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Systemic Mastocytosis Mayhem: Optimizing Outcomes by Addressing the Patient Burden
CME/CE Information

Activity

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1 2 3
Course Completed
Activity Information

Physician Assistants/Physician Associates: 0.50 AAPA Category 1 CME credit

Nurse Practitioners/Nurses: 0.50 Nursing contact hours, includes 0.50 hour of pharmacotherapy credit

Released: May 16, 2025

Expiration: May 15, 2026

Jonathan A. Bernstein
Jonathan A. Bernstein, MD
Kristine J. Kucera
Kristine J. Kucera, PA-C, MPAS, DHSc
Martha L. Sikes
Martha L. Sikes, DMSc, RPh, PA-C

Systemic Mastocytosis Mayhem: Optimizing Outcomes by Addressing the Patient Burden

 

Kristine Kucera: Let us talk about what we have been talking about, the burden, the quality of life. What are these patients going through?

 

Patients with MC disorders are at risk for chronic and/or disabling symptoms. All the symptoms that come along with this disease state, it is a lot. Many patients report symptoms that are moderate to severe. More than 50% having moderate or extreme flushing, itching, diarrhea, stomach pain, fatigue and headache. Most reporting moderate or extreme symptoms reporting, having them daily or occasionally.

 

Patients identify that the greatest stress of living with an MC disorder is the unpredictability of symptoms. You never know when it is going to come and how bad it is going to be.

 

[01:26:02]

 

Patient Reports of Impact on Daily Life, Work, and Social Activities/Settings, Mental Health

 

Patient reports of the impact on their daily life, work, social settings and mental health. Activities: More than 50% report being quite a bit limited in performing things like daily work, hobby, leisure activities. Social activities also affected, 60% say they avoid leaving home due to SM.

 

Work: 50% report that they have reduced work hours. 60% report that pain interferes with work. Mental health: 40% report work and interest affected by their depression and cognitive problems. Up to 85%, that is huge, report cognitive problems that interfere with their productivity and disease management.

 

[01:26:55]

 

Considerations for SM Management

 

What are the considerations on how to manage these patients? Definitely referral to specialized centers is strongly recommended. We talked about this. It takes multiple specialties to manage these patients. Think about a baseline DXA scan. Remember that this measures bone density. Counsel patients regarding the signs and symptoms of disease. Lots and lots of disease education, very important for these patients.

 

Counsel patients to avoid triggers. If they find something such as extreme temperature, fluctuation, stress, stings, venom, anything that makes it worse, try to avoid. They should carry an injectable epinephrine, 2 autoinjectors to manage anaphylaxis. Then assess symptoms, burden and quality of life using questionnaires. There are specific questionnaires that are specific to systemic mastocytosis. The MQLQ, this is a quality of life. Then we have the MSAF. This measures symptoms. These are a diary that patients can keep.

 

[01:28:09]

 

Patient Anaphylaxis Education

 

What about anaphylaxis? What should we tell our patients about this? They should know that it is common. Reported prevalence, 24% to 49%. A 1-patient survey found that within 1 year, 30% had more than 1 emergency room visit for anaphylaxis, 14% used their epinephrine greater than 2 or more times. Patients need to know anaphylaxis symptoms and if they feel it coming on, they need to know how to recognize that.

 

Access to an epinephrine injector. They can use a treatment plan. You can see 1 on the right here, this emergency action plan, and training in injector use.

 

[01:29:00]

 

          Addressing SM Comorbidities: Multidisciplinary Care

 

Now addressing the comorbidities: multidisciplinary care. Guidelines do strongly recommend referring people who have or may have systemic mastocytosis to specialized centers. Remember that there is a lot going on. This is all the different things and specialists that could potentially need to be called in to take care of these patients.

 

Endocrinology for osteoporosis. You need an allergist, an immunologist for sure. Dermatology, psychiatry. These patients probably have a lot of depression and other things going on. Gastro, we have seen all the GI symptoms that can happen, especially even enlarged organs or the organs that are affected.

 

Then diagnosis, a pathologist experienced with SM assessment. I think if you do not work in dermatology, you need to be aware that there is a difference between a general pathologist that reads tissue samples and a dermatopathologist that is very familiar with dermatology skin diseases because they have trained in dermatology as well as pathology, so they do know specifically how to read those slides.

 

[01:30:21]

 

Addressing SM Comorbidities: Polypharmacy Is Common

 

Also, polypharmacy is common. These patients tend to be on a ton of medications. Lots and lots of things which we talked about that you need to use to manage these patients’ symptoms. Patients routinely use multiple medications and 50% use more than 3 medications and 60% use more than 3 over-the-counter medications. They are not only using prescription but over-the-counter. They are polypharmacy-ing themselves as well.

