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Improving Systemic Mastocytosis Detection
Call to Action in Systemic Mastocytosis: Strategies to Advance Recognition and Timely Treatment Across Disciplines

Released: January 06, 2026

Thanai Pongdee
Thanai Pongdee, MD
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Key Takeaways
  • Systemic mastocytosis (SM) is a rare disease that presents with common and nonspecific symptoms such as itching, flushing, rash, abdominal pain, bloating, diarrhea, fatigue, and pain.
  • Healthcare professionals across disciplines should have open dialogue with their dermatology and allergy colleagues to help detect SM early and ensure timely treatment.
  • Targeted therapies like avapritinib and midostaurin are now available to treat patients with indolent SM or advanced SM, respectively. 

There are 2 key issues with detecting systemic mastocytosis (SM) in real-world practice: it can present in multiple ways, and it often includes common symptoms like itching, flushing, and rash. These symptoms occur quite frequently in the general population and are seen by allergy, immunology, and dermatology healthcare professionals (HCPs) frequently. Furthermore, since SM is a rare disease, it may not be the first thing that HCPs consider when patients present with any of these common symptoms. 

Many patients will think they are simply allergic to something they were in contact with or that they ate. It is not a diagnosis that patients or HCPs would jump to and say, “Oh yeah, this must be SM.” Although skin manifestations are common, SM also can cause gastrointestinal symptoms, such as abdominal cramping, diarrhea, and bloating. Some patients do not tolerate eating certain foods, which can lead patients and HCPs to consider many different disorders or diseases first. When you consider the whole body and every system that can be affected, patients with SM may also experience chronic bone or muscle pain, joint issues, fatigue, or difficulty with sleeping or doing their daily activities, among others.

The list of nonspecific symptoms is long, which is why it is hard to drill down to a diagnosis of SM. In addition, because of the rarity of this disease, it is not top of mind for most HCPs. As many have not yet seen a patient with SM, recognizing the disease can be challenging.

Key Symptoms for Detection and Disease Burden
There are 2 symptoms associated with SM that are key, especially from an allergy perspective. Any episode of anaphylaxis, a severe allergic reaction that can be life-threatening—and especially if episodes are recurring—is a red flag. Anaphylaxis due to a bee sting also should be a big red flag.

The second key symptom involves the characteristic skin lesions associated with SM: maculopapular cutaneous mastocytosis, otherwise known as urticaria pigmentosa. Dermatologists and allergists must be aware of this red flag. These lesions have a distinctive appearance on most patients, comprising the characteristic sign where stroking the lesion makes it urticate. Red and itchy skin is characteristic of SM as well. I have seen patients who have noticed a “spot” on them that never goes away and kind of itches. They will get more of these “spots” over time and do not know what they are before presenting to my office. Therefore, it is imperative that HCPs complete a careful skin examination when patients present with skin lesions.

Moving onto disease burden, patients often share 3 main areas in which SM deeply impacts their quality of life. The first includes the gastrointestinal symptoms described previously. They are relatively common, and one can imagine how hard it must be to get through a “normal” day when experiencing these symptoms. Some patients ensure they are close to a restroom wherever they go to have a private moment when needed. Their whole day may be planned around these potential gastrointestinal symptoms. This is especially impactful for those who commute to work, where they must be present in their employment.

The second area comprises the skin manifestations of SM. Not only do we care about the maculopapular cutaneous mastocytosis previously discussed, which can be visibly apparent to others and cause worry, but patients may have frequent episodes of flushing. Their skin can turn beet red periodically and they may start itching. These are recurrent symptoms of SM that can affect patients' daily activities and are visible to everybody around them. That can be challenging for patients to manage.

The third area is made up of the general fatigue and joint pain that many patients experience. It is hard for them to physically get through the day, especially a physically taxing day.

Importance of Detecting SM Early
A clinical challenge that must be overcome is the far too common diagnostic delay. Addressing this gap in care is critical due to the chronic nature of the skin, gastrointestinal, and constitutional symptoms that manifest and place a significant burden on patients’ everyday quality of life. These symptoms affect patients as well as their family and everyone else around them. Furthermore, it takes a physical and mental toll on an individual the longer their diagnostic delay persists.

