize details about the symptoms, but it is helpful to include any information discussed. If patients mention that they have experienced anaphylactic episodes or hypertensive anaphylaxis, that should be included in the notes as well. A bone marrow biopsy is necessary to reach a diagnosis of SM, so prompt referral to a hematologist or allergist who can perform one is needed.

When children with cutaneous mastocytosis present with multiple mastocytomas and high tryptase levels, what is the probability that their disease will progress to SM in adulthood?

SM is a bone marrow disease. Patients with SM have mutated mast cell clones that originate in the bone marrow and then travel through the blood to accumulate in other organs. The KIT mutations in SM are thought to occur in hematopoietic progenitor cells, which are stem cells that remain through the duration of an individual’s life and experience functional decline with age. The pathogenesis of pediatric mastocytosis has not been fully sorted out in the research and literature, but there are some interesting data that suggest that the origin of mutated mast cells may come from the extraembryonic yolk sac, seeding the skin with its first wave of mast cells. These yolk sac–derived mast cells are then lost almost completely by early adulthood because they are replaced with definitive mast cells derived from hematopoietic progenitor cells. So those with initially mutated mast cells probably no longer have mutated progenitor cells in childhood and adolescence. As the first wave of mast cells die off, the clones also die off; therefore, pediatric mastocytosis and SM are truly 2 different diseases.

The exception to this is that in a small percentage of pediatric cases, monomorphic-appearing skin lesions may reflect SM. So if a child has several monomorphic skin lesions, regardless of their tryptase levels, that should prompt HCPs to evaluate them for SM.

In addition, children can have other mast cell activation disorders, with examples including cutaneous mastocytosis and mastocytomas, and usually present with 1 or 2 skin lesions (or mastocytomas). The treatment for these may comprise excision or they may resolve on their own by puberty, so mastocytomas are generally fairly benign. Diffuse cutaneous mastocytosis can look much more dramatic, as patients may present with dark, thickened skin, and they also can be very sick because their tryptase levels can be high. Yet those with these forms of mastocytosis in childhood rarely see their disease persist into adulthood.

What is the cause of osteoporosis in patients with SM? And how often should patients with SM have a bone density scan done? 

This is an active area of research that has not been fully elucidated. Osteoporosis in SM may be related to mast cell functional burden, in which mast cells release a variety of chemicals, cytokines, and chemokines that put increased pressure on osteoclasts to break down bone, rather than on osteoblasts to build up bone. But the pathogenesis of this is not completely understood at present.

A bone density scan is vital for patients with SM in order to diagnose osteoporosis, which can be a significant cause of morbidity. Even atypical populations like younger patients in their 30s and 40s can have vertebral fractures, so it is important to assess for osteoporosis. Typically, it is good to order a bone density scan at diagnosis as a starting point, and repeat frequency depending on the result, with repeat in 5 years for a normal bone density scan. Certainly any evidence of osteopenia or osteoporosis requires referral to an endocrinologist.

Should patients with more than 1 anaphylaxis or angioedema events be evaluated for SM? 

There are many causes of anaphylaxis and angioedema events that are not related to SM, so more than 1 episode of anaphylaxis does not necessarily point to SM.  If a patient presents with anaphylaxis, however, it is reasonable to assess for skin lesions that might reflect SM as the potential etiology for anaphylaxis. However, much of that also will depend on the patient’s history. If they had an exposure to a food and the anaphylaxis event occurred in a kind of a repetitive fashion, there may be more likely explanations than SM. Other symptoms, like GI symptoms, flushing, etc are likely to also occur in someone with SM.

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Do you ask your patients suspected of having SM about their other, nonskin-related symptoms? You can get involved in the conversation by answering the poll question and posting a comment below.

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