 

Risk of polypharmacy increases when multiple healthcare providers and pharmacies are involved without proper interprofessional communication, you have to talk among each other. Also there is not a healthcare professional who knows the patient's full regimen. You really need to know this patient's complete history with the disease, how it was diagnosed and what they have tried and felt.

 

[01:31:33]

 

Including Patients in Discussions About Medications Can Reduce the Risk of Polypharmacy

 

Including patients in discussions about medications. Shared decision-making, we have been talking about this. Patients can help reduce the polypharmacy risk by they need to bring a current list of medications to their appointments. They need to talk with their HCPs before starting non-prescription treatments. Do not just go buy things and start taking them.

 

Talk with their HCP about how long a medication should be taken and if it can be stopped. Reviewing medications prescribed after hospital discharge with their HCP. Trying to get all medications from 1 pharmacy that helps with records for sure and asking about de-prescribing. New treatment landscapes. We have seen this. We talked about this, can definitely change how patients are being treated.

 

In the PIONEER trial, patients using the medications that were talked about were more likely to reduce or discontinue symptom-directed polypharmacy.

 

[01:32:35]

 

          Importance of Shared Decision-making

 

The importance, again of shared decision-making. Patient education with any disease state is so important. Treatments, evidence, individualize the treatment. Not everything works for every patient, we have all seen. Monitor, adjust treatment, consistent follow-up and patient support services are very important. Listen to the patient's perspective on the importance of these elements in the systemic mastocytosis care.

 

We have another video that we will watch

 

[01:33:08]

 

Patient Video 2: My Life After Finding and Effective Treatment and a Provider Who Listens to Me

 

Rachell: After you go through that search period and you do find that provider that puts the pieces together. For me, I was in an MD PhD program on the East Coast and 1 of my immunology professors put the pieces together. She put together that there was multiple ICU stays, that there was urticaria, the immunology response where I was flush from head to toe, the heat, the edema, the word swellings and things like that. She pulled me aside one day and said, “Hey, I think I know what is going on with you”.

 

We then went ahead and did the bone marrow biopsy and it was confirmed that I had ISM. After that came through, I got kind of pushed back on my primary care provider and they and her both were the persons that managed my care. During that time, I got put on the standard protocol for ISM and it didn't immediately work. I think that that is an expectation that we, as patients, have is that we are going to get it and three days later everything is going to be better and magic and it is not.

 

For me, it actually took adding a chemotherapeutic agent to the mix, getting rid of some medications, adjusting some medications. I think that there is this expectation on us as patients that it is a cure and it is magic and it is not.

 

Another thing that happened to me after I was diagnosed is I got pushed, my care got shifted. I am being managed by 2 nurse practitioners who are in primary care who manage me phenomenally. We are a great team. There is a lot of shared decision-making between myself and them. A lot of open communication.

 

I think that when you have a disease such as this and it is so complex and it is so rare and every patient does not present the same, it is important that it is not the care or the protocol for is not just followed like a straight linear process because each patient is different. Again, I think that it is very important that providers and patients do have shared decision-making in this disease, again, because it is so complex and nobody looks the same. Then you have mast cell activation disorder, which mimics SM that it is not.

 

I think, again, education, program and communication and shared decision making is so important in this process and especially with this disease.

 

[01:36:07]

 

Patient Support Resources

 

Kristine Kucera: Remember, it is very, very important to give the patient some resources that they can use for support. We all have those patients that either go to  Dr. Google or TikTok and get bad information. I always want to make sure my patients know where to get good information, especially when you are first diagnosing them, you are hitting them sometimes with what they say, a ton of bricks. They just do not really know how to take it all in. Sometimes they cannot really process everything you have told them. Please make sure they do have support resources they can go to after their visit that are on the up and up and will give them the correct information.

 

[01:38:10]

 

Skill Building and Feedback III: Strategies for Addressing the Burden of SM

 

Let us talk about some strategies for addressing the burden of SM.

 

[01:38:15]

 

Case III: Introduction to 44-Yr-Old Truck Driver

 

Let us talk about this third case. This is a 44-year-old truck driver that was first seen at a spine clinic for back pain after a fall. He was diagnosed with osteoporosis of the spine. Rheumatology and endocrinology assessed osteoporosis diagnosis, but he was referred to a mastocytosis center due to osteoporosis and elevated serum tryptase.

 

Information added to the patient's history. He had reflux that he was being treated with a PPI. He had some right-sided abdominal pain. He did complain of abdominal cramps and loose stools that would be triggered by certain foods, heat, stress, and alcohol. He does have anaphylaxis with loss of consciousness after hornet stings. He complains of intermittent itching, mental fog that makes it difficult to complete routine task and recurrent hives and allergic rhinitis.