Then there are serious issues regarding the increased risk of anaphylaxis and poor bone health (ie, osteopenia and osteoporosis). These things add up over time, and early intervention can certainly improve symptom burden significantly. Targeted treatment with novel therapies can now improve patients’ mast cell burden and quality of life. As with many other diseases, earlier diagnosis leads to timely treatment, which hopefully translates to less disease burden and improved outcomes.

Strategies for Multidisciplinary Care
Due to the many systems in the body that can be affected, caring for patients with SM presents the opportunity to employ effective multidisciplinary care. For example, primary care HCPs should have open dialogue about their concerns when speaking with their dermatology or allergy colleagues. You can say, “I have a patient with these multiple symptoms and skin lesions. They had an athletic event. I am not sure, but could this be SM?” If primary care HCPs can frame their suspicions in terms of patients’ total clinical picture and identify what they are worried about, many dermatology and allergy HCPs should be able to home in on potential diagnoses. They also can rule certain characteristics as relevant or not based on the history provided. If patients’ medical history contains some of the red flags I shared previously, then dermatology HCPs should understand that a biopsy of the skin lesions present is needed right off the bat. From an allergy perspective, there are a variety of tests that can be used to confirm a diagnosis of SM.

Regarding other disciplines, gastroenterology HCPs can help identify SM because of the many patients with chronic gastrointestinal symptoms that may first present here. These HCPs can raise clinical suspicion, asking their allergy or dermatology colleagues if SM could be causing the loose stools and stomach upset their patients are experiencing. Endocrinology HCPs often deal with osteoporosis and osteopenia. I have had many referrals in my practice from endocrinologists with patients who developed poor bone health at an early age. It is generally unexpected for such diseases to develop in young people, so endocrinology HCPs should screen for SM in these patients. In all, there are a lot of disciplines involved and based on their area of expertise, they can help determine if SM is causing this or that symptom in a given patient.

Finally, there are many therapies that we traditionally have used to treat the symptoms of SM (ie, antimediator therapy). This treatment approach is used because mass cells contain different chemicals that cause all the various symptoms associated with this disease when released. So there is a portfolio of different antimediator therapies that target the effects of these chemicals to hopefully improve symptoms. More recently, we have entered a new era in SM management. Novel, targeted therapies are now available that focus on the KIT D816V mutation commonly found in patients with SM. These therapies have drastically changed the landscape in terms of the benefit that we can offer our patients. We can now address the driver of disease and basically turn that mutation off. In addition, patients subsequently see much symptom improvement with the use of these targeted therapies.

It is important to note that some patients do well with nontargeted antimediator therapy. This can be sufficient to take care of their disease. Others require multiple therapies, and polypharmacy can become a huge concern. Furthermore, patients may have refractory symptoms despite antimediator therapy, and they may choose to move onto targeted therapy. We are seeing lots of clinical trials start in this space, and hopefully we will have more targeted therapies available in the near future.

Take-home Messages for Dermatologists, Allergists, and Immunologists
First, consider your differential diagnosis. SM should be on the list of concerns whenever you see patients with anaphylaxis, especially if it is due to insect stings. Next, do not forget to consider the whole patient and their complete symptom picture. Sometimes we get too focused on a single symptom and have a narrow view of patients. Instead, be sure to ask patients if they have had anaphylaxis and skin, gastrointestinal, or other nonskin-related symptoms. If patients’ answers are “yes” to experiencing lot of these different symptoms, there may be more to it than just the skin lesion that you are looking at—consider SM.

Among allergy HCPs, in particular, patients may present to your office with an allergic question. Do they have a food allergy because they cannot eat certain foods? Again, ask additional questions about their other symptoms. That can help clue you in that there is something more going on than the very specific question you were initially presented.

Your Thoughts
How often do you prescribe avapritinib to your patients with advanced or indolent SM? You can get involved in the conversation by answering the poll question and posting a comment below.

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How often do you consider SM in patients presenting with nonspecific gastrointestinal and cutaneous symptoms?

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