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Persistent Barriers in Systemic Mastocytosis Care: How to Ensure Early Recognition, Diagnosis, and Treatment in Your Practice 

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Released: August 24, 2026

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Barriers to timely systemic mastocytosis care persist despite growing awareness, emphasizing the need for early recognition of key signs and symptoms, appropriate diagnostic evaluation, and referral for confirmatory workup. Learn practical strategies for screening and individualizing treatment plans, while coordinating multidisciplinary care across specialties, to improve quality of life and clinical outcomes in patients with systemic mastocytosis.

Carole Bitar
Carole Bitar, MD, FAAD
Ensuring timely systemic mastocytosis care

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Key Takeaways
  • HCPs in dermatology and other settings must be able to recognize and diagnose SM early, especially when patients present without clear cutaneous involvement.
  • Screening, initial diagnostic testing, and patient education about anaphylaxis prevention are tasks that can be completed right away in any specialty setting.
  • Avapritinib is an advanced therapy indicated to treat adults with indolent SM and should be discussed with patients who have confirmed KIT D816V mutations. 

Unfortunately, many healthcare providers are still not familiar with systemic mastocytosis (SM) or the larger spectrum of mast cell disorders. Because some healthcare professionals (HCPs) feel uncomfortable with diagnosing and managing SM, patients are often passed from one HCP to another without getting answers. SM is a high-burden disease, so it is incredibly stressful for patients to have this kind of disease when not enough HCPs know how to diagnose it or direct their care.

Signs and Symptoms of SM
The main issue is a lack of HCP education, with a key group being advanced practice providers (APPs) in dermatology and emergency care settings. These folks are essential for improving timely SM recognition and treatment because they are the HCPs who often see patients first. APPs, especially those in dermatology, must be educated on SM, and they should know exactly what to look for, what to ask patients about, and what the criteria are that need to be met to confirm a diagnosis.

If patients present with intermittent rashes, for example, they are more likely to have a condition in the urticarial family. But when the rashes look more uniform, with red/orange/brown papules and macules that start on the chest or trunk area and travel to the thighs or upper extremities, HCPs should consider cutaneous mastocytosis and potentially SM. Of note, SM-related skin lesions generally do not cross the head and neck area or go away in adult-onset disease. Instead, they are essentially permanent.

Furthermore, some patients with SM may be largely asymptomatic or present with nonspecific symptoms such as pruritus, angioedema, or syncope, which can sometimes be overlooked. When syncope occurs, it is important for HCPs to evaluate the underlying cause, including whether cardiovascular symptoms such as tachycardia or hypotension are present. These systemic manifestations, particularly when they occur alongside angioedema or other symptoms, may help to differentiate SM from conditions such as chronic spontaneous urticaria. HCPs should also assess potential triggers for syncope or other cardiovascular episodes, including bee or other insect stings, certain foods, and medications.

Other systemic symptoms of SM comprise abdominal pain, diarrhea, brain fog, fatigue, headaches, seizures, anxiety or depression, shortness of breath, and fractures. HCPs should ensure they make note of these symptoms because SM can involve the gastrointestinal tract or bone, among other organs, causing systemic disease as it spreads.

Evaluation for Suspected SM
It is equally important for HCPs to know that visits with patients will be longer than usual when evaluating them for SM. Therefore, HCPs must take the time needed to fully assess patients’ physical presentation, history, and current medications.

HCPs should always complete a good review of system, past medical history, and current therapies, especially considering many are on multiple medications. Patients also need to be physically examined from head to toe. If they have monomorphic skin lesions that do not go away, it is best practice to take a sample for biopsy. Some patients might say, “I have had these for many years. They are completely asymptomatic.” I have heard this a lot in my practice, and it can occur because patients have seen too many HCPs who are not familiar with SM. If any maculopapular or monomorphic skin lesions are present, regardless of patients’ own understanding of their disease burden, a sample should be sent out for skin biopsy.

The next step is to send that sample to dermatopathologists, alerting them that you suspect cutaneous mastocytosis. Of note, cutaneous involvement in SM could present via a low burden on the skin. Regardless, it is important to request specific stains like CD117 and tryptase on skin biopsies. That is because the Hematoxylin and eosin (H & E) slide by itself may not be enough to diagnose SM, whereas the stains will further reinforce suspicions if they return positive.

