Systemic mastocytosis is a rare disease in which excess mast cells are produced and activated, resulting in chronic, severe, and heterogenous symptoms. CheckRare spoke with Patrick C. Foy, MD, a Clinical Hematologist practicing at Froedtert Hospital, Milwaukee, and Associate Professor, Medical College of Wisconsin, about the diagnostic challenges of systemic mastocytosis and optimizing patient care.
Systemic mastocytosis can present as a simple rash, cutaneous lesions, generalized fatigue, or even spontaneous anaphylaxis, said Dr. Foy. That is one of the greatest challenges in diagnosing the disorder. “We have a bias that allergists deal with these types of problems in general,” he noted. A patient with skin lesions and an unexplained elevation of blood tryptase level (>15 ng/mL) should tip off that the cause is systemic, not an external allergen, and systemic mastocytosis may be the cause.
Systemic mastocytosis is classified into two categories, indolent (the most common) and aggressive, which is an advanced form that may threaten damage to organs that have been infiltrated by mast cells. “It’s a paradigm that comes from the oncology world,” explained Dr. Foy. Even though patients with indolent systemic mastocytosis have a longer life expectancy than those with the aggressive form, “It does not mean it is a benign disease,” he said. Patients are still at risk for several chronic symptoms, like fatigue, brain fog, pruritic, rash, diarrhea, and bone pain.
Treatment of patients (commonly with antihistamines) with systemic mastocytosis has been directed at symptom control, but these don’t address the root cause of the problem. In the vast majority of patients, the mast cell proliferation is driven by a gene variant, KIT D816V, “and the more we understand about the biology of mast cells and the regulation, the more we understand about treatment targets,” Dr. Foy stated.
Meaningful clinical benefit would include lower tryptase levels (a surrogate for clinical improvement in mast cell status), lower patient-reported fatigue scores, fewer (or clearance of) cutaneous lesions, and improved quality-of-life ratings. Dr. Foy emphasized that “we have therapies that will impact the patient’s quality of life, they are relatively simple to administer and tend to be effective. We can make a big difference in their lives.”
Our greatest unmet need is to reduce or eliminate diagnostic delays, he said: Patients can remain undiagnosed for years or even decades. That calls for increased awareness by both generalists and specialists.
At Dr. Foy’s institution, he works with allergists and immunologists to optimally treat patients with systemic mastocytosis. “It is a multisystem disease, and it needs a multidisciplinary approach,” he concluded.
To learn more about systemic mastocytosis and other rare hematologic conditions, visit https://checkrare.com/diseases/hematologic-disorders/