Systemic mastocytosis (SM) can be divided into 3 main subcategories: advanced SM, indolent SM, and smoldering SM. Each subcategory typically entails different symptoms, disease course, and prognosis.
The clinical presentation of SM is known to be heterogenous. In adult patients, multiorgan dysfunction is often observed, leading to early mortality.
Read more about SM etiology
Establishing a Diagnosis
To arrive at a diagnosis of SM, it is vital that a detailed clinical history is obtained from the patient. It is also important that physicians are aware of the patient’s full drug history. Physicians should also pay particular attention to any history of anaphylaxis to drugs, foods, or other triggers.
“A comprehensive evaluation of symptoms should be taken and triggers of mast cell activation symptoms should be assessed and documented (ie, heat, friction, nonsteroidal anti-inflammatory drugs (NSAIDS), opioids, anaesthetics, contrast, vaccines, dextrans, anxiety, stress and insect bites),” Scherber and Borate wrote in the British Journal of Haematology.
The major diagnostic criteria for SM accepted worldwide is the presence of multifocal, dense infiltrates of mast cells in sections of the bone marrow and/or other organs (extracutaneous). There must be 15 or more mast cells in aggregates detected in the locations mentioned.
Hence, biopsy samples of the bone marrow are often taken for diagnostic purposes. Biopsies from the liver or the spleen, on the other hand, are rarely taken. The bone marrow may also yield important information such as a second hematological neoplasm if one is present.
Another key laboratory investigation for the diagnosis of SM is the evaluation of serum tryptase levels. Studies have demonstrated that a high serum tryptase is linked to possible infiltration of the bone marrow by neoplastic mast cells. The cut-off point for high serum tryptase is 20 ng/mL and above.
Symptom-Focused Outcome Measures
Another important part of establishing a diagnosis of SM is corroborating a patient’s signs and symptoms with the investigations being carried out. In addition, the input of a patient with a confirmed diagnosis of SM on the efficacy of the treatment received is also important.
“A content-valid patient-reported outcome (PRO) questionnaire that assesses concepts relevant and important to individuals with a condition, in a way that is understandable to respondents, is important for assessing the efficacy of novel treatments in clinical studies, as well as supporting product labeling claims,” Taylor and colleagues wrote in the Orphanet Journal of Rare Diseases.
In other words, patients should be front and center throughout the diagnostic and treatment process. As physicians, we need feedback from patients regarding symptom severity and the impact of the disease on their daily lives. Hence, it is highly desirable to have a questionnaire or a checklist of items to ask during an interview in order to quantify the patient experience.
However, it is precisely these sorts of mechanisms that are lacking in SM care. Taylor and colleagues hence decided to develop a single PRO instrument that can be used to evaluate the signs of symptoms in patients with SM.
Read more about SM treatment
Through a combination of literature reviews, discussions with clinical experts, interviews, and questionnaire construction, the research team was able to develop two patient-reported instruments: the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF) and the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF).
“Cognitive debriefing of both instruments with patients with the respective conditions demonstrated the content of each questionnaire to be relevant, the items easy to comprehend, and the response options clear and appropriate,” the researchers wrote. “Together, results presented here support the conclusion that both the AdvSM-SAF and ISM-SAF are content valid in the respective target patient populations.”
Meaningful Patient Involvement
Because SM is such a rare disease, it is vital that patients are educated on some of its basic facts. Aside from skin lesions, patients should be made to understand that the range of symptoms differs from patient to patient. For example, symptoms as diverse as fatigue, abdominal discomfort, bone pain, depression, headache, and hepatosplenomegaly have been reported.
In aggressive SM, organ dysfunction can happen. This is due to mast cell infiltration into various organs in the body. If this occurs, physical and laboratory findings should be able to help physicians identify the organs in question.
Patients should also be made aware that massive mast cell degranulation can lead to anaphylactic shock, which can be life-threatening. The list of potential triggers is long, including stress, medication, insect sting, alcohol, and more. Patients should be made aware of the signs and symptoms of an anaphylactic reaction and advised to seek medical attention immediately.
“The unique clinical profile of SM patients and expansion in our understanding of the molecular underpinnings of disease and pharmacological advancements provides both challenge and opportunity for the SM clinician,” wrote Scherber and Borate. It is up to us physicians to choose to meet the challenge of the moment.
Pardanani A. Systemic mastocytosis in adults: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2021;96(4):508-525. doi:10.1002/ajh.26118
Taylor F, Akin C, Lamoureux RE, et al. Development of symptom-focused outcome measures for advanced and indolent systemic mastocytosis: the AdvSM-SAF and ISM-SAF©. Orphanet J Rare Dis. 2021;16(1):414. doi:10.1186/s13023-021-02035-5
Scherber RM, Borate U. How we diagnose and treat systemic mastocytosis in adults. Br J Haematol. 2018;180(1):11-23. doi:10.1111/bjh.14967