 

[01:40:25]

 

          Case III: Follow-up of 44-Yr-Old Truck Driver

 

They did do a bone marrow biopsy and genetic testing to identify a KIT D816V positive SM. He has received the following prescriptions:

 

  • Full strength aspirin for elevated prostaglandin and flushing;
  • Epinephrine with education on its use;
  • Nonsedating H1 antihistamines;
  • Omalizumab;
  • Compounded ketotifen;
  • Immunotherapy to venoms;
  • Mirtazapine and escitalopram for anxiety and depression; and
  • Single dose of zoledronic acid.

 

I would like to go back and just kind of talk with our faculty and see would you have done anything different when this patient comes in, they have been seen by rheumatology, endocrinology, they are referred to the mastocytosis center. Of these choices that are here in this poll. I feel like there should be more than one potential answer here. What would you do,  Dr. Bernstein?

 

Dr. Bernstein: When you get a baseline serum tryptase obviously, and then I have got a c-KIT mutation, you got to make sure you send it to a lab that has a sensitive assay. I mean it used to be ARUP[?] and LabCorp, but now I think that Quest has a sensitive assay. But you can screen these people in the blood. That is the first thing.

 

Of course, not everybody has a c-KIT mutation or has that D816V mutation, but it is a good starting point. Obviously, they should have an epinephrine injector and understand how to use that. There is not only subcutaneous intramuscular. Now there is intranasal available. I always maximize their H1, H2 blockers, possibly with times to help do that.

 

I do start aspirin if they have elevated biomarkers. You have to get 24-hour urines for methylhistamine, prostaglandin-F2-alpha and leukotriene E4. But if they have biomarkers, I will start them on aspirin, not routinely.

 

Then at that point, we will see them back. But again, these are indolent, they are not aggressive. They are not severe patients who are going to drop dead. You see them back and then you decide based on the test results.

 

In these cases also, if they have elevated tryptase and had no other workup, I will get a TPSAB1 mutation as well to look for hereditary alpha tryptasemia. In the PROSPECTOR study, we did find a subset of patients who did have the mutation of the tryptase gene. It is important to characterize these people.

 

I would make sure that when these people are being seen in what you call centers, that they are part of The American Initiative in Mast Cell Disorders centers of excellence. We are a center of excellence. I do not routinely put everybody on omalizumab for this. There are circumstances where one might want to do that, especially if you are considering starting venom immunotherapy or something of that nature.

 

There is a lot of nuances in how one would approach this. But the first thing is to get the blood tests, the tryptase, the c-KIT. I would also do a TPSAB1 mutation as well. Then once you have that, if there is a mutation, of course, and if they have other clinical features, this guy has got a lot of those features, he should have a bone marrow biopsy. The bone marrow biopsy should be read as mentioned by a pathologist who has experience reading this. These require special stainings with c-KIT stains, tryptase stains. You cannot just read this with H&E.

 

There is a whole criteria for reading bone marrow biopsies. If you are going to do a skin biopsy, a skin biopsy as well because it does require good dermatopathologist to really look at these biopsies carefully.

 

There are standardized approaches now. There is work group reports which talk about how to look at skin, GI, and bone marrow biopsies. This stuff. But again, you have to rather than throw in the kitchen sink, I like to do things. There is no emergency here. There might be an emergency, but there is no emergency characterize the patient. That is how I would approach it initially.

 

Kristine Kucera:  Dr. Bernstein, thank you for elaborating on what other testing you would do because we always want to make sure that if we do run, let us say, serum tryptase and the KIT mutation and they are negative, do not just say, “Great, you do not have it”. You have got to really dig in and give these patients an answer. Thanks for elaborating on the other tests that you would do as well.

 

[01:48:19]

 

          Key Takeaways and Call to Action

 

Key takeaways and call to action that we have here. I think our faculty illustrated this very well, that the patients with systemic mastocytosis face considerable burdens such as severe and unpredictable symptoms, disease impact on multiple symptoms within their own body, polypharmacy and the need for multidisciplinary care.

 

I mean, you saw the drugs that we have on there in addition to specific SM drugs. I think it is really important to have that team approach when treating these patients.

 

Timely diagnosis. Obviously, the sooner the better because effective treatment can relieve some of these burdens associated with SM. Many treatments are targeted to alleviating mast cell mediator-related symptoms. New targeted agents such as specific KIT inhibitors can reduce symptoms and mast cell burden.

 

Many patients with systemic mastocytosis do present with cutaneous signs and symptoms. Definitely dermatology, HCP should routinely consider it. Again, just keep it in your mind. Do not forget about it as being a potential diagnosis. Again, as member of care teams for patients with SM, dermatology HCPs should understand the pathophysiology and burdens of systemic mastocytosis and be aware of the treatment advances.