For patients with a history of relevant symptoms and skin biopsies that return positive, the next step is to order peripheral blood tryptase testing. If HCPs highly suspect SM, we can also order testing to determine if KIT D816V mutations or hereditary α-tryptasemia is present in their blood. A dual-energy x-ray absorptiometry scan should be ordered for anyone with a history of fractures or bone lesions and to get ahead of their potential bone disease.

While these tests are being done, HCPs should educate patients on the importance of carrying 2 epinephrine autoinjectors on them at all times. This is essential since patients with SM face serious, potentially fatal episodes if anaphylaxis is triggered.

Remember that HCPs can order these screening tests and provide patient education right away and that these things do not have to happen sequentially over multiple visits.

When positive results indicate that cutaneous mastocytosis is present (it does not matter if patients’ peripheral tryptase levels are normal or elevated), patients must be referred to hematology/oncology for bone marrow biopsy. Yes, we want HCPs to start screening early and order all those tests in their clinic. However, hematology expertise is required for bone marrow biopsy, which is the gold standard for confirming an SM diagnosis. Unfortunately, most patients with cutaneous involvement have indolent SM, and this disease needs to be treated as early as possible. Therefore, recognizing and detecting SM early, whether it be an indolent or advanced form, is critical for ensuring more positive outcomes and improved quality of life for patients.

Current Treatment Strategies for SM
For patients with a more advanced form of SM, such as SM with an associated hematologic neoplasm or mast cell leukemia, hematology/oncology will take the lead in their care. Other specialties like dermatology and allergy/immunology come into play when indolent SM is the diagnosis. The first treatment step here is initiating antimediator therapy for symptom management. Guideline-directed care emphasizes the use of antihistamines with H1 and H2 blockers, depending on the symptoms present. Furthermore, a combination of first-generation and second-generation antihistamines can be helpful. Other therapies that could be considered and are approved for chronic spontaneous urticaria are omalizumab, an anti-IgE therapy, and dupilumab, an IL4/13 inhibitor. Note that none of the above therapies target the monomorphic skin lesions that are characteristic of SM. 

There is also an advanced treatment option now available for select patients: avapritinib, a kinase inhibitor that targets KIT D816V mutations. In a recent study, avapritinib demonstrated its ability to reduce mast cell burden and to decrease the size and normalize the color of skin lesions. This is great news because we have never had a treatment option like this before. Some patients are covered in skin lesions, which creates a heavy burden when it comes to their appearance. Therefore, HCPs should discuss the option of using this targeted therapy with patients who have confirmed KIT D816V mutations. HCPs can refer patients to allergy/immunology to access avapritinib if they are uncertain about starting themselves. 

Some patients may not care about their skin lesions, and they just want to control their symptoms. In these cases, HCPs can initiate antimediator therapy and monitor their response throughout follow-up.

Tips for Dermatology HCPs
For dermatology HCPs, in particular, the take-home message is to recognize SM early, send samples for skin biopsy, and order all the screening tests needed to diagnose patients. Do not forget to refer them to hematology/oncology for bone marrow biopsy either.

If HCPs feel uncomfortable with managing patients’ disease in their clinics, we can always refer them to a center experienced in treating mast cell disorders. In the same vein, multidisciplinary care is ideal because of the systemic nature of SM. That means coordinating patient care with allergy/immunology, hematology/oncology, gastroenterology, and endocrinology, among others, as needed.

For those with a low lesion burden who want to keep seeing their HCPs as their dermatologist, we can help them control their symptoms with antihistamines and other antimediator therapy and can talk with them about the advanced treatment options if they are interested. Regardless of the treatment approach patients wish to take, HCPs should teach them about the importance of carrying epinephrine autoinjectors on them at all times and ensure they know how to use it.

In dermatology, we follow up with patients approximately every 6 months if they have a low burden and indolent disease. This provides the opportunity to make sure patients are not developing more skin lesions or their disease is not advancing. Remember that SM is a clonal disease. It is not a quiet disease and can change over time. That is why it is important to closely monitor patients, regardless of their treatment choice, to ensure their disease is not advancing.

Your Thoughts
How often are you screening for SM in your patients who present with maculopapular, monomorphic skin lesions? 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 screen for SM in your patients who present with maculopapular, monomorphic skin lesions?

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